Thromb Haemost 1991; 65(05): 491-496
DOI: 10.1055/s-0038-1648178
Original Article
Schattauer GmbH Stuttgart

Acquired Disorder of Platelet Function Associated with Autoantibodies against Membrane Glycoprotein IIb-IIIa Complex - 1. Glycoprotein Analysis

M Meyer
1   The Department of Medical Genetics, Erfurt, F. R. G.
,
C M Kirchmaier
2   The Department of Angiology of the Center of Internal Medicine, J. W. Goethe University Frankfurt/M., FRG
,
A Schirmer
2   The Department of Angiology of the Center of Internal Medicine, J. W. Goethe University Frankfurt/M., FRG
,
P Spangenberg
3   The Department of Pathological Biochemistry of the Medical Academy, Erfurt, F. R. G.
,
Ch Ströhl
1   The Department of Medical Genetics, Erfurt, F. R. G.
,
K Breddin
2   The Department of Angiology of the Center of Internal Medicine, J. W. Goethe University Frankfurt/M., FRG
› Author Affiliations
Further Information

Publication History

Received 22 June 1990

Accepted after revision 01 January 1991

Publication Date:
24 July 2018 (online)

Summary

A patient with idiopathic thrombocytopenic purpura developed after splenectomy a thrombasthenia-like severe haemor-rhagic diathesis characterized by a normal or subnormal platelet count, prolonged bleeding time, strongly reduced platelet adhesion to glass and defective platelet aggregation in response to ADP and collagen. In contrast to hereditary thrombasthenia membrane glycoproteins (GP) lib and Ilia were normally present in the patient’s platelets. Immunoelectrophoretic analysis revealed an abnormal behaviour of the patient’s GP IIb-IIIa complex. Autoantibodies against GP IIb-IIIa were detected in Triton-extracted washed platelets. Incubation of normal platelets with plasma from the patient resulted in a similar immunoelectrophoretic abnormality of the GP IIb-IIIa complex indicating that bound autoantibodies (IgG) are responsible for the abnormal immunoelectrophoretic behaviour of the patient’s GP IIb-IIIa complex. Platelet fibrinogen was severely reduced similar to classical thrombasthenia suggesting that the GP IIb-IIIa complex is involved in platelet fibrinogen storage.

