ticlopidine-Associated Thrombotic Thrombocytopenic Purpura With an IgG-Type Inhibitor to von Willebrand Factor-Cleaving Protease Activity
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A 41-year-old Japanese man complained of a left-sided visual disturbance. Imaging by magnetic resonance angiography revealed a narrowing of the left internal cervical artery. Thus, ticlopidine (Tc) administration was started at a daily dose of 300 mg. However, 2 weeks later, severe thrombocytopenia, fever, nausea, and psychiatric symptoms developed; Tc was therefore discontinued. Based on the diagnostic hallmark of 5 clinical signs, the patient’s disease was diagnosed as thrombotic thrombocytopenic purpura (TTP). Daily plasmapheresis was performed for the first 4 days, and the patient’s clinical signs gradually improved. Von Willebrand factor-cleaving protease (vWF-CPase) activity in his plasma was less than 3% of that of the control sample at diagnosis, but that value recovered steadily following plasmapheresis. In addition, immunoglobulin G purified from the patient plasma inhibited vWF-CPase activity in normal plasma with a specific activity of 0.8 Bethesda units/mg. No sign of TTP relapse has been noted following cessation of Tc. Thus, it was concluded that the patient developed TTP by producing an inhibitory autoantibody against vWF-CPase activity that was presumably triggered by Tc administration.
- Moschcowitz E. Hyalin thrombosis of the terminal arterioles and capillaries: a hitherto undescribed disease.Proc NY Path Soc. 1924;24:21–24.
- Kakishita E. Pathophysiology and treatment of thrombotic throm-bocytopenic purpura/hemolytic uremic syndrome (TTP/HUS).Int J Hematol. 2000;71:320–327.
- Moake JL, Turner NA, Stathopoulos NA, et al. Involvement of large plasma von Willebrand factor (vWF) multimers and unusually large vWF forms derived from endothelial cells in shear stressinduced platelet aggregation.J Clin Invest. 1998;78:1456–1461. CrossRef
- Furlan M, Robles R, Solenthaler M, et al. Deficient activity of von Willebrand factor-cleaving protease in chronic relapsing thrombotic thromcytopenic purpura.Blood. 1997;89:3097–3103.
- Furlan M, Robles R, Solenthaler M, et al. Acquired deficiency of von Willebrand factor-cleaving protease in a patient with thrombotic thrombocytopenic purpura.Blood. 1998;91:2839–2846.
- Furlan M, Robles R, Galbusera M, et al. von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome.N Engl J Med. 1998;339,1578–1584. CrossRef
- Sharis PJ, Canon CP, Loscalzo J. The antiplatelet effects of ticlopi-dine and clopidogrel.Ann Intern Med. 1998;129:394–405.
- Hass WK, Easton JD, Adams HP, et al. A randomized trial comparing ticlopidine hydrocloride with aspirin for the prevention of stroke in high-risk patients.N Engl J Med. 1989;321:501–507.
- Bennet CL, Weinberg PD, Rozenberg-Ben-Dror K, et al. Throm-botic thrombocytopenic purpura associated with ticlopidine: a review of 60 cases.Ann Intern Med. 1998;128:541–544.
- Steinhubl SR, Tan WA, Foody JM, et al. Incidence and clinical course of thrombotic thrombocytopenic purpura due to ticlopidine following coronary stenting.JAMA. 1999;281:806–810. CrossRef
- Bennet CL, Davidson CJ, Raisch DW, et al. Thrombotic thrombo-cytopenic purpura associated with ticlopidine in the setting of coronary artery stents and stroke prevention.Arch Intern Med. 1999;159:2524–2548. CrossRef
- Fujimura Y, Titani K, Holland L, et al. Von Willebrand factor. A reduced and alkylated 52/48-kDa fragment beginning at amino acid residue 449 contains the domain interacting with platelet glycoprotein Ib. J Biol Chem. 1986;261:381–385.
- Ruggeri ZM, Zimmerman TS. Variant von Willebrand’s disease: characterization of two subtypes by analysis of multimeric composition of factor VIII/von Willebrand factor in plasma and platelets.J Clin Invest. 1980;65:1318–1325. CrossRef
- Tsai HM, Chun-Yet Lian E. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura.N Engl J Med. 1998;339:1585–1594. CrossRef
- Kinoshita S, Yoshioka A, Park Y-D, et al. Upshaw-Schulman syndrome revisited: A concept of congential thrombotic thrombocy-topenic purpura.Int J Hematol. 2001;74:101–108. CrossRef
- Furlan M, Robles R, Lammle B. Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis.Blood. 1996;87:4223–4234.
- Tsai HM, Rice R, Sarode R, et al. Antibody inhibitors to von Willebrand factor metalloproteinase and increased binding of von Willebrand factor to platelets in ticlopidine-associated throm-botic thrombocytopenic purpura.Ann Intern Med. 2000;132:794–799.
- Mauro M, Dang C, Raife T, et al. Ticlopidine-linked thrombotic thrombocytopenic purpura: association with endothelial cell apoptosis and disruption of extracellular matrix in vitro and in vivo [abstract].Blood. 1999;94(suppl 1):646a.
- Bennet CL, Connors JM, Carwile JM, et al. Thrombotic thrombo-cytopenic purpura associated with clopidogrel.N Engl J Med. 2000;342:1773–1777. CrossRef
- ticlopidine-Associated Thrombotic Thrombocytopenic Purpura With an IgG-Type Inhibitor to von Willebrand Factor-Cleaving Protease Activity
International Journal of Hematology
Volume 74, Issue 3 , pp 347-351
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- von Willebrand factor-cleaving protease
- Antiplatelet therapy
- Plasma exchange
- thrombocytopenic purpura
- Industry Sectors
- Author Affiliations
- 1. First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka
- 3. Blood Transfusion Medicine and Sports Medicine, Nara Medical University, Nara
- 4. Chihaya Hospital, Fukuoka
- 5. Blood Transfusion Division, Kyushu University Hospital, Fukuoka, Japan