Semin Thromb Hemost 2004; 30(4): 461-471
DOI: 10.1055/s-2004-833481
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Platelet Coagulation-Protein Interactions

Peter N. Walsh1
  • 1Professor of Medicine, Biochemistry and Thrombosis Research Co-Director, The Sol Sherry Thrombosis Research Center, The Sol Sherry Thrombosis Research Center, Departments of Medicine and Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania
Further Information

Publication History

Publication Date:
08 September 2004 (online)

The biochemical mechanisms by which activated platelets participate in exposing receptors for the assembly of enzyme-cofactor-substrate complexes at all stages of the blood coagulation cascade are reviewed. Information derived from studies conducted during the last 30 years supports the concept that the initiation of blood coagulation is triggered by exposure of tissue factor at injury sites, leading to the generation of minute quantities of thrombin (limited by tissue factor pathway inhibitor), sufficient to activate platelets, factors XI, VIII, and V, and trigger the consolidation pathway (i.e., the sequential activation of factors XI, IX, X, and prothrombin on the activated platelet surface), leading to the generation of sufficient thrombin to convert fibrinogen to fibrin and effect hemostasis. Platelets localize coagulation to the hemostatic thrombus and protect coagulation enzymes from inhibition by both plasma and platelet inhibitors (e.g., protease nexin 2), thus preventing disseminated intravascular coagulation.

REFERENCES

  • 1 Walsh P N, Factor X I. In: Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 4th ed. Philadelphia; Lippincott Williams & Wilkins 2001: 191-202
  • 2 Walsh P N. Platelet coagulant activities and hemostasis: a hypothesis.  Blood. 1974;  43 597-605
  • 3 Tracy P B. Role of platelets and leukocytes in coagulation. In: Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 4th ed. Philadelphia; Lippincott Williams & Wilkins 2001: 575-596
  • 4 Ahmad S S, London F S, Walsh P N. The assembly of the factor X-activating complex on activated human platelets.  J Thromb Haemost. 2003;  1 48-59
  • 5 Baglia F A, Walsh P N. Prothrombin is a cofactor for the binding of factor XI to the platelet surface and for platelet-mediated factor XI activation by thrombin.  Biochemistry. 1998;  37 2271-2281
  • 6 Baglia F A, Walsh P N. Thrombin-mediated feedback activation of factor XI on the activated platelet surface is preferred over contact activation by factor XIIa or factor XIa.  J Biol Chem. 2000;  275 20514-20519
  • 7 Gailani D, Broze Jr G J. Factor XI activation in a revised model of blood coagulation.  Science. 1991;  253 909-912
  • 8 Morrissey J H. Tissue factor and factor VII initiation of coagulation. In: Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 4th ed. Philadelphia; Lippincott Williams & Wilkins 2001: 89-102
  • 9 Naito K, Fujikawa K. Activation of human blood coagulation factor XI independent of factor XII. Factor XI is activated by thrombin and factor XIa in the presence of negatively charged surfaces.  J Biol Chem. 1991;  266 7353-7358
  • 10 MacFarlane R G. An enzyme cascade in the blood clotting mechanism, and its function as a biochemical amplifier.  Nature. 1964;  202 498-499
  • 11 Davie E W, Ratnoff O D. Waterfall sequence for intrinsic blood clotting.  Science. 1964;  145 1310-1312
  • 12 Bock S C. Antithrombin III and heparin cofactor II. In: Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN Hemostasis and Thrombosis. Basic Principles and Clinical Practice, 4th ed. Philadelphia; Lippincott Williams & Wilkins 2001: 321-365
