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  • Title: [Clinical features and laboratory findings of thrombotic thrombocytopenic purpura associated with ticlopidine].
    Author: Yagi H.
    Journal: Rinsho Byori; 2005 Jul; 53(7):630-8. PubMed ID: 16104532.
    Abstract:
    Ticlopidine is an antiplatelet agent that interferes with platelet membrane function by inhibiting adenosine diphosphate-induced platelet activation. It is used in an increasing number of cases of cerebrovascular disease, unstable angina, coronary artery stenting, and peripheral vascular diseases. It has rare but serious adverse reactions, including thrombotic thrombocytopenic purpura (TTP). TTP is a life-threatening disease, characterized by Moschcowitz's pentad: thrombocytopenia, microangiopathic hemolytic anemia, fluctuating neurological signs, renal failure, and fever. Recent advances in elucidating the proteolytic processing of plasma von Willebrand factor (VWF) multimers have established assays for VWF-cleaving protease (VWF-CP) activity and its inhibitor(autoantibodies). These assays apparently demonstrated that TTP patients have defective enzymatic activity with or without presence of the inhibitor. VWF-CP is now identified as a metalloproteinase belonging to the ADAMTS (A Disintegrin And Metalloproteinase domain, with ThromboSpondin type 1 motif) family, termed ADAMTS13. Cases of ticlopidine-associated TTP were first reported in 1991. This complication occurs in 1 in 1600 to 1 in 5000 patients who receive ticlopidine. It is known that they develop TTP within 2 to 8 wk of starting ticlopidine treatment and show severely deficient of ADAMTS13 activity with the presence of the inhibitor. These results suggest that ticlopidine or its metabolites induce the production of autoantibodies against ADAMTS13. As treatment, discontinuation of ticlopidine therapy and rapid initiation of plasma exchange is effective: the majority of patients completely recover and relapse is uncommon. It is thus recommended that physicians should perform complete blood count every 2 weeks for 12 weeks for rapid diagnosis. Physicians and patients should be aware of this fatal but curable complication of ticlopidine therapy.
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