A Variant of Glanzmann's Thrombasthenia Characterized by Abnormal Glycoprotein IIb/IIIa Complex Formation

Dominique J Fournier; Arnold Kabral; Peter A Castaldi; Michael C Berndt

doi:10.1055/s-0038-1651038

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1989; 62(03): 977-983
DOI: 10.1055/s-0038-1651038

Original Article

Schattauer GmbH Stuttgart

A Variant of Glanzmann's Thrombasthenia Characterized by Abnormal Glycoprotein IIb/IIIa Complex Formation

Dominique J Fournier

The Research Centre for Thrombosis and Cardiovascular Disease, Department of Medicine, University of Sydney, Westmead Hospital, Westmead, N.S.W., Australia

,

Arnold Kabral

The Research Centre for Thrombosis and Cardiovascular Disease, Department of Medicine, University of Sydney, Westmead Hospital, Westmead, N.S.W., Australia

,

Peter A Castaldi

The Research Centre for Thrombosis and Cardiovascular Disease, Department of Medicine, University of Sydney, Westmead Hospital, Westmead, N.S.W., Australia

,

Michael C Berndt

The Research Centre for Thrombosis and Cardiovascular Disease, Department of Medicine, University of Sydney, Westmead Hospital, Westmead, N.S.W., Australia

› Institutsangaben

Abstract

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Summary

Glanzmann's thrombasthenia is a congenital bleeding abnormality characterized by absent platelet aggregation due to the failure of fibrinogen to bind to activated thrombasthenic platelets. In the majority of cases, this defect is caused by the absence or marked reduction of a specific fibrinogen-binding aggregation receptor, the GP IIb/IIIa complex. E.T., an 18-year-old female with a life-long history of bleeding and easy bruising, had the normal clinical features of Glanzmann's thrombasthenia. Surprisingly, sodium dodecyl sulphate-polyacrylamide gel electrophoresis of her platelets showed no apparent abnormality of the GP IIb/IIIa complex. Control platelets washed in the presence of 2 mM EDTA and control and patient platelets washed in the presence of 2 mM calcium ions showed normal reactivity with anti-GP IIb, anti-GP Ilia, and anti-GP IIb/IIIa complex specific monoclonal antibodies as evaluated by flow cytometry. In contrast, patient's platelets washed in the presence of 2 mM EDTA reacted with anti-GP IIb, anti-GP Ilia, but not with the complex-specific monoclonal antibodies. The increased susceptibility of the patient's GP IIb/IIIa complex to EDTA dissociation was confirmed by crossed immunoelectrophoresis (CIE). CIE analysis further indicated that the patient's GP IIb/IIIa complex did not bind fibrinogen. The combined results suggest that this patient has Glanzmann's thrombasthenia due to an abnormal association of the GP IIb/IIIa complex which results in the failure of the complex to bind fibrinogen.

