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DOI: 10.1055/s-0038-1651072
Significant Reduction in the Binding of a Monoclonal Antibody (LYP 18) Directed Against the IIb/IIIa Glycoprotein Complex to Platelets of Patients Having Undergone Extracorporeal Circulation
Publication History
Received 29 July 1986
Accepted after revision 09 December 1986
Publication Date:
06 July 2018 (online)
Summary
Extracorporeal circulation (ECC) used in open heart surgery gives rise to several hemostatic defects. This work investigates the effect of ECC on patient platelets membrane glycoproteins II b/ IIIa. A monoclonal antibody (LYP 18) directed against the IIb/ IIIa complex was used on patient platelets in binding and flow cytometry studies, before and at the end of ECC. An antithrombospondin (LYP 8) monoclonal antibody and a monoclonal antibody (LYP 7) directed against an a-granule glycoprotein of 136 kdaltons, present on the platelet surface after secretion, were used in binding studies together with electron microscopy to assess the release of α-granules.
Results obtained in 7 patients show a significant reduction (p <0.02) in the number of LYP 18 monoclonal antibody binding to platelets having undergone ECC (n = 49,725 ± 16,275) compared to platelets drawn before ECC (n = 72,671 ± 13,302). Flow cytometry studies indicate a decrease (p <0.02) in the percentage of platelets bearing the LYP 18 determinant following ECC (75 ± 12% vs 66 ± 14%). Binding of monoclonal antibodies LYP 8 and LYP 7 and electron microscopy studies of patient platelets having undergone ECC do not show degranulation. These results suggest possible cleavage of the IIb/IIIa complex following ECC but no release of α-granules.
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References
- 1 Bick RL. Hemostasis defects associated with cardiac surgery, prosthetic devices and other extracorporeal circuits. Sem Throm Hemost 1985; 11: 249-280
- 2 Harker LA. Bleeding after cardiopulmonary bypass. N Engl J Med 1986; 22: 1446-1448
- 3 Beurling-Harbury C, Galvan CA. Acquired decrease in platelet secretory ADP associated with increased postoperative bleeding in post-cardiopulmonary bypass patients with severe valvular heart disease. Blood 1978; 52: 13-23
- 4 Addonizio Jr VP, Strauss 3rd JF, Colman RW, Edmunds Jr LH. Effects of prostaglandin E 1 on platelet loss during in vivo and in vitro extracorporeal circulation with a buble oxygenator. J Thorac Cardiovasc Surg 1979; 77: 119-126
- 5 Cella G, Vittadello O, Galluci V, Girolami A. The release of betathromboglobulin and platelet factor 4 during extracorporeal circulation for open heart surgery. Eur J Clin Invest 1981; 11: 165-169
- 6 Mezzano D, Aranda E, Urzua J, Lema G, Habash J, Irarrazabal MJ, Pereira J. Changes in platelet β-thromboglobulin, fibrinogen, albumin, 5-hydroxytryptarnine, ATP, and ADP during and after surgery with extracorporeal circulation in man. Am J Haemat 1986; 22: 133-142
- 7 Harker LA, Malpass TW, Branson HE, Hessel 2nd EA, Slichter SJ. Mechanism of abnormal bleeding in patients undergoing cardiopulmonary bypass: acquired transient platelet dysfunction associated with selective a-granule release. Blood 1980; 56: 824-834
- 8 Solum NO. Platelet membrane proteins. Sem Hemat 1985; 22: 289-302
- 9 Musial J, Niewiarowski S, Hershock D, Morinelli TA, Colman RW, Edmunds Jr LH. Loss of fibrinogen receptors from the platelet surface during simulated extracorporeal circulation. J Lab Clin Med 1985; 105: 514-522
- 10 Wachtfogel YT, Musial J, Jenkin B, Niewiarowski S, Edmunds Jr LH, Colman RW. Loss of platelet α2-adrenergic receptors during simulated extracorporeal circulation: prevention with prostaglandin E 1. J Lab Clin Med 1985; 105: 601-607
- 11 George JN, Pickett EB, Saucerman S, McEver RP, Kunicki TJ, Kieffer N, Newman PJ. Platelet surface glycoproteins. Studies on resting and activated platelets and platelet membrane rnicroparticules in normal subjects, and observations in patients during adult respiratory distress syndrome and cardiac surgery. J Clin Med 1986; 78: 340-348
- 12 McGregor JL, McGregor L, Lyons M, Bauer AS, Huppert J. Identification of the fibrinogen binding sites on chymotrypsin treated human blood platelets using a monoclonal antibody. Thromb Haemost 1985; 54: 236 (Abstr)
- 13 McGregor JL, McGregor L, Bauer AS, Catimel B, Brochier J, Dechavanne M, Clemetson KJ. Identification of two distinct regions within the binding sites for fibrinogen and fibronectin on the IIb/IIIa human platelet membrane glycoprotein complex by monoclonal antibodies P 2 and P 4. Eur J Biochem 1986; 159: 443-449
- 14 Boukerche H, McGregor L, McGregor JL, Clezardin P, Clemetson KJ, Dechavanne M, Brochier J. Characterization of an anti-thrombospondin murine monoclonal antibody (P 8) that inhibits human blood platelet functions. Thromb Haemost 1985; 54: 218 (Abstr)
- 15 Boukerche H, Brochier J, McGregor JL. Characterization of a new monoclonal antibody that shows enhanced binding to activated platelets. Thromb Haemost 1985; 54: 219 (Abstr)
- 16 Stenberg PE, McEver RP, Shuman MA, Jacques YV, Bainton DF. A platelet alpha-granule membrane protein (GMP-140) is expressed on the plasma membrane after activation. J Cell Biol 1985; 101: 880-886
- 17 McGregor JL, Brochier J, Widl F, Follea G, Trzeciak MC, James E, Dechavanne M, McGregor L, Clemetson KJ. Monoclonal antibodies against platelet membrane glycoproteins. Characterization and effect on platelet function. Eur J Biochem 1983; 131: 427-436
- 18 Levy-Toledano S, Maclouf J, Bryon P, Savariau E, Hardisty RM, Caen JP. Human platelet activation in the absence of aggregation: a calcium-dependent phenomenom independent of thromboxane formation. Blood 1982; 59: 1078-1085