  • 13 Esmon C T, Protein C. Protein S, and thrombomodulin. In: Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN Hemostasis and Thrombosis. Basic Principles and Clinical Practice, 4th ed. Philadelphia; Lippincott Williams & Wilkins 2001: 335-353
  • 14 Pizzo S V, Wu S M. Alpha-macroglobulins and kunins. In: Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN Hemostasis and Thrombosis. Basic Principles and Clinical Practice, 4th ed. Philadelphia; Lippincott Williams & Wilkins 2001: 367-379
  • 15 Walsh P N. Roles of factor XI, platelets and tissue factor-initiated blood coagulation.  J Thromb Haemost. 2003;  1 2081-2086
  • 16 Colman R W. Contact activation pathway: inflammatory, fibrinolytic, anticoagulant, antiadhesive and antiangiogenic activities. In: Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 4th ed. Philadelphia; Lippincott Williams & Wilkins 2001: 103-122
  • 17 Walsh P N. The effects of collagen and kaolin on the intrinsic coagulant activity of platelets. Evidence for an alternative pathway in intrinsic coagulation not requiring factor XII.  Br J Haematol. 1972;  22 393-405
  • 18 Walsh P N. Albumin density gradient separation and washing of platelets and the study of platelet coagulant activities.  Br J Haematol. 1972;  22 205-217
  • 19 Walsh P N. The role of platelets in the contact phase of blood coagulation.  Br J Haematol. 1972;  22 237-254
  • 20 Walsh P N. The effect of dilution of plasma on coagulation. The significance of the dilution-activation phenomenon for the study of platelet coagulant activities.  Br J Haematol. 1972;  22 219-236
  • 21 Walsh P N, Biggs R. The role of platelets in intrinsic factor-Xa formation.  Br J Haematol. 1972;  22 743-760
  • 22 Kaufman R J, Antonarakis S E, Fay P J. Factor VIII and hemophilia A. In: Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 4th ed. Philadelphia; Lippincott Williams & Wilkins 2001: 135-156
  • 23 Thompson A R. Molecular biology of factor IX. In: Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 4th ed. Philadelphia; Lippincott Williams & Wilkins 2001: 123-134
  • 24 Asakai R, Chung D W, Davie E W, Seligsohn U. Factor XI deficiency in Ashkenazi Jews in Israel.  N Engl J Med. 1991;  325 153-158
  • 25 Bolton-Maggs P H, Young Wan-Yin B, McCraw A H, Slack J, Kernoff P B. Inheritance and bleeding in factor XI deficiency.  Br J Haematol. 1988;  69 521-528
  • 26 Hu C J, Baglia F A, Mills D C, Konkle B A, Walsh P N. Tissue-specific expression of functional platelet factor XI is independent of plasma factor XI expression.  Blood. 1998;  91 3800-3807
  • 27 Leiba H, Ramot B, Many A. Hereditary and coagulation studies in ten families with factor XI (plasma thromboplastin antecedent) deficiency.  Br J Haematol. 1965;  11 654-665
  • 28 Ragni M V, Sinha D, Seaman F, Lewis J H, Spero J A, Walsh P N. Comparison of bleeding tendency, factor XI coagulant activity, and factor XI antigen in 25 factor XI-deficient kindreds.  Blood. 1985;  65 719-724
  • 29 Rapaport S I, Proctor R R, Patch M J, Yettra M. The mode of inheritance of PTA deficiency: evidence for the existence of a major PTA deficiency and a minor PTA deficiency.  Blood. 1961;  18 149-155
  • 30 Rosenthal R L, Dreskin O H, Rosenthal N. New hemophilia-like disease caused by deficiency of a third plasma thromboplastin factor.  Proc Soc Exp Biol Med. 1953;  82 171-174
  • 31 Sidi A, Seligsohn U, Jonas P, Many M. Factor XI deficiency: detection and management during urologic surgery.  J Urol. 1978;  119 528-530
  • 32 Anson D S, Choo K H, Rees D J et al.. The gene structure of human anti-haemophilic factor IX.  EMBO J. 1984;  3 1053-1060
  • 33 Di Scipio R G, Kurachi K, Davie E W. Activation of human factor IX (Christmas factor).  J Clin Invest. 1978;  61 1528-1538
