| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia associated with red cell fragmentation, and neurological and renal symptoms. Plasma from patients with TTP has been shown to contain unusually large von Willebrand factor (vWF) multimers that may cause platelet agglutination in vivo. Recently, a metalloprotease responsible for the cleavage of vWF multimers has been isolated from normal human plasma and was found to be deficient in some patients with TTP. We examined the activity of vWF-cleaving protease (vWF-CP), by modified Furlan's method, in plasma from 1 patient with familial TTP, 3 with acquired TTP, 4 with thrombotic microangiopathy(TMA) and 2 with veno-occlusive disease (VOD) associated after allo-BMT. Diluted plasma samples of patients were incubated with protease-free vWF purified from normal human plasma, in the presence of urea and barium ions. The extent of vWF degradation was assayed by e
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lectrophoresis using SDS-agarose gels and immunoblot techniques. Activity of vWF-CP from 12 normal plasma samples has been shown to be 77 - 180% (average 115%), whereas, no vWF-CP(below 5%) was observed in plasma from the single case with familial TTP, before and after plasma exchange, although FFP infusion therapy was effective for this patient in recovering from thrombocytopenia. In the 3 cases of acquired TTP, 2 patients showed lack of vWF-CP activity in plasma, and inhibitors against vWF-CP have been elucidated by plasma cross-mixing test. After extensive plasma exchange and FFP infusion followed by corticosteroid therapy, normal vWF-CP was recovered in plasma from the 2 acquired TTP patients. Among BMT patients, plasma from the 4 BMT-TMA cases showed normal vWF-CP activities of 55 - 111%, whereas plasma from the 2 cases of BMT-VOD revealed low vWF-CP activity, with 24% and 37%, respectively. Thus, measurement of vWF-CP is crucial to predict differentiation of primary forms of TMA to establish the pathogenesis in varied endothelial dysfunction Less
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