Intravascular hemolysis caused by fragmentation of normal red cells passing through abnormal arterioles and other small vessels.
The hemolytic anemia generated by red cell damage in small vessels is referred to as microangiopathic hemolytic anemia, a type of fragmentation hemolytic anemia.
"Split" red cells of varying shapes, referred to as schistocytes, are prominent on blood films.
Less-extensive red cell fragmentation, development of schistocytes, and hemolysis may also occur under conditions of more moderate vascular occlusion or endothelial surface abnormalities, sometimes under conditions of lower shear stress.
Excessive platelet aggregation, fibrin polymer formation, and secondary fibrinolysis in the arterial or venous microcirculation are seen in disseminated intravascular coagulation (see Chap. 86), preeclampsia, giant cavernous hemangiomas (the Kasabach-Merritt phenomenon), or in the HELLP (hemolysis elevated liver enzyme and low platelets) syndrome.
ETIOLOGY AND PATHOGENESIS
Intravascular coagulation, with deposition of platelets and fibrin in small arterioles, is the common antecedent.
Red cells stick to fibrin and are fragmented by force of blood flow, resulting in both intravascular and extravascular hemolysis.
Underlying disorders include:
— Invasive carcinoma, especially mucin-producing adenocarcinomas (see Table 21–1).
— Abruptio placentae.
— Malignant hypertension.
— Thrombotic thrombocytopenic purpura (TTP); hemolytic uremic syndrome (HUS), (see Chap. 91).
The effect of certain drugs:
— Antineoplastic agents are most often the offender (e.g., mitomycin, bleomycin, daunorubicin in combination with cytosine arabinoside, cisplatin (see Chap. 91, Table 91–2 for more comprehensive list).
— A TTP-like syndrome may occur weeks or months after discontinuing mitomycin therapy.
Posttransplantation of kidney or liver. Rejection of kidney graft associated with a vasculitis that can be accompanied by red cell fragmentation.
Postallogeneic or autologous marrow transplantation as a result of high-dose chemotherapy or radiation, immunosuppressive drugs, graft-versus-host disease, or infections.
Generalized vasculitis associated with immune disorders; e.g., systemic lupus erythematosus, polyarteritis nodosa, Wegener granulomatosis, scleroderma.
— Usually develops in early childhood.
— Characterized by thrombocytopenia, microangiopathic hemolytic anemia, consumptive coagulopathy, and hypofibrinogenemia.
— Caused by an enlarging kaposiform hemangioendothelioma or tufted angioma.
Localized vascular abnormalities: cutaneous cavernous hemangiomas, hemangioendothelioma of the liver.
Preeclampsia and HELLP syndrome:
— During normal pregnancy, specialized placental epithelial cells replace the endothelium of the uterine spiral arteries and intercalate within the muscular tunica, increasing the vessels' diameters and decreasing their resistance. As a result, the vasculature is converted into a high flow system much less responsive to vasoconstrictors circulating in the maternal blood.
— In a preeclamptic pregnancy, this process fails and the spiral arteries do not adequately penetrate the uterus. This results in platelet-fibrin deposition in the capillaries and may progress to multiorgan microvascular injury, microangiopathic hemolytic anemia, elevated liver enzymes because of hepatic necrosis, and thrombocytopenia because of peripheral consumption, i.e., the HELLP syndrome.
TABLE 21–1CANCERS ASSOCIATED WITH MICROANGIOPATHIC HEMOLYTIC ANEMIA
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