Fig. 2

Natural history of coagulation during infection and potential therapeutics. The first step is “adaptive haemostasis” associated with the systemic inflammatory syndrome. Platelet count increases and fibrinogen production is dramatically increased (red curve). Thrombin generation is initiated with slight shortening of PT and aPTT (dark blue curve) resulting in fibrin monomers generation (green curve). Natural anticoagulants, antithrombin and protein C are decreased by consumption and downregulation (light blue curve). Inhibition of fibrinolysis by PAI-1 results in low D-dimers (yellow curve). Only low-dose heparin (unfractionated or low molecular weight) could be recommended to prevent thrombosis (inferior part of the graph). Reduction of anticoagulants and continuous thrombin generation results in prolonged clotting times (PT and aPTT) and platelet and fibrinogen consumption that remain in the high normal range. Fibrin monomers increased due to sustained fibrin formation and defective polymerisation by FXIIIa. D-dimers are moderately increased. This step can be called “thrombotic/multiple organ failure DIC” step and could be treated by natural anticoagulant infusion (antithrombin or soluble thrombomodulin) or fresh-frozen plasma. Later in the natural evolution of coagulation, consumption of all factors and platelets results in very low levels of fibrinogen, AT and PC, prolonged PT and aPTT and massive fibrinolysis with very high D-dimers. This “fibrinolytic DIC” step is characterised by oozing and massive bleeding, and supportive therapy associates fresh-frozen plasma and platelet transfusions, fibrinogen supply and tranexamic acid to prevent fibrinolysis