Disturbances of general blood volume




Disturbances of general blood volume. Blood loss


The pathological changes of blood system can arise in any functional part of it, which are closely connected and not strictly isolated. The main components of blood system violations are changes of the blood volume, quantity, structure and function of the blood cells, hemostasis, biochemical, and physical-chemical blood properties.


Changes of total blood volume

The normal quantity of blood is 5-6 liters or 6-8 % of body weight. This volume can change, but its rate does not exceed 5 % of its initial volume. There is 20-25 % of blood volume in the pulmonary circulation; heart receives 8-10 % of it, and lungs 12-15%. The systemic blood circle contains 75-80 % of blood. 15-20 % of blood circulates in the arterial system, 70-75 % in the venous system, and 5-7% in capillaries one. The main blood volume is intended for the maintenance of movement constancy, and for duly heart filling. Normal volume of circulatting blood can be characterized by concept normovolemia. The violations of blood volume develop into hypervolemia and hypovolemia.

Normovolemia, hypervolemia, hypovolemia are distinguished, depending on rate of hematocrite parameter (norm is 0,36-0,48 L/L) as simple, olygocytemic and polycytemic. The normal condition of blood, which is characterized by normal volume and normal hematocrite parameter, is named the simple normovolemia.

Olygocytemic normovolemia is characterized by the decrease of hematocrite index and arises at posthemorrhagic anemia, when blood volume is supplied with extravascular liquid, and the quantity of erythrocytes is not restored yet; the similar state arises at massive hemolysis, cachexia.

Polycytemic normovolemia can occur in the conditions high-altitude hypoxia, at lungs emphysema and heart disease, after the transfusion of erythrocyte mass or blood small quantities.

Hypervolemia is a pathological state, which is characterized by the increase of circulating blood volume. Simple hypervolemia (hematocrite index is normal) can be the consequence of plenty blood transfusion, of intensive physical work and heart failure (in those conditions the deposited blood comes into vessels).

Olygocytemic hypervolemia (hematocrite index is lower than norm, and the blood quantity is increased at the expense of plasma) arises as the result of water excees in the organism at the disorder of renal function after injections of physiological solution or blood-substitutes.



Polycytemic hypervolemia (hematocrite index is higher than norm, and the blood quantity is increased at the expense of erythrocytes) occur as the result of deep hypoxia of the organism at the atmospheric pressure drop, at cardiac defect, at chronic lungs diseases as the compensatory reaction and also as the result of the malignant stimulation of erythrocytes growth (erythrismal). The fast-development hypervolemia can provoke the blood circulation violations, stagnant phenomena in the pulmonary circulation. Besides that, the increase of the circulating blood volume promotes the vessels over-expansion, the decrease of their tonus and permeability, the blood condensation, and this in its turn worsens the heart work.

Hypovolemia is a pathological state, which is characterized by the volume circulating blood reduction. The simple hypovolemia (hematocrite index is normal) can be the result of blood losses, when the blood volume is not restored, of shock states (in this case the significant part of blood does not participate in the circulation).

Olygocytemic hypovolemia (hematocrite index is lower than norm) arises after the acute bleeding, when the blood volume began to be restored, with the extravessel liquid, at malignant Addisone-Birmers anemia (in this case the quantity of plasma is not changed and the quantity of erythrocytes is much lower than norm).

Polycytemic hypovolemia (hematocrite index is higher than norm) is characterized by the relative increase of the erythrocytes amount in blood. Such state can develop at dehydratation caused by diarrhea, vomiting, burns, hyperthermia, and also at shock (the vessels permeability increase and the output of plasma through their limits are characteristic). At that state blood becomes dense, viscous, and that worsens hemodynamic processes.


Blood loss

Blood loss is a pathological state of the organism arising in the reply to the significant blood loss from vessels and is characterized by the development of number compensatory and pathological reactions. Depending on an anatomic type of the damaged vessels there are arterial, venous, capillary and parenchymal bleedings. Arterial bleeding is characterized by massivity and intensity. The bleedings from big vessels are dangerous, when from the damaged vessel blood is streaming by a pulsing jet and the irreversible consequences blood loss can arise within several minutes. The difference between the arterial and venous blood pressure disappears, the right atrium blood inflow diminishes and blood circulation becomes impossible.

Venous bleeding is characterized by blood outflow from the damaged vessel by a continuous jet. Venous bleeding more often than arterial ends with independent hemostasis due to the formation of hematoma and vessel compression, and slowing down of blood flow speed.

The capillary bleedings in the condition of normal blood coagulation are the insignificant and usually stop owing wound filling. The bleeding from capillaries is the mostly widespread at injuries of skin, muscles, mucous membranes and bones. Blood follows from smallest capillaries by a thin jet. In such cases the whole wounds surface bleeds.

Parenchymal bleedings are caused by damage of liver, spleen, kidneys and pancreas. These bleedings can become profuse as the result of plenty microvessels damage of parenchymal tissue. In the absence of large arteries and veins damage the spontaneous stop of the bleeding is possible due to blood clot, which is formed in the area of damaged organ.

Depending on time of occurrence there are primary and secondary bleedings. Primary bleedings arise at the moment of blood vessels damage; the secondary bleedings can develop a bit later after a trauma, as the result of wounds infection development or the repeated trauma of the damaged vessel.

Depending on the localization of bleeding source and the places of blood receipt there are internal, external and mixed bleedings. The internal bleedings can be intracavital, intratissual and mixed. Intracavital bleeding (into abdominal and pleural cavities) are characterized by the violation of clots formation owing to the defibrination of blood by pleura, peritoneum and synovial joint membrane. Intratissual bleedings arise in skin, fat tissue, muscles and interfascial spaces. The reason of the mixed bleedings can be simultaneous damage of abdominal cavitys organs and retroperitoneal space ones. The external bleedings arise because of skin and mucous membranes damages.

Profuse external bleedings arise in the result of limbs big vessels damage, at penetrating thorax wounds and abdominal cavity ones. The mixed bleedings are characterized by combination of internal and external signs. First they arise as internal, when blood gets to a hollow body, for example, digestive tract, bladder uterine cavity, then after some time the signs of external bleeding (bloody vomiting, hematuria, metrorrhagia) appear.

The pathogenic principle of bleedings classification includes three types of them: mechanical origin bleedings, erosive bleedings, and bleedings developing as a result of vessels permeability violation. The mechanical origin bleedings are caused by the effect of blunt trauma (bruises, compressions, pressings, breaks) and wounds caused by cold and fire arms. Incisive wounds cause the most intensive bleedings, when edges of vessels are smooth and the minimum quantity of thromboplastin is formed in tissue. Fragmentary and bruised-compressed wounds are accompanied with less expressed blood loss as the interposition of intimae and fast formation of thrombi occur due to formation of plenty thromboplastin in wound, acidosis and erythrocytes aggregation.

Erosive bleedings are the result of vessel wall disorder at various diseases of internal organs. At the result of necrobiotic processes prevalence and the destruction in tissues of the affected organ the erosion of different caliber vessels and the occurrence of latent bleedings are possible (stomach and duodenum ulcer disease, malignant and benign tumors, portal hypertension, ulcerous colitis, cavernous tuberculosis). The bleedings developing due to the violation of vessels wall permeability arise under the influence of toxic substances, allergic and infectious agents. They occur in the patients suffering a scurvy, hemorrhagic vasculitis, arterial hypertension, acute and chronic leucosis.

Depending on the clinical characteristic of the patient state there are mild blood loss (the quantity of the lost blood doesnt exceed 10 %), middle serious blood loss (30 %), and heavy (dangerous) blood loss (the quantity of the lost blood doesnt exceed 30-50 % ). The loss of over 50 % of blood is very dangerous for patients life and can be fatal, and the decrease of the circulating blood volume by 60 % is fatal the patient.

Blood loss is divided into acute and chronic in clinical practice. The degree of patient stability to blood loss depends on many factors: blood lost volume, bleeding speed, patients age and sex, accompanying diseases, the state of regulator systems. Pathogenesis of organism changes is very complex, but it is possible to divide all reactions, which arise at bleeding into pathological and compensatory. The conditional character of this division is stipulated by the fact that at certain stages of organism struggle with the consequences of a bleeding the compensatory reaction can strengthen the pathological displays and worsen the organs and tissues condition.

Hemodynamic disturbances. Hypovolemia starts the mechanisms of complex hemodynamic disorder. Blood loss is stress, which activates of hypothalamus-hypophisis-adrenal system due to the barroreceptor irritation (in aorta and carotid arteries, where are located the richest receptor zone) because the arterial pressure decreases. In addition to catecholamines, which make vessels spasm, the secretion of glucocorticoids and aldosterone from cortical layer of adrenal gland increase.

First of all the contraction of vessels smooth muscles of the capacitor department venous system arise, because these vessels are more sensitive to catecholamines, than the resistance vessels. 10 % of the lost blood without any change of heart emission can be compensated due to capacitor vessels contraction of skin, lungs and abdominal organs.

The redistribution of blood stream, which is promoted also by the opening of artery-venous anastomosis, increases the blood supply of vital organs, that is heart and brain due to ischemia of other organs. First vasoconstriction of all the organs, and then the systems develops.

This compensation mechanism is urgent; its main result is the reflectory spasm of peripheral vessels, which promotes the centralization blood circulation and the maintenance of normal blood pressure level. The bleeding continuation causes the inclusion of additional adaptation mechanisms the transition of extravessel liquid into vessels; its the so-called hydremic phase of compensation. This is possible due to increase of precapillar resistance under the influence cateholamines and aldosteron.

The precapillar resistance arise due to the contraction of vessels smooth muscles (there are two mechanisms: strengthening of basal myogenic tonus due to the vasopressor nerves activity increase and strengthening of basal myogenic tonus of vessels), and also due to the short-term increase of blood viscosity. Postcapillar resistance also increases, but to a lesser degree. As the result of such changes, the average capillary hydrostatic pressure reduces, and the colloid-osmotic pressure still remains at a sufficient level, that promotes the amplified extravessel liquid inflow into the vessels.

The consequence of this compensatory mechanism is the circulating blood volume increase and the maintenance of normal heart and brain functions. But further blood loss can cause the decompensation and the organs functions violations. Generally this is conditioned by the state of vasoconstriction and depends on its duration. The state of vasoconstriction has phase character of its development. It is conditioned by the division of vessel system into departments with primary function of resistance and capacity and depends on sympathetic-adrenal activity and on tissue metabolism state. The narrowing of the capacitor vessels can be related to the first phase of vasoconstriction state, this compensatory reaction (centralization of blood flow) doesnt promote organs damage.

The second phase of vasoconstriction is characterized by the system narrowing of vessels directed on the maintenance of arterial pressure at a normal level, but in this case some organs damages owing to microcirculation decompensation arise because blood circulates only in large (central) vessels.

The bleeding results in progressive decrease of heart emission. This changes baroreceptors activity promotes the reflectory tachycardia, and also the spread of diffused vasoconstriction state. The decrease of circulating blood volume reduces the average blood pressure; it promotes the reduction of the difference blood pressure between right atrium and vanae cavae, the venous inflow and the heart emission decrease. This changes lead to the decrease of organs blood circulation (at first of kidneys, liver, stomach, intestine, and then of lungs and adrenal glands).

There is blood stream redistribution from cortical layer into medullar one in kidneys. It is carried out according to the type of juxta glomerular shunt due to interlobular arteries and afferent arterioles of cortical glomerules spasm with preservation intensive blood flow in the cortical-medullar zone. Artery-venous anastomoses of kidneys dont function almost in norm. The blood stream redistribution promotes the renal filtration reduction. The kidneys oxygen consumption decreases because the number of open capillaries decreases. The kidney ischemia strengthens the rennin secretion, the angiotensin-2 synthesis, which in its turn stimulates the secretion of aldosteron from adrenal glands. All these humoral substances strengthen vasoconstriction (in kidneys too). The acute renal insufficiency arises in the result of prolonged vessels spasm.

The livers vessels spasm reduces of portal blood flow and promotes change of livers metabolism. The carbons metabolism violation is characterized by the hyperglycemia, lactic and piruvate acids accumulation, metabolic acidosis, violation of glycogen synthesis.

Electrolyte metabolism violations are manifested by the increase of Na, Ca and the decrease of K, Mg and inorganic pH blood.

The protein metabolism violations are characterized by the urea synthesis reduction, the protein synthesis decrease (reduction of albumens, globulins, fibrinogen and prothrombin). Hypoproteinemia and dysproteinemia are the main signs of these violations. Heavy blood loss can cause dystrophy or necrosis of hepatocytes. Mesenteries blood flow is closely connected with the hepatic one because common portal channel containing unites them. The mesenteries blood flow violations in mesenteries come earlier, than in kidneys and brain. The increase of sympathetic-adrenal system activity results in strengthening of intrahepatic sphincters spasm, the portal and mesenteries pressure increase.