 
  • References

  • 1 George JN, Nurden AT, Phillips DR. Molecular defects in interactions of platelets with the vessel wall. N Engl J Med 1984; 311: 1084-1098
  • 2 Nurden AT, Caen JP. An abnormal platelet glycoprotein pattern in three cases of Glanzmann’s thrombasthenia. Br J Haematol 1975; 28: 253-260
  • 3 Phillips DR, Agin PP. Platelet membrane defects in Glanzmann’s thrombasthenia. Evidence for decreased amounts of two major glycoproteins. J Clin Invest 1977; 60: 535-545
  • 4 Bennett JS, Vilaire G. Exposure of platelet fibrinogen receptors by ADP and epinephrine. J Clin Invest 1979; 64: 1393-1401
  • 5 Ruggeri ZM, Bader R, de Marco L. Glanzmann’s thrombasthenia: Deficient binding of von Willebrand factor to thrombin-stimulated platelets. Proc Natl Acad Sci USA 1982; 79: 6038-6041
  • 6 Ginsberg MH, Forsyth J, Lightsey A, Chediak J, Plow EF. Reduced surface expression and binding of fibronectin by thrombin-stimulated thrombasthenic platelets. J Clin Invest 1983; 71: 619-624
  • 7 Coller BS, Peerschke EI, Scudder LE, Sullivan CA. A murine monoclonal antibody that completely blocks the binding of fibrinogen to platelets and binds to glycoprotein IIb and/or IIIa. J Clin Invest 1983; 72: 325-338
  • 8 Levy-Toledano S, Tobelem G, Legrand C, Bredoux R, Degos L, Nurden A, Caen JP. Acquired IgG antibody occurring in a thrombasthenic patient: Its effect on human platelet function. Blood 1978; 51: 1065-1071
  • 9 Van Leeuwen EF, van der Ven JTM, Engelfriet CP, von dem Borne AEGK. Specificity of autoantibodies in autoimmune thrombocytopenia. Blood 1982; 59: 23-26
  • 10 Varon D, Karpatkin S. A monoclonal anti-platelet antibody with decreased reactivity for autoimmune thrombocytopenic platelets. Proc Natl Acad Sci USA 1983; 80: 6992-6995
  • 11 Beardsley DJS, Spiegel JE, Jacobs MM, Handin RI, Lux SE. IV Platelet membrane glycoprotein IIIa contains target antigens that bind anti-platelet antibodies in immune thrombocytopenias. J Clin Invest 1984; 74: 1701-1707
  • 12 Woods VL, Oh EH, Maron D, McMillan R. Autoantibodies against the platelet glycoprotein IIb/IIIa complex in patients with chronic ITP. Blood 1984; 63: 368-375
  • 13 Kubota T, Tanoue K, Murohashi I, Nara N, Yamamoto N, Yamazaki H, Aoki N. Autoantibody against platelet glycoprotein IIb/IIIa in a patient with non-Hodgkin’s lymphoma. Thromb Res 1989; 53: 379-386
  • 14 DiMinno G, Coraggio F, Cerbone AM, Capitanio AM, Manzo C, Spina M, Scarpato P, Dattoli GMR, Mattioli PL, Mancini M. A myeloma paraprotein with specificity for platelet glycoprotein Ilia in a patient with a fatal bleeding disorder. J Clin Invest 1986; 77: 157-164
  • 15 Karpatkin S, Lackner HL. Association of antiplatelet antibody with functional platelet disorders. Am J Med 1975; 599-604
  • 16 Karpatkin S. Autoimmune thrombocytopenic purpura. Semin Hematol 1985; 22: 260-288
  • 17 Niessner H, Clemetson KJ, Panzer S, Mueller-Eckhardt C, Santoso S, Bettelheim P. Acquired thrombasthenia due to GP IIb/IIIa-specific platelet autoantibodies. Blood 1986; 68: 571-576
  • 18 Gogstad GO, Hagen I, Krutnes M-B, Solum NO. Dissociation of the glycoprotein IIb-IIIa complex in isolated human platelet membranes. Dependence of pH and divalent cations. Biochim Biophys Acta 1982; 689: 21-30
  • 19 Lechner K. Blutgerinnungsstörungen. Laboratoriumsdiagnose hämatologischer Erkrankungen 2. Springer Verlag; Berlin: 1982
  • 20 Bohn H, Haupt H. Eine quantitative Bestimmung von Faktor XIII mit Anti-Faktor-XIII-Serum. Thromb Diath Haemorrh 1968; 19: 309-315
  • 21 Born GVR, Gross HJ. The aggregation of blood platelets. J Physiol 1963; 168: 178-184
  • 22 Breddin K. Die Thrombozytenfunktion bei hämorrhagischen Dia-thesen, Thrombosen und Gefäßkrankheiten. Thromb Diath Haemorrh 1968 27 Suppl
  • 23 Breddin K. Zur Messung der Thrombozytenadhäsivität. Thromb Diath Haemorrh 1964; 12: 269-281
  • 24 Niessner H. Messung der Plättchenadhäsivität mit einer modifizierten Form der Hellem-II-Methodik unter besonderer Berücksichtigung des von Willebrand-Jürgens-Syndroms. Thromb Diath Haemorrh 1972; 27: 434-451
  • 25 Hagen I, Bjerrum DJ, Solum NO. Characterization of human platelet proteins solubilized with Triton X-100 and examined by crossed immunoelectrophoresis. Reference patterns of extracts from whole platelets and isolated membranes. Eur J Biochem 1979; 99: 9-22
  • 26 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680-685
  • 27 O’Farrell PH. High resolution two-dimensional electrophoresis of proteins. J Biol Chem 1975; 250: 4007-4021
  • 28 Clemetson KJ, Capitanio A, Lüscher EF. High resolution twodimensional gel electrophoresis of the proteins and glycoproteins of human blood platelets and platelet membranes. Biochim Biophys Acta 1979; 553: 11-24
  • 29 Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: Procedure and some applications. Proc Natl Acad Sci USA 1979; 76: 4350-4354
  • 30 Herrmann FH, Meyer M, Gogstad GO, Solum NO. Glycoprotein IIb-IIIa complex in platelets of patients and heterozygotes of Glanzmann’s thrombasthenia. Thromb Res 1983; 32: 615-622
  • 31 Hagen I, Nurden A, Bjerrum OJ, Solum NO, Caen J. Immunochemical evidence for protein abnormalities in platelets from patients with Glanzmann’s thrombasthenia and Bernard-Soulier syndrome. J Clin Invest 1980; 65: 722-731
  • 32 Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-254
  • 33 Tsubakio T, Tani P, Woods VL, McMillan R. Autoantibodies against platelet GP IIb/IIIa in chronic ITP react with different epitopes. Br J Haematol 1987; 67: 345-348
  • 34 George JN, Saucerman S, Levine SP, Knieriem LK. Immunoglobulin is a platelet alpha granule-secreted protein. J Clin Invest 1985; 76: 2020-2025
  • 35 Caen J. Glanzmann’s thrombasthenia. Clin Hematol 1972; 1: 383-392
  • 36 Belloc F, Hourdille P, Fialon P, Boisseau MR, Soria J. Fibrinogen synthesis by megakaryocyte rich human marrow cell concentrates. Thromb Res 1985; 38: 341-351
  • 37 Harrison P, Wilboum B, Debili N, Vainchenker W, Breton-Gorius J, Lawrie AS, Masse J-M, Savidge GF, Cramer EM. Uptake of plasma fibrinogen into the alpha granules of human megakaryocytes and platelets. J Clin Invest 1989; 84: 1320-1324