Blood transfusion and blood substitutes

Bleeding and blood loss.

Methods temporary control of bleeding.

Methods final control of bleeding.

 

Haemorrhage, or bleeding, is the escape of blood from the blood vessels into the tissues and cavities of human body or outside, as the result of an injury or defect in the permeability of the blood vessel wall. During every damage the bleeding is arised.

The hemorrhage is one of the main reasons of death of persons with trauma. The bleeding, its consequences, methods of a first aid and treatment are studied from the moment of origin of medicine. Despite of it, some questions of this problem till are completely unsolved.

The surgeons are to placing a high emphasis to a problem of a bleeding. One of the basic parameters of qualification of the surgeons skill is reduce a loss of blood during operation and to stop a bleeding.

About a bleeding speak, when the blood actively acts from a vessel (vessels) in an environment, hollow organ or cavities of an organism.

In some cases the blood to ooze into the suurrounded tissues as a result of bleeding. This process is named extravasate.

In other cases when the poured out blood causes stratification of tissues, separation of organs and as a result the dimension cavity arised, which is filled with a blood is formed, - we speak about a hematoma (fig.1). The further development of a hematoma may lead to the following results. These are resorption, suppuration or the organization of a hematoma. The hematoma which is communicating with a lumen of the injured arteria, is called aneurismal (pulsative) hematoma. Clinically it is shown by definition of a pulsation of a hematoma during palpation and presence of systolic hum during auscultation.

 

Classification. There are some classifications of bleeding.

I. Anatomical classification (according to kind of bleeding vessel):

        Arterial hemorrhage;

        Venous hemorrhage;

        Capillary hemorrhage;

        Parenchymatous hemorrhage.

II. According to mechanism of beginning:

        Mechanical failure, vessel rupture (haemorrhagia per rhexin);

        Arrosive hemorrhage (haemorrhagia per diabrosin). This types of bleeding takes place during suppurative melting of wessel wall;

        Diapedetic hemorrhage (haemorrhagia per diapedesin);

        The violation of chemical composition of blood. The hemophilia, scarlet fever, sepsis, scurvy and others are causing bleeding sometimes. Toxins or beriberi to produce defect in the permeability of the vascular walls and caused of hemorrhage;

        Increased of arterial and venous blood pressure. The diseases, such as essential hypertension, atherosclerosis sometimes coursed of an injury of the vascular wall and bleeding (stroke, hemorrhoidal bleeding, etc.);

        Violation of fibrillation (haemophilia, Werlgofs disease, cholemic hemorrhage in patients with jaundice).

III. According to environment the bleeding divided into the two main kinds. There are:

        External bleeding;

        Internal bleeding.

The hemorrhage during damaging of skin or visible mucous membrane is named external. When blood accumulates in the enclosed space of the body or in the cavity or in the hollow organ this is internal bleeding. Internal hemorrage divided into the explicit and occult (without clinical symptoms). Moreover, it can be occult, when diagnosed only by means of specific methods of investigation.

In arterial external bleeding blood of bright red ciliur effuses by pulsative spurt. Such haemorrhage quickly results in acute anemia. The following symptoms characterize an acute anemia: persisting paleness, trembling and small pulse, progressing decrease of blood pressure, dizziness, nausea, vomiting and syncope.

External venous bleeding is characterized by slow effusion of dark blood.

Injury of large veins of neck is dangerous due to a possibility of development of air embolism of cerebral vessels and cardiac pressure in these veins during ingalation.

General symptoms are the same for all types of bleeding, including inner bleeding in various cavities. They are observed in heavy loss of blood and consist of appearance of acute anemia (paleness, dizziness, syncope, trembling small pulse, progressing decrease of blood pressure).

The local symptoms are various.

In internal bleeding, blood effused into closed cavity, may compress a vitally important organ (brain, heart, lung, etc.), violate its function and become dangerous for the patients life.

Bleeding in serous cavities (pleural, abdominal) during internal haemorrhage the especial place is occupied. They stop independently rarely and are noted massiveness of a hemorrhage. It is caused by that the blood in a serous cavity loses ability to coagulation. Walls of these cavities dont obstruct mechanically to the escape of blood through injured vessel. Moreover, owing to negative pressure in a pleural cavity it is formed suction effect. As a result of falling out a fibrin from a blood coagulation is violate. A fibrin settles on a serous cover. Thus process of a thrombogenesis is impairing.

