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With the advent of plasmapheresis, the formerly dismal prognosis of TTP has been dramatically changed Eighty to 90 percent of patients now recover completely Neurologic abnormalities are almost always completely reversed Most complete responses are durable, but in 20% of cases the disease will be chronic and relapsing
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Table 13 18 Causes of microangiopathic hemolytic anemia
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Thrombotic thrombocytopenic purpura Hemolytic-uremic syndrome Disseminated intravascular coagulation Prosthetic valve hemolysis Metastatic adenocarcinoma Malignant hypertension Vasculitis
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untenable without this finding The LDH is usually elevated out of proportion to the degree of hemolysis, and the Coombs test is negative Coagulation tests are normal with the exception of elevated fibrin degradation products As in TTP, levels of ADAMTS13 are usually low Kidney biopsy will show endothelial hyaline thrombi in the afferent arterioles and glomeruli Ischemic necrosis in the renal cortex may occur with obstruction from intravascular coagulation
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Ahmad A et al Rituximab for treatment of refractory/relapsing thrombotic thrombocytopenic purpura (TTP) Am J Hematol 2004 Oct;77(2):171 6 [PMID: 15389904] Fakhouri F et al Efficiency of curative and prophylactic treatment with rituximab in ADAMTS 13-deficient thrombotic thrombocytopenic purpura: a study of 11 cases Blood 2005 Sep 15;106(6):1932 7 [PMID: 15933059] Sadler JE Thrombotic thrombocytopenic purpura: a moving target Hematology Am Soc Hematol Educ Program 2006: 415 20 [PMID: 17124092]
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HEMOLYTIC-UREMIC SYNDROME
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Differential Diagnosis
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DIC is excluded by normal coagulation results Other causes of microangiopathic hemolytic anemia (Table 13 18) should be entertained Occasionally, vasculitis or acute glomerulonephritis is considered, and in these cases renal biopsy may be necessary to establish the diagnosis if the platelet count will allow it HUS is arbitrarily distinguished from TTP by the consistent presence of renal failure and the lack of neurologic findings
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ESSENTIALS OF DIAGNOSIS
Microangiopathic hemolytic anemia Thrombocytopenia and renal failure Elevated serum LDH Normal coagulation tests Absence of neurologic abnormalities
Treatment
In children, HUS is almost always self-limited and requires only conservative management of acute renal failure In adults, however, without treatment, there is a high rate of permanent renal insufficiency and death The treatment of choice (as in TTP) is large-volume plasmapheresis with fresh-frozen replacement (exchange of up to 80 mL/kg), repeated daily until remission is achieved
General Considerations
Hemolytic-uremic syndrome (HUS) is an uncommon disorder consisting of microangiopathic hemolytic anemia, thrombocytopenia, and renal failure due to microangiopathy (with decreased glomerular filtration, proteinuria, and hematuria) The cause is unclear The disease is similar to TTP except that different vascular beds are involved In fact, the two diseases are probably best considered as part of a spectrum of HUS TTP disorders The pathogenesis of the two disorders is probably similar, and a platelet-agglutinating factor found in plasma may be involved In children, HUS frequently occurs after a diarrheal illness secondary to infections with Shigella, Salmonella, E coli strain O157:H7, or viral agents The mortality rate of this form is low (< 5%) In adults, this syndrome is often precipitated by estrogen use or by the postpartum state HUS may be seen as a delayed complication of high-dose corticosteroid therapy and autologous bone marrow or stem cell transplantation, or of the use of cyclosporine or tacrolimus as immunosuppression in allogeneic transplantation A familial (hereditary) type has been identified in which members of a family have recurrent episodes over several years
Prognosis
The prognosis of HUS in adults remains unclear Without effective therapy, up to 40% of patients have died, and 80% have had chronic renal insufficiency Early institution of aggressive therapy with plasmapheresis promises to be beneficial Survival and correction of hematologic abnormalities are the rule, but restoration of renal function requires that treatment be initiated early
Garg AX et al Long-term renal prognosis of diarrhea-associated hemolytic uremic syndrome: a systematic review, meta-analysis, and meta-regression JAMA 2003 Sep 10;290(10):1360 70 [PMID: 12966129] Vesely SK et al ADAMTS13 activity in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients Blood 2003 Jul 1;102(1):60 8 [PMID: 12637323]
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