Subscribe to RSS
DOI: 10.1055/s-0038-1651119
Platelet Release in Hemophilia
Publication History
Received 27 January 1987
Accepted 17 February 1987
Publication Date:
06 July 2018 (online)
Summary
Platelet function abnormalities have been described in some patients with hemophilia. This study reports measurements of plasma β-thromboglobulin (BTG) and platelet factor 4 (PF4), sensitive and specific markers of platelet α-granule release in 72 hemophiliacs. Patients were studied on multiple occasions depending on their clinical condition and the treatment given. Stable patients without recent bleeding showed significantly elevated BTG levels: 29.72 ± 12.77 ng/ml, control 23.22 ± 8.22, p = 0.006. This appears to be independent of the presence of liver disease, human immune deficiency virus infection (HIV) and the acquired immune deficiency syndrome (AIDS). The increased BTG level seems to correlate with the severity of the disease as reflected by the frequency of bleeding and the quantity of factor concentrate used but not with plasma factor VIII or IX procoagulant activity. Patients who have experienced recent bleeding showed a marked rise in BTG level (77.26 ± 51.37 ng/ml, p = 0.0002), indicating enhanced in vivo platelet activation. These observations suggest that enhanced platelet release in hemophilia most likely reflects sustained activation of hemostasis secondary to frequent bleeding characteristic of the severe form of the disease.
-
References
- 1 Hope W, Martin TJ, Chesterman CN, Morgan FJ. Human β-thromboglobulin inhibits PGI2 production and binds to a specific site in bovine aortic endothelial cells. Nature 1979; 282: 210-212
- 2 Shattil SJ, Bennett JS. Platelets and their membrane in hemostasis: physiology and pathology. Ann Intern Med 1980; 94: 108-118
- 3 Bolton AE, Ludlam CA, Pepper DS, Moore S, Cash JD. A radioimmunoassay for platelet factor 4. Thromb Res 1976; 8: 51-58
- 4 Bolton AE, Ludlam CA, Moore S, Pepper DS, Cash JD. Three approaches to the radioimmunoassay of β-thromboglobulin. Brit J Haematol 1976; 33: 233-238
- 5 Kaplan KL, Nossel HL, Drillings M, Lesznik G. Radioimmunoassay of platelet factor 4 and β-thromboglobulin: Development and application of studies of platelet release in relation to fibrinopeptide A generation. Brit J Haematol 1978; 39: 129-146
- 6 Smith RC, Duncanson J, Ruckley CV, Webber RG, Allan NC, Dawes J, Bolton AE, Hunter WM, Pepper DS, Cash JD. β-thromboglobulin and deep vein thrombosis. Thromb Haemostas 1978; 39: 338-345
- 7 Weiss HJ, Witte L, Kaplan KL, Lager BA, Chernoff A, Nossel HL, Goodman DS, Baumgartner HR. Heterogeneity in storage pool deficiency: studies on granule-bound substances in 18 patients including variants deficient in α-granules, platelet factor 4, β-thromboglobulin, and platelet growth factor. Blood 1979; 54: 1296-1319
- 8 Cella G, Zahavi J, DeHaas HA, Kakkar VV. β-thromboglobulin, platelet production time and platelet function in vascular disease. Brit J Haematol 1979; 43: 127-136
- 9 Preston FE, Ward JD, Marcola BH, Porter NR, Timperley WR. Elevated β-thromboglobulin levels and circulating platelet aggregates in diabetic microangiopathy. Lancet 1978; 1: 238-239
- 10 Nichols AB, Owen J, Kaplan KL, Sciacca RR, Cannon PJ, Nossel HL. Fibrinopeptide A. Platelet factor 4 and β-thromboglobulin levels in coronary heart disease. Blood 1982; 60: 650-654
- 11 Files JC, Malpass TW, Yee EK, Ritchie JL, Harker LA. Studies of human platelet α-granule release in vivo. Blood 1981; 58: 607-618
- 12 White GC, Marouf AA. Platelet factor 4 levels in patients with coronary artery disease. J Lab Clin Med 1981; 97: 369-378
- 13 Ireland H, Lane DA, Wolff S, Foadi M. In vivo platelet release in myeloproliferative disorders. Thrombos Haemostas 1982; 48: 41-45
- 14 Parbtani A, Frampton G, Cameron JS. Measurement of platelet release substances in glomerulonephritis: a comparison of betathromboglobulin (BTG), platelet factor 4 (PF4) and serotonin assays. Thrombosis Res 1980; 19: 177-189
- 15 DeBoer AC, Turpie A GG, Butt RW, Duke RJ, Bloch RF, Genton E. Plasma betathromboglobulin and serum fragment E in acute partial stroke. Brit J Haematol 1982; 50: 327-334
- 16 Al-Mondhiry H. Beta-thromboglobulin and platelet factor 4 in patients with cancer: Correlation with the stage of disease and the effect of chemotherapy. Am J Hematol 1983; 14: 105-111