Keywords

Platelet - Glycoprotein IIb - Variant Glanzmann's thrombasthenia

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Referenzen

References
1 Caen JP. Glanzmann's thrombasthenia. Clin Haematol 1972; 1: 383-392
2 Castaldi PA, Caen JP. Platelet fibrinogen. J Clin Pathol 1965; 18: 579-585
3 Nurden AT, Caen JP. An abnormal platelet glycoprotein pattern in three cases of Glanzmann's thrombasthenia. Br J Haematol 1974; 28: 258-260
4 Bemdt MC, Caen JP. Platelet glycoproteins. In: Progress in Haemostasis and Thrombosis VII. Spaet TH. (ed). Grune and Stratton Inc.; Orlando: 1984: 111
5 Nurden AT. Abnormality of platelet glycoprotein in inherited disorders of platelet function. In: Platelets in Biology and Pathology III. MacIntyre DE, Gordon JL. (eds). Elsevier; Amsterdam: 1987: 37
6 Mustard JF, Kinlough-Rathbone RL, Packham MA, Perry DW, Harfenist EJ, Pai KR M. Comparison of fibrinogen association with normal and thrombasthenic platelets on exposure to ADP or chymotrypsin. Blood 1979; 54: 987-993
7 Peerschke EI B, Zucker MB, Grant RA, Egan JJ, Johnson MM. Correlation between fibrinogen binding to human platelets and platelet aggregability. Blood 1980; 55: 841-847
8 Lee H, Nurden AT, Thromaidis A, Caen JP. Relationship between fibrinogen binding and the platelet glycoprotein deficiencies in Glanzmann's thrombasthenia type I and II. Br J Haematol 1981; 48: 47-57
9 Kunicki TJ, Pidard D, Rosa JP, Nurden AT. The formation of Ca²⁺-dependent complexes of platelet membrane glycoproteins IIb and IIIa in solution as determined by crossed immunoelectrophoresis. Blood 1981; 58: 268-278
10 Shattil SJ, Brass LF, Bennett JS, Pandhi P. Biochemical and functional consequences of dissociation of the membrane glycoprotein IIb-IIIa complex. Blood 1985; 66: 92-98
11 Gogstad GO, Brosstad F, Krutnes MB, Hagen I, Solum NO. Fibrinogen binding properties of the human platelet glycoprotein IIb-IIIa complex: a study using crossed-immunoelectrophoresis. Blood 1982; 60: 663-671
12 Pidard D, Didry D, Kunicki TJ, Nurden AT. Temperature-dependent effects of EDTA on the membrane glycoprotein IIb-IIIa complex and platelet aggregability. Blood 1986; 67: 604-611
13 Ginsberg MH, Lightsey A, Kunicki TJ, Kaufman A, Marguerie G, Plow EF. Divalent cation regulation of the surface orientation of platelet membrane glycoprotein IIb. Correlation with fibrinogen binding function and definition of a novel variant of Glanzmann's thrombasthenia. J Clin Invest 1986; 78: 1103-1111
14 Nurden AT, Rosa JP, Fournier D, Legrand C, Didry D, Paquet A, Pidard D. A variant of Glanzmann's thrombathenia with abnormal glycoprotein IIb-IIIa complexes in the platelet membrane. J Clin Invest 1987; 79: 962-969
15 Caen JP. Variant of thrombasthenia Paris-I-Lariboisiére. Functional abnormality of the human platelet aggregation system. C R Acad Sci Paris 1985; 300: 417-419
16 Ruan C, Du X, Wan H, Hu X, Xi X, Li P. Characterization of the fibrinogen binding sites using monoclonal antibodies to human platelet membrane glycoproteins IIb/IIIa. Thromb Haemostas 1987; 58: 243 (Abstr).
17 Bemdt MC, Du X, Booth WJ. Ristocetin-dependent reconstitution of binding of von Willebrand factor to purified human platelet membrane glycoprotein Ib-IX complex. Biochemistry 1988; 27: 633-640
18 Pidard D, Montgomery RR, Bennett JS, Kunicki TJ. Interaction of AP-2, a monoclonal antibody specific for the human platelet glycoprotein IIb-IIIa complex, with intact platelets. J Biol Chem 1983; 258: 12582-12586
19 Burns GF, Cosgrove L, Triglia T, Beall JA, Lopez AF, Werkmeister JA, Begley CG, Haddad AP, D'Apice AJ F, Vadas MA, Cawley JC. The IIb-IIIa glycoprotein complex that mediates platelet aggregation is directly implicated in leukocyte adhesion. Cell 1986; 45: 269-280
20 Bradstock KF, Favaloro EJ, Kabral A, Kerr A, Hughes WG, Bemdt MC, Musgrove E. Human myeloid differentiation antigens identified by monoclonal antibodies: Expression on leukemic cells. Pathology 1985; 17: 392-399
21 Johnson AM, McNamara PJ, Neoh SH, McDonald PJ, Zola H. Hybridomas secreting monoclonal antibody to Toxoplasma Gondii. Aust J Exp Biol Med 1981; 59: 303-306
22 Ruan C, Du X, Xi X, Castaldi PA, Bemdt MC. A murine antiglycoprotein Ib complex monoclonal antibody, SZ 2, inhibits platelet aggregation induced by both ristocetin and collagen. Blood 1987; 69: 570-577
23 Bemdt MC, Gregory C, Kabral A, Zola H, Fournier DJ, Castaldi PA. Purification and preliminary characterization of the glycoprotein Ib complex in the human platelet membrane. Eur J Biochem 1985; 151: 637-649
24 Bemdt MC, Phillips DR. Purification and preliminary physicochemical characterization of human platelet membrane glycoprotein V. J Biol Chem 1981; 256: 59-65
25 Booth WJ, Bemdt MC, Castaldi PA. An altered platelet granule glycoprotein in patient with essential thrombocythemia. J Clin Invest 1984; 73: 291-297
26 Legrand C, Dubemard V, Nurden AT. Characteristics of collagen induced fibrinogen binding to human platelets. Biochim Biophys Acta 1985; 812: 802-810
27 Patscheke H. Shape and functional properties of human platelets washed with acid citrate. Haemostasis 1981; 10: 14-27
28 Castaldi PA, Berndt MC, Booth W, Gregory C, Bull H, Greaves M. Evidence for a platelet membrane defect in the myeloproliferative syndromes. Thromb Res 1982; 27: 601-609
29 Fournier D, Pidard D, Nurden AT. Analyse des glycoprotéines membranaires par immunoelectrophorese en double dimension. In: Techniques Biochimique d'Analyse des Antigénes de Membrane. Charron D. (ed). INSERM; Paris: 1987: 67
30 Coller BS. Disorders of platelets. In: Disorders of Hemostasis. Ratnoff OD, Forbes CD. (eds). Grune and Stratton; Orlando: 1984: 73
31 Kunicki TJ, Nurden AT, Pidard D, Russel NR, Caen JP. Characterization of human platelet glycoprotein antigens giving rise to individual immunoprecipitates in crossed immunoelectrophoresis. Blood 1981; 58: 1190-1197
32 Hagen I, Bjerrum DJ, Solum NO. Characterization of human platelet proteins solubilized with Triton X-100 and examined by crossed-immunoelectrophoresis. Eur J Biochem 1979; 99: 9-22
33 Phillips DR, Charo IF, Parise LV, Fitzgerald LA. The platelet membrane glycoprotein IIb-IIIa complex. Blood 1988; 71: 831-843
34 Loftus JC, Frelinger AL, D'Souza SE, Dixon D, Lacy J, Sorge J, Ginsberg MH. Molecular cloning and chemical synthesis of a region of platelet glycoprotein IIb in involved in adhesive function. Proc Natl Acad Sci USA 1987; 84: 7114-7118
35 Wencel-Drake JD, Plow EF, Kunicki TJ, Woods VL, Keller DM, Ginsberg MH. Localization of internal pools of membrane glycoproteins involved in platelet adhesive response. Am J Pathol 1986; 124: 324-334