Pathophysiology of intravascular coagulation and fibrinolysis.

When tissue is damaged one reaction is the initiation of the haemostatic mechanism. This involves initially platelet interaction with the damaged vessel walls, platelet aggregation and release at the sites of damage, and subsequent local fibrin formation due to the activation of the coagulation cascade after the 'release' of various factors from the activated platelets -namely, Ca++ ions and phospholipid (PF3). In trauma or disease in man the injury to tissue directly and indirectly can invoke a similar mechanism and, if the stimulus is very strong, the normally protective haemostatic mechanism is activated to such an extent that serious destruction of platelets and significant fibrin formation may occur both at the site of injury and also in normal tissue. In order to limit the spread of fibrin the fibrinolytic mechanism is activated along with or as a consequence of fibrin formation. This 'pathological' activation of the physiological haemostatic process has been called intravascular coagulation and fibrinolysis (ICF), a term which is considered by some to be synonymous with the diffuse intravascular coagulation syndrome (DIC). Either term has been used to define the explosive and sometimes fatal activation of the platelet/coagulation sequence as a complication of infections, malignancy, trauma, and immune complex disease in man.1 A similar sequence may also complicate abnormal events in pregnancyfor example, abruptio placentae and septic abortion. In each instance the platelet, coagulation, fibrinolysis activation is the sequel to tissue damage or the introduction into the blood of a 'trigger'. Experimentally various triggers have been found to produce ICF/DIC in animals which is almost identical to that seen as a complication of disease in man.2 'Direct' triggers in the form of tissue thromboplastin or snake venoms have been described which activate the coagulation cascade directly.1 'Indirect' triggers, endotoxin and immune complexes, require an interaction with coagulation proteins (XII) or platelets/white cells before activating the platelet/ fibrin interaction. Further these indirect triggers may also first produce tissue or vessel wall damage, invoking a direct activation as well as an indirect effect. While the ICF/DIC syndrome is considered as a separate entity from conventional forms of arterial and venous thrombosis the pathophysiology of both is similar and may represent only a variable expression of the degree of activation.3 Whatever the trigger the sequence of events leads to platelet activation in the vessel wall or in the circulating blood leading to destruction of circulating platelets and eventual thrombocytopenia. If the stimulus is sufficient local or diffuse activation of the coagulation cascade (directly or indirectly) leads to thrombin formation or the conversion of fibrinogen to fibrin. The resultant reaction may be mild and detectable only by laboratory tests or may be so strong that both platelets and coagulation factors are consumed, leading to a tendency to abnormal bleeding (consumption coagulopathy) or to the widespread dissemination of fibrin with significant irreversible tissue damage (DIC) (Fig. 1). An acute stimulus (amniotic fluid embolism) can produce this reaction in minutes while a chronic one (for example, dead fetus syndrome, malignancy) the evolution of change may take some weeks.