- 17 Levine SP, Lindenfeld J, Ellis JB, Raymond NJ, Krentz IS. Increased plasma concentrations of platelet factor 4 in coronary artery disease. Circulation 1981; 46: 626-632
- 18 Douglas JT, Shah J, Lowe G DO, Belch J JF, Forbes CD, Prentice C RM. Plasma fibrinopeptide A and beta-thromboglobulin in preeclampsia and pregnancy hypertension. Thromb Hemostas 1979; 47: 54-55
- 19 Sobel M, Salzman EW, Davies GC, Handin RI, Sweeney J, Ploetz J, Kurland G. Circulating platelet products in unstable angina pectoris. Circulation 1981; 63: 300-306
- 20 Al-Mondhiry H, Pierce WS, Pennock JL. Platelet release in coronary heart disease: Effect of antiplatelet drugs and coronary artery bypass surgery. J Lab Clin Med 1985; 105: 397-402
- 21 Borok Z, Weitz J, Owen J, Auerbach M, Nossel HL. Fibrinogen proteolysis and platelet a-granule release in pre-eclampsia/eclampsia. Blood 1984; 63: 525-531
- 22 Borchgrevink CF. Platelet adhesion invivo in patients with bleeding disorders. Act Med Scand 1961; 170: 231-243
- 23 Sixma JJ, van den Berg A. The hemostatic plug in hemophilia A. A morphological study of hemostatic plug formation in bleeding time skin wounds of patients with severe hemophilia A. Brit J Haematol 1984; 58: 741-753
- 24 Hathaway WE, Mahosandana C, Clarke S, Humbert JR. Paradoxical bleeding in intensively transfused hemophiliacs. Transfusion 1973; 13: 6-12
- 25 Buchanan GR, Holtkamp CA. Prolonged bleeding time in children and young adults with hemophilia. Pediatrics 1980; 66: 951-955
- 26 Eyster ME, Gordon RA, Ballard JO. The bleeding time is longer than normal in hemophilia. Blood 1981; 58: 719-723
- 27 Update: Acquired immune deficiency syndrome (AIDS) among patients with hemophilia in the United States. MMWR 1984; 33: 589-591
- 28 Eyster ME, Goedert JJ, Sarangadharan MG, Weiss S HD, Gallo RC, Blattner WA. Development and early natural history of HTLV-III antibodies in persons with hemophilia. JAMA 1985; 253: 2219-2223
- 29 Goedert JJ, Bigger RJ, Weiss SH, Eyster ME, Melbye M, Wilson S, Ginzburg HM, Grossman RJ, DiGioia RA, Sanchez WC, Giron JA, Ebbesen P, Gallo RC, Blattner WA. Three year incidence of AIDS in five cohorts of HTLV-III-infected risk group members. Science 1986; 231: 992-995
- 30 Zar J HG. Binomial distribution. In Biostatistical Analysis. Englewood Cliffs NJ: 1974. Prentice Hall: p. 292
- 31 Zazatchkine MD, Sultan Y, Burton-Kee EJ, Mowbray JF. Circulating immune complexes containing anti-VIII antibodies in multi-transfused patients with hemophilia A. Clin Exp Immunol 1980; 39: 315-320
- 32 Poskitt TR, Poskitt P KF, Bean CA, Arkel YS. Immune complexes in hemophilia. Am J Hematol 1981; 11: 147-152
- 33 Goodnight SH, Britell CW, Wuepper KD, Osterud B. Circulating factor IX antigen-inhibitor complexes in hemophilia B following infusion of a factor IX concentrate. Blood 1979; 53: 93-103
- 34 Verroust F, Adam C, Kourilsky O, Allain JP, Verroust P. Circulating immune complexes and complement levels in hemophiliac children. J Clin Lab Immunol 1981; 6: 127-130
- 35 McVerry BA, Voke J, Mohammed I, Dormandy KM, Holborow EJ. Immune complexes and abnormal liver function in hemophilia. J Clin Pathol 1977; 30: 1142-1146
- 36 Lambert PH. Effect of circulating immune complexes on transfusional therapy in patients with hemophilia or von Willebrand disease. Transfusion 1984; 24: 24-32
- 37 Henser P, Spiegelberg HL. Release of serotonin from human platelets induced by aggregated immunoglobulins of different classes and subgroups. J Clin Invest 1973; 52: 1282-1288
- 38 Clark WF, Tevaarwerk G JM, Bandali K, Lindsay RM, Linton AL. Platelet aggregation and release associated with immune complex formation in pig plasma. J Lab Clin Med 1980; 96: 654-665
- 39 Dawes J, Smith RC, Pepper DS. The release, distribution and clearance of human beta-thromboglobulin and platelet factor 4. Thrombo Res 1978; 12: 851-861
- 40 Kaplan K, Owen J. Plasma levels of beta-thromboglobulin and platelet factor 4 as indices of platelet activation in vivo. Blood 1981; 57: 199-202
- 41 Ludlam CA. Evidence for the platelet specificity of -thromboglobulin and studies on its plasma concentration in healthy individuals. Brit J Haematol 1979; 41: 271-278
- 42 Zahavi J, Kakkar VV. β-thromboglobulin - a specific marker of in vivo platelet release reaction. Thromb Haemostas 1980; 44: 23-29