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Proteins Secreted by Platelets: Significance in Detecting Thrombosis

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Thrombosis

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 102))

Abstract

Because platelet survival measurements are time-consuming and may not completely reflect platelet involvement in hemostasis and thrombosis, other tests have been sought. Measurement of two proteins released by platelets, platelet factor 4 (PF4) and β-thromboglobulin (βTG),may provide simpler, more direct means of quantitating platelet involvement. The radioimmunoassays for these proteins reviewed in this paper are sensitive and specific. Although there are technical problems still to be resolved in their clinical application, clinical studies to date suggest that such assays will be useful in studying the pathogenesis and course of thromboembolic disorders. PF4 and βTG levels apparently do reflect in vivo platelet release. Because release of PF4 and βTG parallels release of platelet-derived growth factor, plasma PF4 and βTG levels should also reflect release of that protein. The PF4 and βTG assays along with an assay for fibrinopeptide A in clinical samples should help elucidate the relative importance of platelet release and fibrin formation in thromboembolic disorders.

This work was supported by research grants from the National Institutes of Health (Program Project grants HL-15486 and HL-21006).

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References

  1. Baumgartner HR: The subendothelial surface and thrombosis. In THROMBOSIS: PATHOGENESIS AND CLINICAL TRIALS, edited by Deutsch E, Lechner K, and Brinkhous KM. Stuttgart, F. K. Schattauer Verlag, 1974, p. 91.

    Google Scholar 

  2. Stemerman MB: Thrombogenesis of the rabbit arterial plaque: An electron microscopic study. AM J PATHOL 73: 7–26, 1973.

    PubMed  CAS  Google Scholar 

  3. Harker LA, Slichter SJ: Platelet and fibrinogen consumption in man. N ENGL J MED 287: 999–1005, 1972.

    Article  PubMed  CAS  Google Scholar 

  4. Weily HS, Steele PP, Davies H, Pappas G, Genton E: Platelet survival in patients with substitute heart valves. N ENGL J MED 290: 534–547, 1974.

    Article  PubMed  CAS  Google Scholar 

  5. Steele PP, Weily HS, Davies H, Genton E: Platelet survival in patients with rheumatic heart disease. N ENGL J MED 290: 537–539, 1974.

    Article  PubMed  CAS  Google Scholar 

  6. Harker LA, Slichter SJ, Scott CR, Ross R: Homocystinemia: Vascular injury and arterial thrombosis. N ENGL J MED 290: 539–543, 1974.

    Google Scholar 

  7. Steele P, Battock D, Genton E: Effects of clofibrate and sulfinpyrazone on platelet survival time in coronary artery disease. CIRCULATION 52: 473–476, 1975.

    Article  PubMed  CAS  Google Scholar 

  8. Harbury CB: Evidence for pre-release in circulating platelets. CLIN RES 24: 310A, 1976.

    Google Scholar 

  9. Reimers HJ, Packham MA, Kinlough-Rathbone RL, Mustard JF: Effect of repeated treatment of rabbit platelets with low concentrations of thrombin on their function, metabolism, and survival. BR J HAEMATOL 25: 675–689, 1973.

    Article  PubMed  CAS  Google Scholar 

  10. Reimers HJ, Kinlough-Rathbone RL, Cazenave JP, Senyi AF, Hirsh J, Packham MA, Mustard JF: In vitro and in vivo function of thrombin-treated platelets. THROMB HAEMOSTAS 35: 151–166, 1976.

    CAS  Google Scholar 

  11. Niewiarowski S, Thomas DP: Platelet factor 4 and adenosine diphosphate release during human platelet aggregation. NATURE 222: 1269–1270, 1969.

    Article  PubMed  CAS  Google Scholar 

  12. VanCreveld S, Paulssen MMP: Significance of clotting factors in blood platelets in normal and pathological conditions. LANCET 2: 242–244, 1951.

    Article  Google Scholar 

  13. VanCreveld S, Paulssen MMP: Isolation and properties of the third clotting factor in blood platelets. LANCET 1: 23–25, 1952.

    Article  CAS  Google Scholar 

  14. Deutsch E, Johnson SA, Seegers WH: Differentiation of certain platelet factors related to blood coagulation. CIRCULATION RES 3: 110–115, 1955.

    Article  PubMed  CAS  Google Scholar 

  15. Moore S, Pepper DS, Cash JD: The isolation and characterization of a platelet-specific ß-globulin (ß-thromboglobulin) and the detection of anti-urokinase and anti-plasmin released from thrombin-aggregated washed human platelets. BIOCHIM BIOPHYS ACTA 379: 360–369, 1975.