The venous vessels tonus reduces, the blood stagnation in abdominal cavity organs arises. The microcirculation violations (contraction of arterioles, venules and capillaries, the stasis, the increase of plasmatic capillaries quantity, the blood cells aggregation) provoke of intestine and stomach ischemia. Synthesis and secretion of vasodilatators into blood (histamine and histamine -similar substances, acetylcholine, kinines, lactic and piruvate acids), and also of intestine toxins are the result of intestine hypoxia. The danger of this state consists in the derivation of stomach and intestine trophic ulcers, which can become complicated by a bleeding and perforations.

Breath plays the important role in the development at first of compensating and then decompensation reactions. The circulating blood volume reduction causes hypoxia. The pulmonary blood flow decreases parallel with heart output lessening. Compensatory reactions (the increase of O2 tissues supply) promote the development of hyperventilation (due to the chemoreceptors and partially baroreceptors activation) and the more effective 2 utilization.

It results in the increase of arterial and the decrease of 2 partial pressure in arterial blood. Such changes promote the reduction of brain blood flow, and brain ischemia strengthens vasoconstriction, from which lungs suffer too.

The lungs blood flow limitation promotes the decrease of lungs elasticity, the increase of air ways resistance, the cells aggregations formation in pulmonary capillaries, bleedings in alveoluses and small-sized bronchi, the damage of vascular endothelium and alveoluses epithelium, the decrease of surphactant synthesis, the increase of respiratory dead space and leads to ventilation insufficiency.

The 1/3 part of minute blood volume is spent for the maintenance of brain blood circulation. Brain vessels are exposed to constant vasodilatation influences from the synocarotid receptor zone. The sympathetic stimulation renders vasopressor influences but of lesser degree, than on other organs vessels. Brain vessels are very sensitive to 2 and O2 blood level; they extend at 2 surplus and at 2 lack and contract due to the increase of 2 and the decrease of 2 blood level. Moderate blood loss (up to 20 % of volume) promotes the expansion a brain arteries and the increase of brain blood flow (the effect of blood flow centralization).

But the decrease of circulating blood volume lower than 20 % worsens the brain blood supply, causes the infringement of the central nervous system activity because the arterial blood increases, the 2 concentration decreases, arteries extend and the blood flow insufficiency progresses.

Peripheral compensatory vasoconstriction causing the skin cooling causes the hypothalamic reaction, which is manifested by the strengthening of vessels constriction. The subsequent development of metabolic acidosis reduces cerebral blood flow, brain ischemia strengthens the system vasoconstriction and limits the hydremic compensation mechanism. The heart activity depends on a degree of acute blood loss and the deficiency of circulating blood volume.

Blood loss up to 10 % of volume does not reduce the heart output. The further reduction of blood volume reduces the minute blood flow volume, infringes myocardium metabolism, and reduces heart output. The lasting bleeding exhausts all compensatory capacities of the organism.

Vessels capacity cannot be decrease by vasoconstriction, and the decrease of heart output is not compensated by the tachycardia. On the contrary, tachycardia reduces a diastolic interval and on the background of the reduced gradient of pressure between the right atrium and central veins worsens the heart filling; the arterial pressure is lowered, the heart and vessels insufficiency develops.

Blood loss more than 10 % of blood worsens the microcirculation and its signs arise much earlier, than in macrocirculatory channel. The microcirculation disorders have some stages: vasoconstriction stage; the stage of duplicated violations (arterioles spasm, venules and capillaries dilatation); the stage of all vessels dilatation. The microcirculation violations are the result of prolonged vasoconstriction, of the disclosure of arterial-venous shunts, of the increase of plasmatic capillaries quantity, of the increase of blood viscosity and erythrocytes aggregation, of the intravessels thrombosis, of vessels damage by vasotoxic substances.

Microvessels sensitivity to endogen pressor amines reduces and gradually the capillaries disclosure appears, and as the result of this the blood stagnation up to stasis, especially in small-sized venules, develops. Such changes aggravate the decrease of arterial pressure, the decrease of 2 blood concentration, the increase of capillary blood hematocrite index, the infringements of capillary hemodillution, the decrease of tissues perfusion and cells metabolism disorder, the development of secondary heart failure, violations of the central nervous system activity, and shock condition. The tissues metabolism disorders depend on the degree of blood loss and hypovolemia, the changes of macro- and microcirculation.

Arterial hypoxemia and the reduced peripheral blood flow results in the total hypoxia. Blood loss of easy and mild seriousness due to start of compensatory reactions save the O2 consumption. Heavy blood loss amplifies the aorta-venous shunting and tissues perfusion sharply reduces.

Hypoxia reduces aerobic metabolism and macroergic substances synthesis, but promote the activation of anaerobic reactions. The carbons metabolism changes are manifested with hyperglycemia, lactic and pyruvate acids accumulation, metabolic acidosis development because the mobilization glycogen from depot takes place catecholamines, glucocorticoids and thyroxin influence. The glycogen and macroergic substances stocks are rapidly exhausted and anaerobic glycolysis is activated. In the conditions of heavy blood loss and the decrease of pancreass blood supply the insulin synthesis is decreased, the cells glucose contents reduces and diabetes-like state develops (despite of hyperglycemia, the cells keep the requirement in glucose, which can not penetrate through their membrane).

Lipid metabolism in conditions of sympathetic system activation and pancreas insufficiency is characterized by lipolysis activation. The fatty acids and triglycerides concentration increases, and this can promote the fatty infiltration of organs, ketone bodies accumulation and ketoneacidosis development.

Plasmal hyperlipemia violates blood viscosity and provokes the erythrocytes aggregation and the decreases of O2 blood capacity. The disorders of protein metabolism are mainly provoked by the insufficiency of liver protein-synthesis function and are manifested by hypoproteinemia, dysproteinemia. Oncotic (osmotic) blood pressure lowers and this promotes the infringement of transcapillar liquid flow. Heavy blood loss is characterized by the reserve protein catabolism activation, which are used in the reactions gluconeogenesis (formation of tricarbonic acids from proteins and lipids), the losses irreplaceable aminoacids (leucine, izoleucine, metionine), infringement of nitrogen balance, and reduction of fibrinogen and prothrombine blood concentration.

Blood loss violates the acid-base balance, but the blood changes are characterized by phases, which are determined by the inclusion of certain compensatory reactions. At first hyperventilation, which arises during development of hypoxia, provokes the gas alkalosis, and then subsequent pathological changes in lungs and disorder ventilation provokes gas acidosis. The tissues blood perfusion violations and anaerobic metabolism activation promote the organic acids accumulation and metabolic acidosis.

Tissue acidosis increases the permeability of capillaries, the liquid leaves vessels, secondarily the circulating blood volume is reduced thus volume of blood inflow and heart emission decreases. Heavy blood losses can become complicated by metabolic alkalosis of aldosteron secretion activation (for Na setback in kidneys and hypovolemia compensation).

The changes of blood structure and its functions are characterized by the decrease of hemoglobin level, of hematocrite index (in capillaries it is increased), of blood oxygen capacity. Blood viscosity and erythrocytes aggregation on the contrary increases and this promotes the blood sequestration, the microcirculation violation and amplification of hemic and tissue hypoxia.

Red bone marrow cells formation at blood loss is one of the main protective factors, which promotes the restoration of blood mass and structure. The red bone marrow depends on erythropoietins quantity, which are formed in reply to blood loss and hypoxia. Blood cells formation at blood loss of an easy degree proceeds as regeneratory normoblast type and is accompanied with moderate hyperregeneration and occurrence of big reticulocytes quantity in the peripheral blood. This is promoted by moderate hypoxia of kidneys, which intensively produce erythropoietins. The newly formed erythrocytes restore the cellular balance within 14-20 days, but their accelerated maturing cause the lowered saturation with hemoglobin and the development of hypochromic anemia.

A blood loss of average gravity is characterized by regeneratory normoblastic type of blood poem, but attributes of erythropoiesis oppression appear (insignificant reticulocytes quantity) owing to blood flow violation in kidneys and red bone marrow (the result of peripheral vasoconstriction). The normoblastic type of blood cells formation is still preserved at grave blood losses, however, the maturing process and the washing away of blood cells are infringed.

The bleeding can be complicated by hemorrhagic shock. Acute decrease of circulating blood volume, of heart emission and tissues perfusion, the exhaust of protective reactions, pathological changes in organism are the main attributes of this state. An initial link of shock is the infringement of biological balance between the capacity of vessels channel and the mass of circulating blood, which the organism cannot support at a normal level due to compensatory reactions.

Clinics consider that main signs of hemorrhagic shock development are the symptoms of microcirculation infringement (the decrease of arterial pressure, tachycardia, venous hypotonia, dyspnoe, oliguria, infringement of consciousness, cooling of limbs, cold sweat). The pathological changes in the organism develop much earlier, than the signs of blood circulation insufficiency and the determination of hemorrhagic shock stages is a little bit conditional (1-st stage - compensated shock; 2-nd stage - decompensated shock; 3-d stage - irreversible shock).

Alteration of hemostasis system. DIC-syndrome. Hemophilia


The hemostasis violations are classificated acording to: the etiology, the directivity of variations and the mechanism of progressing. The directivity of variations there are hypocogulation and hypercoagulation, acording to the mechanism of violations progressing there are vessel-throbocyte hemostasis disorder and coagulative hemostasis disorder. Hypocogulation is characterized by the reduced of blood capacity to coagulate. All reasons of hypocoagulation are united in four groups: thrombocytopenia, thrombocytopathy, angiopathy, coagulopathy.





Thrombocytopenia includes a diseases groups, which are characterised by the decrease of thrombocytes blood level less than 150x109/l. There are the congenital and acquired forms of thrombocytopenias. The congenital thrombocytopenias are mostly followed by the changes of thrombocytes functional properties, that makes it possible to refer these illnesses to thrombocytopathies group.

The aquired thrombocytopenias are the result of immune and mechanical damages, the depression of thrombocytes forming, and increased thrombocytes using.

There are four groups of immune thrombocytopenias:

a) alloimmune- thrombocytes distruction is the result of noncompatibility at one of blood group systems;

b) transimmune- thrombocytes demage can be carried out by mother autoantibodies, who suffers from autoimmunal thrombocytopenia, and these immunoglobulins penetrate through placenta and cause the thrombocytes amount decrease in infant;

c) heteroimmune-thrombocytes damage is the result of their injury by antigenic pattern under the influence of viruses or the appearance of a new antigene or gapten;

d) autoimmune-thrombocytes destruction of is a result antibodies synthesis against own thrombocytic antigene.

Heteroimmune thrombocytopenia are mostly common for children's age, and autoimmune one for adult. Werlhof's disease (so-called idiopathic purpura) is the one example of the autoimmune thrombocytopenia, the main reason of it is the decrease of immune tolerance to own antigenes. T-suppressors deficit predetermines B-lymphocytes activation and autoimmune process beginning. The reason of suppression function lymphocytes failure at the idiopathic autoimmune thrombocytopenia isnt know so far, may be this is T-suppressors genetic trouble.




Figure. Acute idiopathic thrombocytopenic purpura


The possible mechanism provoking autoagression is the alteration of thrombocytes antigene under the influence of drugss, viruses, bacterias. In some cases the bacterial antigenes, probably, have similarity with the thrombocytic antigenes determinants. Macrophages of the spleen plays the main role in pathogenesis of autoimmune thrombocytopenias, they kill of thrombocytes and decrease their number. At heteroimmune thrombocytopenias, the antibodies are synthesized against alien antigene, which are fixed on thrombocytes surface and which have stipulated the alteration of antigenic pattern (this antigene there can be medicines: quinidine, digitoxinum, sulfonilamid drugs, rifampicinum, hypothiazidum, viruses of rubella, chickenpox, influenza and adenoviral infection, vaccine). Thrombocytopenia is dangerous with progressing hematencephalons, gastrointestinal tract bleedings, hematuria

Thrombocytopathies is characterised by hemostasis disorder in the result of platelets dysfunction. The first group is congenital desaggregative thrombocytopathies without any failures of reaction of granules release. This group consist of Glantsman's thrombasthenia (absence of thrombocytes glycoproteins 2 and 3b complex in shells, which are indispensable components of thrombocytes adhesion stimulators and fibrinogen interaction), essential athrombia, May-Heglin's anomaly, partial desaggregative thrombocytopathies. Signs of this group diseases are the petechias, frequent nose bleedings, menorrhagia, hematencephalon.

