Acquired thrombotic thrombocytopenic purpura: ADAMTS13 activity, anti-ADAMTS13 autoantibodies and risk of recurrent disease.

Satoh A, et al. Familial essential thrombocythemia associated with a dominant-positive activating mutation of the MPL gene, which encodes for the receptor for thrombopoi-etin. Identification of an acquired JAK2 mutation in poly-cythemia vera. Lacout C, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Huntly BJ, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Boggi S, et al. JAK2 (V617F) as an acquired somatic mutation and a secondary genetic event associated with disease progression in familial myeloproliferative disorders. Markers of myeloproliferative diseases in childhood poly-cythemia vera and essential thrombocythemia. Micalizzi C, et al. Pediatric patients with essential throm-bocythemia are mostly polyclonal and V617FJAK2 negative. Hanson CA, et al. Proposals and rationale for revision of the World Health Organization diagnostic criteria for poly-cythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. The revised WHO diagnostic criteria for Ph-negative myeloproliferative diseases are not appropriate for the diagnostic screening of childhood polycythemia vera and essential thrombocythemia. T hrombotic thrombocytopenic purpura (TTP), first described by Moschcowitz in 1924, 1 has long been known as a generally fatal acute disease occurring in previously healthy subjects 2. Despite its rarity, over the past eight decades it has attracted the interest of many researchers and clinicians whose many hypotheses as to its pathophysiological mechanisms have been widely discussed (for reviews see refs. #3-7). The outcome of affected patients has been dramatically improved by the largely empirical introduction of plasma therapy in the 1970s, 8 and a prospective study by the Canadian Apheresis Study Group demonstrated the superiority of plasma exchange with fresh frozen plasma (FFP) replacement over simple FFP infusion. 9 However, in spite of the use of plasma exchange and FFP replacement (and corticosteroids in many patients), the mortality from acute TTP is still high even today, with some 10-20% of patients dying from the acute disease episode. 5 In 1982, Moake et al. 10 suggested that unusually large von Willebrand factor multimers (ULVWF), observed in plasma during the remission phase in 4 patients with a chronically relapsing form of TTP, were responsible for the recurring platelet clumping in the microvasculature of their patients. They hypothesized that a deficiency of a VWF depolymerase was causing the persistence in plasma of these highly adhesive ULVWF multimers. 10 In 1996, such a " depolymerase " , …