    Article  PubMed  CAS  Google Scholar 

  16. Moore S, Pepper DS: Identification and characterization of a platelet specific release product: -thromboglobulin. In PLATELETS IN BIOLOGY AND PATHOLOGY, edited by Gordon JL. Amsterdam, North Holland Publishing Co., 1976, p. 293.

    Google Scholar 

  17. Nachman RL, Weksler B, Ferris B: Increased vascular permear bility produced by human platelet granule cationic extract. J CLIN INVEST 49: 274–281, 1970.

    Article  PubMed  CAS  Google Scholar 

  18. Nachman, RL, Weksler B, Ferris B: Characterization of human platelet vascular permeability-enhancing activity. J CLIN INVEST 51: 549–556, 1972.

    Article  PubMed  CAS  Google Scholar 

  19. Weksler BB, Coupai CE: Platelet-dependent generation of chemotactic activity in serum. J EXP MED 137: 1419–1430, 1973.

    Article  PubMed  CAS  Google Scholar 

  20. Weksler BB, Nachman RL: Rabbit platelet bactericidal protein. J EXP MED 134: 1114–1130, 1971.

    Article  PubMed  CAS  Google Scholar 

  21. Keenan JP, Solom NO: Quantitative studies on the release of platelet fibrinogen by thrombin. BR J HAEMATOL 23: 461–466, 1972.

    Article  PubMed  CAS  Google Scholar 

  22. Ross R, Glomset J, Kariya B, Harker L: A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. PROC NATL ACAD SCI USA 71: 1207 1210, 1974.

    Google Scholar 

  23. Kohler N, Lipton A: Platelets as a source of fibroblast growth-producing activity. EXP CELL RES 87: 297–301, 1974.

    Article  PubMed  CAS  Google Scholar 

  24. Antoniades HN, Stathakos D, Scher CD: Isolation of a cationic polypeptide from human serum that stimulates proliferation of 3T3 cells. PROC NATL ACAD SCI USA 72: 2635–2639, 1975.

    Article  PubMed  CAS  Google Scholar 

  25. Busch C, Wasteson A, Westermark B: Release of a cell growth promoting factor from human platelets. THROMB RES 8: 493500, 1976.

    Google Scholar 

  26. Holmsen H: Biochemistry of the platelet release reaction. In BIOCHEMISTRY AND PHARMACOLOGY OF PLATELETS, Ciba Foundation Symposium 35. Amsterdam, Elsevier, 1975, p. 175.

    Google Scholar 

  27. Antoniades HN, Scher CD: Radioimmunoassay of a human serum growth factor for Balb/c-3T3 cells: Derivation from platelets. PROC NATL ACAD SCI USA 74: 1973–1977, 1977.

    Article  PubMed  CAS  Google Scholar 

  28. Waugh TR, Ruddick DW: Studies on increased coagulability of the blood. CANAD MED ASSOC J 51: 11, 1944.

    PubMed  CAS  Google Scholar 

  29. Allen JG, Bogardus G, Jacobson LO, Spurr CL: Some observations on bleeding tendency in thrombocytopenic purpura. ANN INT MED 27: 382–395, 1947.

    PubMed  CAS  Google Scholar 

  30. Conley CL, Hartmann RC, Lalley JS: The relationship of heparin activity to platelet concentration. PROC SOC EXP BIOL MED 69: 284–287, 1948.

    PubMed  CAS  Google Scholar 

  31. Käser-Glanzmann R, Jakabova M, Luscher EF: Isolation and some properties of the heparin-neutralizing factor (PF4) released from human blood platelets. EXPERIENTIA 28: 1221–1223, 1972.

    Article  PubMed  Google Scholar 

  32. Moore S, Pepper DS, Cash JD: Platelet anti-heparin activity: The isolation and characterization of platelet factor 4 released from thrombin-aggregated washed human platelets and its dissociation into subunits and the isolation of membrane-bound anti-heparin activity. BIOCHIM BIOPHYS ACTA 379: 370–384, 1975.

    Article  PubMed  CAS  Google Scholar 

  33. Levine SP, Wohl H: Human platelet factor 4 (PF4): Purification and characterization by affinity chromatography. J BIOL CHEM 251: 324–328, 1976.

    PubMed  CAS  Google Scholar 

  34. Handin RI, Cohen JH: Purification and binding properties of human platelet factor 4. J BIOL CHEM 251: 4273–4282, 1976.

    PubMed  CAS  Google Scholar 

  35. Kaplan KL, Nossel HL, Drillings M, Lesznik G: Radioimmunoassay of platelet factor 4 and ß-thromboglobulin: Development and application to studies of platelet release in relation to fibrinopeptide A generation. BR J HAEMATOL, 1978 (In Press).

