DIC — MRCS Part B Applied surgical science and critical care

A coagulopathy station built around disseminated intravascular coagulation, then the physiology behind it: haemostasis, platelets, the cascade, the tests and the anticoagulants.

Coagulopathy in hospital patients

Dilution after massive transfusion, liver disease, vitamin K deficiency (poor intake, antibiotics, obstructive jaundice), anticoagulant drugs, consumption in DIC, thrombocytopenia from sepsis or heparin, hypothermia and acidosis in the trauma patient, and uraemia impairing platelet function.

DIC

Widespread activation of coagulation inside the circulation, driven by tissue factor exposed by a systemic insult, which lays down fibrin in small vessels, consumes platelets and clotting factors, and switches on fibrinolysis. The patient therefore clots and bleeds at once: organ failure from microvascular thrombosis, and oozing from lines, wounds and mucosa. Causes: sepsis (the commonest), major trauma and burns, obstetric catastrophe (abruption, amniotic fluid embolism, retained dead fetus), malignancy (acute promyelocytic leukaemia, mucinous adenocarcinoma), incompatible transfusion, snake bite, and severe pancreatitis.

Diagnosis is clinical with supporting tests: a falling platelet count, prolonged PT and APTT, a low fibrinogen, and raised D-dimer or fibrin degradation products; a blood film shows fragmented red cells. The ISTH score combines them. Management is to treat the cause, and to replace what is being consumed only when the patient is bleeding or needs a procedure: platelets, fresh frozen plasma and cryoprecipitate for fibrinogen. Heparin is reserved for the thrombotic picture.

Haemostasis

Vasoconstriction, then the platelet plug (adhesion to exposed collagen through von Willebrand factor, activation, and aggregation through fibrinogen bridging the glycoprotein IIb/IIIa receptors), then the coagulation cascade producing thrombin, which converts fibrinogen to fibrin and cross-links the plug, and finally fibrinolysis by plasmin as the vessel heals. Platelets are fragments of megakaryocyte cytoplasm from the bone marrow, made under the control of thrombopoietin from the liver, and circulate for about 7–10 days before the spleen removes them.

The cascade

The extrinsic pathway (tissue factor and factor VII) and the intrinsic pathway (XII, XI, IX, VIII) both activate factor X. The common pathway is X, V, prothrombin (II) and fibrinogen (I), ending in thrombin converting fibrinogen to fibrin, with factor XIII cross-linking it. All the factors are made in the liver except VIII, which comes largely from endothelium; II, VII, IX and X need vitamin K. The PT tests the extrinsic and common pathways and is the basis of the INR; the APTT tests the intrinsic and common pathways and is used to monitor unfractionated heparin.

Massive transfusion

Dilutional coagulopathy and thrombocytopenia, hypocalcaemia from citrate, hyperkalaemia, hypothermia, acidosis, transfusion reactions, transfusion-related lung injury and circulatory overload. It is why major haemorrhage protocols give plasma and platelets with red cells from the start.

Anticoagulants

Warfarin blocks the vitamin K-dependent synthesis of II, VII, IX and X (and proteins C and S, which is why it is briefly prothrombotic); it is slow to start, interacts with much else, needs INR monitoring and is reversed with vitamin K and prothrombin complex concentrate. Heparins potentiate antithrombin: unfractionated heparin inhibits thrombin and Xa, has a short half-life, is monitored by APTT and reversed by protamine; low-molecular-weight heparin acts mainly on Xa, is given once or twice daily by weight without monitoring, and is only partly reversed. Direct oral anticoagulants inhibit Xa (rivaroxaban, apixaban, edoxaban) or thrombin (dabigatran); andexanet and idarucizumab are their reversal agents. Antiplatelet drugs (aspirin, clopidogrel) are a separate class.