Porth's Essentials of Pathophysiology, 4e

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Hematopoietic Function

U N I T 3

Intrinsic pathway (Endothelial injury) Trauma Burns Gram-negative sepsis

Extrinsic pathway (Tissue injury)

Trauma Obstetric complications Complications of cancer

Hypoxia Acidosis Shock Vasculitis

Thrombin generation

Platelet consumption

Intravascular fibrin deposition

Plasminogen activation

Thrombocytopenia

Plasmin generation

Thrombosis

Clotting factor degradation

Fibrinolysis

Fibrin degradation products (inhibit thrombin and platelet aggregation)

Tissue ischemia

Hemolytic anemia

Bleeding

FIGURE 12-5. Pathophysiology of disseminated intravascular coagulation.

evidence that the underlying cause of DIC is infection or inflammation, and the cytokines (tumor necrosis fac- tor, interleukin-1, and others) liberated in the process are the pivotal mediators. 29,30 These cytokines not only mediate inflammation, but can also increase the expres- sion of tissue factor on endothelial cells and simulta- neously decrease the expression of thrombomodulin. Thrombomodulin is a glycoprotein, present on the cell membrane of endothelial cells, that binds thrombin (IIa) and acts as an additional regulatory mechanism in coagulation. The net effect is a shift in balance toward a procoagulant state. 28 Common clinical conditions that may cause DIC include obstetric disorders, accounting for 50% of cases; massive trauma; shock; sepsis; and malignant dis- ease. Chart 12-2 summarizes the conditions associated with DIC. The factors involved in the conditions that cause DIC are often interrelated. In obstetric complica- tions, tissue factors released from necrotic placental or fetal tissue or amniotic fluid may enter the circulation, inciting DIC. The hypoxia, shock, and acidosis that may coexist also contribute by causing endothelial injury. Gram-negative bacterial infections result in the release of endotoxins, which activate both the extrinsic path- way by release of tissue factor and the intrinsic pathway through endothelial damage. Endotoxins also inhibit the activity of protein C. Antigen–antibody complexes associated with infection can activate platelets through complement fragments. Although coagulation and formation of microem- boli characterize DIC, its acute manifestations usually

CHART 12-2   ConditionsThat Have Been Associated with Disseminated Intravascular Coagulation Obstetric Conditions Abruptio placentae Dead fetus syndrome Preeclampsia and eclampsia Amniotic fluid embolism Cancers Metastatic cancer Acute promyelocytic leukemia Infections Acute bacterial infections (e.g., meningococcal meningitis) Histoplasmosis, Aspergillosis Rickettsial infections (e.g., Rocky Mountain spotted fever) Parasitic infections (e.g., malaria) Sepsis/septic shock Trauma or Surgery Burns Massive trauma Surgery involving extracorporeal circulation

Snake bite Heatstroke

Hematologic Conditions Blood transfusion reactions