J. Paul Scott, Leslie J. Raffini
Thrombotic microangiopathy refers to a heterogeneous group of conditions, including disseminated intravascular coagulation (DIC ), that result in consumption of clotting factors, platelets, and anticoagulant proteins. Consequences of this process include widespread intravascular deposition of fibrin, leading to tissue ischemia and necrosis, a generalized hemorrhagic state, and microangiopathic hemolytic anemia.
Any life-threatening severe systemic disease associated with hypoxia, acidosis, tissue necrosis, shock, or endothelial damage may trigger DIC (Table 510.1 ). Better understanding of the pathophysiology of hemostasis has led to an appreciation of the critical interaction of the coagulation pathways with the innate immune system and inflammatory response that likely contributes to the widespread dysregulation present in DIC. Activation and release of cytokines and chemokines alter endothelial function to a more prothrombotic state, enhancing the formation of microvascular thromboses, with resultant consumption of pro- and anticoagulant proteins. Excessive activation of clotting consumes both the physiologic anticoagulants (protein C, protein S, and AT III) and the procoagulants, resulting in a deficiency of factor V, factor VIII, prothrombin, fibrinogen, and platelets. Typically, the clinical result of this sequence of events is hemorrhage . The hemostatic dysregulation may also result in thromboses in the skin, kidneys, and other organs.
Table 510.1
Causes of Disseminated Intravascular Coagulation
| INFECTIONS |
| TISSUE INJURY |
| MALIGNANCY |
| VENOM OR TOXIN |
| MICROANGIOPATHIC DISORDERS |
| GASTROINTESTINAL DISORDERS |
| HEREDITARY THROMBOTIC DISORDERS |
| Homozygous/compound heterozygous protein C, protein S, or AT III deficiency |
| NEWBORN |
| MISCELLANEOUS |
Adapted from Montgomery RR, Scott IP: Hemostasis: diseases of the fluid phase. In Nathan DG, Oski FA, editors: Hematology of infancy and childhood , vol 2, ed 4, Philadelphia, 1993, Saunders.
DIC accompanies a severe systemic disease process, usually with shock . Bleeding frequently first occurs from sites of venipuncture or surgical incision. The skin may show petechiae and ecchymoses. Tissue necrosis may involve many organs and can be most spectacularly seen as infarction of large areas of skin, subcutaneous tissue, or kidneys. Anemia caused by hemolysis may develop rapidly because of microangiopathic hemolytic anemia.
There is no well-defined sequence of events. Certain coagulation factors (factors II, V, and VIII; fibrinogen) and platelets may be consumed by the ongoing intravascular clotting process, with resultant prolongation of the prothrombin (PT), partial thromboplastin (PTT), and thrombin (TT) times. Platelet counts may be profoundly depressed. The blood smear may contain fragmented, burr- and helmet-shaped red blood cells (schistocytes). In addition, because the fibrinolytic mechanism is activated, fibrinogen degradation products (D-dimers) appear in the blood. The D-dimer is formed by fibrinolysis of a cross-linked fibrin clot. The D-dimer assay is as sensitive as the fibrinogen degradation product test and more specific for activation of coagulation and fibrinolysis.
The 1st 2 steps in the treatment of DIC are the most critical: treat the trigger that caused DIC and restore normal homeostasis by correcting the shock, acidosis, and hypoxia that usually complicate DIC. If the underlying problem can be controlled and the patient can be stabilized, bleeding quickly ceases, and the abnormal laboratory findings improve. Blood components are used for replacement therapy in patients with hemorrhage and may consist of platelet infusions (for thrombocytopenia), cryoprecipitate (for hypofibrinogenemia), and/or fresh-frozen plasma (for replacement of other coagulation factors and natural inhibitors).
The role of heparin in DIC is limited to patients who have vascular thrombosis in association with DIC or who require prophylaxis because they are at high risk for venous thromboembolism. Such individuals should be treated as outlined in Chapter 506.1 , with careful attention to replacement therapy to maintain an adequate platelet count and thus limit bleeding complications.
The prognosis of patients with DIC is primarily dependent on the outcome of the treatment of the primary disease and prevention of end-organ damage.