PDF herunterladen
Semin Thromb Hemost 2013; 39(06): 663-673
DOI: 10.1055/s-0033-1353442
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Platelet-Type von Willebrand Disease: New Insights into the Molecular Pathophysiology of a Unique Platelet Defect

Maha Othman
1   Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada
2   St Lawrence College Kingston, Ontario, Canada
,
Harmanpreet Kaur
1   Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada
,
Jonas Emsley
3   School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, United Kingdom
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
11. August 2013 (online)

    Lizenzen und Reprints

Abstract

Compared with coagulation factor defects, little attention is given to defects of platelet function as causes of rare bleeding disorders. Platelet-type von Willebrand disease (PT-VWD) is an autosomal dominant bleeding disorder and is unique among platelet disorders because it is characterized by platelet hyperresponsiveness rather than decreased function. The disease is caused by gain-of-function mutations in the platelet GP1BA gene, which codes for the platelet von Willebrand factor (VWF) receptor, GPIbα. Only five mutations (four missense and one deletion) have so far been reported. Affected patients suffer from mild to moderate mucocutaneous bleeding, low VWF activity compared with antigen, decreased high-molecular-weight VWF multimers, variable degree of thrombocytopenia and typically platelet aggregation in response to low concentrations of ristocetin. All reported PT-VWD missense mutations occur within the R-loop of GPIbα and it was speculated that the introduction of short branched chain mutations such as Val in PT-VWD stabilized the extended β-hairpin. Examination of this theory by surveying all the available GPIbα structures showed that a distinct conformation predominates for the R-loop when GPIbα is not bound to VWF-A1 and this provides the framework of a new hypothesis for the molecular basis of PT-VWD. Worldwide efforts to improve diagnosis of PT-VWD continue, and international systematic studies are required to further our understanding of the phenotype and the influence of the hyperresponsive GPIbα beyond hemostasis.

Keywords

GPIbα - platelet glycoproteins - platelet functional defects - gain-of-function mutations - crystal structure of GPIb-VWF complex
 

  • References

  • 1 Peyvandi F, Palla R, Menegatti M, Mannucci PM. Introduction. Rare bleeding disorders: general aspects of clinical features, diagnosis, and management. Semin Thromb Hemost 2009; 35 (4) 349-355
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 2 Cattaneo M. Inherited platelet-based bleeding disorders. J Thromb Haemost 2003; 1 (7) 1628-1636
    CrossrefPubMedGoogle Scholar
  • 3 Weiss HJ. Scott syndrome: a disorder of platelet coagulant activity. Semin Hematol 1994; 31 (4) 312-319
    PubMedGoogle Scholar
  • 4 Ruggeri ZM. The role of von Willebrand factor in thrombus formation. Thromb Res 2007; 120 (Suppl. 01) S5-S9
    CrossrefPubMedGoogle Scholar
  • 5 Suva LJ, Hartman E, Dilley JD , et al. Platelet dysfunction and a high bone mass phenotype in a murine model of platelet-type von Willebrand disease. Am J Pathol 2008; 172 (2) 430-439
    CrossrefPubMedGoogle Scholar
