Paper I
Question
Pathogenesis and lab diagnosis of Disseminated intravascular coagulation.
Answer
Disseminated intravascular coagulation (DIC) is an acquired thrombohaemorrhagic syndrome characterized by systemic activation of the coagulation pathway, resulting in widespread formation of microthrombi throughout the microcirculation, followed by consumption of platelets and clotting factors and secondary activation of fibrinolysis.
Pathogenesis
- Triggered by widespread activation of coagulation, typically via one of two mechanisms:
- Release of tissue factor: Obstetric complications (placental abruption, amniotic fluid embolism), massive trauma, malignancy (mucin-secreting adenocarcinomas), acute promyelocytic leukaemia
- Widespread endothelial injury: Sepsis (Gram-negative endotoxin), severe burns, ABO-incompatible transfusion reactions, snake bite
- Systemic activation of thrombin causes widespread deposition of fibrin microthrombi in small vessels, leading to ischaemic organ damage
- Consumption of platelets and clotting factors (fibrinogen, factors V and VIII) during this process outpaces production, resulting in a bleeding tendency
- Secondary activation of the fibrinolytic system (to clear microthrombi) generates fibrin degradation products (including D-dimer), which further impair clot formation, compounding the bleeding tendency
- Microangiopathic haemolytic anaemia occurs as red cells are mechanically fragmented passing through fibrin strands in the microcirculation
Laboratory diagnosis
- Platelet count: Decreased (thrombocytopenia, from consumption)
- Prothrombin time (PT) and aPTT: Prolonged (consumption of clotting factors)
- Fibrinogen level: Decreased (consumed)
- D-dimer/fibrin degradation products: Markedly elevated (evidence of both clot formation and fibrinolysis)
- Peripheral smear: Schistocytes (fragmented red cells) — evidence of microangiopathic haemolysis
- Thrombin time: Prolonged