  • 34 Fujikawa K, Legaz M E, Kato H, Davie E W. The mechanism of activation of bovine factor IX (Christmas factor) by bovine factor XIa (activated plasma thromboplastin antecedent).  Biochemistry. 1974;  13 4508-4516
  • 35 Jagadeeswaran P, Lavelle D E, Kaul R, Mohandas T, Warren S T. Isolation and characterization of human factor IX cDNA: identification of Taq I polymorphism and regional assignment.  Somat Cell Mol Genet. 1984;  10 465-473
  • 36 Jaye M, de la Salle H, Schamber F et al.. Isolation of a human anti-haemophilic factor IX cDNA clone using a unique 52-base synthetic oligonucleotide probe deduced from the amino acid sequence of bovine factor IX.  Nucleic Acids Res. 1983;  11 2325-2335
  • 37 Kurachi K, Davie E W. Isolation and characterization of a cDNA coding for human factor IX.  Proc Natl Acad Sci USA. 1982;  79 6461-6464
  • 38 Osterud B, Bouma B N, Griffin J H. Human blood coagulation factor IX. Purification, properties, and mechanism of activation by activated factor XI.  J Biol Chem. 1978;  253 5946-5951
  • 39 Sinha D, Seaman F S, Walsh P N. Role of calcium ions and the heavy chain of factor XIa in the activation of human coagulation factor IX.  Biochemistry. 1987;  26 3768-3775
  • 40 Yoshitake S, Schach B G, Foster D C, Davie E W, Kurachi K. Nucleotide sequence of the gene for human factor IX (antihemophilic factor B).  Biochemistry. 1985;  24 3736-3750
  • 41 Osterud B, Rapaport S I. Activation of factor IX by the reaction product of tissue factor and factor VII: additional pathway for initiating blood coagulation.  Proc Natl Acad Sci USA. 1977;  74 5260-5264
  • 42 Baglia F A, Badellino K O, Li C Q, Lopez J A, Walsh P N. Factor XI binding to the platelet glycoprotein Ib-IX-V complex promotes factor XI activation by thrombin.  J Biol Chem. 2002;  277 1662-1668
  • 43 Baglia F A, Shrimpton C N, Lopez J A, Walsh P N. The glycoprotein Ib-IX-V complex mediates localization of factor XI to lipid rafts on the platelet membrane.  J Biol Chem. 2003;  278 21744-21750
  • 44 Broze G JJ, Miletich J P. Isolation of the tissue factor inhibitor produced by HepG2 hepatoma cells.  Proc Natl Acad Sci USA. 1987;  84 1886-1890
  • 45 Broze G JJ, Miletich J P. Characterization of the inhibition of tissue factor in serum.  Blood. 1987;  69 150-155
  • 46 Hubbard A R, Jennings C A. Inhibition of tissue thromboplastin-mediated blood coagulation.  Thromb Res. 1986;  42 489-498
  • 47 Hubbard A R, Jennings C A. Inhibition of the tissue factor-factor VII complex: involvement of factor Xa and lipoproteins.  Thromb Res. 1987;  46 527-537
  • 48 Morrison S A, Jesty J. Tissue factor-dependent activation of tritium labeled factor IX and factor X in human plasma.  Blood. 1984;  63 1338-1347
  • 49 Rao L VM, Rapaport S I. Studies on the mechanisms of inactivation of the extrinsic pathway of coagulation.  Blood. 1987;  69 645-651
  • 50 Sanders N L, Bajaj S P, Zivelin A, Rapaport S I. Inhibition of tissue factor/factor VIIa activity in plasma requires factor X and an additional plasma component.  Blood. 1985;  66 204-212
  • 51 Baglia F A, Jameson B A, Walsh P N. Identification and characterization of a binding site for platelets in the Apple 3 domain of coagulation factor XI.  J Biol Chem. 1995;  270 6734-6740
  • 52 Greengard J S, Heeb M J, Ersdal E, Walsh P N, Griffin J H. Binding of coagulation factor XI to washed human platelets.  Biochemistry. 1986;  25 3884-3890
  • 53 Ho D H, Baglia F A, Walsh P N. Factor XI binding to activated platelets is mediated by residues R(250), K(255), F(260), and Q(263) within the Apple 3 domain.  Biochemistry. 2000;  39 316-323