The second group is characterized by the failure of granules release, which leads to absence of thrombocytes aggregation during their contact with collagen fibers of basal mambrane and the absence of the second surge aggregation, and as the result thromboxan 2 synthesis, ADP, serotonin, adrenaline, 2+ disengagement is violated. The key role in the pathogeny of this defect is played by cyclogenase and thromboxan-synthetase deficit, decrease of membrane phospholypase activity. Clinical signs are petechias, mild appearance of ecchymoses, nose and gem bleedings are possible.

The third group are the result of thrombocytes disability to store and to select granules content (ADP, serotonin, adrenaline, factor IV) at hemostasis. One of examples is the Herdimansky's-Pudlac's disease, which is characterized by not dangerous bleeding. Another example is TAR-syndrome (pathology of megacaryocytic-thrombocytes with bones anomalies).

The fourth group of thrombocytopathies are caused by failures of adhesive and agregational thrombocytes (different variants of Willebrand's and Willebrand's-Urgens' diseases - thrombocytes disfunction is the result of Willebrand's factor deficit; Bernar's-Syle's syndrome, which is the result of megacaryocytes and thrombocytes anomaly, suhc as the increase blood platelets sizes, the absence of glycoprotein 1 in megacaryocytes and thrombocytes cytoplasmic membrane, that being indispensable for the interaction with Willebrand's, V and XI factors. Severe danger even of mild of this disease arises during sexual maturation of the girl (juvenile menorrhagias arise) and at labours.

The fifth group are caused by the deficit and the decrease accessibility of factor III (Boyes and Ovens thrombocytopathies). The thrombocytes pathology is characterized by the deficit of membrane phospholipids, that activate of factor III, so normal structural modification of membranes doesnt take place during adhesion and aggregation of thrombocytes.

Wiscott-Oldridge's syndrome is the example of the sixth group thrombocytopathies. A reason of thrombocytes pathology is the low content of dense and alpha granules, the small conservation of ATP, ADP, serotonin and reductants of alpha granules, decrease of thrombocytes adhesive properties.

The prognosis for life thus is unfavorable. The majority of the aquired thrombocytopathies are characterized by the complication of pathogeny. Only some medicines and toxins (conditioned by aspirin) have legible and stable functional marker. Aquired thrombocytopathies arise at acute leukoses (blastal surrounding provokes disorder of thrombocytes maturation). Thrombocytes dysfunction and hemorrhagic syndrome can be immune inhibition. Immune thrombocytopathies are coused by the capacity of antibodies to damage cytoplasmic membrane and to lock up the receptors. The 12-deficient anemia is also called thrombocytopathy, which is characterized by the disorders of granules release reaction.

Thrombocytopathies can arise at uremia, diseases of the liver. Very often the applying of medical drugs can be the reason of the thrombocytes functions disorder. However the mechanism of many medicines action is well studied and this enables to distinguish the following links of pathogeny of thrombocytes activity disorders: 1) suppression of thromboxan 2 synthesis, such operating mechanism is characterized for phospholypase inhibitors, which violate the arachidonic acid synthesis (hinacrinum, glucocorticoids), for cyclogenase inhibitors (acetylsalycilic acid, indomethacinum, butadionum, ibuprofenum, naproxenum), for thromboxan-synthetase inhibitors (prostacyclinum, imidazole); 2) the decrease of thrombocytes cAMP level, such mechanism of action is characterized for stimulators adenilatcyclase (prostacyclinum, prostaglandinum ), for inhibitors of phosphodieterase, which conduce the cAMP degradation (dipiridamolum, papaverine, euphilinum, flavonoids), for stimulators of prostocycline synthesis, (anabolic steroids, niacin); 3) infringement of Ca2+ transportation (verapamilum, corinfarum).

Vassopathies (angiopathies) are the diseases, which are characterized by the bleeding in the result of vascular wall pathology. All congenital vassopathies, despite their variety, are united by the same pathology - congenital inferiority and improper development of the connective tissue, including vessels subendothelium. Congenital angiopathies are presented by heritable hemorrhagical teleangioectazias, diffusal trunk angiokeratoma, heritable thrombocytopenic microangiomatosis etc.

Bleeding is the basic performance of this disease and is conditioned by the low resistance and easy vunurability of a vascular wall, by very gentle stimulation in these adhesion sections by both the thrombocytes aggregation and blood coagulation. Most often bleedings nose start, however possible are profuse and sometimes fatal bleedings from teleangioectazias of bronchi and gastrointestinal truck, sometimes brain and internal organs hemorrhages are registered.

The group of acquired (secondary) angiopathies (vascular purpuras) includes mostly dermal bleedings, which arise in the result of exogenic or endogenic vessels injuries. There are idiopathic, stagnant (orthostatic), atrophic (dystrophic), neurogenic, mechanical and other acquired vassopathies. The etiology of idiopathic angiopathies is not known (example is the idiopathic hemorrhagic Caposhis sarcoma - reticulihystiocytic system malignant tumor with skin bleeding in the result of vessels hemostasis failure). The stagnant angiopathies can be caused by chronic heart failure, local venous insufficiency (Klots' haemostatic dermatitis, Favr-Racusho's dermatitis) and are the result of long-time tissues hypoxia and vassal dystrophy.




Figure. Skin rashes in patients with hemorrhagic vasculitis (Shenlyayn-Henoch disease)



Steroid purpura is the example of atrophic-dystrophic angiopathies, it arises after the durable treatment by glucocorticoids, which suppress the fibroblasts proliferation, decrease the collagen and mucopolysaccharides synthesis that predetermines the dot hemorrhages.

Vessels dystrophy and the following bleeding can be the result of vascular walls damage by immune complexes (Shanline-Genokhs hemorrhagical vasculitis). The vit. C deficit (scorbutus) also promotes the infringement of collagen fibres synthesis (they ensure the continuity of capillary endothelial covering) and is the reason of bleeding in pericappilar spaces (in fascia, aponeurosis, fatty tissue, muscles, joint cavities, in very severe cases the hemothorax and hemopericardium can develops.

Coagulopathy is the example of hypocoagulation in the result of coagulative blood system pathology development. There are primary (hereditary) and secondary (aquired).

The primary coagulopathies are divided on such group as:

1) failure of internal mechanisms prothrobinase activity forming (hemophilia A procoagulant unit of factor-VIII deficit, hemophilia B factor-IX deficit and hemophilia C factor-XI deficit, Willebradns disease, Hagemans defect factor-XII deficit),

2) failure of external mechanisms prothrombinase activity forming (hypoproconvertinaemia factor - VII deficit),

3) the combined failure of external and internal mechanisms prothrombinase activity forming (parahemophilia factor-V deficit),

4) failure of final stage blood coagulation (hypofibrinogenemia, dysfibrinogenemia).

The patients number, which suffer hemophilia A, B, C and Willebrands disease occur more often in clinical practice. The hemophilia A is the result of heritable deficit or molecular anomaly of VIII-factors procoagulative part, and is characterized by the coagulative hemostasis failure. Normally factor-VIII circulates in blood in the large molecular protein form and consists of a subunits series: glucoprotein having procoagulative property (V:); glucoprotein with property to cause of thrombocytes adhesion (Willebrand's factor - V:W), ristomicine-cofactor (VIII:R-cf.), and also antigenic markers of VIII:K and VIII:R-cof.. Activity of both factor VIII:K and V:W is being decreased at the decrease of complex structure mass. Synthesis of factor-VIII all components is controlled by X-chromosome.

The gene of hemophilia is recessive, thus men are suffered mostly (woman, having the second normal X-chromosome, as a rule, dont suffer from bleeding, but the VIII-factor activity is reduced in twice and this fact should be taken into consideration surgical operations referring to mothers, sisters and especially daughters the person, which is ill with hemophilia. The hemophilia A an be caused by poor synthesis of VIII:K factor, thus its antigen isnt discovered in patients plasma (so-called antigen negative hemophilia or hemophilia A-). In other cases antigen activity of VIII:K factor prevails the activity of this component, as the result of abnormal VIII:K factor synthesis (so-called antigen positive hemophilia A or hemophilia A).






Clinically the hemophilia A is manifested by hemorrhages in major joints of finitenesses, deep hypodermic, intermuscular and intramuscular hematomas, massive and prolonged posttraumatic bleedings. Man, who have cariotype 46,h and women, who have cariotype 46,hh or 45,h suffer with hemophilia A, but woman, who have cariotype 46,h are the carriers only.



Figure. Acute knee hemarthrosis in hemophilia patients Hematoma in hemophilia patients





The Willebrand's disease is the example of autosomal heritable coagulopathy. This is not single disease, but a group of related of hemorrhagic diathesises, which are caused by the infringement of synthesis or the quality anomalies of VIII: factor. The great number of Willebrand's disease variations is the proof of factor-VIII structure complication. The patients frequently have hypodermic hematomas, parent bleedings with women can be last 15-25 days, are hardly treated, the hemorrhages in large joints are possible. The heritable factor-IX deficit is called hemophilia B or Cristmas disease; it is inherited by the recessive type and is joined with X-chromosome, however the structural gene of the factor-IX is localized in the other end of this chromosome and isnt connected with the gene of VIII: K factor.



Hemophilia B is antigene positive (hemophilia B+) and antigene negative one (hemophilia B-). Such patients have caryotypes 46,XhY, 46,hh, 45,h or 46,XX/45,XhO). Hemophilia B is identical to hemophilia A by clinical developments, by gravity and complications. These hemophilias are distinguished only by the results of laboratory studies. The hemophilia C is the example of autosomal heritable coagulopathies, which caused by the factor-XI deficit.




Figure. Hematoma in a newborn child with hemophilia Figure. Hematoma in a child with hemophilia after injection



The acquired coagulopathies, as a rule, are caused by the complex infringement in the coagulative system and have much more complicated pathogeny, than the heritable ones. The insulated deficit of the some coagulation factors occurs not often (amiloidosis provokes factor-X deficit, factor-VIII deficit may be result of its immune inhibition at the antigenic noncompatibility of the mother and the fetus. The simultaneous deficit of several factors is frequent in clinical practice.

Hemorrhagic syndrome, as a result of of K-vitamin dependent coagulation factors deficit, is characterized by the disorder of synthesis in hepatocytes and the decrease of factors VII, X, IX and II blood concentrations. Reasons of hemostasis violations and poor vitamin K synthesis can be dysbacteriosis, profusal diarrhea, enteropathies, failures of this liposoluble vitamin suction at bile deficit (mechanical icterus), failure of the final stage vitamin-K dependent coagulation factors synthesis (process of their decarboxilation) due to displacement of vitamin K from the metabolism by competitive antagonists anticoagulants of the indirect action, dangerous liver destructions. The depression of the VII, X, IX, XII factors activity arises thus in succession, this depends on the different lifetime of these factors in blood. the medical drugs using can be complicated by coagulopathies. This happens if the drugs have the anthithrombical activity and are overdosed (heparin especially).

Hypercoagulation is the organism state characterized by excessive activation of coagulative blood systems. The examples are thrombosis and dessiminative intravascular blood coagulation syndrome (DIC-syndrome). Most often DIC-syndrome arises at the development of infections (especially generalized one); at septic states coused by bacteriemia or virusemia, including at abortions, after labors, at a long-term vessels catheterization; at shock (traumatic, hemorrhagical, anaphylactic, cardiogenic, septic, in conditions of septic shock the acute DIC-sindrome is registered in 100 % of cases); at traumatic surgical operations; at long-term usage of an artificial blood circulation apparatus; at all terminal states the DIC-syndrome (in 100 % of cases); at acute hemolysis; at anticipatory flaking-off of placenta, at thermal and chemical burns, at immune diseases, at allergic reactions.

The main DIC-syndrome mechanisms are the following:

1) the activation of thrombocytic and coagulative hemostasis components by the endogenenic factors - tissues thromboplastin, factors of tissues and blood cells disintegration, leukocytic proteases, factors of endothelium injured;

2) the activation of hemostasis system by such exogenic factors as bacterias, viruses, medicines, snake poisons;

3) the injure of vascular endothelium, followed by the decrease its antithrombical potential;

4) the dissipated intravascular blood coagulation, thrombocytes and erythrocytes aggregation with the formation of many microclots and the block of microcirculation;

5) deep dystrophic failures in organs-targets, the failures of their function;

6) circulatory disturbances which predetermine tissues hypoxia, hemocoagulational shock, acidosis, microcirculation failure caused by the disability of the organism to promote the capillary hemodilution process, and stop blood flow;

7) the development of the consumption coagulopathy followed by complete disability of blood to coagulate, the exhaustion of anticoagulative mechanisms (deficit of antithrombin III and protein ), component of fibrinolytic and calicrein-kinin systems;

8) the secondary high-gravity endogene intoxication by toxic substances of proteolysis and tissues destruction.

