Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Clinical presentation and diagnosis of von Willebrand disease

Margaret E Rick, MD
Section Editor
Lawrence LK Leung, MD
Deputy Editor
Jennifer S Tirnauer, MD


Von Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting up to 1 percent of the population as assessed by random laboratory screening, although only approximately 1 percent of these individuals are appreciably symptomatic [1]. It is characterized by mutations that lead to a decrease in the level or impairment in the action of von Willebrand factor (VWF) (table 1). Most cases are transmitted as an autosomal dominant trait that affects males and females equally [2]. There are also acquired forms of VWD that are caused by several different pathophysiologic mechanisms. (See "Classification and pathophysiology of von Willebrand disease" and "Biology and normal function of von Willebrand factor".)

The clinical presentation and diagnosis of VWD will be reviewed here. Separate topic reviews discuss the pathophysiology and treatment of VWD, acquired von Willebrand syndrome (aVWS), and the functions of VWF:

Pathophysiology of VWD – (See "Classification and pathophysiology of von Willebrand disease".)

Treatment of VWD – (See "Treatment of von Willebrand disease".)

aVWS (pathophysiology, diagnosis, and treatment) – (See "Acquired von Willebrand syndrome".)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Apr 2017. | This topic last updated: Mar 20, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Sadler JE, Mannucci PM, Berntorp E, et al. Impact, diagnosis and treatment of von Willebrand disease. Thromb Haemost 2000; 84:160.
  2. Nilsson IM. Von Willebrand's disease--fifty years old. Acta Med Scand 1977; 201:497.
  3. Wagner DD. Cell biology of von Willebrand factor. Annu Rev Cell Biol 1990; 6:217.
  4. Ruggeri ZM, Ware J. von Willebrand factor. FASEB J 1993; 7:308.
  5. Brinkhous KM, Sandberg H, Garris JB, et al. Purified human factor VIII procoagulant protein: comparative hemostatic response after infusions into hemophilic and von Willebrand disease dogs. Proc Natl Acad Sci U S A 1985; 82:8752.
  6. Moake JL, Turner NA, Stathopoulos NA, et al. Involvement of large plasma von Willebrand factor (vWF) multimers and unusually large vWF forms derived from endothelial cells in shear stress-induced platelet aggregation. J Clin Invest 1986; 78:1456.
  7. Moake JL. von Willebrand factor, ADAMTS-13, and thrombotic thrombocytopenic purpura. Semin Hematol 2004; 41:4.
  8. Tuley EA, Gaucher C, Jorieux S, et al. Expression of von Willebrand factor "Normandy": an autosomal mutation that mimics hemophilia A. Proc Natl Acad Sci U S A 1991; 88:6377.
  9. Mazurier C, Dieval J, Jorieux S, et al. A new von Willebrand factor (vWF) defect in a patient with factor VIII (FVIII) deficiency but with normal levels and multimeric patterns of both plasma and platelet vWF. Characterization of abnormal vWF/FVIII interaction. Blood 1990; 75:20.
  10. Nishino M, Girma JP, Rothschild C, et al. New variant of von Willebrand disease with defective binding to factor VIII. Blood 1989; 74:1591.
  11. Lukes AS, Kadir RA, Peyvandi F, Kouides PA. Disorders of hemostasis and excessive menstrual bleeding: prevalence and clinical impact. Fertil Steril 2005; 84:1338.
  12. Ahr DJ, Rickles FR, Hoyer LW, et al. von Willebrand's disease and hemorrhagic telangiectasia: association of two complex disorders of hemostasis resulting in life-threatening hemorrhage. Am J Med 1977; 62:452.
  13. Bush RW, Huff JW. Von Willebrand's disease and severe gastrointestinal bleeding. Report of a kindred. West J Med 1984; 140:781.
  14. Alhumood SA, Devine DV, Lawson L, et al. Idiopathic immune-mediated acquired von Willebrand's disease in a patient with angiodysplasia: demonstration of an unusual inhibitor causing a functional defect and rapid clearance of von Willebrand factor. Am J Hematol 1999; 60:151.
  15. Sohal M, Laffan M. Von Willebrand disease and angiodysplasia responding to atorvastatin. Br J Haematol 2008; 142:308.
  16. Hirri HM, Green PJ, Lindsay J. Von Willebrand's disease and angiodysplasia treated with thalidomide. Haemophilia 2006; 12:285.
  17. Drews CD, Dilley AB, Lally C, et al. Screening questions to identify women with von Willebrand disease. J Am Med Womens Assoc (1972) 2002; 57:217.
  18. Elbatarny M, Mollah S, Grabell J, et al. Normal range of bleeding scores for the ISTH-BAT: adult and pediatric data from the merging project. Haemophilia 2014; 20:831.
  19. https://c.ymcdn.com/sites/www.isth.org/resource/resmgr/ssc/isth-ssc_bleeding_assessment.pdf (Accessed on February 09, 2016).
  20. Deforest M, Grabell J, Albert S, et al. Generation and optimization of the self-administered bleeding assessment tool and its validation as a screening test for von Willebrand disease. Haemophilia 2015; 21:e384.