  • 54 Biggs R, Denson K W, Riesenberg D, McIntyre C. The coagulant activity of platelets.  Br J Haematol. 1968;  15 283-296
  • 55 Baglia F A, Seaman F S, Walsh P N. The Apple 1 and apple 4 domains of factor XI act synergistically to promote the surface-mediated activation of factor XI by factor XIIa.  Blood. 1995;  85 2078-2083
  • 56 Ho D H, Badellino K, Baglia F A et al.. The role of high molecular weight kininogen and prothrombin as cofactors in the binding of factor XI A3 domain to the platelet surface.  J Biol Chem. 2000;  275 25139-25145
  • 57 Sun M F, Baglia F A, Ho D et al.. Defective binding of factor XI-N248 to activated human platelets.  Blood. 2001;  98 125-129
  • 58 Baird T R, Walsh P N. The interaction of factor XIa with activated platelets but not endothelial cells promotes the activation of factor IX in the consolidation phase of blood coagulation.  J Biol Chem. 2002;  277 38462-38467
  • 59 Gailani D, Ho D, Sun M F, Cheng Q, Walsh P N. Model for a factor IX activation complex on blood platelets: dimeric conformation of factor XIa is essential.  Blood. 2001;  97 3117-3122
  • 60 Sinha D, Seaman F S, Koshy A, Knight L C, Walsh P N. Blood coagulation factor XIa binds specifically to a site on activated human platelets distinct from that for factor XI.  J Clin Invest. 1984;  73 1550-1556
  • 61 Ahmad S S, London F S, Walsh P N. Binding studies of the enzyme (factor IXa) with the cofactor (factor VIII) in the assembly of factor-X activating complex on the activated platelet surface.  J Thromb Haemost. 2003;  1 2348-2355
  • 62 Ahmad S S, Rawala-Sheikh R, Walsh P N. Comparative interactions of factor IX and factor IXa with human platelets.  J Biol Chem. 1989;  264 3244-3251
  • 63 Ahmad S S, Rawala-Sheikh R, Walsh P N. Platelet receptor occupancy with factor IXa promotes factor X activation.  J Biol Chem. 1989;  264 20012-20016
  • 64 Ahmad S S, Wong M Y, Rawala R, Jameson B A, Walsh P N. Coagulation factor IX residues G4-Q11 mediate its interaction with a shared factor IX/IXa binding site on activated platelets but not the assembly of the functional factor X activating complex.  Biochemistry. 1998;  37 1671-1679
  • 65 London F S, Walsh P N. Zymogen factor IX potentiates factor IXa-catalyzed factor X activation.  Biochemistry. 2000;  39 9850-9858
  • 66 Ahmad S S, Rawala R, Cheung W F, Stafford D W, Walsh P N. The role of the second growth-factor domain of human factor IXa in binding to platelets and in factor-X activation.  Biochem J. 1995;  310 427-431
  • 67 Ahmad S S, Rawala-Sheikh R, Ashby B, Walsh P N. Platelet receptor-mediated factor X activation by factor IXa. High-affinity factor IXa receptors induced by factor VIII are deficient on platelets in Scott syndrome.  J Clin Invest. 1989;  84 824-828
  • 68 Ahmad S S, Rawala-Sheikh R, Cheung W F, Jameson B A, Stafford D W, Walsh P N. High-affinity, specific factor IXa binding to platelets is mediated in part by residues 3-11.  Biochemistry. 1994;  33 12048-12055
  • 69 Ahmad S S, Rawala-Sheikh R, Cheung W F, Stafford D W, Walsh P N. The role of the first growth factor domain of human factor IXa in binding to platelets and in factor X activation.  J Biol Chem. 1992;  267 8571-8576
  • 70 Ahmad S S, Rawala-Sheikh R, Monroe D M, Roberts H R, Walsh P N. Comparative platelet binding and kinetic studies with normal and variant factor IXa molecules.  J Biol Chem. 1990;  265 20907-20911
  • 71 Rawala-Sheikh R, Ahmad S S, Ashby B, Walsh P N. Kinetics of coagulation factor X activation by platelet-bound factor IXa.  Biochemistry. 1990;  29 2606-2611
  • 72 Rawala-Sheikh R, Ahmad S S, Monroe D M, Roberts H R, Walsh P N. Role of gamma-carboxyglutamic acid residues in the binding of factor IXa to platelets and in factor-X activation.  Blood. 1992;  79 398-405