The key role in a pathogeny of a DIC-syndrome is given to the increase of thrombinum concentrationin (hypethrombinemia), to the exhaustion of hemocoagulational potential.

The main initiator of the coagulation process is the tissues thromboplastin, that comes into the blood from the injured tissues and endothelium. Activated monocytes provoke to produce tissues thromboplastin and this mechanism plays an important role in DIC-syndrome pathogeny at virusemia, at endotoxemia, at immune diseases (activated monocytes start to produce partially activated such factors as VII, X, IX, II.

The thrombocytes aggregation and their using for the thrombforming is the obligatory component of DIC-syndrome pathogeny. The erythrocytes at DIC-syndrome are injured, their lifetime in blood is shortened and the intravascular hemolysis appears. This process activates the blood coagulation because much ADP and other agents from injured erythrocytes came into the blood, promotes thrombocytes aggregation, conduces the DIC-syndrome progressing, and microcirculation disorder in tissues.

The very important pathogenetic link of this pathology is the activation not only the system of blood coagulation, but also of such plasma proteolytic systems, as fibrinolytic, calicrein-kinin and complement ones. There of the imagination about the acute DIC-syndrome as about the "humoral protease detonating" was developed in the result of which the patients blood is filled up with the great amount of proteins disintegration metabolites. These substances can damage a vascular wall; promote bleeding and secondarilly strendhen blood coagulation. DIC-syndrome progressing provokes the decrease of anticoagulants concentration, especially antithrombin III, which is the coagulation enzyme factors inhibitor and protein C, which is the not enzyme factors (f.-VIII and f.-V) inhibitor. Similarly the fibrinolytic components (precallicrein, kininogene) are utilized.

The hemorrhagic syndrome at these conditions is the result of coagulative blood properties failure, namely:

1) the anticoagulative action of toxic substances,

2) usage of the factors VIII and V;

3) failure of thrombocytic hemostasis in the result of hypoxia;

4) toxic influence on a vascular wall of proteolysis products;

5) the decrease in blood of the most active thrombocytes and their block by the fibrin dissociation products.

Thrombocytopenia and thrombocytopathy, which arise at this condition, is the important bleeding factor.

Gravity of DIC-syndrome depends on infringement of microcirculation in organs. Constant satellites of DIC-syndrome are shock lung, acute renal insufficiency and other organ failures. Their development is the result of massive capillary block by fibrin clots and blood cells aggregates. Hematocrite capillary blood index increases until 0,45 - 0,55 l/l at DIC-syndrome. The indicated failure and microvessels thrombosis plays the key role in the development of stasis, hypoxia and organs dystrophy. The current of DIC-syndrome can be acute, lingering, the relapsing, chronic, and latent.

Stages of DIC-syndrome are following: the first stage - hypercoagulation and thrombocytes aggregation; the second stage - consumption coagulopathy and thrombocytopathia; the third stage - hypocoagulation; the fourth stage - recovery or consequences and complications (at the unfavorable current the death of the patient is possible). By the gravity of the current DIC-syndrome may be acute, subacute and chronic.

The main signs of DIC-syndrome are hemocoagulative or mixed shock (at acute form), failure of hemostasis (thrombosis and hemorrhagia), hypovolemia, anemia, disfunction and dystrophy of organs, metabolic disorders. Hemocoagulative shock is the result of microcirculation violations in organs and tissuel hypoxia, the formation of proteolysis toxic substances. This is characterised by the decrease of arterial and central venous pressure, by organs microcirculation violations and acute organs functional insufficiency (acute renal or hepatorenal insufficiency, shock lung). The development of profusal bleeding promotes the transformation of hemocoagulative shock into the hemorrhagic one.

There are different phases at hemostasis failure - from hypercoagulation up to hypocoagulation (at first we can observe massive thrombogenesis, but then thrombogenesis depression and bleeding). The thrombocytopenia and thrombocytopathy in this condition is the result of great number microthrombuses forming, of the thrombocytes injury and returning to circulation of degranulated thrombocytes. Hemorrhagic syndrome (bleeding) mostly arises at acute DIC-syndrome in hypocoagulation stage. The main pathogenetic mechanisms of bleeding are pathological influence on vessels of toxic proteolysis substances, the failure of thrombocytes angiothrophical function, thrombocytopenia, thrombocytopathy of consumption, fibrinolytic system activation.



Figure. DIC-syndrome at case of septicemia


The microcirculation block predetermines the disfunction and dystrophy of organs. The organs-targets (lung, kidneys, intestine) suffer mostly. The combined forms of organ violations are more difficult, for example, the combination of pulmonary and renal insufficiencies. The stomach and intestine also belong to the group of organs, which are frequently damaged at a DIC-syndrome. Microcirculation violations provoke mucous membrane dystrophy and profusal bleedings. In complicated cases the failures of cerebral circulation, of paranephroses, of pituitary body, and liver are possible.




The anemia is decrease of erythrocytes amount and hemoglobin maintenances in unit of blood volume which is accompanied by qualitative changes of erythrocytes.

Hematological attributes of anemias are subdivided on quantitative and qualitative.

The quantitative displays include:

1) reduction of the maintenance of erythrocytes in unit of blood volume in men is lower than 4×1012, in women is lower than 3,5×1012 in 1L of blood;

2) reduction of hemoglobin concentration in men is lower than 130 g/l, in women is lower than 120 g/l;

3) reduction of hematocrit in men is lower than 0,43 l/l, in women is lower than 0,40 l/l;

4) change of a color index is not lower than0,85 and not higher than 1,15.

Qualitative attributes of anemias are presence in blood of:

1) regenerative, but not mature forms of erythrocytes;

2) degenerative changes of erythrocytes;

3) cells of pathological regeneration.

Regenerative forms of erythrocytes (cells of physiological regeneration) are young immature cells of red blood sprout appearance of which in peripheral blood testifies to amplification of regeneration of cells erythroid lines in red bone marrow or increase of medullar barrier permeability.

Regenerative forms include:

) reticulocytes. They are found in smear of blood after supravital staining. Represent denuclearized cells dirty staining colouring with black inclusions as granules (substantia granulofilamentosa). In norm their contents in blood is 0,2-2 %. At the strengthened regeneration of cells red sproud blood their quantity may increase to 50 %.

b) polychromatophils. They are found in blood smear colored as in the method bu Romanovsky-Gimza. They are denuclearized cells cytoplasm of which shows property to perceive both acid, and the basic dye-stuffs. Therefore polychromatophils different from mature erythrocytes by cyanotic shade of the colouring. In essence reticulocytes and polychromatophils are cells of an identical degree of maturity direct predecessors of erythrocytes. Different names are connected with their different properties which come to light at different ways of staining.

c) normocytes (basophilic, acidophilic, polychromatophilic). They are nuclear predecessors of erythrocytes. In norm its absent in peripheral blood, and contain only in a red bone marrow. At the intensification of regeneration of cells erythroid lines they may occur in blood as acidophilic and polychromatophilic rarely as basophilic normocytes. Sometimes, erythroblasts can be found in blood (predecessors of normocytes) during hyperregenerative anemias.

Changes of erythrocytes, which testify about inferiority of these cells, named degenerative. Such changes are characterized by the following phenomena:

) anisocytosis change in the size of the erythrocytes. Occurrence of macrocytes and microcytes;


Figure. Anisocytosis


b) poikilocytosis change in the form of the erythrocytes. In conditions of a pathology may occur pear-shaped, extended, sickle-cell, oval erythrocytes, and also erythrocytes with the spherical form (spherocytes);

c) change in the staining of the erythrocytes, that depends on the contents of hemoglobin in them. Erythrocytes, intensively colored, are named hyperchromatic, with pale staining hypochromatic.

d) presence of pathological inclusions. They include Jollys bodies are the rests of nuclear substance; Cabots rings the rests of nuclear environment having the form of ring or eight; basophilic granularity the rests basophilic substances of cytoplasm significative of toxic defeat of red bone marrow.


Cells of pathological regeneration occur when there is changed of erythropoesis from erythroblastic to megaloblastic:

) megaloblasts are big cells with basophilic, polychromatophilic or acidophilic cytoplasm, containing large, located usually eccentrically nucleus with soft chromatin grid;

b) megalocytes denuclearized cells which are formed during maturing of megaloblasts. They usually intensively stained, some the oval form, non an brighten up in the central part.

Occurrence of the specified cells in red bone marrow and blood is typical for megaloblastic anemias, in particular of the B12-deficiency anemia.


Classifications of anemias.

. According to color index:

) normochromic (the color index is within the limits of 0,85-1; for example, acute posthemorrhagic anemia during first days after hemorrhage);

b) hypochromic (the color index is lower than 0,85; for example, irondeficiency anemia);

c) hyperchromic (the color index is higher than 1,0; for example, B12-deficiency anemia).

. Pathogenetic classification:

. posthemorrhagic anemias:

a) acute posthemorrhagic anemia;

b) chronic posthemorrhagic anemia.

B. hemolytic anemias.

1. acquired:

) toxic-hemolytic;

b) immune;

c) mechanical;

d) acquired membranopathy.

2. hereditary:

) hereditary membranopathy;

b) enzymopathy;

c) hemoglobinopathy.

C. Anemias as a result of erythropoiesis disorders.

1. deficient:

) irondeficient;

b) B12-deficient;

c) proteindeficient.

2. hypo-, aplastic.

3. metaplastic.

4. Dysregulative


Posthemorrhagic anemia is an anemia which develops as a result of hemorrhage. There are two types of anemias of this group according to the character of hemorrhage: 1) acute posthemorrhagic and 2) chronic posthemorrhagic anemia.

Acute posthemorrhagic anemia arises after fast massive hemorrhage as a result wounding of vessels or their damage by pathological process.

Chronic posthemorrhagic anemia develops after repeated hemorrhages, caused by injury of blood vessels during number diseases (dysmenorrhea, ulcer of stomach, hemorrhoids etc.)

The picture of blood of acute posthemorrhagic anemias depends on time which has passed after hemorrhage. Depending on it it is possible pick out three periods, each of them is characterized by the certain picture of peripheral blood.

1. The first several hours after acute hemorrhage. At this period of time the total amount of blood, and also total number of erythrocytes in an organism decreases. However in unit of blood volume the contents of erythrocytes and concentration of hemoglobin do not vary.

2. The period of time from several hours untill several days after acute hemorrhage. Dillution of blood takes place as a result of transition of liquid from interstitial spaces into blood vessels. As a result of it the quantity of erythrocytes and hemoglobin in unit of volume of blood decreases, as well as hematocrit. A color index stays without changes (normochromic anemia). Qualitative changes of erythrocytes in blood smear are not found yet.

3. The period of time from several days untill 1-2 weeks after acute hemorrhage. The most typical feature of picture of blood in this period is occurrence of plenty regenerative forms of erythrocytes, due to amplification of erythropoiesis in red bone marrow. Because young unripe erythrocytes contain less hemoglobin in comparison with mature cells, the color index decreases also and anemia becomes hypochromic.



Figure. Reticulocytosis in acute posthemorrhagic anemia



During chronic posthemorrhagic anemia after the loss of iron hematologic attributes of irondeficiency anemia develop: concentration of hemoglobin and color index decrease, in blood smear there are degenerate forms of erythrocytes (micro- and poikilocytosis, hypochromy). Quantity of erythrocytes and hematocrit may remain without changes.


hypochromic iron deficiency anemia




Figure. Chronic posthemorrhagic anemia - blood


The characteristic of hemolytic anemias. Anemias which arise after destruction (hemolysis) of erythrocytes are called hemolytic. According to the mechanism of development hemolysis anemias may be: 1) anemias with intravascular hemolysis; 2) anemias with endocellular hemolysis.

Intravascular hemolysis arises in blood vessels under the action of factors that damage erythrocytes. These factors are called hemolytic. They include:

) Factors of physical nature (mechanical trauma, ionizing radiation, ultrasound, temperature);

b) Chemical agents (hemolytic poisons);

c) Biological factors (causative agents of infectious diseases, toxins, enzymes);

d) Immune factors (antibodies).

Intravascular hemolysis it is accompanied by an output of hemoglobin from cells to blood plasma where it partially connects with protein haptoglobin.

Endocellular hemolysis develops after absorption and digestion of erythrocytes by macrophages. In its basis the following reasons may lay: ) occurrence of defective erythrocytes. b) occurrence on surface of erythrocytes the chemical groups capable to cooperate specifically with receptors of macrophages. In this case antibodydependent phagocytosis of erythrocytes is activated; c ) hypersplenism increase of phagocytic activity of spleen macrophages.

Acquired hemolytic anemias. Depending on the reasons of development is allocated the following kinds of acquired hemolytic anemias.

