Factor V (Quebec): a bleeding diathesis associated with a qualitative platelet Factor V deficiency. (2024)

PMCID: PMC425288

P B Tracy, A R Giles, K G Mann, L L Eide, H Hoogendoorn, and G E Rivard

Copyright and License information PMC Disclaimer

Abstract

Studies were performed on a French-Canadian family afflicted with a bleeding disorder exhibiting an autosomal dominant inheritance pattern and a severe bleeding diathesis after trauma. Clinical laboratory coagulation tests were unimpressive; the only persistent abnormalities include mild thrombocytopenia and moderately reduced Factor V clotting activities. Some individuals had prolonged Stypven times when platelet-rich plasma was used, suggesting that their platelets could not support functional prothrombinase complex assembly. Detailed studies were performed by use of plasma and isolated, washed platelets from a sister and brother. Bioassay data indicate that both individuals had Factor V activities of approximately 40 and 36% of normal, respectively. A comparison of the Factor V radioimmunoassay and bioassay data on the brother's plasma indicated that the circulating amount of Factor V functional activity was low relative to Factor V antigen concentration (approximately 65-75%). In both individuals, the platelet Factor V functional activities were extremely low (2-4%) relative to antigen levels present as determined by radioimmunoassay. These discrepancies between Factor V activities and antigen concentration do not appear to be due to an unstable Factor V molecule or to the presence of a Factor V or Factor Va inhibitor or inactivator. Kinetics of prothrombin activation by use of purified clotting factors indicated that thrombin-activated platelets from both individuals supported prothrombinase complex assembly identical to controls in the presence of added purified Factor Va. Consequently, their bleeding diathesis appears to reflect their platelet, rather than their plasma, Factor V activity. These results suggest that platelet Factor V is an essential component in maintaining stable and prolonged hemostasis after trauma.

