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Thrombotic
thrombocytopenic purpura and hemolytic-uremic syndrome are acute, fulminant disorders
characterized by thrombocytopenia and microangiopathic
hemolytic anemia. Other manifestations include fever, alterations
in level of consciousness, and renal failure. Diagnosis requires demonstrating
characteristic laboratory test abnormalities, including Coombs'-negative hemolytic
anemia. Treatment is plasma exchange.
Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) involve nonimmunologic platelet destruction. Loose strands of fibrin are deposited in multiple small vessels, which damage passing platelets and RBCs.Platelets are also destroyed within multiple small thrombi. Multiple organs develop bland platelet-fibrin thrombi (without the vessel wall granulocytic infiltration characteristic of vasculitis) localized primarily to arteriocapillary junctions, described as thrombotic microangiopathy. TTP and HUS differ only in the relative degree of renal failure. Diagnosis and management in adults are the same. Therefore, in adults, TTP and HUS can be grouped together.
Causes and associations of TTP and HUS include congenital or acquired deficiency of the plasma enzyme ADAMTS13, which cleaves von Willebrand's factor (VWF) and thus eliminates abnormally large VWF multimers that can cause platelet thrombi; hemorrhagic colitis resulting from Shiga toxin–producing bacteria (eg, Escherichia
coli O157:H7 and some strains of Shigella dysenteriae); pregnancy (often indistinguishable from severe preeclampsia or eclampsia); and drugs (such as quinine , cyclosporine , mitomycin C). Many cases are idiopathic.
Symptoms,
Signs, and Diagnosis
Fever and manifestations of ischemia develop with varying severity in multiple organs. These manifestations include confusion and coma, abdominal pain, and arrhythmias caused by myocardial damage. The various clinical syndromes are indistinguishable, except that the epidemic disease of children (typically referred to as HUS) associated with enterohemorrhagic E. coli O157 and related Shiga toxin–producing bacteria more often localizes in the kidney and more often spontaneously remits.
TTP-HUS is suspected in patients with suggestive symptoms, thrombocytopenia, and anemia. If the disease is suspected, urinalysis, peripheral blood smear, reticulocyte count, serum LDH, renal functions, serum bilirubin (direct and indirect), and Coombs' test are obtained. The diagnosis is suggested by thrombocytopenia and anemia, with fragmented RBCs on the blood smear (helmet cells, triangular-shaped RBCs, distorted-appearing RBCs—these changes describe microangiopathic hemolysis); evidence of hemolysis (falling Hb level, polychromasia, elevated reticulocyte count, elevated serum LDH); and negative direct antiglobulin (Coombs') test. Otherwise unexplained thrombocytopenia and microangiopathic hemolytic anemia are sufficient evidence for a presumptive diagnosis. Although causes (eg, quinine sensitivity) or associations (eg, pregnancy) are clear in some patients, in most patients TTP-HUS appears suddenly and spontaneously without apparent cause. TTP-HUS is often indistinguishable, even with biopsy, from syndromes that cause identical thrombotic microangiopathies (eg, preeclampsia, scleroderma, accelerated hypertension, acute renal allograft rejection).
Prognosis
and Treatment
Epidemic HUS in children associated with enterohemorrhagic infection usually spontaneously remits and is treated with supportive care and not plasma exchange. In other cases, untreated TTP-HUS is almost always fatal. With plasma exchange, however, about 85% of patients recover completely. Plasma exchange is continued daily until evidence of disease activity has subsided, which may be several days to many weeks. Corticosteroids and antiplatelet drugs (eg, aspirin ) have also been used but are controversial. Most patients experience only a single episode of TTP-HUS. However, because relapses may occur years later, patients must be evaluated quickly if symptoms suggestive of a relapse develop.
Last full review/revision November 2005
Content last modified November 2005
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