1. Toxic hemolytic anemias.

2. Immune hemolytic anemias.

3. The anemias caused by mechanical damage of erythrocytes.

4. Acquired membranopathy.

Mechanical hemolysis of erythrocytes arises at prosthetics vessels or valves of heart traumas of erythrocytes in capillaries of foot during a long march (marching hemoglobinuria), at their collision with strings of fibrin (microangiopathic hemolytic anemia of DIC-syndrome).

Immune hemolytic anemias arise due to participation of specific immune mechanisms. They are caused by interaction of humoral antibodies with the antigenes fixed on a surface of erythrocytes. Their reason may be: )receipt from the outside antibodies against own of erythrocytes (hemolytic desease of newborn); b)receipt into organism of erythrocytes which in plasma there are antibodies (the blood transfusion, not compatible on groups AB0 or Rh); c)fixing on a surface of erythrocytes foreing antigenes (haptens), in particular, medical products (antibiotics, sulfanilamides), viruses; d)formation of antibodies against own erythrocytes.

Toxic hemolytic anemia may be caused by:

) exogenous chemical agents: phenylhydrasin, lead, copper salts, arsenous hydrogen etc.;

b) endogenous chemical factors: bile acids, products formed at burn desease, uraemia;

c) poisons of biological origin: snake, beer, poison of some kinds of spiders, aumber of infectious agents, in particular, hemolytic streptococcus, malarial plasmodium, toxoplasma, leishmania.

Acquired membranopathy arise due to the acquired defects of erythrocytes membranes. As an example may be paroxysmal noctural hemoglobinuria. This disease as a results of a somatic mutation erythropoietic cells with defects of membrane. It is considered that disorders of membranes are connected with changes of ratio of fat acids which are part of their phospholipids. Erythrocytes of abnormal population get ability to fix complement and hemolyse.

The picture of blood of acquired hemolytic anemias is characterized by reduction of erythrocytes quantity and hemoglobin. The color index in norm, however may be higher than 1 unit that is connected with extraerythrocytic hemoglobin. In blood smear the significant amount regenerative forms of erythrocytes is found out: reticulocytes, polychromatophils, normocytes.



Figure. Reticulocytes


Hereditary hemolytic anemias

All hereditary caused hemolytic anemias are subdivided into three groups.

1. Membranopathies. Defects of erythrocytes membranes are in basis of this anemias group.

2. Enzymopathies. Anemias of this group are caused by disorder of erythrocytes enzymes.

3. Hemoglobinopathies. Arise after qualitative changes of hemoglobin.

Hereditary membranopathies may be caused by two groups of defects erythrocytic membranes:

1) membranopathies, caused by disorders of membrane proteins: ) microspherocytic anemia Minkovsky-Shoffars; b) ovalocytic hemolytic anemia;

Anemia Minkovsky-Shoffars is hereditary, endoerythrocytic (membranopathy) hemolytic anemia with endocellular hemolysis. Type of inheritance autosomal dominant. Hereditary defect mentions membrane proteins of erythrocytes, in particular spectrin. Therefore permeability of erythrocytic membranes for ions sodium is considerably increased. Sodium and water pass from plasma inside of erythrocytes. In spleen they lose part of erythrocytes membrane and turn into microspherocytes. Life expectancy of erythrocytes decreases untill 8-12 days instead of 120.


Figure. Membranopathia. Inherited microspherocytosis blood



The group also includes hereditary membranopathias: hereditary eliptocytosis, hereditary piropoykilocytosis, hereditary stomatocytosis, hereditary akantocytosis, and hereditary ehinocytosis.



Figure. Membranopathia. Hereditary eliptocytosis blood




Figure. Membranopathia. Hereditary piropoykilocytosis blood




Figure. Membranopathia. Hereditary stomatocytosis blood




Figure. Membranopathia. Hereditary akantocytosis blood




Figure. Membranopathia. Hereditary ehinocytosis blood


Hereditary enzymopathias arise due to defect of erythrocytes enzymes systems:

1) deficiency of enzymes pentose cycle. The most widespread enzymopathy is glucose-6-phosphatedehydrogenase deficiency anemia, caused by absence or significant decrease(reduction) of glucose-6-phosphatedehydrogenase activity;

2) deficiency of enzymes of glycolysis. The most widespread is deficiency of pyruvatekinase which results to disorders of energy provision Na-K-pumps of plasmatic membranes. Erythrocytes thus turn into spherocytes which are exposed to phagocytosis by macrophages;

3) deficiency of enzymes of glutathion cycle (glutathionsynthetase, glutathionreductase, glutathionperoxidaza) results in oppression antioxidant systems of erythrocytes, barrier properties of erythrocytic membranes to ions and osmotic hemolysis;

4) deficiency of utilization P enzymes. An example is deficiency of albuminous components Na-K-pump of erythrocytic membranes. Thus concentration of sodium that results them to hemolysis is increased in a cell.

Qualitative and quantitative changes of hemoglobin lay in basis of development of hereditary hemoglobinopathies. The most widespread clinical form is sickle-cell anemia at which in β-chain of a molecule of hemoglobin glutamine acid is replaced on valine (HbS.) HbS is crystallized easily, erythrocyte loses its shape and cells of red blood get the sickle-like form.




Figure. Scanning electron micro photo of oxygenated (A) and dezoxyhenated (B)

erythrocytes of patient with sickle cell anemia.

.F.Bunn et al. (1977).



Figure. Sickle cell anemia blood



Figure. Sickle cell anemia blood on the left - sickle-shaped red blood cells,

on the right test hypoxia



Macrophages phagocytose and hemolyse them, especially when hypoxia is present.

Quantitative hemoglobinopathies are characterized by disorder of hemoglobin chains synthesis. An example of this group is α- and β-thalassemia.


Figure. Small (heterozygous) thalassemia blood


Thalassemias are hereditary caused hemolytic anemias with endocellular hemolysis. Pathological forms of hemoglobin which can easily drop out in deposit are appeared in the erythrocytes during α-thalassemia and erythrocytes look like targets (target cell anemia). Macrophages phagocytose and hemolyse the erythrocytes.

Synthesis of β-chains of hemoglobin molecule is broken during β- thalassemia (disease of Cooley).

Anemias as a result of erythropoiesis disorder

The reasons of anemias with disorders of erythropoiesis may be:

1) disorder of formation of erythrocytes: deficiency of hemopoietic cells due to their damage or replacement, disorder of cells maturation of hemopoiesis (disorders of DNA resynthesis), defects of erythrocytes maturing and their output(exit) into blood flow (deficiency erythropoiesis);

2) disorders of hemoglobin synthesis: deficiency of iron, disorder of synthesis porphyrines (hereditary disorders of enzymes, poisonings by lead, deficiency of vitamin B6, frustration of albuminous chains synthesis of hemoglobin molecules).


Deficiency anemias

Irondeficiency anemia arises as a result of:

1) Insufficient receipt of iron with organism: ) an alimentary anemia in the infants (feeding with cow or goat milk); b) disorder of iron absorbtion (resection of stomach, intestines, gastritises, enteritis);

2) Hemorrhage. It is the most widespread reason of iron deficiency in organism;

3) Strengthened use of iron pregnancy, lactation.


Figure. Irondeficiency anemia blood




Figure. Irondeficiency anemia blood


Insufficiency of iron in organism results in disorder of ferriferous proteins synthesis and consequently to the following disorders:

1) disorder of heme synthesis,

2) disorder of cytochromes formation and tissue hypoxia,

3) decrease of catalase activity hemolysis of erythrocytes and development of dystrophic changes in cells,

4) reduction of synthesis myoglobin and decrease(reduction) of resistance to hypoxia.

Decrease of hemoglobin concentration in peripheral blood and reduction of color index are typical for iron deficiency anemia. The quantity of erythrocytes decreases a little.



In blood smear the quantity regenerative forms of erythrocytes (reticulocytes, polychromatophils) decreases and their degenerative forms (anulocytes, microcytosis, poikilocytosis).

Iron refractory anemia results from disorder of iron inclusion in heme at decrease of enzymes activity, which catalase synthesis of porphyrines and heme. The reasons may be:

1) genetic down turn of decarboxylase activity of coproporphyrinogen the enzyme providing one of final stages of heme synthesis (it is inherited recessively, is linked to the X-chromosome);

2) reduction of the maintenance pyridoxalphosphate the active form of vitamin B6 and as a result of this iron is not taken from mitochondria of erythroblasts and is not included in heme;

3) lead blockade of sulfhydryl groups of the enzymes participating in synthesis of heme.

B12-(folate)deficiency anemia. The reasons of vitamin B12 insufficiency in an organism:

1. Exogenous (alimentary) insufficiency insufficient receipt in an organism with food stuffs. May develop in small children as a result feeding goat milk or dry dairy mixes.

2. Disorders of vitamin B12 absorbtion:

) Disorder of formation and secretion of gastromucoprotein (internal Castles factor). It happens at hereditary caused disorders, an atrophy of a mucous membrane of stomach, autoimmune damages of parietal cells of stomach mucous, due to gastrectomy or removal of more than two thirds of stomach;




b) Disorder of small intestine function: chronic diarrheas (celiac disease, sprue), resection of the big parts of intestine;

c) Competitive use of vitamin B12 by helmints and microflora of intestines (diphyllobothriasis).

3. Disorder of transcobalamines formation in liver.

4. Disorder of vitamin B12 deposition in liver.

5. Increased use of vitamin B12 (at pregnancy).




Deficiency of vitamin B12 results in development of the frustration connected with formation disorder of its two coenzyme forms: methylcobalamine and 5-desoxyadenosilcobalamine. In a red bone marrow erythroblastic type of hemopoiesis is replaced on megaloblastic, inefficient erythropoesis increases, life expectancy of erythrocytes is shortened. The anemia with the expressed degenerate shifts not only in a bone marrow, but also in blood develops. Changes in cells of myeloid and megacariocytic lines are shown by reduction of leukocytes quantity and thrombocytes, expressed by atypia of cells (huge neutrophils, megacaryocytes with degenerative changes in a nucleus). Occurrence of atypic mitosis and huge cells of epithelium digestive tract results in development of inflammatory-atrophic processes in mucous membrane of its parts (glossitis, stomatitis, esophagitis, achylic gastritis, enteritis).

As a result of the second coenzyme forms insufficiency of vitamin B12-5-desoxyadenosilcobalamine in organism propionic and methylmalonic acids, which are toxic for nervous cells. Besides fatty acids with the changed structure are synthesised in nervous fibres results in disorder formation of myeline and to damage of axones. The degeneration of back and lateral columns of a spinal cord develops (funicular myelosis), cranial and peripheral nerves are damaged.

Occurrence in blood and red bone marrow of pathological regeneration cells megaloblasts, megalocytes is the most typical feature of this anemia. the color index is increased, that is explained by the big saturation of cells by hemoglobin. The phenomenon of degeneration erythrocytes is typical: anisocytosis (macrocytosis), poikilocytosis (occurrence of the oval form cells), pathological inclusions (Jollys bodies, Cabots rings). The maintenance granulocytes (especially neutrophils) and thrombocytes in blood is reduced. Huge neutrophils with the hypersegmented nucleus are found out.


Figure. B12-deficiency anemia bone marrow. Megaloblasts and megalocytes




Figure. Jollys bodies Figure. Cabots rings


Such syndromes are observed for B12-(folate)deficiency anemia:

1. hematologic syndrome: ) anemia; b) leukopenia; c) thrombocytopenia.

2. Damages of the digestive tract which are shown by development inflammatory atrophic changes in mucous membrane.

3. Damages of the central and peripheral nervous system: funicular myelosis, degeneration of peripheral nerves.

Hypoplastic (plastic) anemia is characterized by oppression hemopoietic functions of red bone marrow and shown by insufficient formation of erythrocytes, granulocytes and throrombocytes or only erythrocytes.

There are acquired and is hereditary caused forms of hypoplastic anemia. The type of hereditary is autosomal-recessive type of inheritance concerns.

The acquired forms may be caused by the following reasons:

1) physical factors (ionizing radiation);

2) chemical agents (benzene, lead, steams of mercury, medical products: cytostatic agents, chloramphenicol, sulfanilamids);

3) biological factors (virus of hepatites).

Essential forms of anemia, which reason is not established belongs to acquired anemias.

Reduction of erythrocytes maintenance and concentration of hemoglobin when color index is within the limits of norm is characterised for the peacture of peripheral blood. Regenerative of erythrocytes (reticulocytes, polychromatophils) as a role are not found in a blood smear. The maintenance of granulocytes (especially neutrophils) and thrombocytes decreases. The quantity of lymphocytes may remain without changes.

In a red bone marrow the quantity of hemopoietic cells decreases with increase of maintenance of fatty tissue (picture of devastation red bone marrow). Because of iron is not used for the purposes hemopoiesis, its maintenance in erythroblasts and extracelulary is increased.