  • 73 Wilkinson F H, Ahmad S S, Walsh P N. The factor IXa second epidermal growth factor (EGF2) domain mediates platelet binding and assembly of the factor X activating complex.  J Biol Chem. 2002;  277 5734-5741
  • 74 Wilkinson F H, London F S, Walsh P N. Residues 88-109 of factor IXa are important for assembly of the factor-X activating complex.  J Biol Chem. 2002;  277 5725-5733
  • 75 Ahmad S S, Scandura J M, Walsh P N. Structural and functional characterization of platelet receptor-mediated factor VIII binding.  J Biol Chem. 2000;  275 13071-13081
  • 76 Ahmad S S, Walsh P N. Coordinate binding studies of the substrate (factor X) with the cofactor (factor VIII) in the assembly of the factor X activating complex on the activated platelet surface.  Biochemistry. 2002;  41 11269-11276
  • 77 Scandura J M, Ahmad S S, Walsh P N. A binding site expressed on the surface of activated human platelets is shared by factor X and prothrombin.  Biochemistry. 1996;  35 8890-8902
  • 78 Scandura J M, Walsh P N. Factor X bound to the surface of activated human platelets is preferentially activated by platelet-bound factor IXa.  Biochemistry. 1996;  35 8903-8913
  • 79 Dahlback B, Stenflo J. Binding of bovine coagulation factor Xa to platelets.  Biochemistry. 1978;  17 4938-4945
  • 80 Kane W H, Majerus P W. The interaction of human coagulation factor Va with platelets.  J Biol Chem. 1982;  257 3963-3969
  • 81 Miletich J P, Jackson C M, Majerus P W. Interaction of coagulation factor Xa with human platelets.  Proc Natl Acad Sci USA. 1977;  74 4033-4036
  • 82 Miletich J P, Jackson C M, Majerus P W. Properties of the factor Xa binding site on human platelets.  J Biol Chem. 1978;  253 6908-6916
  • 83 Miletich J P, Kane W H, Hofmann S L, Stanford N, Majerus P W. Deficiency of factor Xa-factor Va binding sites on the platelets of a patient with a bleeding disorder.  Blood. 1979;  54 1015-1022
  • 84 Miletich J P, Majerus D W, Majerus P W. Patients with congenital factor V deficiency have decreased factor Xa binding sites on their platelets.  J Clin Invest. 1978;  62 824-831
  • 85 Tracy P B, Eide L L, Mann K G. Human prothrombinase complex assembly and function on isolated peripheral blood cell populations.  J Biol Chem. 1985;  260 2119-2124
  • 86 Tracy P B, Nesheim M E, Mann K G. Coordinate binding of factor Va and factor Xa to the unstimulated platelet.  J Biol Chem. 1981;  256 743-751
  • 87 Tracy P B, Nesheim M E, Mann K G. Platelet factor Xa receptor.  Methods Enzymol. 1992;  215 329-360
  • 88 Tracy P B, Peterson J M, Nesheim M E, McDuffie F C, Mann K G. Interaction of coagulation factor V and factor Va with platelets.  J Biol Chem. 1979;  254 10354-10361
  • 89 Tracy P B, Mann K G. Prothrombinase complex assembly on the platelet surface is mediated through the 74,000-dalton component of factor Va.  Proc Natl Acad Sci USA. 1983;  80 2380-2384
  • 90 Tracy P B, Nesheim M E, Mann K G. Proteolytic alterations of factor Va bound to platelets.  J Biol Chem. 1983;  258 662-669
  • 91 Bouchard B A, Catcher C S, Thrash B R, Adida C, Tracy P B. Effector cell protease receptor-1, a platelet activation-dependent membrane protein, regulates prothrombinase-catalyzed thrombin generation.  J Biol Chem. 1997;  272 9244-9251
  • 92 Walsh P N. Platelet-coagulant protein interactions. In: Colman RW, Hirsh J, Marder VJ, Salzman EW Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 3rd ed. Philadelphia; JB Lippincott Company 1994: 629-651
  • 93 Walsh P N, Griffin J H. Contributions of human platelets to the proteolytic activation of blood coagulation factors XII and XI.  Blood. 1981;  57 106-118