At bleedings in empty space of a gastrointestinal tract the blood in a stomach changes the color. In ample quantity of its accumulation a vomiting, like ground coffe (hematemesis), is originated. Further or at a bleeding from underlaying departments of a gastrointestinal tract it is observed weak tarry stool in large quantity (melena). This is example of explicit bleeding.

Occult bleeding this is hemorrhage without any clinical symptoms. For example, there is bleeding from ulcer of stomach or duodenum. This type of heamorrhage doesnt have clinical symptoms. Such bleeding is possible to reveal only by laboratory method. This is research of occult blood in feces. Continued long time concealed hemorrhages which are not revealed, may result in development of an anemia.

Some kinds of internal bleeding have specific name:

        Haemobilia haemorrhage from diliary ducts;

        Haematuria - haemorrhage from kidneys and urinary system;

        Haemoperitoneum - haemorrhage in abdominal cavity;

        Haemothorax - haemorrhage in pleural cavity;

        Haemopericardium - haemorrhage in pericardial cavity;

        Haemartrosis haemorrhage in joint cavity;

        Metrorrhagia uterine bleeding;

        Proctorrhagia rectal bleeding;

        Hemorrhagic insult cerebral hemorrhage.

IV. According to time of beginning all bleeding are: primary and secondary.

A beginning of primary bleeding is concemed with direct damaging of vessel during trauma. Straight off onset symptoms or durig first hours after injuring be developed.

The secondary bleedings are early (usually from some hours to 4-5 days after damaging) and late.

There are two main reasons of early secondary bleeding development:

1.     Slide of ligature off damaging vessel, which was imposition during operation;

2.     Washing-out the clot from the injured vessel. This complication we have in connection with increased of blood pressure, blood flow acceleration or through reduction of spastic vessel contraction, which to occur during acute blood loss.

Late secondary or arrosive hemorrhage concemed with vessel wall destruction. This is result of development of wound infected process. This case is one of very complicated, because all vessel wall change in this region and hemorrhage replace in every moment is possible.

V. According to clinical course all bleedings are divided into acute and chronic.

During acute haemorrhage to bleed occurs at short time period.

During chronic haemorrhage to bleed is gradually, a little at a time. Sometimes during some days narrow or periodic discharge of blood is observable. In cases of stomach ulcer, duodenum ulcer, malignant tumors, uterine fibromyoma, hemorrhoids the chronic haemorrhare is observe.

VI. According to degree of severity.

Estimation of blood loss severity is very important, because it determined of character of blood supply disturbance in sick organism and finally, danger of bleeding for patients life.

According V.I.Struchkov and E.W.Lutzevich there four levels of blood loss.

        I level easy degree blood loss is even to 10 12% of blood circulating volume (500 700 ml). Haemorrhage is causing little changes to hemodynamic. The general condition of patient is satisfactory. Pulse is slightly quickened, arterial pressure is normal (standart). Blood hemoglobin is rised above 100 g/l (10 g %). During capillaroscopy: background is rosy, 3 4 capillary loops with quick gomogenous bloodstream are determined.

        II level middle degree - blood loss is even to 15 20 % of blood circulating volume (1000 1400 ml). Apparent bleeding is distinguished. The general condition is medium-scale difficalty. Limpness, dizziness, hyperhidrosis, syncope are observed. Coverlet is pale. Respiration is accelerated. Reflexes are decrease. Single vomitting or melena may be observed. Pulse become noticeably more rapid (90 100 per min.). Arterial pressure is decreased to 90 mm Hg. Leucocytosis, deviation of the differential count to the left are determined. Hematocrit is 0,38 0,32, hemoglobin is 80 100 g/l (8 10 g %). Quantity of urination is decreased.

        III level heavy degree blood loss is 20 30 % of blood circulating volume (1500 2000 ml). The general condition of patient is bad (grave condition). Paleness of skin, cold sweat is observed. Rapid vomiting and melena are determined. The bleeding is accompanied by syncope. Visible mucous membranes are colourless. The patient yawns, feels thirst. Pulse is rapid and thready. Arterial pressure is decreased to 60 mm Hg. Hematocrit is 0,30 0,32, hemoglobin is 50 80 g/l (5 8 g %). Oliguria is observed.