Appearence of hypoplastic anemias are connected with reduction of three kinds formation of form blood elements: erythrocytes, granulocytes and thrombocytes. It results in development of the following clinical syndromes:

1. the anemia and connected to it hypoxic syndrome.

2. hemorrhagic syndrome.

3. the inflammatory processes caused by infectious agents (pneumonia, otitis, pyelitis etc.).

The metaplastic anemia is the result of hemopoietic tissue replacement on tissues: leucosis cells, connective tissue (fibrosis), metastasises of tumor.

Dysregulative anemias. Dysregulative anemias arise as a result of erythropoiesis regulation disorders (infringement of ratio between erythropoietins and inhibitors of erythropoiesis due to insufficiency of kidneys, damage of strome elements microenvironments of erythropoietins cells, hypofunction of hypophysis, thyroid gland).




Leukemia (leucosis) is a tumour, which arises from bloodforming cells and is primary damages bone marrow. The most characteristic signs of leucosis is the filling bone marrow by malignant cells of the local origin. It can be leucocytes and their predecessors, erhytroblasts, megacaryoblasts. They are made multiple copies in quantities, overcome a natural barrier between bone marrow and blood and get in vessels channel. There is leucocytosis very often, though also unessential symptom of leucosis.

The reason why quantitative and qualitative diagnosis based on the cellular components of the blood is so important is that blood cells are easily accessible indicators of disturbances in their organs of origin or degradation which are much less easily accessible.

Thus, disturbances in the erythrocyte, granulocyte, and thrombocyte series allow important conclusions to be drawn about bone marrow function, just as disturbances of the lymphatic cells indicate reactions or disease states of the specialized lymphopoietic organs (basically, the lymph nodes, spleen, and the diffuse lymphatic intestinal organ). All blood cells derive from a common stem cell. Under the influences of local and humoral factors, stem cells differentiate into different cell lines.




Erythropoiesis and thrombopoiesis proceed independently once the stem cell stage has been passed, whereas monocytopoiesis and granulocytopoiesis are quite closely related. Lymphocytopoiesis is the most independent among the remaining cell series. Granulocytes, monocytes, and lymphocytes are collectively called leukocytes (white blood cells), a term that has been retained since the days before staining methods were available, when the only distinction that could be made was between erythrocytes (red blood cells) and the rest.



Figure. Scheme of hematopoiesis



All these cells are eukaryotic, that is, they are made up of a nucleus, sometimes with visible nucleoli, surrounded by cytoplasm, which may include various kinds of organelles, granulations, and vacuoles. Despite the common origin of all the cells, ordinary light microscopy reveals fundamental and characteristic differences in the nuclear chromatin structure in the different cell series and their various stages of maturation.

The developing cells in the granulocyte series (myeloblasts and promyelocytes), for example, showa delicate, fine net-like (reticular) structure. Careful microscopic examination (using fine focus adjustment to view different depth levels) reveals a detailed nuclear structure that resembles fine or coarse gravel. With progressive stages of nuclear maturation in this series (myelocytes, metamyelocytes, and band or staff cells), the chromatin condenses into bands or streaks, giving the nucleus which at the same time is adopting a characteristic curved shape a spotted and striped pattern.

Lymphocytes, on the other hand particularly in their circulating forms always have large, solid-looking nuclei. Like cross-sections through geological slate, homogeneous, dense chromatin bands alternate with lighter interruptions and fissures.

Each of these cell series contains precursors that can divide (blast precursors) andmature or almostmature forms that can no longer divide; the morphological differences between these correspond not to steps in mitosis, but result from continuous maturation processes of the cell nucleus and cytoplasm.

Once this is understood, it becomes easier not to be too rigid about morphological distinctions between certain cell stages. The blastic precursors usually reside in the hematopoietic organs (bone marrow and lymph nodes). Since, however, a strict blood bone marrow barrier does not exist (blasts are kept out of the bloodstream essentially only by their limited plasticity, i.e., their inability to cross the diffusion barrier into the bloodstream), it is in principle possible for any cell type to be found in peripheral blood, and when cell production is increased, the statistical frequency with which they cross into the bloodstream will naturally rise as well.

Conventionally, cells are sorted left to right from immature to mature, so an increased level of immature cells in the bloodstream causes a left shift in the composition of a cell seriesalthough it must be said that only in the precursor stages of granulopoiesis are the cell morphologies sufficiently distinct for this left shift to show up clearly.

The distribution of white blood cells outside their places of origin cannot be inferred simply from a drop of capillary blood. This is because the majority of white cells remain out of circulation, marginated in the epithelial lining of vessel walls or in extravascular spaces, from where they may be quickly recruited back to the bloodstream.

This phenomenon explains why white cell counts can vary rapidly without or before any change has taken place in the rate of their production.

Cell functions. A brief indication of the functions of the various cell groups follows. Neutrophil granulocytes with segmented nuclei serve mostly to defend against bacteria. Predominantly outside the vascular system, in inflamed tissue, they phagocytose and lyse bacteria. The blood merely transports the granulocytes to their site of action.

The function of eosinophilic granulocytes is defense against parasites; they have a direct cytotoxic action on parasites and their eggs and larvae. They also play a role in the down-regulation of anaphylactic shock reactions and autoimmune responses, thus controlling the influence of basophilic cells.

The main function of basophilic granulocytes and their tissue-bound equivalents (tissue mast cells) is to regulate circulation through the release of substances such as histamine, serotonin, and heparin. These tissue hormones increase vascular permeability at the site of various local antigen activity and thus regulate the influx of the other inflammatory cells.

The main function of monocytes is the defense against bacteria, fungi, viruses, and foreign bodies. Defensive activities take place mostly outside the vessels by phagocytosis.

Monocytes also break down endogenous cells (e.g., erythrocytes) at the end of their life cycles, and they are assumed to perform a similar function in defense against tumors. Outside the bloodstream, monocytes develop into histiocytes; macrophages in the endothelium of the body cavities; epithelioid cells; foreign body macrophages (including Langhans giant cells); and many other cells. Lymphocytes are divided into two major basic groups according to function.

Thymus-dependent T-lymphocytes, which make up about 70% of lymphocytes, provide local defense against antigens fromorganic and inorganic foreign bodies in the form of delayed-type hypersensitivity, as classically exemplified by the tuberculin reaction. T-lymphocytes are divided into helper cells and suppressor cells.

The small group of NK (natural killer) cells, which have a direct cytotoxic function, is closely related to the T-cell group. The other group is the bone-marrow-dependent B-lymphocytes or Bcells, which make up about 20% of lymphocytes. Through their development into immunoglobulin-secreting plasma cells, B-lymphocytes are responsible for the entire humoral side of defense against viruses, bacteria, and allergens.




Erythrocytes are the oxygen carriers for all oxygen-dependent metabolic reactions in the organism. They are the only blood cells without nuclei, since this allows them to bind and exchange the greatest number of O2 molecules. Their physiological biconcave disk shape with a thick rim provides optimal plasticity.

Thrombocytes form the aggregates that, along with humoral coagulation factors, close up vascular lesions. During the aggregation process, in addition to the mechanical function, thrombocytic granules also release factors that promote coagulation. Thrombocytes develop from polyploid megakaryocytes in the bone marrow. They are the enucleated, fragmented cytoplasmic portions of these progenitor cells.





Classification of leucosis

On clinical picture leucosis divide on two groups acute and chronic. This classification is entered into clinical practice and in a scientific turn-over at the end of ղ centuries Roux (1890) and Cabot (1894). The classification was based to duration of illness.

In 1964 in Cambridge the new classification was created, according to which to acute leucosis is believed such forms them, when the disorders of differentiation of cells took place. For want of acute leucosis differentiation bloodforming cells in base mass do not go further V classes. The grow up of cells, which do not mature, lead to accumulation blast cells , and V classes. They there is more take territory of bone marrow at the expense of volume, which should be occupied normal hemopoietic elements. Eventually cells certain growth, which were accumulated much in bone marrow, leave in blood.

At the end of 70-th beginning of the 80-th years of the last century the French, American and British experts created a modern, so-called FAB-classification of acute leucosis. It is constructed on stable morphological and cytochemical characteristics of leucosis cells. These characteristics reflect features them metabolism.

According to modern conception, all bloodforming at level of the class is divided into two shoot myeloid and lymphoid. Therefore all acute leucosis divide on two groups myeloblast and lymphoblast. They are represented by many nosologic forms.

Acute myeloblastic leucosis differentiate on five cytochemical signs presence or absence in leucosis cells of the following substances: peroxidase, acid phosphatase, unspecific esterase, lipids and glycogen. To them belong undifferentiated leucosis.




Figure. Reaction of myeloblasts and other neutrophil cells for peroxidase




Figure. Reaction of myeloblasts and monoblasts for acid phosphatase




Figure. Reaction of monoblasts for alpha naftylatsetatesterase




Figure. Reaction with Sudan black for lipids




Figure. Reaction for acidic sulfated mucopolysaccharides



This group includes the following forms of acute leukemia:

M0 acute undifferentiated leukemia.





red bone marrow:




red bone marrow, atypical cells:





1 acute myeloblastic leucosis without signs of maturing (worse 3 % of promyelocytes).

2 acute myeloblastic leucosis with signs of maturing (over 3 % of promyelocytes).

Illustrations: 1-2:

Red bone marrow. Initial stage. Granular myeloblasts, Auer rod:





Red bone marrow. The total myeloid metaplasia:



Blood. Reaction of myeloblasts for peroxidase:



Blood. Reaction of myeloblasts for peroxidase:



3 acute promyelocytic leucosis (over 30 % of promyelocytes).

4 acute myelomonoblastic leucosis (over 20 % of promyelocytes and over 20 % of promonocytes).

(4) red bone marrow, reaction for esterase:





5 acute monoblastic leucosis.

6 acute erythroblastic leucosis.

(6) red bone marrow. Erythroblasts. Myeloblasts with Auer rod:





7 acute megacaryoblastic leucosis, red bone marrow:




Acute lymphoid leukemia is distinguished for cytochemical, and morphological features. There are following forms:

1. Acute leucosis general type

2. T-lymphoblastic leucosis,

3. B-lymphoblastic leucosis.



Acute lymphoblastic leukemia (blood). Lymphocytes (2) and lymphoblasts (1):




Acute lymphoblastic leukemia (blood):





Acute lymphoblastic leukemia (red bone marrow):




Acute -lymphoblastic leukemia (red bone marrow). Big lymphoblasts:





Acute lymphoblastic leukemia (red bone marrow). The initial stage:





Acute lymphoblastic leukemia (red bone marrow). The total lymphoblastic metaplasia:





In the FBA-classification, as against Cambridge, unusual is that acute undifferentiated leucosis belongs to group myeloid leucosis. Before it selected separately or even carried to lymphoid. The rearrangement is explained that now amount acute undifferentiated leucosis was sharply reduced in connection with selection as separate nosologic form of leucosis general type from cells predecessors in lymphocytes. And those leucosis, which have remained in group undifferentiated, are very similar on leucosis of myeloid line.

Chronic leucosis differ from acute, that the cells bone marrow mature normally (up to V class), but proliferate in very plenty. Chronic leucosis passes in the development three stages:

1. Chronic stage, during which the illness represents a benign tumour and can be treatment.

2. The stage of accelerated development of illness, during which illness progresses in the party malignisation. Dynamics of illness it is ever more and leaves from under control. The treatment becomes all less effective.

3. The stage crisis of blastic cells, during which illness is exposed to radical transformation: chronic leucosis passes in acute (in 70 % - in acute myeloblastic, in 30 % - in acute lymphoblastic). Crisis of blastic cells approaches suddenly and becomes the reason of majority patients death.

Chronic leucosis also are divided on myeloid and lymphoid. To myeloid leucosis belong myelocytic leucosis.

The change in the cellular composition of the red bone marrow as an indicator of progression of chronic myelocytic leukemia indicate the following figures.


