Lack of Platelet Response to Collagen Associated with an Autoantibody against Glycoprotein Ia: A Novel Cause of Acquired Qualitative Platelet Dysfunction^[*]

Summary

Platelets from a patient with an acquired hemorrhagic disorder had a severely impaired response to collagen, whereas platelet aggregation to other agonists and coagulations tests were normal. No abnormalities of the patient’s platelet membrane glycoproteins (GP) were seen.

Tleatment of the patient with immunosuppressive agents temporarily improved both the bleeding tendency and the collagen responsiveness of the platelets. An IgG was found to be present in the plasma, directed against a protein comigrating with GPIa, and coadsorbing with GPIa to insoluble collagen fibers in a Mg⁺²-dependent manner. Furtherrnore, GPIa was recognized by the patient’s antibody when affinity-purified GPIa-IIa was used as antigen. Finally, the GPIa-IIa complex was immunoprecipitated from a platelet lysate by patient’s plasma.

In addition, purified platelet specific IgG’s from the patient inhibited aggregation of normal platelets induced by collagen or by wheat germ agglutinin. We conclude that the lack of response to collagen of the patient’s platelets may well be due to the presence of an autoantibody against GPIa.

• References

• 1 Nieuwenhuis HK, Sakariassen KS, Houdijk WP M, Nievelstein PF E M, Sixma JJ. Deficiency of platelet membrane glycoprotein la associated with a decreased platelet adhesion to subendothelium. A defect in platelet spreading. Blood 1986; 68: 692-695
• 2 Nieuwenhuis HK, Akkerman JW N, Houdijk WP M, Sixma JJ. Human blood platelets showing no response to collagen fail to express surface glycoprotein Ia. Nature 1985; 318: 470-472
• 3 Santoro SA. Identification of a 160,000 dalton platelet membrane protein that mediates the initial divalent cation-dependent adhesion of platelets to collagen. Cell 1986; 46: 913-920
• 4 Santoro SA, Rajpara SM, Staatz WD, Woods Jr VL J. Isolation and characterization of a platelet surface collagen binding complex related to VLA-2. Biochem Biophys Res Commun 1988; 153: 217-223
• 5 Staatz WD, Rajpara SM, Wagner EA, Carter WG, Santoro SA. The membrane glycoprotein Ia - IIa (VLA-2) complex mediates the Mg2+-dependent adhesion of platelets to collagen. J Cell Biol 1989; 108: 1917-1924
• 6 Kehrel B, Balleisen L, Kokott R, Mesters R, Stenzinger W, Clemet-son KJ, van de Loo J. Deficiency of intact thrombospondin and membrane glycoprotein la in platelets with defective collagen-induced aggregation and spontaneous loss of disorder. Blood 1988; 71: 1074-1078
• 7 Devine DV, Currie MS, Rosse WF, Greenberg CS. PSeudo-Bemard-Soulier Syndrome-thrombocytopenia caused by an autoantibody to glycoprotein Ib. Blood 1987; 70: 428-431
• 8 Strieker RB, Wong D, Saks SR, Corash L, Shuman MA. Acquired Bernard-Soulier syndrome. Evidence for the role of a 210,000-molecular weight protein in the interaction of platelets with von Willebrand factor. J Clin Invest 1985; 76: 1274-1278
• 9 Niessner H, Clemetson KJ, Panzer S, Mueller-Eckhardt C, Santoso S, Bettelheim P. Acquired thrombasthenia due to GPIIb/IIIa-specific platelet autoantibodies. Blood 1986; 68: 571-576
• 10 Balduini CL, Grignani G, Sinigaglia F, Bisio A, Pacchiarini L, Rota Scalabrini D, Balduini C, Mauri C, Ascari E. Severe platelet dysfunction in a patient with autoantibodies against membrane glycoproteins IIb - IIIa. Haemostasis 1987; 17: 98-104
• 11 Baenziger NL, Majerus PW. Isolation of human platelets and platelet surface membranes. Meth Enzymol 1974; 31: 149-155
• 12 Moroi M, Jung SM, Okuma M, Shinmyozu K. A patient with platelets deficient in glycoprotein VI that lack both collagen-induced aggregation and adhesion. J Clin Invest 1989; 84: 1440-1445
• 13 Kehrel B, Stenzinger W, Rauterberg J, Klein-Gunnewigk ML, van de Loo J. Acquired defect in collagen platelet interaction. Haemostasis 1986; 18S2: 24
• 14 Anderson MJ, Woods VL, Tani P, Lindstrom JM, Schmidt D, McMillan R. Autoantibodies to platelet glycoprotein Ilb/IIIa and to the acetylcholine receptor in a patient with chronic idiopathic thrombocytopenic purpura and myasthenia gravis. Ann Intern Med 1984; 100: 829-831
• 15 Nieuwenhuis HK, Korteweg J, Sixma JJ. Interaction of wheat germ agglutinin with GPIa deficient blood platelets: evidence for a common mechanism of platelet activation by wheat germ agglutinin and collagen. In: Nieuwenhuis HK. Thesis. University of Utrecht; Utrecht: 1986: 51-60
• 16 Pischel KD, Bluestein HG, Woods Jr VL. Platelet glycoprotein Ia, Ic and IIa are physicochemically indistinguishable from the very late activation antigens adhesion related proteins of lymphocytes and other cell types. J Clin Invest 1988; 81: 505-513
• 17 Giltay JC, Brinkman HJ M, Modderman PW, von dem Borne AE G K, Van Mourik JA. Human vascular endothelial cells express a membrane protein complex immunochemically indistinguishable from the platelet VLA-2 (glycoprotein Ia-IIa) complex. Blood 1989; 73: 1235-1241
• 18 Kunicki TJ, Nugent DJ, Staats SJ, Orchekowski RP, Wayner EA, Carter WG. The human fibroblast class II extracellular matrix receptor mediates platelet adhesion to collagen and is identical to the platelet glycoprotein Ia-IIa complex. J Biol Chem 1988; 263: 4516-4519
• 19 Coller BS, Beer JH, Scudder LE, Steinberg MH. Collagen-platelet interactions: evidence for a direct interaction of collagen with platelet GPIa/IIa and an indirect interaction with platelet GPIIb/IIIa mediated by adhesive proteins. Blood 1989; 7: 182-192
• 20 Sonnenberg A, Modderman PW, Hogervorst E. Laminin-receptor on platelets is the integrin VLA-6. Nature 1988; 336: 487-489
• 21 Castaldi PA, Mehrabani PA, Fournier DJ, Bemdt MC. Autoimmune thrombocytopenia associated with B-CLL and an IgG autoantibody directed against the human platelet membrane GPIa-IIa complex (VLA-2). Thromb Haemostas 1989; 62: 151 (Abstr)
• 22 Kiefel V, Santoso S, Katzmann B, Mueller-Eckhardt C. The Bra/Brb alloantigen system on human platelets. Blood 1989; 73: 2219-2223