  • 94 Berman C L, Yeo E L, Wencel-Drake J D, Furie B C, Ginsberg M H, Furie B. A platelet alpha granule membrane protein that is associated with the plasma membrane after activation. Characterization and subcellular localization of platelet activation-dependent granule-external membrane protein.  J Clin Invest. 1986;  78 130-137
  • 95 Conde I, Shrimpton C N, Thiagarajan P, Lopez J A. Tissue factor-bearing microparticles arise from monocyte lipid rafts and can fuse with activated platelets, consolidating all of the membrane-bound coagulation reactions on the platelet surface.  J Thromb Haemost. 2003;  I 146 (Abstr)
  • 96 Falati S, Gross P, Merrill-Skoloff G, Furie B C, Furie B. Real-time in vivo imaging of platelets, tissue factor and fibrin during arterial thrombus formation in the mouse.  Nat Med. 2002;  8 1175-1181
  • 97 Giesen P L, Rauch U, Bohrmann B et al.. Blood-borne tissue factor: another view of thrombosis.  Proc Natl Acad Sci USA. 1999;  96 2311-2315
  • 98 Himber J, Kling D, Fallon J T, Nemerson Y, Riederer M A. In situ localization of tissue factor in human thrombi.  Blood. 2002;  99 4249-4250
  • 99 Morrissey J H. Tissue factor: in at the start... and the finish?.  J Thromb Haemost. 2003;  1 878-880
  • 100 Rauch U, Bonderman D, Bohrmann B et al.. Transfer of tissue factor from leukocytes to platelets is mediated by CD15 and tissue factor.  Blood. 2000;  96 170-175
  • 101 Rauch U, Nemerson Y. Tissue factor, the blood, and the arterial wall.  Trends Cardiovasc Med. 2000;  10 139-143
  • 102 Walsh P N. Roles of platelets and factor XI in the initiation of blood coagulation by thrombin.  Thromb Haemost. 2001;  86 75-82
  • 103 Baglia F A, Badellino K O, Ho D H, Dasari V R, Walsh P N. A binding site for the kringle II domain of prothrombin in the apple 1 domain of factor XI.  J Biol Chem. 2000;  275 31954-31962
  • 104 Baglia F A, Walsh P N. A binding site for thrombin in the apple 1 domain of factor XI.  J Biol Chem. 1996;  271 3652-3658
  • 105 Baird T R, Walsh P N. Activated platelets but not endothelial cells participate in the initiation of the consolidation phase of blood coagulation.  J Biol Chem. 2002;  277 28498-28503
  • 106 Walsh P N, Sinha D, Koshy A, Seaman F S, Bradford H. Functional characterization of platelet-bound factor XIa: retention of factor XIa activity on the platelet surface.  Blood. 1986;  68 225-230
  • 107 Walsh P N, Sinha D, Kueppers F, Seaman F S, Blankstein K B. Regulation of factor XIa activity by platelets and alpha 1-protease inhibitor.  J Clin Invest. 1987;  80 1578-1586
  • 108 Bush A I, Martins R N, Rumble B et al.. The amyloid precursor protein of Alzheimer’s disease is released by human platelets.  J Biol Chem. 1990;  265 15977-15983
  • 109 Scandura J M, Zhang Y, Van Nostrand W E, Walsh P N. Progress curve analysis of the kinetics with which blood coagulation factor XIa is inhibited by protease nexin-2.  Biochemistry. 1997;  36 412-420
  • 110 Smith R P, Higuchi D A, Broze Jr G J. Platelet coagulation factor XIa-inhibitor, a form of Alzheimer amyloid precursor protein.  Science. 1990;  248 1126-1128
  • 111 Van Nostrand W E, Schmaier A H, Farrow J S, Cunningham D D. Protease nexin-II (amyloid beta-protein precursor): a platelet alpha-granule protein.  Science. 1990;  248 745-748
  • 112 Zhang Y, Scandura J M, Van Nostrand W E, Walsh P N. The mechanism by which heparin promotes the inhibition of coagulation factor XIa by protease nexin-2.  J Biol Chem. 1997;  272 26139-26144
  • 113 Komiyama Y, Nomura S, Murakami T et al.. Purification and characterization of platelet-type factor XI from human platelets.  Thromb Haemost. 1993;  69 1238 (Abstr)