Chronic myelocytic leukemia (blood). Chronic stage:




Chronic myelocytic leukemia (blood). Stage of blast cells crisis:




Chronic myelocytic leukemia (red bone marrow). Extensive stage:




Chronic myelocytic leukemia (red bone marrow). Stage of blast cells crisis:




Chronic myelocytic leukemia (blood). Neutrophils at different stages of maturation:





Chronic myelocytic leukemia (blood). Rejuvenation of blood cell in dynamics of leukemia progression:




Chronic myelocytic leukemia with eosinophilia (red bone marrow):




Chronic myelocytic leukemia, eosinophilic variant, (red bone marrow):




Chronic myelocytic leukemia, basophilic variant (red bone marrow). Extensive stage:





Chronic myelocytic leukemia, basophilic variant (red bone marrow). Stage of blast cells crisis:




Chronic monocytic leukemia (blood):



1.                        Chronic erythroblastic leucosis.

2.                        Chronic megacaryocytic leucosis.


Chronic lymphoid leucosis

1. Chronic B-lymphocytic leucosis.


Chronic B-lymphocytic leucosis (blood):




Chronic lymphocytic leucosis (blood). Gumpreht bodies:




Chronic lymphocytic leucosis (red bone marrow). The total lymphoid metaplasia





Chronic lymphocytic leucosis (red bone marrow). The total lymphoid metaplasia




2. Chronic - lymphocytic leucosis.

3. Haircell leucosis.


Chronic haircell lymphocytic leucosis (blood):




Chronic haircell lymphocytic leucosis (blood):




Chronic haircell lymphocytic leucosis (blood). The reaction for acid phosphatase:





Etiology and pathogenesis of the leucosis

On modern conception, leucosis arise on genetic, mutational basis. The speech does about specific of bloodforming cells mutations, which result to superexpression of cells oncogenes, or protooncogenes. These genes are an integral part of cells genome and answer for proliferation of cells. Cells oncogenes vitally are necessary. Without them would become impossible fill of the cells, worn out and lost during vitality. At the same time cells oncogenes, as has appeared, have latent blastomogenic potentions. Excessive expression them the regeneration normal of bone marrow cells in leucosis stipulates.

To major etiological factors, which are capable to transform protooncogenes in active oncogenes, the chemical agents, ionising rays and retroviruses concern. It is know a few mechanisms of the cell oncogenes activation.



Point mutations.


Consider, that in most cases protooncogenes are activated as a result of structural changes them under influence of the chemical and physical agents.

From chemical substances in this plan the most better is investigated benzol. There is an increased risk to be ill leucosis on productions, where is used benzol: chemical clearing of materials with use of the solvents benzolcontaining, production of film materials on the basis of rubber, paper and woodworking an industry. The mechanism of chemical leucosogenesis consists that chemical leucosogenes cause chromosomal and genes mutations. Some from these mutations seize cells oncogenes or them regulatory genes environment and initiate leucosis transformation of bone marrow cells.

From the physical agents strongest leucosogenic by action has ionising rays. Is exactly proved, that increase of frequency leucosis take place after nuclear bombardment of Hiroshima and Nagasaki in 1945. The appearance leucosis is fixed also in case of use ionising radiation with the medical purpose in the patients with ancilosing spondilitis (Bechterevs illness), myelomic illness, lymphogranulomatosis, autoimmune diseases, some dermatoses. The approximately 25-35 % of cells, mainly lymphocytes, after therapeutical of an irradiation contain chromosomal aberrations as ring chromosomes, dicentric chromosomes and acentric of fragments.

It is known leucosogenic action of radioactive isotopes. The radioactive phosphorum, which is used for treatment erythremia, caused acute leucosis at 15-18 % of the patients.

It was detected also chromosomal aberrations in the specialists as a result of professional irradiation. Here, first of all, the staff belongs which serves nuclear reactors. The anomalies of chromosomes are found too in the people which have got in to breakedawn with throw away of radiation.


Chromosomal aberrations.


The precise correlation between lay out oncogenes and specific translocations of chromosomes is marked. It is established, that cell oncogenes frequently place just in those sites chromosomes, where it is easy and naturally there are their breaks with consequent translocations of deleted fragments. From here also there was an assumption, that translocations can be by original activators protooncogenes.

To the present time in chromosomes of malignant cells more than 80 points are registered, where the breaks are observed. The analysis of distribution has shown these malignant spesific points and localization protooncogenes in genome of the person, that the majority protooncogenes places just in zones of specific breaks chromosomes.

Significant practical interest in the plan of the analysis of chromosomal role aberrations in activation of protooncogenes represent chromosomal and genes of illness, which are characterized by increased instability of chromosomes. To them belong Dawns illness, Fankonys anemia, Blums syndrome, Louis-Bars syndrome and etc.

It is established, that among patients with Dawns illness the frequency leucosis in 20 times is higher, than among persones without Dawns illness. Fankonys anemia the diverse deviations karyotype from norm are found: chromatide breaks, acentric fragmentation, dicentric chromosomes, chromatide exchanges. In children with the Blums syndrome large percent of breaks chromosomes, as for want of Fankonys anemia is observed. The frequency of exchanges between sister chromatides in 9 times is higher, than in the healthy people. The chromosomal instability consists in breaks and translocations of a long shoulder of 14-th chromosome in Louis-Bars syndrome.

The persones burdened with any of these illnesses, are exposed to strong risk of development in them malignant tumor, including leucosis. The approximately half of patients with Fankonys anemia suffers acute myeloid leucosis. About 80 % of the patients with Louis-Bars syndrome are sick lymphoid leucosis or various lymphomas.

With the help of precision methods of differential colouring chromosomes it was possible to clarify, that for each type leucosis are characteristic specific chromosomal aberrations. The most better is investigated translocation 9/22, characteristic for chronic myelocytic leucosis. This anomaly for the first time was described in 1960 in Philadelphia (USA). Changed chromosome have named philadelphian. That chromosome will be derivated in result reciprocal translocation between 9-th and 22-nd chromosome. Long shoulder of 9-th chromosome contains protooncogene abl (Abelsons), which in mice causes leucosis, and long shoulder of 22-nd chromosome contains protooncogene sis, which causes sarcoma in haired monkeys.

For want of mutual translocation protooncogene Abelsons 22-nd moves from 9-th chromosome on long shoulder of protooncogene, and the fragment of long shoulder of 22-nd chromosome moves on 9-th chromosome. Redislocation of oncogenes abl and sis is not equivalent.

The appearance of oncogene sis in structure of 9-th chromosome is not reflected in vital activity of bone marrow stem cell. In other words, expression of oncogene sis in bone marrow cells does not occur. Absolutely 22-nd in another way behaves oncogene abl in structure chromosome. It is exposed very high expression as transcription abnormal RNA. Such RNA is not present neither in normal bone marrow cells, nor in leucosis cells, where there is not 9/22. Therefore consider, that exactly the activation Abelsons oncogene is that critical mechanism, which initiates development chronic myelocytes leucosis.

Expression of Abelsons oncogene in bone marrow to a cell stipulate appearance in it special oncoprotein with molecular weight 210 kD and by thyrosine activity. This oncoproteine is coded simultaneously Abelsons oncogene from 9-th chromosome and site 22-nd chromosome, which adjoins to the point of break.

The data about a role of chromosome aberrations in leucosis ethiology can be generalized as follows. The anomalies karyotype only when can cause leucosis, if they seize chromosome locuses, where are located protooncogenes. The activation stipulates these protooncogenes pathological proliferation and leucosis. Each chromosome has so-called fragile sites, which can be identified with the help of differential colouring. Just here there are deletion, inversions and translocation, which become by the initiators of activation protooncogenes more often. Therefore, all hereditary syndromes, with which is peculiar high chromosomal instability, should be considered as causes factors of leucosogenesis.


Virus transduction.


On leucosogenic properties retroviruses divide on two groups fast-transformed (viruses acute leucosis) and slow- transformed (viruses of chronic leucosis).

Retroviruses of the acute leucosis differ by that their gene has an additional gene. It represents cells oncogene, which was snatched out from genome of cell and is built in virus RNA. Only now of it to name uncellular, and virus oncogene. Just this additional gene consider as the specific factor, which causes malignant transformation of a cell, and the process of massage cells oncogene through a virus is named virus transduction.

After repeated introduce in a cell virus (form cells) oncogene shows high propensity to expression. The reason, first of all, that it is seized by virus without surrounding regulatoring repressors genes. The second reason that a DNA-copy retrovirus is not absolutely exactly reading out return transcriptase. When the again created virus particles are introduced into the following cell, their DNA-copies with an additional gene (virus oncogene) are built in cell by the gene and easily expression or because mutational virus oncogene becomes inaccessible repressoring gene to environment, or because this environment in general is absent.

Highoncogenic retroviruses the most effective leucosogenes. It is explained by that presence in them oncogenes have cell origin and in norm answer for proliferation of cells. Therefore in conditions of loss genome and epigenome control they are exposed stronger expression, than for want of chemical and physical mutation.


Insertion of provirus.


Most of viruses leucosis belongs not to fasttransformational, and to slowtransformational retroviruses. They do not contain oncogenes and induce experimental leucosis in an animal less effectively, than fasttransformational. Slowtransformational retroviruses cause transformation of cells because their DNA-copies are inserted in cells by a gene near to cells oncogene. The presence of another's DNA somehow activates cells oncogene up to very high level expression.



Genes amplification.

This increase of copies of separate genes in reply to change of the external environment. In leucosis cells are detected amplificated of copy some protooncogenes. In itself amplification of oncogene does not concern to initiating events in leucogenesis. It is connected to a progression already of initiated cells. But in any case amplification of gene results in increase of level expressed RNA and precisely is proportional to level amplificated DNA.


Leucosis clone

The pathogenetical analysis of leucosis is compound. The first question, which arises for want of consideration pathogenesis leucosis: which cells bone marrow are targets for action various leucosogenis of factors ionising rays, chemical leucosogenes retroviruses? The modern researches testify that cells targets are stem cell of bone marrow, though it is possible, that cells and classes also can be involved in process leucosogenesis. However stem of cell much earlier and more often are included in leucosis process, therefore submission about leucosis as about illnesses of stem cells now dominates.

The second major question of pathogenesis arises on base of transformation by one stem cell or many simultaneously?

Normal hemopoiesis is polyclonic. It provides valuablis and uniform development all shoots of bloodforming lymphoid myeloid erythroid megacaryoblastic. For want of leucosis the picture varies. For want of leucosis the special pathological autonomous clone of the transformed cells will be derivated. Cells of this clone have selective advantage before other cells they are capable to very intensive proliteration. The cells of leucosic clone can be differentiated in the party anyone called above shoot. Already there will be no uniform development of all shoots. On the contrary, any one of them, originating from transformed stem cell, will prevail above others and to supplant their from bone marrow.

It is proved, that all cells leucosis of clone occur from one transformed cell. The system character of leucosis testifies like against this rule. Its leucosis very fast inclusions all bloodforming tissue. However, all this only external symptom, which does not reflect true events. Actually all weight leucosis cells, where they were not, (in other words, all leucosis the clone) is descendants by one transformed stem cell. The difference from usual tumours consists only that metastasing for want of leucosis begins at very early stages of illness.

Leucosis clone is not homogeneous. It consists of cells of two populations proliferational (G1) and non- proliferational (G0). Proliferational population makes only 10 % leucosis cells. Others 90 % of cells not proliferational. On proliferational of ability the population G1 differs from normal cells. It proliferative the activity much below also makes approximately 40 % of activity of normal cells. For example, the time of reproduction of normal cells bone marrow is equal to 12-20 hours. The time of reproduction leucosis cells in 4-5 times more also makes 40-80 hours.

How then to explain, what proliferational cell of leucosis a clone for short time give huge cells weight? Its they make only 10 % of total leucosis cells and are made multiple copies in 4-5 times slower, than normal cells. Its founded, that affair here not in speed of division, and in an amount of divisions. In normal bone marrow sten cell has enough 5-10 divisions, that it has reached up to myelocyte. For want of leucosis the amount of divisions is sharply increased. Leucosis the cell becomes not submit to a limit Heiflicks. For want of acute leucosis cell in addition to completely lose ability to differentiation. Their maturing, as a rule, does not go further blast forms (V classes).

Count show, that one leucose transformed stem cell for 40 divisions gives cells weight equal to 1 kg. This weight is considered critical. Just for want of such cell to weight begin to occur the first clinical signs of leucosis. It will be derivated approximately during 4-5 months.

The G0-population of leucosis cells executes role of reserve. These cells can long time stay in sleeping state both in bone marrow and in blood. From time to time they leave from vessels in serround tissue, subside there and give extramedullar centers of bloodforming. The correlation between two populations leucosis cells G1 and G0 determines state of leucosis process progression, remission, recurrence.

Major chain of pathogenesis leucosis is oppression by leucosis cells normal of hemopoiesis. Select some mechanisms of this phenomenon. Firstly, leucosis cell are capable produced in redundant amount colonialstimulation factor stimulator of myelopoiesis. Secondly, this factor acts on leucosis cell, than on the normal predecessors hemopoiesis stronger. Thirdly, leucosis of a cell have property selectively to oppress proliferation and differentiation of normal cells predecessors with the help humoral inhibitors. Forthly, leucosis cell is more active, than normal, answer to action of the growth factors.

