Disseminated intravascular coagulation syndrome

Generalities

Disseminated intravascular coagulation syndrome was discovered by Hardaway and Mac Kay in 1961.

REMINDER ON THE COAGULATION MECHANISM

Fibrinogen is a protein found in blood plasma, produced by the liver, and plays an important role in blood clotting. Also known as coagulation factor I, it is a precursor to fibrin. It is part of a cascade that constitutes the complex mechanism of blood clotting in general.

Thrombin , another element involved in blood clotting, is another blood protein capable of activating fibrin. When it activates fibrinogen, the latter is transformed into fibrin, which then polymerizes, meaning that many monomers (pieces) adhere to each other, and becomes insoluble because it has stabilized thanks to the action of another factor, factor XIII. From this point, a set of proteins is assembled, forming a kind of plug whose purpose is to stop the bleeding: this is the closure of the wound.

CAUSES OF DIC

Disseminated intravascular coagulation syndrome is the result of the sudden appearance of thrombin-activating factors leading to fibrin deposits in microvessels, causing their obliteration by thromboses.
Following this mechanism, the blood becomes incoagulable because it has "consumed" fibrinogen, other clotting factors (factors V and VIII) and the plateletsThis phenomenon causes hemorrhages.

The coagulation disorders that are observed are the result (reaction phase) of heparinemia (presence of heparin, which is an anticoagulant, in the blood) produced by the body itself (endogenous origin) accompanied by fibrinolysis (destruction of fibrin).
Blood clotting disorders are most often caused by substances such as endotoxins (during infections), certain lipids which come from the destruction of red blood cells, or from the destruction of tissues in general.

Disseminated intravascular coagulation syndrome can occur after (non-exhaustive list) :

• A surgical intervention, especially of the thorax
   
• A birth
   
• The action of certain drugs
   
• A retained fetus
   
• A detachment of the placenta
   
• A amniotic fluid embolism
   
• Bleeding during the deliverance
   
• A soft hydatidiform
   
• Un retroplacental hematoma
   
• A pregnancy toxemia
   
• An acute infection (sepsis germ-ridden Gram negative, meningococcus, pneumococcus)
   
• A stay in intensive care (around 10% of patients)
   
• Un malaria to plasmodium falciparum
   
• A serious bite by a venomous animal (especially certain snakes)
   
• An incompatible blood transfusion
   
• The establishment of extracorporeal circulation
   
• Un lupus erythematosus
   
• Cardiovascular surgery
   
• Prostate surgery
   
• Un septic shock
   
• A coagulopathy (blood disease)
   
• Certain cancers, mainly acute promyelocytic leukemia, lung cancer, pancreatic cancer and prostate cancer (especially if metastases are present)
   
• A sepsis
   
• A poisoning
   
• Serious trauma
   
• A major (extensive) burn
   
• An organ transplant
   
• Blood disease (purpura fulminans among others)
   
• Liver damage such as cirrhosis etc.

SYMPTOMS OF DIC

• Haemorrhages aggravated by secondary fibrinolysis, which are sometimes very intense (childbirth, surgical intervention) leading to a state of shock (inability for the main organs to perform their normal function) causing acute renal filtration failure, accompanied by microthrombosis (tiny clots) occurring inside the capillaries (tiny arteries) of glomeruli leading to complete or partial destruction of the renal cortex (peripheral part of this organ).
   
• During Waterhouse-Friderichsen syndrome, the patient has microthrombosis in the adrenal glands, and more specifically at the level of the sinuses of these organs.

The severity of disseminated intravascular coagulation syndrome is directly related to the extent of the hemorrhages and the intensity of the thromboses (occurrence of blood clots) causing ischemia (reduction in the vascularization of certain organs), particularly the kidneys.

LABORATORY

Blood tests can reveal:

• A deficit in clotting factors affecting fibrinogen, factor II, V and VIII.
   
• Thrombocytopenia (decrease in the number of platelets in the blood) around 10000 platelets per microliter.
   
• The blood count (quantity of white blood cells and red blood cells) shows the presence of fragmented red blood cells called schistocytes.
   
• Fibrin and fibrinogen degradation products (PDF) are increased. This is the result of digestion of fibrinogen or fibrin by the plasmin and the action of other enzymes as well.
   
• The level of fibrinogen in the blood (fibrinogenemia) is more or less reduced below 2 g per liter. Sometimes it appears normal.
   
• A high rate of D-dimers, which are specific degradation products of fibrin. The test is requested whenever thrombosis is suspected. Dosage by the method ELISA which shows a positivity threshold > 0,50 micrograms per milliliter or 500 micrograms per liter, is a sensitive test in approximately 90% of cases.
   
• The clot formation is insufficient, that is, it is much smaller than normal and sometimes even invisible.
   
• Soluble complexes which are formed by fibrin monomers are also highlighted using a latex immunoassay. The protamine sulfate flocculation test is also used.
   
• The lysis time of globulins is decreased. It reflects secondary fibrinolysis.

DIFFERENTIAL DIAGNOSIS

Disseminated intravascular coagulation syndrome should not be confused with:

• An extension of the prothrombin time when there is a deficit in vitamin KGiving a dose (called a test dose) to the patient helps confirm the diagnosis.
   
• Pure primary fibrinolysis. In this case, it is the laboratory tests that are slightly different: thrombocytopenia is moderate, and the protamine sulfate flocculation test is negative.
   
• In vitro clot formation disorders after heparin administration occurring duringhaemophilia, and in circulating anticoagulant syndrome.

TREATMENT OF DIC

• Use of heparin, fibrinolysin inhibitors (Kunitz inhibitor). Heparin, intravenously, is used at a rate of 100 units per kilo every four to six hours. This requires regular clinical and biological checks, in order to avoid aggravating the hemorrhage. It can only be used if the disease in question is quickly uncontrollable, and especially if the patient does not have a cerebral hemorrhage.
   
• Whole blood or plasma transfusion is used when there is a state of shock. This helps to compensate for hemorrhages, thereby providing the patient with a supply of clotting factors that he is lacking. Platelet transfusion is used when there is severe thrombocytopenia.
   
• Some medical teams use the administration of fibrinogen (therapeutic controversy: in fact, there seems to be a possibility of stimulating intravascular coagulation).
   
• Administration of antithrombin III has also been proposed in people with very intense bleeding.
   
• Very rarely, in the presence of pure primary fibrinolysis, treatment consists of administering fresh blood, associated with fibrinogen and antifibrinolytics blocking the activation of fibrinolysins, and restoring hemostasis.