Abstract
The requirement of Factor VIII-related antigen (VIIIR:Ag) for platelet damage by quinine-and quinidine-dependent antibodies was studied in platelet-rich plasma (PRP) of four patients with severe von Willebrand's disease (vWd) (Factor VIII deficiency). Platelet factor 3 availability, platelet aggregation, and release of [14C]serotonin from labeled vWd-PRP by drug-dependent antibodies were significantly reduced in comparison with PRP from normal controls. Addition of purified VIIIR:Ag restored levels of platelet damage to that of normal PRP. In vWd-PRP, platelet damage by two human antiplatelet sera, not dependent on drugs, and by a rabbit antiplatelet serum did not differ from that in normal PRP. PRP from patients deficient in Factor VIII coagulant activity, Factor IX, or Factors II, VII, IX, and X behaved like normal PRP.
The role of VIIIR:Ag in forming antigen able to transform lymphocytes of patients who had recovered from drug-induced thrombocytopenia was investigated by measuring incorporation of [methyl-3H]thymidine into DNA. When lymphocytes were cultured for 7 d, significantly less transformation occurred in response to platelets and the drug in the presence of vWd sera than in normal sera or sera deficient only in Factor VIII coagulant activity or Factor IX. Addition of purified VIIIR:Ag to vWd sera restored transformation to that obtained in normal sera. Nonspecific lymphocyte transformation by pokeweed mitogen was not affected by VIIIR:Ag.
Thus VIIIR:Ag is involved both in platelet damage by drug-dependent antibodies and in the interaction between platelet and drug which produces an antigen able to transform sensitized lymphocytes.
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Selected References
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- ACKROYD J. F. Allergic purpura, including purpura due to foods, drugs and infections. Am J Med. 1953 May;14(5):605–632. doi: 10.1016/0002-9343(53)90377-5. [DOI] [PubMed] [Google Scholar]
- HARDISTY R. M., MACPHERSON J. C. A one-stage factor VIII (antihaemophilic globulin) assay and its use on venous and capillary plasma. Thromb Diath Haemorrh. 1962 May 15;7:215–228. [PubMed] [Google Scholar]
- HOROWITZ H. I., RAPPAPORT H. I., YOUNG R. C., FUJIMOTO M. M. CHANGE IN PLATELET FACTOR 3 AS A MEANS OF DEMONSTRATING IMMUNE REACTIONS INVOLVING PLATELETS: ITS USE AS A TEST FOR QUINIDINE-INDUCED THROMBOCYTOPENIA. Transfusion. 1965 Jul-Aug;5:336–343. doi: 10.1111/j.1537-2995.1965.tb01182.x. [DOI] [PubMed] [Google Scholar]
- Hosseinzadeh P. K., Firkin B. G., Pfueller S. L. Study of the factors that cause specific transformation in cultures of lymphocytes from patients with quinine- and quinidine-induced immune thrombocytopenia. J Clin Invest. 1980 Oct;66(4):638–645. doi: 10.1172/JCI109899. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
- Howard M. A., Montgomery D. C., Hardisty R. M. Factor-VIII-related antigen in platelets. Thromb Res. 1974 May;4(5):617–624. doi: 10.1016/0049-3848(74)90218-7. [DOI] [PubMed] [Google Scholar]
- Jenkins C. S., Phillips D. R., Clemetson K. J., Meyer D., Larrieu M. J., Lüscher E. F. Platelet membrane glycoproteins implicated in ristocetin-induced aggregation. Studies of the proteins on platelets from patients with Bernard-Soulier syndrome and von Willebrand's disease. J Clin Invest. 1976 Jan;57(1):112–124. doi: 10.1172/JCI108251. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Koutts J., Howard M. A., Firkin B. G. Factor VIII physiology and pathology in man. Prog Hematol. 1979;11:115–145. [PubMed] [Google Scholar]
- Kunicki T. J., Johnson M. M., Aster R. H. Absence of the platelet receptor for drug-dependent antibodies in the Bernard-Soulier syndrome. J Clin Invest. 1978 Sep;62(3):716–719. doi: 10.1172/JCI109181. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Macfarlane D. E., Stibbe J., Kirby E. P., Zucker M. B., Grant R. A., McPherson J. Letter: A method for assaying von Willebrand factor (ristocetin cofactor). Thromb Diath Haemorrh. 1975 Sep 30;34(1):306–308. [PubMed] [Google Scholar]
- Massini P., Lüscher E. F. The induction of the release reaction in human blood platelets by close cell contact. Thromb Diath Haemorrh. 1971;25(1):13–20. [PubMed] [Google Scholar]
- Montgomery R. R., Zimmerman T. S. von Willebrand's disease antigen II. A new plasma and platelet antigen deficient in severe von Willebrand's disease. J Clin Invest. 1978 Jun;61(6):1498–1507. doi: 10.1172/JCI109070. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nurden A. T., Caen J. P. The different glycoprotein abnormalities in thrombasthenic and Bernard-Soulier platelets. Semin Hematol. 1979 Jul;16(3):234–250. [PubMed] [Google Scholar]
- SHULMAN N. R. Immunoreactions involving platelets. I. A steric and kinetic model for formation of a complex from a human antibody, quinidine as a haptene, and platelets; and for fixation of complement by the complex. J Exp Med. 1958 May 1;107(5):665–690. doi: 10.1084/jem.107.5.665. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SPAET T. H., CINTRON J. STUDIES ON PLATELET FACTOR-3 AVAILABILITY. Br J Haematol. 1965 May;11:269–275. doi: 10.1111/j.1365-2141.1965.tb06587.x. [DOI] [PubMed] [Google Scholar]
- Tschopp T. B., Weiss H. J., Baumgartner H. R. Decreased adhesion of platelets to subendothelium in von Willebrand's disease. J Lab Clin Med. 1974 Feb;83(2):296–300. [PubMed] [Google Scholar]
- Zimmerman T. S., Ratnoff O. D., Powell A. E. Immunologic differentiation of classic hemophilia (factor 8 deficiency) and von Willebrand's dissase, with observations on combined deficiencies of antihemophilic factor and proaccelerin (factor V) and on an acquired circulating anticoagulant against antihemophilic factor. J Clin Invest. 1971 Jan;50(1):244–254. doi: 10.1172/JCI106480. [DOI] [PMC free article] [PubMed] [Google Scholar]