Gradually pool of normal cells predecessors is exhausted. Bone marrow is filled in leucosis with weight. This modification stipulates main clinical signs leucosis metaplastic anemia, thrombocytopenia, hemorrhagic syndrome, secondary immunodeficiency, decrease of resistantion to infectious agents. The patients die or from bleeding in brain, or from an infection. In conditions immunedeficiency even saprofit flora can become pathogenic.




As was already told, the disorders of hemopoiesis for want of acute and chronic leucosis are not identical. These distinctions define an originality hematological picture for want of each them. For want of acute leucosis in peripheral blood will be a lot of young cells forms , and V classes and there are not enough of mature cells V class for want of complete absence of the transition forms V classes. Absence of the transition forms in peripheral blood very characteristic morphological difference acute leucosis from chronic. This hematological symptom is called leucemic failure (hiatus leucemicus).

The reason that the absolute majority of cells leucosis of a clone is not differentiated further of the blast forms. At the first they are stored in bone marrow, and then break in blood. Only single cells manage to pass usual path of differentiation and to get in blood in mature state. Lets give for example acute myeloblastic leucosis. For want of it leucosis in peripheral blood will be much myeloblasts (V classes), of cells predecessors - classes and there are not enough of mature forms (sticknucleus and segmentnucleus neutrophils). Characteristics will be absence of the transition forms V classes promyelocytes, myelocytes, metamyelocytes (leucemic failure).

Completely other hematological picture for want of chronic leucosis. As the maturing of cells goes up to the end, in blood there will be an abundance of cells of all classes young, transition and mature. Leucomic failure is absent. For want of chronic myelocytic leucosis blood there will be cells predecessor and classes, myeloblasts (V classes), cell V classes promyelocytes myelocytes metamyelocytes sticknucleus neutrophils and mature cells of the V class (neutrophils).

For want of chronic lymphocytic leucosis the picture of peripheral blood is characterized by the following features: it is a lot of mature lymphocytes, is prolymphocytes and lymphoblasts, and also desroyed cells lymphoid number (Gumprechts bodies).


Leukocytosis. Leukopenias. Leukaemoid reaction


Leukocytosis is an increase in the total white cell count. The most common cause is neutrophilia, followed by lymphocytosis. Much less commonly seen is an increase in eosinophils or monocytes. Leukocytosis is most frequently due to a normal bone marrow response to relatively benign causes such as inflammation, infection or drugs. However, more serious causes of leukocytosis include primary bone marrow pathology leukaemia and myeloproliferative disorders.




When looking at an abnormal full blood count that reports a leukocytosis, it is important to look not only at the total number of white cells, but also the lineage (or lineages) that are increased, as well as the other components (haemoglobin, platelets).

Clinical findings such as weight loss and enlarged lymph nodes, liver and spleen may increase suspicion for an underlying bone marrow disorder.

Neutrophilia. Healthy neonates and pregnant women frequently have a physiologically normal mild neutrophilia. The various causes of neutrophilia are discussed in this section and can be classified into malignant and non-malignant causes. The most non-malignant common cause of neutrophilia is the bone marrow response to an external stimulus. A neutrophilia is commonly associated with many bacterial infections (and some viral infections). Occasionally, immature cells of the granulocyte series (e.g. band forms, metamyelocytes and myelocytes), which are not normally seen in the peripheral blood, may also be seen with neutrophilia during infections. This is termed left shift. The neutrophilia, in part, is thought to be mediated from cytokine and complement release. Acute and chronic inflammation can stimulate bone marrow granulocyte production, resulting in an increase in the white cell count.

Examples include gout, rheumatoid arthritis and ulcerative colitis. Occasionally, there may be a marked increase in reactive white cells (>50 x 109/L) with left shift in the blood; this is termed a leukaemoid reaction. Leukaemoid reactions can also be seen in severe septicaemia, pancreatitis and malignancies. The main differential diagnosis of a leukaemoid reaction is chronic myeloid leukaemia. A variety of medications can cause an increase in the peripheral neutrophil count. Common examples include gluco-corticosteroids (e.g. prednisone, dexa-methasone), lithium and granulocyte colony-stimulating factor. Physiological stress (such as vigorous exercise, seizures and acute myocardial infarction) can lead to a transient increase in neutrophils. This is thought to be due to the release of catecholamines, adrenaline and cortisol, which shifts more neutrophils into the circulation.

A moderate neutrophilia and lymphocytosis can be associated with either congenital or post-surgical asplenia, due to the absence of the spleen, which acts as a storage pool for neutrophils. The congenital causes for neutrophilia are very rare. Congenital idiopathic neutrophilia is a chronic form of leukocytosis in people who are otherwise healthy. The other blood counts are normal and there is no associated clinical disease. Leucocyte adhesion deficiency is another rare congenital disorder of neutrophil function. As a consequence, neutrophils are unable to leave the circulation in response to sites of infection, resulting in recurrent infections (mainly skin abscesses).

Malignant causes. Chronic myeloid leukaemia (CML) is a common myeloproliferative disease. In the chronic phase of CML, the peripheral blood shows a marked leucocytosis, usually >100 x 109/L. This is due to increased marrow production and results in the presence of granulocytes at different stages of maturation, in particular, mature neutrophils and myelocytes. Chronic neutrophilic leukaemia is a very rare myeloproliferative disorder characterised by sustained peripheral blood neutrophilia. Diagnosis is by excluding other causes of reactive neutrophilia and other myeloproliferative diseases. Polycythemia vera is a clonal haematopoietic stem cell disorder that results in an increase in red blood cell production (an increase in haemoglobin and haematocrit). Neutrophilia and basophilia are commonly seen in up to 20% of patients.

Lymphocytosis. Lymphocytosis is an absolute increase in the lymphocyte count above the reference range for a given age in a healthy individual. The normal absolute lymphocyte count is higher in childhood. This usually persists until age 4-6, following which the count falls to within the adult range. Therefore, it is important to use age-specific ranges when dealing with children. The various causes of lymphocytosis can be classified into malignant and reactive causes.

Reactive causes. Reactive lymphocytosis refers to lymphocytosis in a patient who does not have an underlying haematological disorder, with the lymphocytosis being a secondary reaction to infections, stress or other medical conditions. When this resolves, the lymphocyte count should normalise. Reactive lymphocytosis occurs during the course of many viral infections, including infectious mononucleosis (caused by the Epstein-Barr virus), rubella, cytomegalovirus, varicella and herpes zoster. One of the most common causes is EBV infection, in which there is often a characteristic reactive lymphocytosis. The peripheral lymphocyte count may often be as high as 20-30 x 109/L. Diagnosis is often made by a rapid slide test (monospot test) and/or testing for antibodies (IgG, IgM) specific for EBV.

While bacterial infections are an uncommon cause of lymphocytosis, a well-recognised example is infection with Bordetella pertussis, a gram- negative bacterium that is the aetiological agent of whooping cough. The total lymphocyte count can be up to 15-50 x 109/L. Transient stress-related lymphocytosis can be associated with myocardial infarction, trauma, obstetric complications or status epilepticus.

Malignant causes. Lymphoproliferative disorders occur when there is an increase in a malignant clone of lymphocytes. In chronic lymphocytic leukaemia, there is a clonal proliferation of small B lymphocytes in the peripheral blood, bone marrow and lymph nodes. This is perhaps the most common cause of lymphocytosis in individuals older than 60 years. The lymphocyte count in the peripheral blood is usually defined as >10 x 109/L, and the malignant B cells display characteristic immunophenotype on flow cytometry.A wide variety of lymphomas can occasionally result in a peripheral blood lymphocytosis with morphologically abnormal lymphocytes. Some of the lymphoproliferative disease with distinctive morphological features include mantle cell lymphoma, hairy cell leukaemia and Sezary syndrome cutaneous T cell lymphoma.

Eosinophilia. Eosinophils play an important role in inflammatory and allergic responses, as well as defence against parasites. Eosinophilia can be due to reactive, idiopathic or malignant causes. Information regarding allergic symptoms, travel history, current and recent medications, and constitutional symptoms help when trying to work out the underlying cause of eosinophilia. For patients at risk of parasitic infections, stool specimens should be examined for ova, cysts and parasites. Eosinophilia may also occur as a reaction to lymphoid malignancies, espec-ially Hodgkin lymphoma and acute lymphoblastic leukaemia. The hypereosinophilic syndrome is defined by persistent eosinophilia >1.5 x 109/L (for more than six months); the absence of other causes of eosinophilia; and heterogeneous organ involvement (heart, lungs, skin).

Monocytosis. Monocytes comprise less than 10% of leucocytes. The most common causes of a reactive monocytosis are infections and inflammatory conditions. Malignant causes of monocytosis include: chronic myelomonocytic leukaemia: this is a chronic haematological condition which has features of both myelodysplasia and myeloproliferation. Peripheral blood monocytosis (>1 x 109/L), dysplasia involving one or more myeloid lineages, and splenomegaly are common features. The median age of diagnosis is 65-75 years. Acute leukaemia: two subtypes of acute myeloid leukaemias can present with an elevated peripheral monocyte count. Juvenile myelomonocytic leukaemia: this is a very rare clonal haemopoietic disorder affecting children, usually younger than three years, although the age of presentation can range from one month to adolescence. Apart from a monocytosis (>1.0 x 109/L), other associated features include anaemia, splenomegaly and, occasionally, hepatomegaly.

Leukopenia. Neutropenia. A decrease in the total white cell count is invariably due to a decrease in neutrophils and/or lymphocytes. Neutropenia may be an isolated phenomenon or as part of a pancytopenia. The number of neutrophils in the peripheral blood is influenced by several factors, including age and ethnicity. The degree of neutropenia predicts the infection risk. Neutropenia is often categorised as mild, moderate or severe, based on the level of neutrophils: mild (neutrophil count 1.0-1.5 x 109/L); moderate (neutrophil count 0.5-1.0 x 109/L); severe (neutrophil count <0.5 x 109/L). Patients with severe neutropenia are at increased risk of developing life-threatening infections. Fever or other signs of infection are a medical emergency requiring prompt treatment with broad-spectrum antibiotics.

Primary inherited neutropenias are rare. Recurrent bacterial infections are the only significant consequence of neutropenia and, as noted, the risk is related to the degree of neutropenia. Acquired causes. Chronic idiopathic neutropenia/benign chronic neutropenia is a term used to describe chronic neutropenia for which there is no obvious cause. These patients most often have a benign course despite the degree of neutropenia. It is most commonly seen in women. Neutropenia is an early and consistent feature of megaloblastic anaemia due to either vitamin B12 or folate deficiency. There is usually associated macrocytic anaemia and thrombocytopenia.

Chemotherapy is the most common cause of drug-related neutropenia. The degree and duration of neutropenia is dependent on the agents used and the intensity of chemotherapy, combined with the patients pre-treatment bone marrow reserve. Certain groups of patients are at particular risk. These include the elderly and those with significant comorbidities, such as liver and renal dysfunction. Non-chemotherapy drugs can also cause neutropenia, either by immune-mediated destruction of circulating neutrophils, or by dose-dependent marrow suppression. The neutropenia usually develops within 1-2 weeks of starting the drugs. Drugs commonly associated with neutropenia include: psychotropic drugs (clozapine); anti-thyroid drugs (carbimazole, propylthiouracil); NSAIDs; anti-convulsants (phenytoin, valproate, carbamazepine); and antibiotics (vancomycin, cephalosporins).

An isolated neutropenia can be seen in patients with various autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and autoimmune haemolytic anaemia. Moderate to severe neutropenia can occur in newborn infants secondary to the passive transfer of maternal IgG antibodies directed against fetal neutrophils. The neutropenia is usually noted in an otherwise normal infant and usually resolves without significant sequelae.

Pure white cell aplasia is a very rare disorder characterised by the complete absence of granulopoiesis in the bone marrow. It is often associated with a thymoma. Hypersplenism. Diseases associated with splenomegaly and neutropenia include sarcoidosis, Gauchers disease and rheumatoid arthritis (Feltys syndrome). In most cases, the neutropenia is not severe enough to warrant splenectomy.Infectious diseases Although the most common reaction to a bacterial infection is neutrophilia, occasionally, neutropenia can occur. Certain infections, such as typhoid fever, shigella enteritis and tuberculosis, are classically associated with neutropenia.

Lymphocytopenia. Lymphocytopenia is less common than neutropenia. The most common cause of lymphocytopenia is part of an acute response to stress (e.g. burns, infections, surgery and trauma) Lymphocytopenia is characteristic of HIV infections with an absolute reduction in CD4-positive T cells. As the disease progresses, there is increasing severity of lymphocytopenia. Lymphocytopenia can also be a feature of Hodgkin lymphoma, with a lymphocyte count of less than 0.6 x 109/L associated with an adverse prognosis. Congenital forms of lymphocytopenia include severe combined immuno-deficiency syndromes, which lead to a profound deficiency in B and T lymphocytes.