    Google Scholar 

  36. Deuel TF, Keim PS, Farmer M, Heinrikson RL: Amino acid sequence of human platelet factor 4. PROC NATL ACAD SCI USA 74: 2256 2258, 1977.

    Google Scholar 

  37. Morgan FJ, Chesterman CN, McGready JR, Begg GS. Studies on the chemistry of human platelet factor 4. HAEMOSTASIS 6: 5358, 1977.

    Google Scholar 

  38. Hermodsen M, Schmer G, Kurachi K: Isolation, crystallization and primary amino acid sequence of human platelet factor 4. J BIOL CHEM 252: 6276–6279, 1977.

    Google Scholar 

  39. Nath N, Lowery CT, Niewiarowski S: Antigenic and antiheparin properties of human platelet factor 4. BLOOD 45: 537–550, 1975.

    PubMed  CAS  Google Scholar 

  40. Rucinski B, Niewiarowski S, Budzynski AZ: Separation of two anti-heparin proteins secreted by human platelets. FED PROC 36: 1082, 1977.

    Google Scholar 

  41. Käser-Glanzmann R, Jakabova M, Luscher EF: Heparin neutralizing factor (PF4) from human blood platelets and its reactivity with fibrinogen and soluble fibrin-monomer complexes. HAEMOSTASIS 1:136–147, 1972/73.

    Google Scholar 

  42. Barber AJ, Käser-Glanzmann R, Jakabova M, Luscher EF: Characterization of a chondroitin-4-sulfate proteoglycan carrier for heparin neutralizing activity (PF4) released from human blood platelets. BIOCHIM BIOPHYS ACTA 286: 312–329, 1972.

    Article  PubMed  CAS  Google Scholar 

  43. Morgan FJ, Begg GS, Chesterman CN: The amino acid sequence of human platelet factor 4. THROMB HAEMOSTAS (In Press).

    Google Scholar 

  44. Weber K, Osborn M: Proteins and sodium dodecylsulfate: Molecular weight determination on polyacrylamide gels and related procedures. Chapter 3 in THE PROTEINS, edited by Neurath H, Hill RL, Third Edition, New York, Academic Press, Inc., 1975, p. 179.

    Google Scholar 

  45. Gjesdahl K: An electro-immunoassay for platelet factor 4 in human plasma. SCAND J HAEMATOL 13: 232–240, 1974.

    Article  Google Scholar 

  46. Bolton AE, Ludlam CA, Pepper DS, Moore S, Cash JD: A radio-immunoassay for platelet factor 4. THROMB RES 8: 51–58, 1976.

    Article  PubMed  CAS  Google Scholar 

  47. Handin RI, McDonough M, Lesch M: Elevated platelet factor 4 in plasma following myocardial infarction. CIRCULATION 54 (Suppl II): 198, 1976.

    Google Scholar 

  48. Chesterman CN, McGready JR, Morgan FJ: Radioimmunoassay of human platelet factor 4. THROMB HAEMOSTAS 38: 211, 1977.

    Google Scholar 

  49. O’Brien JR, Etherington M, Jamieson S, Lawford P: Heparin thrombin clotting time and platelet factor 4. LANCET 2: 656657, 1974.

    Google Scholar 

  50. Salmon J, Bounameaux Y: Etude des antigenes plaquettaires et, en particulier, du fibrinogene. THROMB DIATH HAEMORRH 2: 93110, 1958.

    Google Scholar 

  51. Sokal G: Etude methodologique des plaquettes sanguines et de la metamorphose visqueuse aux moyens d’antiserums fluorescents, antifibrinogenes et antiplaquettes. ACTA HAEMATOL (Basel) 28: 313–325, 1962.

    Article  CAS  Google Scholar 

  52. Nachman RL: Immunologic studies of platelet protein. BLOOD 25: 703–711, 1965.

    PubMed  CAS  Google Scholar 

  53. Davey MG, Luscher EF: Release reactions of human platelets induced by thrombin and other agents. BIOCHIM BIOPHYS ACTA 165: 490–506, 1968.

    Article  CAS  Google Scholar 

  54. Dzoga K, Stoltzner G, Wissler RW: The production of a highly specific antiserum to human platelets. LAB INVEST 27: 351–356, 1972.

    PubMed  CAS  Google Scholar 

  55. Ludlam CA, Moore S, Bolton AE, Pepper DS, Cash JD: The release of a human platelet specific protein measured by a radio-immunoassay. THROMB RES 6: 543–548, 1975.

    Article  PubMed  CAS  Google Scholar 

  56. Bolton AE, Ludlam CA, Moore S, Pepper DS, Cash JD: Three approaches to the radioimmunoassay of human ß-thromboglobulin. BR J HAEMATOL 33: 233–238, 1976.