  • 6 Ware J. Dysfunctional platelet membrane receptors: from humans to mice. Thromb Haemost 2004; 92 (3) 478-485
    PubMedGoogle Scholar
  • 7 Ware J, Russell SR, Marchese P, Ruggeri ZM. Expression of human platelet glycoprotein Ib alpha in transgenic mice. J Biol Chem 1993; 268 (11) 8376-8382
    PubMedGoogle Scholar
  • 8 Guerrero JA, Kyei M, Russell S , et al. Visualizing the von Willebrand factor/glycoprotein Ib-IX axis with a platelet-type von Willebrand disease mutation. Blood 2009; 114 (27) 5541-5546
    CrossrefPubMedGoogle Scholar
  • 9 Othman M. Differential identification of PT-VWD from type 2B VWD and GP1BA nomenclature issues. Br J Haematol 2008; 142 (2) 312-314 , author reply 314–315
    CrossrefPubMedGoogle Scholar
  • 10 Facey DA, Favaloro EJ, Koutts J, Berndt MC, Hertzberg MS. Identification and characterization of a novel mutation in von Willebrand factor causing type 2B von Willebrand's disease. Br J Haematol 1999; 105 (2) 538-541
    CrossrefPubMedGoogle Scholar
  • 11 Favaloro EJ. Phenotypic identification of platelet-type von Willebrand disease and its discrimination from type 2B von Willebrand disease: a question of 2B or not 2B? A story of nonidentical twins? Or two sides of a multidenominational or multifaceted primary-hemostasis coin?. Semin Thromb Hemost 2008; 34 (1) 113-127
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 12 Favaloro EJ. 2B or not 2B? Differential identification of type 2B, versus pseudo-von Willebrand disease. Br J Haematol 2006; 135 (1) 141-142 , author reply 143
    CrossrefPubMedGoogle Scholar
  • 13 Favaloro EJ, Bonar R, Meiring M, Street A, Marsden K ; RCPA QAP in Haematology. 2B or not 2B? Disparate discrimination of functional VWF discordance using different assay panels or methodologies may lead to success or failure in the early identification of type 2B VWD. Thromb Haemost 2007; 98 (2) 346-358
    PubMedGoogle Scholar
  • 14 Favaloro EJ, Koutts J. 2B or not 2B? Masquerading as von Willebrand disease?. J Thromb Haemost 2012; 10 (2) 317-319
    CrossrefPubMedGoogle Scholar
  • 15 Favaloro EJ, Patterson D, Denholm A , et al. Differential identification of a rare form of platelet-type (pseudo-) von Willebrand disease (VWD) from Type 2B VWD using a simplified ristocetin-induced-platelet-agglutination mixing assay and confirmed by genetic analysis. Br J Haematol 2007; 139 (4) 623-626
    CrossrefPubMedGoogle Scholar
  • 16 Hamilton A, Ozelo M, Leggo J , et al. Frequency of platelet type versus type 2B von Willebrand disease. An international registry-based study. Thromb Haemost 2011; 105 (3) 501-508
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 17 Othman M, Favaloro EJ. Genetics of type 2B von Willebrand disease: “true 2B,” “tricky 2B,” or “not 2B.” What are the modifiers of the phenotype?. Semin Thromb Hemost 2008; 34 (6) 520-531
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 18 Miller JL. Platelet-type von Willebrand disease. Thromb Haemost 1996; 75 (6) 865-869
    PubMedGoogle Scholar
  • 19 Othman M. Platelet-type Von Willebrand disease: three decades in the life of a rare bleeding disorder. Blood Rev 2011; 25 (4) 147-153
    CrossrefPubMedGoogle Scholar
  • 20 Weiss HJ, Meyer D, Rabinowitz R , et al. Pseudo-von Willebrand's disease. An intrinsic platelet defect with aggregation by unmodified human factor VIII/von Willebrand factor and enhanced adsorption of its high-molecular-weight multimers. N Engl J Med 1982; 306 (6) 326-333