        IV level massive blood loss loss of blood is more then 30 % of blood circulating volume (more than 2000 ml). Plentiful bleeding with prolonged loss of consciousness may be observed. The general condition of patient is very grave, preagony. Pulse and arterial pressure are not fixed. Hematocrit is 0,23 and lower, hemoglobin is 50 g/l and lower. Anuria is observed.

Clinical picture of haemorrhage.

The clinic is characterized by local and general appearances.

The local symptoms depend on kind of bleeding (external or internal), and in what body or a cavity the blood is flowing into.

The general symptoms are some already. The massive hemorrhage is characterized by paleness of a skin, cold sweat, breathlessness, fast thready pulse and drop of arterial and venous pressure, sometimes syncope. The patient has dizziness, flashing before eyes, dryness in a mouth, thirst, nausea, weakness, irritability, an excessive sweating and decrease of urination. In a blood there are fall in erythrocytes, haemoglobin, hematocrit content and relative density.However, owing to the fact to development compensatory - adaptive mechanisms at the first hours after a hemorrhage hematological parameters may stay kept within the normal limits. It sometimes will disorient the doctor.

Sometimes the bleeding from the big arterias may stop on its own. These can occue the influence of series of circumstances:

1. Drop of arterial pressure, as consequence of a bleeding which continues;

2. The general vasospasm, as compensatory parameter;

3. Reduction of the injured vessel, especially after the complete cutting it;

4. Inverting inside internal and average walls of a vessel in a place of its break.

The compensatory - adaptive mechanisms during acute blood loss are:

        Spasm of veins;

        Interstitial fluid inflow;

        Tachycardia;

        Oliguria;

        Hyperventilation;

        Peripheral arteriolespasm;

        Sympaticoadrenal system activation;

        Activation of fibrillation system and haemopoiesis stimulation.

Features of a major bleed?

        Tachypnoea

        Tachycardia >100 bpm.

        Hypotension SBP <100mmHg supine or postural drop at any stage. Relate BP to the patients normal e.g. hypertensive.

        Clammy, cold and peripherally shutdown.

        Conscious level reduced/confusion.

        History of syncope.

Is the patient at Significant Risk of Death?

        Hypotensive after initial resuscitation.

        Variceal bleed likely.

        Obvious signs of chronic liver disease or deranged clotting indicative of liver disease.

        Continuing melaena, haematemesis, or rebleed.

        Existing co-morbidity e.g. IHD, renal failure, disseminated malignancy.

        Age >60 years.

Complicating factors

        Co-morbid disease e.g. cardiovascular, respiratory, renal, malignancy.

        Rate limiting drugs prevent compensatory tachycardia e.g. ß-blockers, verapamil.

        Vasodilators prevent compensatory vasoconstriction, e.g. ACE inhibitors.

TREATMENT

Laboratory investigations. Checking for levels of the erythrocytes, haemoglobin and hematocrit should be done on admission and repeated afterwards. In severe haemorrhage, the results of the investigations mentioned may not serve as objective indicators of the degree of bleeding in the first few hours, since autohaemodilution occurs with time, reaching its maximum within 1,5 2 days.

It is haematocrit and blood specific gravity which can be relied upon in judging about the interrelationship between the cellular components of blood and plasma.

The blood specific gravity of as much as 1,057 1,054, haemoglobin 65 62 g/l, haematocrit 44 40 suggest blood loss as high as 500 ml, while those of 1,049 1,044, haemoglobin 53 38 g/l and haematocrit 30 23, respectively, mean that the amount of the blood loss is above 1000 ml.

A progressive fall in venous blood pressure suggests that the heart is not receiving enough blood due to a reduction in blood circulating volume. It is measured either in the superior or inferior vena cava. This is performed with a catheter passing through the median cubital or saphenous vein. The most factual method is whereby the amount of blood loss is checked by calculating the deficit in blood circulating volume and its components (i.e. circulating plasma volume, volume of cellular blood components, etc.). The method consists in the introduction of specific indicators (Evans blue, radioisotopes, etc.) into the vascular system. The concentration of the diluted indicator in the blood helps determine the plasma volume; using the standard table and the haematocrit value allows for the calculation of blood circulating volume and globular volume. The normal values of blood circulating volume and its components are found from the standart table based on the patoents body weight and sex. The difference between the normal and the actual values is used to estimate the deficit in blood circulating volume, circulating plasma volume and the globular volume, i.e. the amount of blood lost.