  • 114 Lipscomb M S, Walsh P N. Human platelets and factor XI. Localization in platelet membranes of factor XI-like activity and its functional distinction from plasma factor XI.  J Clin Invest. 1979;  63 1006-1014
  • 115 Schiffman S, Rapaport S I, Chong M M. Platelets and initiation of intrinsic clotting.  Br J Haematol. 1973;  24 633-642
  • 116 Schiffman S, Yeh C H. Purification and characterization of platelet factor XI.  Thromb Res. 1990;  60 87-97
  • 117 Tuszynski G P, Bevacqua S J, Schmaier A H, Colman R W, Walsh P N. Factor XI antigen and activity in human platelets.  Blood. 1982;  59 1148-1156
  • 118 Hsu T C, Shore S K, Seshsmma T, Bagasra O, Walsh P N. Molecular cloning of platelet factor XI, an alternative splicing product of the plasma factor XI gene.  J Biol Chem. 1998;  273 13787-13793
  • 119 Asakai R, Chung D W, Ratnoff O D, Davie E W. Factor XI (plasma thromboplastin antecedent) deficiency in Ashkenazi Jews is a bleeding disorder that can result from three types of point mutations.  Proc Natl Acad Sci USA. 1989;  86 7667-7671
  • 120 Giannelli F, Green P M, Sommer S S et al.. Haemophilia B: database of point mutations and short additions and deletions-eighth edition.  Nucleic Acids Res. 1998;  26 265-268
  • 121 Hancock J F, Wieland K, Pugh R E et al.. A molecular genetic study of factor XI deficiency.  Blood. 1991;  77 1942-1948
  • 122 Martincic D, Zimmerman S A, Ware R E, Sun M F, Whitlock J A, Gailani D. Identification of mutations and polymorphisms in factor XI genes of an African-American family by dideoxy fingerprinting.  Blood. 1998;  92 3309-3317
  • 123 Meijers J C, Davie E W, Chung D W. Expression of human blood coagulation factor XI: characterization of the defect in factor XI type III deficiency.  Blood. 1992;  79 1435-1440
  • 124 Meijers J C, Mulvihill E R, Davie E W, Chung D W. Apple four in human blood coagulation factor XI mediates dimer formation.  Biochemistry. 1992;  31 4680-4684
  • 125 Peretz H, Zivelin A, Usher S, Seligsohn U. A 14-bp deletion (codon 554 del AAGgtaacagagtg) at exon 14/intron N junction of the coagulation factor XI gene disrupts splicing and causes severe factor XI deficiency.  Hum Mutat. 1996;  8 77-78
  • 126 Pugh R E, McVey J H, Tuddenham E G, Hancock J F. Six point mutations that cause factor XI deficiency.  Blood. 1995;  85 1509-1516
  • 127 Seligsohn U, Weiss E, Kulka T, Eichel R, Zwang E, Pereta H. The frequency of the type II and type III mutations causing factor XI deficiency in the general Jewish population.  Thromb Haemost. 1993;  69 1296 (Abstr)
  • 128 Shirk R A, Konkle B A, Walsh P N. Nonsense mutation in exon V of the factor XI gene does not abolish platelet factor XI expression.  Br J Haematol. 2000;  111 91-95
  • 129 Wistinghausen B, Reischer A, Oddoux C, Ostrer H, Nardi M, Karpatkin M. Severe factor XI deficiency in an Arab family associated with a novel mutation in exon 11.  Br J Haematol. 1997;  99 575-577
  • 130 Berliner S, Horowitz I, Martinowitz U, Brenner B, Seligsohn U. Dental surgery in patients with severe factor XI deficiency without plasma replacement.  Blood Coagul Fibrinolysis. 1992;  3 465-468
  • 131 Gailani D. Advances and dilemmas in factor XI.  Curr Opin Hematol. 1994;  1 347-353
  • 132 Kitchens C S. Factor XI: a review of its biochemistry and deficiency.  Semin Thromb Hemost. 1991;  17 55-72
  • 133 Seligsohn U. Factor XI deficiency.  Thromb Haemost. 1993;  70 68-71
  • 134 Martincic D, Kravtsov V, Gailani D. Factor XI messenger RNA in human platelets.  Blood. 1999;  94 3397-3404
  • 135 Wong M Y, Gurr J A, Walsh P N. The second epidermal growth factor-like domain of human factor IXa mediates factor IXa binding to platelets and assembly of the factor X activating complex.  Biochemistry. 1999;  38 8948-8960