    CrossrefPubMedGoogle Scholar
  • 21 Miller JL, Castella A. Platelet-type von Willebrand's disease: characterization of a new bleeding disorder. Blood 1982; 60 (3) 790-794
    PubMedGoogle Scholar
  • 22 Takahashi H, Nagayama R, Hattori A, Ihzumi T, Tsukada T, Shibata A. Von Willebrand disease associated with familial thrombocytopenia and increased ristocetin-induced platelet aggregation. Am J Hematol 1981; 10 (1) 89-99
    CrossrefPubMedGoogle Scholar
  • 23 Takahashi H, Sakuragawa N, Shibata A. Von Willebrand disease with an increased ristocetin-induced platelet aggregation and a qualitative abnormality of the factor VIII protein. Am J Hematol 1980; 8 (3) 299-308
    CrossrefPubMedGoogle Scholar
  • 24 Enayat MS, Guilliatt AM, Lester W, Wilde JT, Williams MD, Hill FG. Distinguishing between type 2B and pseudo-von Willebrand disease and its clinical importance. Br J Haematol 2006; 133 (6) 664-666
    CrossrefPubMedGoogle Scholar
  • 25 Giannini S, Cecchetti L, Mezzasoma AM, Gresele P. Diagnosis of platelet-type von Willebrand disease by flow cytometry. Haematologica 2010; 95 (6) 1021-1024
    CrossrefPubMedGoogle Scholar
  • 26 Franchini M, Montagnana M, Lippi G. Clinical, laboratory and therapeutic aspects of platelet-type von Willebrand disease. Int J Lab Hematol 2008; 30 (2) 91-94
    CrossrefPubMedGoogle Scholar
  • 27 Hellgren M. Hemostasis during normal pregnancy and puerperium. Semin Thromb Hemost 2003; 29 (2) 125-130
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 28 Stirling Y, Woolf L, North WR, Seghatchian MJ, Meade TW. Haemostasis in normal pregnancy. Thromb Haemost 1984; 52 (2) 176-182
    PubMedGoogle Scholar
  • 29 Clark P, Brennand J, Conkie JA, McCall F, Greer IA, Walker ID. Activated protein C sensitivity, protein C, protein S and coagulation in normal pregnancy. Thromb Haemost 1998; 79 (6) 1166-1170
    PubMedGoogle Scholar
  • 30 Brenner B. Haemostatic changes in pregnancy. Thromb Res 2004; 114 (5-6) 409-414
    CrossrefPubMedGoogle Scholar
  • 31 Bonnar J. Hemostatic function and coagulopathy during pregnancy. Obstet Gynecol Annu 1978; 7: 195-217
    PubMedGoogle Scholar
  • 32 Coopland AAN, Alkjaersig N, Fletcher AP. Reduction in plasma factor 13 (fibrin stabilizing factor) concentration during pregnancy. J Lab Clin Med 1969; 73 (1) 144-153
    PubMedGoogle Scholar
  • 33 O'Brien WF, Saba HI, Knuppel RA, Scerbo JC, Cohen GR. Alterations in platelet concentration and aggregation in normal pregnancy and preeclampsia. Am J Obstet Gynecol 1986; 155 (3) 486-490
    PubMedGoogle Scholar
  • 34 Holthe MR, Staff AC, Berge LN, Lyberg T. Different levels of platelet activation in preeclamptic, normotensive pregnant, and nonpregnant women. Am J Obstet Gynecol 2004; 190 (4) 1128-1134
    CrossrefPubMedGoogle Scholar
  • 35 Noller KL, Bowie EJ, Kempers RD, Owen Jr CA. Von Willebrand's disease in pregnancy. Obstet Gynecol 1973; 41 (6) 865-872
    PubMedGoogle Scholar
  • 36 Othman M, Notley C, Lavender FL , et al. Identification and functional characterization of a novel 27-bp deletion in the macroglycopeptide-coding region of the GPIBA gene resulting in platelet-type von Willebrand disease. Blood 2005; 105 (11) 4330-4336
    CrossrefPubMedGoogle Scholar
