Subscribe to RSS
DOI: 10.1055/s-0038-1645967
Thrombin-Induced Platelet Factor Va Formation in Patients with a Gray Platelet Syndrome
Publication History
Received 18 July 1986
Accepted after revision 28 April 1987
Publication Date:
23 July 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/198702/lookinside/thumbnails/10-1055-s-0038-1645967-1.jpg)
Summary
The present study was initiated to establish the functional factor V concentration in platelets of patients with a mild bleeding disorder ascribed to a gray platelet syndrome. This inherited platelet disorder has been characterized by a specific deficiency of alpha-granules and subsequent deficiencies in the alpha-granule proteins. We found that the concentration of plasma factor V was slightly decreased (70% of normal values). In contrast, platelet factor Va formation was severely impaired. Besides a much lower factor V content than in control platelets (10-20% of normal), the dependency of platelet factor Va formation on tlnumbin concentration was altered. Increasing the thrombin concentration 4-lold compared to the concentration that results in maximal factor Va generation from normal platelets did not result in a maximal factor Va formation from gray platelets. When a suspension of washed gray platelets was incubated with a prostacyclin analogue prior to the stimulation with thrombin, a 10-fold lower factor VQ activity was measured. Thus, thrombin-induced factor Va formation in a suspension of gray platelets is the result of a release reaction, followed by the thrombin-catalyzed activation of released factor V. Whereas the kinetics of the former reaction are apparently impaired, the kinetics of the latter one were found to be identical to those observed for normal platelet and plasma factor V activation.
-
References
- 1 Kane WH, Lindhout T, Jackson CM, Majerus PW. Factor Va-dependent binding of factor Xa to human platelets. J Biol Chem 1980; 255: 1170-1174
- 2 Kane WH, Mruk JS, Majerus PW. Activation of coagulation factor V by platelet protease. J Clin Invest 1982; 70: 1092-1100
- 3 Vicic WJ, Lages B, Weiss HJ. Release of V activity is induced by both collagen and ADP and is inhibited by aspirin. Blood 1980; 56: 448-455
- 4 Baruch D, Hemker HC, Lindhout T. Kinetics of thrombin-induced release and activation of platelet factor V. Eur J Biochem 1986; 154: 213-218
- 5 Tracy PB, Eide LL, Bowie E JW, Mann KG. Radioimmunoassay of factor V in human plasma and platelets. Blood 1982; 60: 59-63
- 6 Borchgrevink CF, Owren PA. The hemostatic effect of normal platelets in hemophilia and factor V deficiency. Acta Med Scand 1961; 170: 375-383
- 7 Chediak J, Ashenhurst JB, Garlick I, Desser RK. Successful management of bleeding in a patient with factor V inhibitor by platelet transfusion. Blood 1980; 56: 835-841
- 8 Tracy PB, Giles AR, Mann KG, Eide LL, Hoogendoorn H, Rivard EG. Factor V (Quebec): A bleeding diathesis associated with a qualitative platelet factor V deficiency. J Clin Invest 1984; 74: 1221-1228
- 9 Nesheim ME, Nichols WL, Cole TL, Houston JG, Schenk RB, Mann KG, Bowie E JW. Isolation and study of an acquired inhibitor of human coagulation factor V. J Clin Invest 1986; 77: 405-415
- 10 Raccuglia G. Gray platelet syndrome. A variety of qualitative platelet disorder. Am J Med 1971; 51: 818-828
- 11 Gerrard JM, Phillips DR, Rao G HR, Plow EF, Walz DA, Ross R, Barker LA, White JG. Biochemical studies of two patients with the Gray platelet syndrome. J Clin Invest 1982; 66: 102-109
- 12 Breton-Gorius J, Vainchenker W, Nurden A, Levy-Toledano S, Caen JP. Defective alpha-granule production in megakaryocytes from gray platelet syndrome. Ultrastructural studies of bone marrow cells and megakaryocytes growing in culture from blood precursors. Am J Pathol 1981; 102: 10-19
- 13 Cramer EM, Vainchenker W, Vinci G, Guichard J, Breton-Gorius J. Gray platelet syndrome: immunoelectron microscopic localization of fibrinogen and von Willebrand factor in platelets and megakaryocytes. Blood 1986; 66: 1309-1316
- 14 Nurden AT, Kunicki TJ, Dupuis D, Soria C, Caen JP. Specific protein and glycoprotein deficiencies in platelets isolated from two patients with the gray platelet syndrome. Blood 1982; 59: 709-718
- 15 Levy-Toledano S, Caen JP, Breton-Gorius J, Rendu F, Cywiner-Golenzer C, Dupuy E, Legrand Y, Maclouf J. Gray platelet syndrome: alpha-granule deficiency. J Lab Clin Med 1981; 98: 831-848
- 16 Miletich JP, Brose GJ, Majerus PW. The synthesis of sulphated dextran beads for isolation of human plasma coagulation factor II, IX and X. Anal Biochem 1980; 105: 304-310
- 17 Fujikawa K, Legaz ME, Davie EW. Bovine factor Xj (Stuart factor). Mechanism of activation by a protein from Russell’s viper venom. Biochemistry 1972; 11: 4892-4899
- 18 Pletcher CH, Nelsestuen GL. The rate determining step of the heparin-catalyzed antithrombin/thrombin reaction is independent of thrombin. J Biol Chem 1982; 257: 5342-5345
- 19 Lundblad RL, Kingdon HS, Mann KG. Thrombin. Methods Enzymol 1976; 45: 156-176
- 20 Tracy PB, Rohrbach MS, Mann KG. Functional prothromhinase complex assembly on isolated monocytes and lymphocytes. J Biol Chem 1983; 258: 7264-7267
- 21 Wencel-Drake JD, Dahlback B, White JG, Ginsberg MH. Ultrastructural localization of coagulation factor V in human platelets. Blood 1986; 68: 244-249
- 22 Gewirtz AM, Keefer M, Doshi K, Annamalai AE, Chin HC, Colman RW. Biology of human megakaryocyte factor V. Blood 1986; 76: 1639-1648
- 23 Bevers EM, Comfurius P, Nieuwenhuis HK, Levy-Toledano S, Esnouf J, Belluci S, Caen JP, Zwaal R FA. Platelet prothrombin converting activity in hereditary disorders of platelet function. Br J Haematol" 1986; 63: 335-345