• Davie EW, Fujikawa K. Basic mechanisms in blood coagulation. Annu Rev Biochem. 1975;44:799–829. [PubMed] [Google Scholar]
• Tracy PB, Nesheim ME, Mann KG. Coordinate binding of factor Va and factor Xa to the unstimulated platelet. J Biol Chem. 1981 Jan 25;256(2):743–751. [PubMed] [Google Scholar]
• Kane WH, Majerus PW. The interaction of human coagulation factor Va with platelets. J Biol Chem. 1982 Apr 10;257(7):3963–3969. [PubMed] [Google Scholar]
• Nesheim ME, Taswell JB, Mann KG. The contribution of bovine Factor V and Factor Va to the activity of prothrombinase. J Biol Chem. 1979 Nov 10;254(21):10952–10962. [PubMed] [Google Scholar]
• Suttie JW, Jackson CM. Prothrombin structure, activation, and biosynthesis. Physiol Rev. 1977 Jan;57(1):1–70. [PubMed] [Google Scholar]
• Mann KG. Prothrombin. Methods Enzymol. 1976;45:123–156. [PubMed] [Google Scholar]
• Miletich JP, Jackson CM, Majerus PW. Properties of the factor Xa binding site on human platelets. J Biol Chem. 1978 Oct 10;253(19):6908–6916. [PubMed] [Google Scholar]
• Miletich JP, Majerus DW, Majerus PW. Patients with congenital factor V deficiency have decreased factor Xa binding sites on their platelets. J Clin Invest. 1978 Oct;62(4):824–831. [PMC free article] [PubMed] [Google Scholar]
• Katzmann JA, Nesheim ME, Hibbard LS, Mann KG. Isolation of functional human coagulation factor V by using a hybridoma antibody. Proc Natl Acad Sci U S A. 1981 Jan;78(1):162–166. [PMC free article] [PubMed] [Google Scholar]
• Tracy PB, Peterson JM, Nesheim ME, McDuffie FC, Mann KG. Interaction of coagulation factor V and factor Va with platelets. J Biol Chem. 1979 Oct 25;254(20):10354–10361. [PubMed] [Google Scholar]
• Bajaj SP, Rapaport SI, Prodanos C. A simplified procedure for purification of human prothrombin, factor IX and factor X. Prep Biochem. 1981;11(4):397–412. [PubMed] [Google Scholar]
• Downing MR, Butkowski RJ, Clark MM, Mann KG. Human prothrombin activation. J Biol Chem. 1975 Dec 10;250(23):8897–8906. [PubMed] [Google Scholar]
• Kisiel W, Hermodson MA, Davie EW. Factor X activating enzyme from Russell's viper venom: isolation and characterization. Biochemistry. 1976 Nov 2;15(22):4901–4906. [PubMed] [Google Scholar]
• Lundblad RL, Uhteg LC, Vogel CN, Kingdon HS, Mann KG. Preparation and partial characterization of two forms of bovine thrombin. Biochem Biophys Res Commun. 1975 Sep 16;66(2):482–489. [PubMed] [Google Scholar]
• Nesheim ME, Prendergast FG, Mann KG. Interactions of a fluorescent active-site-directed inhibitor of thrombin: dansylarginine N-(3-ethyl-1,5-pentanediyl)amide. Biochemistry. 1979 Mar 20;18(6):996–1003. [PubMed] [Google Scholar]
• Mustard JF, Perry DW, Ardlie NG, Packham MA. Preparation of suspensions of washed platelets from humans. Br J Haematol. 1972 Feb;22(2):193–204. [PubMed] [Google Scholar]
• PROCTOR RR, RAPAPORT SI. The partial thromboplastin time with kaolin. A simple screening test for first stage plasma clotting factor deficiencies. Am J Clin Pathol. 1961 Sep;36:212–219. [PubMed] [Google Scholar]
• FLETCHER AP, ALKJAERSIG N, SHERRY S. The maintenance of a sustained thrombolytic state in man. I. Induction and effects. J Clin Invest. 1959 Jul;38(7):1096–1110. [PMC free article] [PubMed] [Google Scholar]
• Zimmerman TS, Ratnoff OD, Littell AS. Detection of carriers of classic hemophilia using an immunologic assay for antihemophilic factor (factor 8(). J Clin Invest. 1971 Jan;50(1):255–258. [PMC free article] [PubMed] [Google Scholar]
• Weiss HJ, Hoyer LW, Rickles FR, Varma A, Rogers J. Quantitative assay of a plasma factor deficient in von Willebrand's disease that is necessary for platelet aggregation. Relationship to factor VIII procoagulant activity and antigen content. J Clin Invest. 1973 Nov;52(11):2708–2716. [PMC free article] [PubMed] [Google Scholar]
• Peake IR, Bloom AL, Giddings JC. Inherited variants of factor-VIII-related protein in von Willebrand's disease. N Engl J Med. 1974 Jul 18;291(3):113–117. [PubMed] [Google Scholar]
• Young VP, Giles AR, Pater J, Corbett WE. Sex differences in bleeding time and blood loss in normal subjects following aspirin ingestion. Thromb Res. 1980 Dec 1;20(5-6):705–709. [PubMed] [Google Scholar]
• Nesheim ME, Katzmann JA, Tracy PB, Mann KG. Factor V. Methods Enzymol. 1981;80(Pt 100):249–274. [PubMed] [Google Scholar]
• Tracy PB, Eide LL, Bowie EJ, Mann KG. Radioimmunoassay of factor V in human plasma and platelets. Blood. 1982 Jul;60(1):59–63. [PubMed] [Google Scholar]
• Nesheim ME, Myrmel KH, Hibbard L, Mann KG. Isolation and characterization of single chain bovine factor V. J Biol Chem. 1979 Jan 25;254(2):508–517. [PubMed] [Google Scholar]
• Tracy PB, Rohrbach MS, Mann KG. Functional prothrombinase complex assembly on isolated monocytes and lymphocytes. J Biol Chem. 1983 Jun 25;258(12):7264–7267. [PubMed] [Google Scholar]
• Raccuglia G. Gray platelet syndrome. A variety of qualitative platelet disorder. Am J Med. 1971 Dec;51(6):818–828. [PubMed] [Google Scholar]
• Ittyerah TR, Rawala R, Colman RW. Immunochemical studies of factor V of bovine platelets. Eur J Biochem. 1981 Nov;120(2):235–241. [PubMed] [Google Scholar]
• Chesney CM, Pifer D, Colman RW. Subcellular localization and secretion of factor V from human platelets. Proc Natl Acad Sci U S A. 1981 Aug;78(8):5180–5184. [PMC free article] [PubMed] [Google Scholar]
• Gerrard JM, Phillips DR, Rao GH, Plow EF, Walz DA, Ross R, Harker LA, White JG. Biochemical studies of two patients with the gray platelet syndrome. Selective deficiency of platelet alpha granules. J Clin Invest. 1980 Jul;66(1):102–109. [PMC free article] [PubMed] [Google Scholar]
• Vicic WJ, Lages B, Weiss HJ. Release of human platelet factor V activity is induced by both collagen and ADP and is inhibited by aspirin. Blood. 1980 Sep;56(3):448–455. [PubMed] [Google Scholar]