  • 37 Grover N, Boama V, Chou MR. Pseudo (platelet-type) von Willebrand disease in pregnancy: a case report. BMC Pregnancy Childbirth 2013; 13: 16
    CrossrefPubMedGoogle Scholar
  • 38 O'Connor D, Lester W, Willoughby S, Wilde JT. Pregnancy in platelet-type VWD: a case series. Thromb Haemost 2011; 106 (2) 386-387
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 39 Reininger AJ, Heijnen HF, Schumann H, Specht HM, Schramm W, Ruggeri ZM. Mechanism of platelet adhesion to von Willebrand factor and microparticle formation under high shear stress. Blood 2006; 107 (9) 3537-3545
    CrossrefPubMedGoogle Scholar
  • 40 Andrews RK, Gardiner EE, Shen Y, Berndt MC. Structure-activity relationships of snake toxins targeting platelet receptors, glycoprotein Ib-IX-V and glycoprotein VI. Curr Med Chem Cardiovasc Hematol Agents 2003; 1 (2) 143-149
    CrossrefPubMedGoogle Scholar
  • 41 Li R, Emsley J. The organizing principle of the platelet glycoprotein Ib-IX-V complex. J Thromb Haemost 2013; 11 (4) 605-614
    CrossrefPubMedGoogle Scholar
  • 42 Gawaz M, Langer H, May AE. Platelets in inflammation and atherogenesis. J Clin Invest 2005; 115 (12) 3378-3384
    CrossrefPubMedGoogle Scholar
  • 43 Romo GM, Dong JF, Schade AJ , et al. The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin. J Exp Med 1999; 190 (6) 803-814
    CrossrefPubMedGoogle Scholar
  • 44 Simon DI, Chen Z, Xu H , et al. Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18). J Exp Med 2000; 192 (2) 193-204
    CrossrefPubMedGoogle Scholar
  • 45 Andrews RK, López JA, Berndt MC. Molecular mechanisms of platelet adhesion and activation. Int J Biochem Cell Biol 1997; 29 (1) 91-105
    CrossrefPubMedGoogle Scholar
  • 46 Wang Y, Sakuma M, Chen Z , et al. Leukocyte engagement of platelet glycoprotein Ibalpha via the integrin Mac-1 is critical for the biological response to vascular injury. Circulation 2005; 112 (19) 2993-3000
    PubMedGoogle Scholar
  • 47 Langer HF, Daub K, Braun G , et al. Platelets recruit human dendritic cells via Mac-1/JAM-C interaction and modulate dendritic cell function in vitro. Arterioscler Thromb Vasc Biol 2007; 27 (6) 1463-1470
    CrossrefPubMedGoogle Scholar
  • 48 Weeterings C, de Groot PG, Adelmeijer J, Lisman T. The glycoprotein Ib-IX-V complex contributes to tissue factor-independent thrombin generation by recombinant factor VIIa on the activated platelet surface. Blood 2008; 112 (8) 3227-3233
    CrossrefPubMedGoogle Scholar
  • 49 Lisman T, de Groot PG. The interaction of recombinant factor VIIa with platelet glycoprotein Ib. Thromb Res 2010; 125 (Suppl. 01) S13-S15
    CrossrefPubMedGoogle Scholar
  • 50 Baglia FA, Badellino KO, Li CQ, Lopez JA, Walsh PN. Factor XI binding to the platelet glycoprotein Ib-IX-V complex promotes factor XI activation by thrombin. J Biol Chem 2002; 277 (3) 1662-1668
    CrossrefPubMedGoogle Scholar
  • 51 Joseph K, Nakazawa Y, Bahou WF, Ghebrehiwet B, Kaplan AP. Platelet glycoprotein Ib: a zinc-dependent binding protein for the heavy chain of high-molecular-weight kininogen. Mol Med 1999; 5 (8) 555-563
    PubMedGoogle Scholar
  • 52 Bradford HN, Pixley RA, Colman RW. Human factor XII binding to the glycoprotein Ib-IX-V complex inhibits thrombin-induced platelet aggregation. J Biol Chem 2000; 275 (30) 22756-22763
    CrossrefPubMedGoogle Scholar
