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16.1 Exposure of the blood to a source of tissue factor.
16.2 Sudden exposure of blood to triggers such as tissue factor generates intravascular coagulation leading to increased fibrin formation within the vessels. Loss of localisation mechanisms leads to systemic activation of coagulation and fibrin formation is not restricted to the surface of activated platelets at a site of vessel injury. Excessive thrombin generation can overwhelm regulatory systems and consume regulatory molecules. Elevated PAI-1 suppresses fibrinolysis leading to failure to effectively clear intravascular fibrin thrombi. Multiple circulating fibrin clots in the circulation ineffectively cleared by plasmin, results in thrombosis. Fibrin clots can entrap platelets to become larger clots which lodge in the microcirculation and lead to organ damage and failure. Red blood cells passing through the fibrin meshwork in the microvasculature can be sheared by the fibrin strands, resulting in haemolysis arising from fragmentation of the cells. If the excessive, unregulated activation of coagulation continues unabated, production of coagulation factors in the liver is ultimately unable to compensate for their consumption and levels begin to decline. Platelets are consumed beyond the ability to compensate. Bleeding ensues.
16.3 Acute DIC occurs suddenly in response to sudden exposure of blood to tissue factor and bleeding is the predominant haemostatic symptom. Chronic DIC involves long term, lower level exposure to tissue factor where clotting occurs but progression to bleeding does not.
16.4 PT, APTT, fibrinogen, D-dimers, platelet count.
16.5 Reduced production, splenic sequestration, immune-mediated accelerated destruction, consumption in DIC.
16.6 Reduced functioning of the protein-producing liver cells, the hepatocytes.
16.7 Early VKDB manifests within the first 24 hours of life and arises from maternal ingestion of substances that cross the placenta and interfere with vitamin K metabolism. Classic VKDB manifests within a week of birth, bleeding sites can be gastrointestinal, skin and mucous membranes arises in breastfed infants who have not received prophylactic vitamin K, and may also be related to maternal drug usage. Late VKDB manifests within 2 weeks - 6 months of birth and occurs in breastfed infants who did not receive vitamin K at birth, cholestatic liver disease, cystic fibrosis, coeliac disease and deficiency of α1-antitrypsin.
16.8 Fibrinogen, FII, FV, FX.
16.9 Hypothermia, acidosis, dilutional coagulopathy, increased fibrinolysis, reduced fibrinogen, impaired platelet function.
16.10 Fragile blood vessels.
16.11 Hereditary TTP is a congenital deficiency of ADAMTS13 due to reduced synthesis or secretion. Acquired TTP reduces ADAMTS13 due to the presence of antibodies that inhibit function or induce increased clearance of ADAMTS13.
16.12 There are hereditary and acquired forms of both TTP and HUS. Both forms of TTP result from ADAMTS13 deficiency, whilst acquired HUS arises from toxin-induced damage but hereditary HUS arises from deficiency of complement factor H. Both TTP and HUS involve non-immune platelet destruction. Both TTP and HUS give rise to thrombosis and microangiopathic haemolytic anaemia.