Special diagnostic methods. If internal bleeding is suspected, diagnostic puncture should be performed (thoracocentesis during haemothorax, laparocenthesis during haemoperitoneum, arthrocentesis during haemartrosis and puncture of the posterior vaginal fornix during ruptured ectopic gestation or ovarian cyst). If indicated, X-ray, ultrasound scanning and computerised tomography can also be used. Endoscopic methods include gastroscopy, rectoscopy, cystoscopy and arthroscopy.

It will be noted that clinical symptoms and syndromes as well as the laboratory findings are used to evaluate the severity of blood loss.

Complications of bleeding

The hemorrhagic shock may arise at an acute hemorrhage and volume of a circulating blood reduction. The hemorrhagic shock is one kind of a hypovolemic shock. The clinical picture of it may occur since a blood loss 20 - 30 % of volume of a circulating blood. But much depends on an initial condition of the patient.

Allocate three stages of a hemorrhagic shock (G.A.Rjabov and co-authors, 1983).

1 stage - is the compensated convertible shock (a set of symptoms of small emission). It is characterized by such volume of a hemorrhage which is well filled with compensatory - adaptive abilities of the patients organism.

2 stage is irreversible (decompensated) convertible shock. It is characterized by deeper circulatory disturbances. The spastic stricture of arterioles may not support the central hemodynamics any more and normal amount of arterial pressure. Further at accumulation of metabolites in tissues to occur paresis of capillary channel. Decentralization of bloodstream develops.

3 stage - is irreversible shock. It is characterized by long (more than 12 hours) an uncontrollable hypotonia, an inefficiency of transfusion therapy and development of multiple organ failure.

Among other complications it is possible to name a false aneurysm (arterial and arteriovenous), an air embolism.

The basic disorders which develop during a bleeding:

1. A hypovolemic shock caused by decrease of a circulating blood volume;

2. Renal insufficiency caused by decrease of a filtration and a hypoxia of kidneys parenchyma;

3. Hepatic insufficiency as a result of decrease of hepatic bloodstream and hypoxia;

4. A myocardium anoxia which results in cardiac infarction;

5. A hypoxia of a brain which results in an edematization of a brain;

6. By products of protein hydrolysis of blood intoxication, this was poured out in an intestine or other cavities.

MalloryWeiss Syndrome

Introduction

Mallory and Weiss first described gastroesophageal tears causing gastrointestinal bleeding in 15 alcoholic patients in 1929. Since this time, longitudinal mucosal lacerations, associated with forceful retching, has become a well-known cause of upper gastrointestinal bleeding. The prevalence of MalloryWeiss Syndrome is reported to be approximately 5% of patients suffering acute upper gastrointestinal bleeding, but may be higher. The presence of MalloryWeiss tears without acute bleeding is difficult to quantify and their clinical significance is debatable.

Etiology and Pathogenesis

The pathogenesis of MalloryWeiss tears is not completely understood, but it is thought that they are most likely caused by a sudden increase in intra-abdominal pressure. This is most likely secondary to forceful emesis, but can be due to straining, lifting, or blunt abdominal trauma. Additionally, MalloryWeiss tears can be iatrogenic, due to esophageal instrumentation, such as nasogastric tube placement or upper endoscopy, or polyethylene glycol administration. Despite frequent interventions, iatrogenic causes of MalloryWeiss tears are infrequent. Bleeding from MalloryWeiss tears occurs when the laceration involves either the esophageal arterial or the venous plexus. Most frequently, the tears are single, but may be multiple in up to one-quarter of patients.

Alcoholism and hiatal hernias are the two main risk factors identified for the development of MalloryWeiss tears. Heavy alcohol use associated with emesis has been noted in up to 80% of MalloryWeiss syndrome. Similarly, hiatal hernia is found in almost all patients with bleeding. It has been proposed that a higher pressure gradient develops in the intra-thoracic portion of the stomach and GE junction, thus increasing acute distension and mucosal tears. Although age has been postulated as a risk factor for development of MalloryWeiss tears, the majority occur in patients in their forties and fifties. It does appear that age may be a predisposing factor for iatrogenic tears after endoscopy, likely due to atrophic mucosa.