  • 136 Nesheim M E, Pittman D D, Wang J H, Slonosky D, Giles A R, Kaufman R J. The binding of 35S-labeled recombinant factor VIII to activated and unactivated human platelets.  J Biol Chem. 1988;  263 16467-16470
  • 137 Foster P A, Fulcher C A, Houghten R A, Zimmerman T S. Synthetic factor VIII peptides with amino acid sequences contained within the C2 domain of factor VIII inhibit factor VIII binding to phosphatidylserine.  Blood. 1990;  75 1999-2004
  • 138 Saenko E L, Scandella D. A mechanism for inhibition of factor VIII binding to phospholipid by von Willebrand factor.  J Biol Chem. 1995;  270 13826-13833
  • 139 Pratt K P, Shen B W, Takeshima K, Davie E W, Fujikawa K, Stoddard B L. Structure of the C2 domain of human factor VIII at 1.5 A resolution.  Nature. 1999;  402 439-442
  • 140 Ahmad S S, Walsh P N. Lipid raft association of the factor VIII C2 domain mediates platelet membrane assembly of factor VIIIa into the factor-X-activating complex.  Blood. 2002;  100 126A
  • 141 Mann K G, Jenny R J, Krishnaswamy S. Cofactor proteins in the assembly and expression of blood clotting enzyme complexes.  Annu Rev Biochem. 1988;  57 915-956
  • 142 Mann K G, Nesheim M E, Church W R, Haley P, Krishnaswamy S. Surface-dependent reactions of the vitamin K-dependent enzyme complexes.  Blood. 1990;  76 1-16
  • 143 Kane W H, Lindhout M J, Jackson C M, Majerus P W. Factor Va-dependent binding of factor Xa to human platelets.  J Biol Chem. 1980;  255 1170-1174
  • 144 Comp P C, Esmon C T. Activated protein C inhibits platelet prothrombin-converting activity.  Blood. 1979;  54 1272-1281
  • 145 Dahlback B, Stenflo J. Inhibitory effect of activated protein C on activation of prothrombin by platelet-bound factor Xa.  Eur J Biochem. 1980;  107 331-335
  • 146 Tracy P B, Eide L L, Bowie E J, Mann K G. Radioimmunoassay of factor V in human plasma and platelets.  Blood. 1982;  60 59-63
  • 147 Sims P J, Faioni E M, Wiedmer T, Shattil S J. Complement proteins C5b-9 cause release of membrane vesicles from the platelet surface that are enriched in the membrane receptor for coagulation factor Va and express prothrombinase activity.  J Biol Chem. 1988;  263 18205-18212
  • 148 Sims P J, Rollins S A, Wiedmer T. Regulatory control of complement on blood platelets. Modulation of platelet procoagulant responses by a membrane inhibitor of the C5b-9 complex.  J Biol Chem. 1989;  264 19228-19235
  • 149 Sims P J, Wiedmer T, Esmon C T, Weiss H J, Shattil S J. Assembly of the platelet prothrombinase complex is linked to vesiculation of the platelet plasma membrane. Studies in Scott syndrome: an isolated defect in platelet procoagulant activity.  J Biol Chem. 1989;  264 17049-17057
  • 150 Tans G, Rosing J, Thomassen M C, Heeb M J, Zwaal R F, Griffin J H. Comparison of anticoagulant and procoagulant activities of stimulated platelets and platelet-derived microparticles.  Blood. 1991;  77 2641-2648
  • 151 Thiagarajan P, Tait J F. Collagen-induced exposure of anionic phospholipid in platelets and platelet-derived microparticles.  J Biol Chem. 1991;  266 24302-24307
  • 152 Weiss H J, Lages B. Platelet prothrombinase activity and intracellular calcium responses in patients with storage pool deficiency, glycoprotein IIb-IIIa deficiency, or impaired platelet coagulant activity-a comparison with Scott syndrome.  Blood. 1997;  89 1599-1611

 Professor
Peter N WalshM.D. Ph.D. 

Sol Sherry Thrombosis Research Center, Temple University School of Medicine

3400 North Broad Street

Philadelphia, PA 19140

Email: pnw@temple.edu

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