Differing Susceptibilities of Platelets from Normal Individuals and Patients with von Willebrand’s Disease to Attack by Quinine- and Quinidine-Dependent Antiplatelet Antibodies

Summary

Reactivity of quinine- and quinidine-dependent antiplatelet antibodies has been compared in platelet-rich-plasma (PRP) from normal donors and from patients with von Willebrand’s disease (vWd). One quinine-dependent antibody (Q. Ab) caused platelet aggregation and [¹⁴C] serotonin release with only 7 of 12 normal donors, while another Q. Ab and a quinidine-dependent antibody (Qd. Ab) caused aggregation and release with all 12. Drug- dependent IgG binding and PF 3 availability induced by the antibodies were, however, comparable in all donors. Differences in responsiveness were associated with platelets and not plasma. vWd platelets showed normal drug-dependent IgG binding, but decreased aggregation and serotonin release to most drug- dependent antibodies. Responsiveness was not restored by purified vWf:Ag, but, in one case, was corrected by normal plasma or cryoprecipitate. Drug-dependent binding of the Q. Ab which caused variable responsiveness in normals was to the same platelet antigens (GPIb and GPIIIa) in both normal and vWd platelets and did not require plasma components. Reduced PF 3 availability was seen with some antibodies in some vWd patients. Plasma from two of these patients inhibited aggregation of normal platelets to Q. Ab and one of these inhibited aggregation to ADP. Antiplatelet antibodies were detected in these two plasmas by ELISA. Thus some Q. Ab produce different responses with platelets from different donors. In vWd, reduced responsiveness to Q.Ab and Qd. Ab may result from production of inhibitory antiplatelet antibodies.

Key words

Platelets - Thrombocytopenia - Drug-dependent antibodies - von Willebrand’s disease - Quinine

• References

• 1 Ackroyd JF. Allergic purpura, including purpura due to foods, drugs and infections. Am J Med 1953; 14: 605-632
• 2 Chong BH, Berndt MC, Koutts J, Castaldi PA. Quidine-induced thrombocytopenia and leukopenia: Demonstration and characterisation of distinct antiplatelet and antileucocyte antibodies. Blood 1983; 62: 1218-1223
• 3 Kunicki TJ, Russell N, Nurden AT, Aster RH, Caen JP. Further studies of the human platelet receptor for quinine- and quinidine- dependent antibodies. J Immunol 1981; 126: 398-402
• 4 Kunicki TJ, Johnson MM, Aster RH. Absence of the platelet receptor for drug-dependent antibodies in the Bernard-Soulier syndrome. J Clin Invest 1978; 62: 716-719
• 5 George JN, Reimann TA, Moake JL, Morgan RK, Cimo PL, Sears DA. Bernard-Soulier disease: A study of four patients and their parents. Br J Haematol 1981; 48: 459-467
• 6 Pfueller SL, Bilston RA, Logan D, Gibson JM, Firkin BG. Heterogeneity of drug-dependent platelet antigens and their antibodies in quinine- and quinidine-induced thrombocytopenia: Involvement of glycoproteins I b, II b, III a and IX. Blood 1988; 1155-1162
• 7 Van Leeuwen EF, Engelfreit CP, von dem Borne AE G K. Studies on quinine- and quinidine-dependent antibodies against platelets and their reaction with platelets in the Bernard-Soulier syndrome. Br J Haematol 1982; 51: 551-560
• 8 Pfueller SL, Hosseinzadeh PK, Firkin BG. Quinine- and quinidine- dependent antiplatelet antibodies. Requirement of factor VIII-related antigen for platelet damage and for in vitro transformation of lymphocytes from patients with drug-induced thrombocytopenia J Clin Invest 1981; 67: 907-910
• 9 Jenkins CS P, Phillips DR, Clemetson KJ, Meyer D, Larrieu MJ, Luscher EF. Platelet membrane glycoproteins implicated in ristocetin-induced aggregation. J Clin Invest 1976; 57: 112-124
• 10 Christie DJ, Aster RH. Drug-antibody-platelet interaction in quinine- and quinidine-induced thrombocytopenia. J Clin Invest 1982; 70: 989-988
• 11 Pfueller SL, Firkin BG. Retraction. J Clin Invest 1984; 73: 1243
• 12 Koutts J, Howard MA, Firkin BG. Factor VIII physiology and pathology in man. Prog Haematol 1979; 11: 115-145
• 13 Hardisty RM, Macpherson JC. A one-stage factor VIII (anti-haemophilic globulin) assay and its use on venous and capillary plasma. Thromb Diath Haemorrh 1962; 7: 215-229
• 14 Zimmerman TS, Ratnoff OD, Powell AE. Immunologic differentiation of classic haemophilia (Factor VIII deficiency) and von Wille- brand’s disease, with observations on combined deficiences of an antihemophilic factor and proaccelerin (Factor V) on an acquired anticoagulant against antihemophilic factor. J Clin Invest 1971; 50: 244-254
• 15 McFarlane DE, Stibbe J, Kirby EP, Zucker MB, Grant RA, McPherson J. A method for assaying von Willebrand Factor (Ristocetin Cofactor). Thromb Diath Haemorrh 1975; 34: 306-308
• 16 Koutts J, Walsh PN, Plow EF, Fenton JW, Bouma BN, Zimmerman TS. Active release of human platelet factor VIII-related antigen by adenosine diphosphate, collagen and thrombin. J Clin Invest 1978; 62: 1255-1263
• 17 Massini P, Luscher EF. The induction of the release reaction in human blood platelets by close cell contact. Thromb Diath Haemorrh 1971; 25: 13-20
• 18 Pfueller SL, Weber S, Luscher EF. Studies of the mechanism of the human platelet release reaction induced by immunologic stimuli III. Relationship between the binding of soluble IgG aggregates to the Fc receptor and cell response in the presence and absence of plasma J Immunol 1977; 118: 514-524
• 19 Pfueller SL, Firkin BG, McGrath KM, Logan D. Analysis of immunoglobulins that bind to platelets from serum of patients with immune thrombocytopenia: molecular weight distribution. Thromb Res 1987; 47: 305-314
• 20 Van Leeuwen A, Goulmy E, Van Rood JJ. Major histocompatibility complex-restricted antibody reactivity mainly, but not exclusively, directed against cells from male donors. J Exp Med 1979; 150: 1075-1083
• 21 Claas FH J, Langerak J, Van Rood JJ. Drug-induced antibodies with restricted specificity. Immunol Lett 1981; 2: 323-326
• 22 Christie DJ, Weber RW, Mullen PC, Cook J, Aster RA. Structural features of the quinidine and quinine molecules necessary for binding of drug-induced antibodies to human platelets. J Lab Clin Med 1984; 104: 730-740
• 23 George JN, Pickett EB, Heinz R. Platelet membrane microparticles in blood bank fresh frozen plasma and cryoprecipitate. Blood 1986; 68: 307-309