Han-Mou Tsai, MD; Lawrence Rice, MD; Ravindra Sarode, MD; Thomas W. Chow, PhD; Joel L. Moake, MD
Grant Support: By grants HL62131 (H-MT) and HL18584 and HL 54169 (JLM) from the National Heart, Lung, and Blood Institute of the National Institutes of Health.
Requests for Single Reprints: Han-Mou Tsai, MD, Division of Hematology, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467.
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Current Author Addresses: Dr. Tsai: Division of Hematology, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467.
Drs. Rice and Moake: Department of Medicine/Hematology-Oncology, The Methodist Hospital, 6565 Fannin, MS 902-Main, Houston, TX 77030.
Dr. Sarode: Blood Bank/Pathology, University Hospitals of Cleveland, 11100 Euclid Avenue, RB&C-568, Cleveland, OH 44106.
Dr. Chow: Cox Laboratory for Biomedical Engineering, Rice University, 6100 South Main, Houston, TX 77005.
Author Contributions: Conception and design: H.-M. Tsai, L. Rice, T.W. Chow, J.L. Moake.
Analysis and interpretation of the data: H.-M. Tsai, L. Rice, T.W. Chow, J.L. Moake.
Drafting of the article: H.-M. Tsai, L. Rice, J.L. Moake.
Critical revision of the article for important intellectual content: H.-M. Tsai, L. Rice, R. Sarode, J.L. Moake.
Final approval of the article: H.-M. Tsai, L. Rice, R. Sarode, T.W. Chow, J.L. Moake.
Provision of study materials or patients: H.-M. Tsai, R. Sarode, J.L. Moake.
Statistical expertise: H.-M. Tsai, R. Sarode,
Obtaining of funding: H.-M. Tsai
Administrative, technical, or logistic support: H.-M. Tsai, T.W. Chow, J.L. Moake
Collection and assembly of data: H.-M. Tsai, T.W. Chow, J.L. Moake.
Thrombotic thrombocytopenic purpura (TTP) affects 1 in 1600 to 1 in 5000 patients who receive ticlopidine, but little is known about the pathogenesis of this complication.
To investigate whether von Willebrand factor (vWF), which has been associated with idiopathic TTP, is involved in the pathogenesis of ticlopidine-associated TTP.
Three tertiary care, university-affiliated medical centers.
Seven patients who developed TTP 2 to 7 weeks after initiation of ticlopidine therapy. Controls were 7 consecutive patients without thrombocytopenia who had been receiving ticlopidine for 3 to 5 weeks and 10 randomly selected hospitalized patients.
Platelet-bound vWF in patients' EDTA-anticoagulated whole blood samples; vWF proteinase activity in patients' plasma samples; inhibitory activity of IgG isolated from patients' plasma samples against the proteinase from the controls' plasma samples; and vWF multimeric patterns in patients' EDTA-anticoagulated plasma samples.
Binding of vWF to single platelets was increased in the three patients tested during the most thrombocytopenic phase of TTP episodes. Initial plasma samples from all seven patients lacked the largest vWF multimers and were severely deficient in vWF metalloproteinase. IgG molecules, isolated from plasma samples of five patients, inhibited metalloproteinase in plasma samples from the controls. In patients examined, these abnormalities resolved upon the remission that accompanied plasma exchange and discontinuation of ticlopidine therapy.
In the patients who developed ticlopidine-associated TTP, autoantibodies to the vWF metalloproteinase were formed; this led to the same type of vWF abnormalities observed in patients with idiopathic acute TTP. The findings suggest that failure to process large and unusually large vWF multimers in vivo caused binding of vWF to platelets, systemic platelet thrombosis, and TTP.
Tsai H, Rice L, Sarode R, Chow TW, Moake JL. Antibody Inhibitors to von Willebrand Factor Metalloproteinase and Increased Binding of von Willebrand Factor to Platelets in Ticlopidine-Associated Thrombotic Thrombocytopenic Purpura. Ann Intern Med. 2000;132:794–799. doi: 10.7326/0003-4819-132-10-200005160-00005
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Published: Ann Intern Med. 2000;132(10):794-799.
Coagulopathies, Hematology/Oncology, Platelet Disorders.
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