  • 53 Baglia FA, Gailani D, López JA, Walsh PN. Identification of a binding site for glycoprotein Ibalpha in the Apple 3 domain of factor XI. J Biol Chem 2004; 279 (44) 45470-45476
    CrossrefPubMedGoogle Scholar
  • 54 Baglia FA, Shrimpton CN, Emsley J , et al. Factor XI interacts with the leucine-rich repeats of glycoprotein Ibalpha on the activated platelet. J Biol Chem 2004; 279 (47) 49323-49329
    CrossrefPubMedGoogle Scholar
  • 55 Celikel R, McClintock RA, Roberts JR , et al. Modulation of alpha-thrombin function by distinct interactions with platelet glycoprotein Ibalpha. Science 2003; 301 (5630) 218-221
    CrossrefPubMedGoogle Scholar
  • 56 Dumas JJ, Kumar R, Seehra J, Somers WS, Mosyak L. Crystal structure of the GpIbalpha-thrombin complex essential for platelet aggregation. Science 2003; 301 (5630) 222-226
    CrossrefPubMedGoogle Scholar
  • 57 Adam F, Guillin MC, Jandrot-Perrus M. Glycoprotein Ib-mediated platelet activation. A signalling pathway triggered by thrombin. Eur J Biochem 2003; 270 (14) 2959-2970
    CrossrefPubMedGoogle Scholar
  • 58 Andrew RK, Berndt MC. Bernard-Soulier syndrome: an update. Semin Thromb Hemost 2013; ; DOI: 10.1055/s-0033-1353390
    PubMedGoogle Scholar
  • 59 Cauwenberghs N, Meiring M, Vauterin S , et al. Antithrombotic effect of platelet glycoprotein Ib-blocking monoclonal antibody Fab fragments in nonhuman primates. Arterioscler Thromb Vasc Biol 2000; 20 (5) 1347-1353
    CrossrefPubMedGoogle Scholar
  • 60 Cauwenberghs N, Vanhoorelbeke K, Vauterin S , et al. Epitope mapping of inhibitory antibodies against platelet glycoprotein Ibalpha reveals interaction between the leucine-rich repeat N-terminal and C-terminal flanking domains of glycoprotein Ibalpha. Blood 2001; 98 (3) 652-660
    CrossrefPubMedGoogle Scholar
  • 61 Fontayne A, Vanhoorelbeke K, Pareyn I , et al. Rational humanization of the powerful antithrombotic anti-GPIbalpha antibody: 6B4. Thromb Haemost 2006; 96 (5) 671-684
    PubMedGoogle Scholar
  • 62 Wu D, Meiring M, Kotze HF, Deckmyn H, Cauwenberghs N. Inhibition of platelet glycoprotein Ib, glycoprotein IIb/IIIa, or both by monoclonal antibodies prevents arterial thrombosis in baboons. Arterioscler Thromb Vasc Biol 2002; 22 (2) 323-328
    CrossrefPubMedGoogle Scholar
  • 63 Wu D, Vanhoorelbeke K, Cauwenberghs N , et al. Inhibition of the von Willebrand (VWF)-collagen interaction by an antihuman VWF monoclonal antibody results in abolition of in vivo arterial platelet thrombus formation in baboons. Blood 2002; 99 (10) 3623-3628
    CrossrefPubMedGoogle Scholar
  • 64 Hennan JK, Swillo RE, Morgan GA , et al. Pharmacologic inhibition of platelet vWF-GPIb alpha interaction prevents coronary artery thrombosis. Thromb Haemost 2006; 95 (3) 469-475
    PubMedGoogle Scholar
  • 65 Benard SA, Smith TM, Cunningham K , et al. Identification of peptide antagonists to glycoprotein Ibalpha that selectively inhibit von Willebrand factor dependent platelet aggregation. Biochemistry 2008; 47 (16) 4674-4682
    CrossrefPubMedGoogle Scholar
  • 66 Miller JL, Cunningham D, Lyle VA, Finch CN. Mutation in the gene encoding the alpha chain of platelet glycoprotein Ib in platelet-type von Willebrand disease. Proc Natl Acad Sci U S A 1991; 88 (11) 4761-4765
    CrossrefPubMedGoogle Scholar
