Disseminated intravascular coagulation

Definition. An acquired syndrome of widespread intravascular activation of coagulation with loss of localisation, causing microvascular thrombosis with organ dysfunction and simultaneous consumption of platelets and clotting factors leading to bleeding. It is always secondary to an underlying disorder — never a primary diagnosis.

Causes. Sepsis (the commonest, especially Gram-negative); malignancy — adenocarcinoma of pancreas, prostate and stomach (chronic, thrombotic DIC) and acute promyelocytic leukaemia (fulminant bleeding); trauma, burns, major surgery, head injury; obstetric causes (abruption, amniotic fluid embolism); transfusion reactions, snake envenomation, heat stroke, severe pancreatitis, aortic aneurysm and giant haemangioma.

Pathogenesis. Tissue factor exposure and cytokine release trigger excess thrombin generation, while the natural anticoagulants (antithrombin, protein C, tissue factor pathway inhibitor) are consumed and fibrinolysis is suppressed by raised PAI-1. Fibrin deposition in the microvasculature causes ischaemic organ failure and microangiopathic haemolysis; ongoing consumption then produces the bleeding phase.

Clinical features. Bleeding — oozing from venepuncture and cannula sites, petechiae, ecchymoses, mucosal and gastrointestinal bleeding. Thrombosis — acral cyanosis, digital gangrene, purpura fulminans, and organ failure (renal, respiratory, hepatic, cerebral). Chronic compensated DIC in malignancy may present only as migratory thrombophlebitis or venous thromboembolism.

Laboratory diagnosis and the ISTH score. Thrombocytopenia with a falling trend, prolonged PT and aPTT, low fibrinogen, and markedly raised D-dimer/fibrin degradation products; the film shows schistocytes. The ISTH overt DIC score (in a patient with a predisposing condition) awards points for platelet count (<100 = 1, <50 = 2), fibrin marker elevation (moderate 2, strong 3), PT prolongation (≥3 s = 1, ≥6 s = 2) and fibrinogen <1 g/L (=1); a score of 5 or more is compatible with overt DIC. Serial trends matter more than a single value, and fibrinogen may be spuriously normal because it is an acute-phase reactant.

Management. Vigorous treatment of the precipitating cause is the cornerstone — antibiotics and source control in sepsis, delivery in obstetric DIC, ATRA in acute promyelocytic leukaemia. Give blood products only if there is bleeding or a planned procedure, not to correct numbers: platelets if <50 × 109/L with bleeding (<20 if not bleeding but high risk), fresh frozen plasma 15 mL/kg for prolonged PT/aPTT, and cryoprecipitate or fibrinogen concentrate if fibrinogen <1.5 g/L. Therapeutic heparin is reserved for the predominantly thrombotic phenotype (purpura fulminans, digital ischaemia, chronic DIC of malignancy); prophylactic-dose heparin for VTE prevention is appropriate in non-bleeding patients. Tranexamic acid is generally contraindicated except in hyperfibrinolytic states such as APL.

Sepsis-induced coagulopathy (SIC) and earlier recognition. Current ISTH guidance recommends using the simpler two-step SIC score (platelet count, INR and SOFA score) to detect coagulopathy before overt DIC develops, since by the time the ISTH overt DIC score reaches 5 the mortality is already very high. Practice has also moved towards viscoelastic testing (ROTEM/TEG) and fibrinogen concentrate rather than empirical fresh frozen plasma for targeted correction, and away from routine antithrombin or recombinant thrombomodulin, which have not shown consistent survival benefit.