Presentation

The majority of patients present with hematemesis often associated with epigastric, chest, or back pain. Classically, patients will give a history of antecedent non-bloody emesis or retching but a significant minority will give a history of bleeding with the initial emesis. In the majority of cases, bleeding is self-limited, but lifethreatening hemorrhage requiring blood transfusion, hemodynamic support, and endoscopic or operative intervention may be required. A 1997 study identified active bleeding at the time of endoscopy as a risk factor for higher transfusion rate and portal hypertension or coagulopathy as a risk for re-bleeding.

Diagnosis

Early endoscopy is the diagnostic modality of choice with MalloryWeiss tears. Endoscopy is diagnostic and can rule out other causes of upper gastrointestinal bleeding, such as varices, esophageal lesions, esophagitis, or ulcers. Additionally, endoscopy can be therapeutic. Most lesions will heal within 48 h, so delayed esophagoscopy may not be diagnostic. Endoscopically, MalloryWeiss tears appear as longitudinal lacerations through the mucosa, occasionally exposing the muscular layer of the esophagus (Fig. 1). These tears can be non-bleeding, actively bleeding, or covered in clotted blood.


Fig. 1
Endoscopic image of MalloryWeiss tear

Treatment

Although up to 70% of patients with MalloryWeiss syndrome ultimately require blood transfusion, the majority of lacerations heal spontaneously. As with any GIB patient, large-bore intervenous access should be obtained and adequate intervenous fluid resuscitation should be instituted. Coagulopathy should be reversed, with vitamin K or fresh frozen plasma as indicated. Patients should be closely monitored for hemodynamic changes. Most patients are started on proton pump inhibitors, although their effectiveness for MalloryWeiss tears is doubtful. Additionally, patients should be put on bowel rest during their initial observation.

Early endoscopy is critical in the diagnosis and treatment of patients with MalloryWeiss tears. If, on endoscopy, active bleeding is not observed, no endoscopic therapy is indicated and the patient should be observed for re-bleeding for 48 h. If bleeding is observed, endoscopic therapy (such as injections, electrocautery, or clipping) is the first-line treatment of patients with on-going bleeding from MalloryWeiss tears. Injection of epinephrine, ethanol, or other sclerosing agents is the most commonly used treatment (Fig. 2). Epinephrine (1:10,000) with or without an additional sclerosing agent (such as polidocanol) appears to be very effective with an approximately 5% re-bleeding rate. Thermal coagulation with either bipolar or multipolar electrocautery (Fig. 3) has also been described.


Fig. 2
Injection of epinephrine via needle catheter in esophagus


Fig. 3
Multipolar electrocautery catheter (Bicap)

Although this treatment modality may be used, caution must be exhibited. The technique of electrocoagulation is similar to that used for bleeding ulcers but usually less tamponade force and lower total energy because of the smaller size area and to avoid perforation (e.g., bipolar probe at 1518W, short pulse such as one second and moderate tamponade force often laterally with a stiff probe). Electrocautery should be avoided in patients with portal hypertension and esophageal varices, as this may worsen bleeding and may be life threatening. Additionally, because the esophagus lacks a serosal layer, coagulation may cause full thickness injury and perforation and should be used judiciously. Electrocautery is best indicated in small, limited lesions, where minimal electrocautery can be used.

Multiple small trials have reported excellent results with the application of hemoclips (Figs. 4a, 4b) to MalloryWeiss tears. These studies reported excellent hemostasis and minimal to no re-bleeding. Despite this, a recent meta-analysis of endoscopic clipping for acute non-variceal upper gastrointestinal bleeding reported that clipping alone was not superior to other endoscopic modalities. These results may be slightly skewed due to the fact this analysis contained a majority of patients with lesions other than MalloryWeiss tears. Variceal banding has been reported for treatment of MalloryWeiss tears with good results for these patients. Just as with treatment of bleeding ulcers, multiple endoscopic therapeutic techniques have been shown to be effective and the technique used should probably be dependent upon the experience and comfort level of the endoscopist.

Re-bleeding is treated with repeat endoscopic treatment. Patients with refractory bleeding can be treated with angiographic embolization, balloon tamponade, or intervenous infusion of vasopressin. Very rarely, patients with refractory bleeding will require surgical intervention. This usually consists of creating a longitudinal esophagotomy and over-sewing the bleeding vessels. With the improvement of endoscopic therapies, surgery is the last line therapy and is required in a very small percentage of patients. After successful intervention, the patient should be observed for bleeding for at least 48 h.