    Article  PubMed  CAS  Google Scholar 

  57. Niewiarowski S, Lowery CT, Hawiger J, Millman M, Timmons S: Immunoassay of human platelet factor 4 (PF4, antiheparin factor) by radial immunodiffusion. J LAB CLIN MED 87: 720–733, 1976.

    PubMed  CAS  Google Scholar 

  58. Youssef A, Barkhan P: Release of platelet factor 4 by adenosine diphosphate and other platelet-aggregating agents. BR MED J 1: 746–747, 1968.

    Article  PubMed  CAS  Google Scholar 

  59. Niewiarowski S, Poplawski A, Lipinski B, Farbiszewski R: The release of platelet clotting factors during aggregation and viscous metamorphosis. EXP BIOL MED 3: 121–128, 1968.

    CAS  Google Scholar 

  60. Harada K, Zucker MB: Simultaneous development of platelet factor 4 activity and release of 14C-serotonin. THROMB DIATH HAEMORRH 25: 41–46, 1971.

    PubMed  CAS  Google Scholar 

  61. Walsh PN, Gagnatelli G: Platelet antiheparin activity: Storage sites and release mechanism. BLOOD 44: 157–168, 1974.

    PubMed  CAS  Google Scholar 

  62. Witte LD, Kaplan KL, Nossel HL, Lages BA, Weiss HJ, Goodman, DeWS: Studies of the release from human platelets of the growth factor for cultured human arterial smooth muscle cells. CIRCULATION RES, March 1978 (In Press).

    Google Scholar 

  63. Holmsen H, Setknowsky CA, Lages B, Day HJ, Weiss HJ, Scrutton MC: Content and thrombin-induced release of acid hydrolases in gel-filtered platelets from patients with storage pool disease. BLOOD 46: 131–142, 1975.

    PubMed  CAS  Google Scholar 

  64. Weiss HJ, Lages BA, Witte LD, Kaplan KL, Goodman DeWS, Nossel HL, Baumgartner HR: Storage pool disease: Evidence for clinical and biochemical heterogeneity. THROMB HAEMOSTAS 38: 3, 1977.

    Google Scholar 

  65. Nossel HL, Younger LR, Wilner GD, Procupez T, Canfield RE, Butler VP Jr.: Radioimmunoassay of human fibrinopeptide A. PROC NATL ACAD SCI USA 68: 2350–2353, 1971.

    Article  PubMed  CAS  Google Scholar 

  66. Nossel HL, Yudelman I, Canfield RE, Butler VP Jr., Spanondis K, Wilner GD, Qureshi GD: Measurement of fibrinopeptide A in human blood. J CLIN INVEST 54: 43–53, 1974.

    Article  PubMed  CAS  Google Scholar 

  67. Ludlam CA, Cash JD: Studies on the liberation of ß-thromboglobulin from human platelets in vitro. BR J HAEMATOL 33: 239247, 1976.

    Google Scholar 

  68. Ludlam CA, Bolton AE, Moore S, Cash JD: New rapid method for the diagnosis of deep venous thrombosis. LANCET 2: 259–260, 1975.

    Article  PubMed  CAS  Google Scholar 

  69. Smith RC, Ruckley CV, Duncanson J, Allan NC, Dawes J, Pepper DS, Cash JD: ß-thromboglobulin and deep vein thrombosis in surgical patients. THROMB HAEMOSTAS 38: 166, 1977.

    Google Scholar 

  70. Ludlam CA, Davies BA, MacKay AD, Bentley NJ: ß-thromboglobulin and platelet survival in patients with arterial thromboembolic disease. THROMB HAEMOSTAS 38: 124, 1977.

    Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY, USA

    Karen L. Kaplan M.D.,Ph.D.

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  1. Karen L. Kaplan M.D.,Ph.D.
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Editors and Affiliations

  1. Department of Medicine, Section of Hematology, Temple University, Health Sciences Center, 19140, Philadelphia, PA, USA

    H. James Day M.D.

  2. Diabetes and Atherosclerosis Research, The Upjohn Company, 49001, Kalamazoo, MI, USA

    Basil A. Molony M.D. , Edward E. Nishizawa Ph.D.  & Ronald H. Rynbrandt Ph.D. ,  & 

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© 1978 Springer Science+Business Media New York

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Kaplan, K.L. (1978). Proteins Secreted by Platelets: Significance in Detecting Thrombosis. In: Day, H.J., Molony, B.A., Nishizawa, E.E., Rynbrandt, R.H. (eds) Thrombosis. Advances in Experimental Medicine and Biology, vol 102. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-1217-9_6

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  • DOI: https://doi.org/10.1007/978-1-4757-1217-9_6

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-1219-3

  • Online ISBN: 978-1-4757-1217-9

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