  • 67 Russell SD, Roth GJ. Pseudo-von Willebrand disease: a mutation in the platelet glycoprotein Ib alpha gene associated with a hyperactive surface receptor. Blood 1993; 81 (7) 1787-1791
    CrossrefPubMedGoogle Scholar
  • 68 Kunishima S, Heaton DC, Naoe T , et al. De novo mutation of the platelet glycoprotein Ib alpha gene in a patient with pseudo-von Willebrand disease. Blood Coagul Fibrinolysis 1997; 8 (5) 311-315
    CrossrefPubMedGoogle Scholar
  • 69 Murata M, Russell SR, Ruggeri ZM, Ware J. Expression of the phenotypic abnormality of platelet-type von Willebrand disease in a recombinant glycoprotein Ib alpha fragment. J Clin Invest 1993; 91 (5) 2133-2137
    CrossrefPubMedGoogle Scholar
  • 70 Moriki T, Murata M, Kitaguchi T , et al. Expression and functional characterization of an abnormal platelet membrane glycoprotein Ib alpha (Met239 —> Val) reported in patients with platelet-type von Willebrand disease. Blood 1997; 90 (2) 698-705
    PubMedGoogle Scholar
  • 71 Matsubara Y, Murata M, Sugita K, Ikeda Y. Identification of a novel point mutation in platelet glycoprotein Ibalpha, Gly to Ser at residue 233, in a Japanese family with platelet-type von Willebrand disease. J Thromb Haemost 2003; 1 (10) 2198-2205
    CrossrefPubMedGoogle Scholar
  • 72 Nurden P, Lanza F, Bonnafous-Faurie C, Nurden A. A second report of platelet-type von Willebrand disease with a Gly233Ser mutation in the GPIBA gene. Thromb Haemost 2007; 97 (2) 319-321
    PubMedGoogle Scholar
  • 73 Enayat S, Ravanbod S, Rassoulzadegan M , et al. A novel D235Y mutation in the GP1BA gene enhances platelet interaction with von Willebrand factor in an Iranian family with platelet-type von Willebrand disease. Thromb Haemost 2012; 108 (5) 946-954
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 74 Uff S, Clemetson JM, Harrison T, Clemetson KJ, Emsley J. Crystal structure of the platelet glycoprotein Ib(alpha) N-terminal domain reveals an unmasking mechanism for receptor activation. J Biol Chem 2002; 277 (38) 35657-35663
    CrossrefPubMedGoogle Scholar
  • 75 Dumas JJ, Kumar R, McDonagh T , et al. Crystal structure of the wild-type von Willebrand factor A1-glycoprotein Ibalpha complex reveals conformation differences with a complex bearing von Willebrand disease mutations. J Biol Chem 2004; 279 (22) 23327-23334
    CrossrefPubMedGoogle Scholar
  • 76 Huizinga EG, Tsuji S, Romijn RA , et al. Structures of glycoprotein Ibalpha and its complex with von Willebrand factor A1 domain. Science 2002; 297 (5584) 1176-1179
    CrossrefPubMedGoogle Scholar
  • 77 Dong J, Schade AJ, Romo GM , et al. Novel gain-of-function mutations of platelet glycoprotein IBalpha by valine mutagenesis in the Cys209-Cys248 disulfide loop. Functional analysis under statis and dynamic conditions. J Biol Chem 2000; 275 (36) 27663-27670
    PubMedGoogle Scholar
  • 78 Fukuda K, Doggett T, Laurenzi IJ, Liddington RC, Diacovo TG. The snake venom protein botrocetin acts as a biological brace to promote dysfunctional platelet aggregation. Nat Struct Mol Biol 2005; 12 (2) 152-159
    CrossrefPubMedGoogle Scholar
  • 79 Laskowski RA. PDBsum new things. Nucleic Acids Res 2009; 37 (Database issue): D355-D359
    CrossrefPubMedGoogle Scholar
  • 80 McEwan PA, Andrews RK, Emsley J. Glycoprotein Ibalpha inhibitor complex structure reveals a combined steric and allosteric mechanism of von Willebrand factor antagonism. Blood 2009; 114 (23) 4883-4885