Fig. 4a
MalloryWeiss tear in patient with acute bleeding


Fig. 4b
Multiple endoclips applied to MalloryWeiss tear

Conclusion

MalloryWeiss syndrome is characterized by bleeding esophageal lacerations most commonly caused by forceful retching. Although up to 70% of patients received blood transfusions, the majority of bleeding is self-limited and requires no intervention. Early endoscopy is the diagnostic and therapeutic modality of choice. If no bleeding is visualized, the patient can be observed for 48 h. If the laceration is actively bleeding, endoscopic therapies, such as sclerotherapy, electrocautery, or clipping, are highly effective with a re-bleeding rate of approximately 5%.

Methods to control bleeding (hemostasis)

There are two basic methods to control of bleeding: operative and conservative. They all also divided on temporary and final methods of hemostasis.

Temporary methods to control of bleeding of ones nature are mechanical.

There are applying:

- An applying a arresting bleeding tourniquet (fig. 2);

- Digital compression of artery;

- The maximal flexion or a raised position of an extremity;

- A pressure bandage;

- A tamponade of a wound;


- Applying clamp on bleeding vessel;

- A temporarily shunting.

 

Rules of tourniquet application:

1. Before applying a tourniquet elevate an extremity;

2. Arresting bleedind toutniquet is applied proximally of wounds (during an arterial bleeding), as closer as possible to it;

3. Under arresting bleeding toutniquet it is necessary to line a material (clothes);

4. In the time of applying of arresting bleedind toutniquet make two - three rounds, uniformly stretching it. Thus rounds of arresting bleedind toutniquet should not lie down one on another.

5. After end of procedure it is necessary to indicate an exact times of an applying a tourniquet;

6. The part of a body where tourniquet is applied should be accessible to examination;

7. The tourniquet has to be on that area of an extremity where there is one bone.

Criterias of a correct applying a tourniquet are:

- Control of haemorrhage;

- Absence of a peripheric pulsation;

- Colourless (pale) and cold an extremity.

Very important that the tourniquet cannot stay more than two hours on the low extremities and 1,5 hours on upper. In the other case the development of necrosis of an extremity is probably. As a result of a long ischemia of an extremity the necrosis is arised. If necessary long transportation of the victim, doctor must to loosen the tourniquet each hour approximately on 10 - 15 minutes. At this time replace this method with other temporary method control to bleeding (for example - digital compression of artery).

 

Final methods to control bleeding (final hemostasis)

Depending on the nature of methods which are applied, the last are divided on mechanical, physical (thermal), chemical and biological.

Mechanical:

        Ligating a vessel in a wound;

        Ligating a vessel at a distance (fig. 3);

        Under-runing a bleeding vessel;

        Vasoversion, a crush of a vessel;

        Tamponade of a wound (cavity), a pressure bandage (serves as a temporary method, but sometimes - as a final method to control bleeding);

        Embolization of vessel;

        Special methods (splenectomy at a parenchymatous bleeding from a lien, a resection of a stomach at a bleeding from a ulcer or a tumour, a lobectomy at a pulmonary bleeding, Blaekmor probe, etc.);

       

A vascular seam, reconstruction of vessels.

Physical:

        Action of low temperature (a local hypothermia, a cryosurgery);

        Action of high temperature (action of hot solutions, a electrocoagulation, a laser photocoagulation, a plasma scalpel).

Chemical:

-            Local hemostatics (hydrogen peroxide, vasoconstrictive agents, inhibitors of a fibrinolysis, preparations of gelatin, wax);

-            Hemostatics of absorbtion action (inhibitors of a fibrinolysis, calcium chloride, an agent which accelerate formation of a thromboplastin, substances of specific action - Pituitrinum, synthetic analogues of vitamin K, substances which normalize a vessel wall permeability).

Biological:

-            Packing the bleeding wound with the patients own tissues (omentum, muscular tissue, subcutaneous fat, fascia);

-            Transfusion of small quantities of blood, fresh plasma, serum, thrombocytes, fibrinogen, etc., injection of protrombin complex concentrated coagulation factors II VII IX X, antihemophilic globulin A;

-            Injection of vitamins;

-            Intramuscular injection of human or animal serum;

-            Local application of blood derivates (trombin, haemostatic sponge, isogenic fibrinous film, biological antiseptic pack, etc.).