Disseminated Intravascular Coagulation: Pathophysiology and Diagnosis

Disseminated intravascular coagulation (DIC) should be recognized as consumptive coagulopathy since it is not a primary disease. It is always a complication of an underlying disease that not only triggers it but also fuels it. Disease or trauma associated tissue injury with a release of thromboplastic material into the circulation is the major cause of DIC. The clotting system as well as the fibrinolytic system (bleeding system) are involved in the pathophysiology of disseminated intravascular coagulation. Clinically, coagulopathy could be recognized as acute hemorrhagic DIC and subacute or chronic DIC. A third type of consumptive coagulopathy could be recognized with fibrinolysis. Disseminated intravascular coagulation is an acquired coagulation disorder in which formation of microthrombi, consumption of coagulation factors, activation of fibrinolysis and a bleeding tendency may occur consecutively or simultaneously. In brief, it is a systemic pathologic process characterized by a disseminated (generalized) activation of clotting and/or fibrinolytic systems in the circulatory system of the patient. The common pathway of all inciting causes (independent of etiologies) is the formation of thrombin and plasmin (fibrinolysin).

Thrombin plays a vital role in DIC. The alterations of coagulation system detected in the laboratory during DIC reflect the multiple actions of thrombin. Thrombin cleaves fibrinogen to release fibrinopeptide-A (FPA) and fibrinopeptide-B (FPB). Subsequently the remaining fibrin monomers may combine with fibrinogen and circulate as soluble fibrin monomer complexes (SFMC) or polymerize to form fibrin microthrombi. Thrombin also activates factor XIII (fibrin stabilizing factor) to form factor XIIIa, and the factor XIIIa creates bridges, linking any two adjacent monomers of fibrin. Thrombin activates procoagulant cofactors, factors VIII and V, to participate in the process of its own generation. Thrombin also plays a regulatory role by activating protein-C, which acts as an anticoagulant to inactivate factors VIIIa and Va. In brief, thrombin alone accounts for decreased levels of fibrinogen and factors II, V, VIII & XIII and decreased count of platelets in patients with DIC.

Screening tests for DIC are: Prothrombin time (PT), Partial thromboplastin time (PTT), Fibrinogen assay and Platelet count. Platelet count, PT, Fibrinogen assay and Determination of Antithrombin-III (AT-III) should always be done to diagnose consumptive DIC.

Confirmatory tests for DIC are: Fibrin monomer assay (it measures thrombin cleaved fibrinogen), Detection of fibrin split products (i.e. detection of plasmin-cleaved fibrinogen or fibrin) and Detection of D-dimer (i.e. detection of plasmin-cleaved cross-linked fibrin). Activation of coagulation could be assessed by the detection of soluble fibrin monomer complexes(SFMC). Detection of fibrinogen degradation products (FDPs) is indicative of reactive fibrinolysis.

Medical conditions which may lead to 'Acute Hemorrhagic DIC':

• Infections: Typhoid fever, Gram-positive and Gram-negative septicemia, viremia, parasites etc.
• Tissue injury: Renal allograft rejection, snake bite, heat stroke, brain injury, crush injury, necrotizing enterocolitis, hemolytic transfusion reaction etc.
• Malignancy: Acute promyelocytic leukemia.
• Obstetric: Amniotic fluid embolism, eclampsia, abruptio placentae, hypertonic saline abortion.
• Other causes: Severe liver disease.

Medical conditions which may lead to 'Subacute Chronic DIC':

• Vascular: Chronic renal disease, connective tissue disorders, venous thrombosis, arterial embolization, pulmonary embolus etc
• Obstetric: Retained dead fetus.
• Malignancy: Mucin-producing adenocarcinomas.