    CrossrefPubMedGoogle Scholar
  • 81 McEwan PA, Yang W, Carr KH , et al. Quaternary organization of GPIb-IX complex and insights into Bernard-Soulier syndrome revealed by the structures of GPIbβ and a GPIbβ/GPIX chimera. Blood 2011; 118 (19) 5292-5301
    CrossrefPubMedGoogle Scholar
  • 82 Ware J, Russell SR, Marchese P , et al. Point mutation in a leucine-rich repeat of platelet glycoprotein Ib alpha resulting in the Bernard-Soulier syndrome. J Clin Invest 1993; 92 (3) 1213-1220
    CrossrefPubMedGoogle Scholar
  • 83 Nowak AA, Canis K, Riddell A, Laffan MA, McKinnon TA. O-linked glycosylation of von Willebrand factor modulates the interaction with platelet receptor glycoprotein Ib under static and shear stress conditions. Blood 2012; 120 (1) 214-222
    CrossrefPubMedGoogle Scholar
  • 84 Auton M, Sowa KE, Behymer M, Cruz MA. N-terminal flanking region of A1 domain in von Willebrand factor stabilizes structure of A1A2A3 complex and modulates platelet activation under shear stress. J Biol Chem 2012; 287 (18) 14579-14585
    CrossrefPubMedGoogle Scholar
  • 85 Law RH, Caradoc-Davies T, Cowieson N , et al. The X-ray crystal structure of full-length human plasminogen. Cell Rep 2012; 1 (3) 185-190
    CrossrefPubMedGoogle Scholar
  • 86 Bowman M, Mundell G, Grabell J , et al. Generation and validation of the Condensed MCMDM-1VWD Bleeding Questionnaire for von Willebrand disease. J Thromb Haemost 2008; 6 (12) 2062-2066
    CrossrefPubMedGoogle Scholar
  • 87 Kaur H, McEacern K, James P, Othman M. International systematic study for assessment of bleeding phenotype in platelet type von Willebrand disease. Paper presented at: 26th Congress of the International Society on Thrombosis and Haemostasis; June 29–July 4, 2013; Amsterdam, The Netherlands
    PubMedGoogle Scholar
  • 88 Cranmer SL, Pikovski I, Mangin P , et al. Identification of a unique filamin A binding region within the cytoplasmic domain of glycoprotein Ibalpha. Biochem J 2005; 387 (Pt 3) 849-858
    CrossrefPubMedGoogle Scholar
  • 89 Shimizu A, Matsushita T, Kondo T , et al. Identification of the amino acid residues of the platelet glycoprotein Ib (GPIb) essential for the von Willebrand factor binding by clustered charged-to-alanine scanning mutagenesis. J Biol Chem 2004; 279 (16) 16285-16294
    CrossrefPubMedGoogle Scholar
  • 90 De Cristofaro R, De Candia E, Rutella S, Weitz JI. The Asp(272)-Glu(282) region of platelet glycoprotein Ibalpha interacts with the heparin-binding site of alpha-thrombin and protects the enzyme from the heparin-catalyzed inhibition by antithrombin III. J Biol Chem 2000; 275 (6) 3887-3895
    CrossrefPubMedGoogle Scholar
  • 91 De Marco L, Mazzucato M, Masotti A, Ruggeri ZM. Localization and characterization of an alpha-thrombin-binding site on platelet glycoprotein Ib alpha. J Biol Chem 1994; 269 (9) 6478-6484
    PubMedGoogle Scholar
  • 92 Ward CM, Andrews RK, Smith AI, Berndt MC. Mocarhagin, a novel cobra venom metalloproteinase, cleaves the platelet von Willebrand factor receptor glycoprotein Ibalpha. Identification of the sulfated tyrosine/anionic sequence Tyr-276-Glu-282 of glycoprotein Ib alpha as a binding site for von Willebrand factor and alpha-thrombin. Biochemistry 1996; 35 (15) 4929-4938
    CrossrefPubMedGoogle Scholar