  21. Enayat MS, Guilliatt AM, Lester W, et al. Distinguishing between type 2B and pseudo-von Willebrand disease and its clinical importance. Br J Haematol 2006; 133:664.
  22. The Diagnosis, Evaluation and Management of von Willebrand Disease -- 2008 Clinical Practice Guidelines, National Heart, Lung and Blood Institute www.nhlbi.nih.gov/guidelines/vwd (Accessed on July 25, 2011).
  23. Weiss HJ, Pietu G, Rabinowitz R, et al. Heterogeneous abnormalities in the multimeric structure, antigenic properties, and plasma-platelet content of factor VIII/von Willebrand factor in subtypes of classic (type I) and variant (type IIA) von Willebrand's disease. J Lab Clin Med 1983; 101:411.
  24. Zimmerman TS, Ratnoff OD, Powell A. Immunologic differentiation of classic hemophilia (factor VIII deficiency) and von Willebrand's disease. J Clin Invest 1971; 50:224.
  25. Mazurier C, Parquet-Gernez A, Goudemand M. The assay of Factor VIII related antigen by an immuno-enzymatic method. Thromb Haemost 1980; 43:71.
  26. Ingerslev J. A sensitive ELISA for von Willebrand factor (vWf:Ag). Scand J Clin Lab Invest 1987; 47:143.
  27. Veyradier A, Fressinaud E, Sigaud M, et al. A new automated method for von Willebrand factor antigen measurement using latex particles. Thromb Haemost 1999; 81:320.
  28. Weiss HJ, Hoyer LW, Rickles FR, et al. 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; 52:2708.
  29. Howard MA, Sawers RJ, Firkin BG. Ristocetin: a means of differentiating von Willebrand's disease into two groups. Blood 1973; 41:687.
  30. Scott JP, Montgomery RR, Retzinger GS. Dimeric ristocetin flocculates proteins, binds to platelets, and mediates von Willebrand factor-dependent agglutination of platelets. J Biol Chem 1991; 266:8149.
  31. Berndt MC, Du XP, Booth WJ. Ristocetin-dependent reconstitution of binding of von Willebrand factor to purified human platelet membrane glycoprotein Ib-IX complex. Biochemistry 1988; 27:633.
  32. Allain JP, Cooper HA, Wagner RH, Brinkhous KM. Platelets fixed with paraformaldehyde: a new reagent for assay of von Willebrand factor and platelet aggregating factor. J Lab Clin Med 1975; 85:318.
  33. Strandberg K, Lethagen S, Andersson K, et al. Evaluation of a rapid automated assay for analysis of von Willebrand ristocetin cofactor activity. Clin Appl Thromb Hemost 2006; 12:61.
  34. Salem RO, Van Cott EM. A new automated screening assay for the diagnosis of von Willebrand disease. Am J Clin Pathol 2007; 127:730.
  35. Bodó I, Eikenboom J, Montgomery R, et al. Platelet-dependent von Willebrand factor activity. Nomenclature and methodology: communication from the SSC of the ISTH. J Thromb Haemost 2015; 13:1345.
  36. Favaloro EJ, Grispo L, Exner T, Koutts J. Development of a simple collagen based ELISA assay aids in the diagnosis of, and permits sensitive discrimination between type I and type II, von Willebrand's disease. Blood Coagul Fibrinolysis 1991; 2:285.
  37. Chang P, Aronson DL. Plasma derived von Willebrand factor preparations: collagen binding and ristocetin cofactor activities. Thromb Haemost 1997; 78:930.
  38. Favaloro EJ, Henniker A, Facey D, Hertzberg M. Discrimination of von Willebrands disease (VWD) subtypes: direct comparison of von Willebrand factor:collagen binding assay (VWF:CBA) with monoclonal antibody (MAB) based VWF-capture systems. Thromb Haemost 2000; 84:541.
  39. Favaloro EJ, Facey D, Grispo L. Laboratory assessment of von Willebrand factor. Use of different assays can influence the diagnosis of von Willebrand's disease, dependent on differing sensitivity to sample preparation and differential recognition of high molecular weight VWF forms. Am J Clin Pathol 1995; 104:264.
  40. Casonato A, Pontara E, Bertomoro A, et al. Von Willebrand factor collagen binding activity in the diagnosis of von Willebrand disease: an alternative to ristocetin co-factor activity? Br J Haematol 2001; 112:578.
  41. Favaloro EJ. Detection of von Willebrand disorder and identification of qualitative von Willebrand factor defects. Direct comparison of commercial ELISA-based von Willebrand factor activity options. Am J Clin Pathol 2000; 114:608.
  42. Riddell AF, Jenkins PV, Nitu-Whalley IC, et al. Use of the collagen-binding assay for von Willebrand factor in the analysis of type 2M von Willebrand disease: a comparison with the ristocetin cofactor assay. Br J Haematol 2002; 116:187.
  43. Riddell AF, Gomez K, Millar CM, et al. Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor. Blood 2009; 114:3489.
  44. Flood VH, Schlauderaff AC, Haberichter SL, et al. Crucial role for the VWF A1 domain in binding to type IV collagen. Blood 2015; 125:2297.
  45. Cinotti S, Longo G, Messori A, et al. Reproducibility of one-stage, two-stage and chromogenic assays of factor VIII activity: a multi-center study. Thromb Res 1991; 61:385.
  46. Hoyer LW. Immunologic studies of antihemophilic factor (AHF, factor VIII). IV. Radioimmunoassay of AHF antigen. J Lab Clin Med 1972; 80:822.
  47. Flood VH, Gill JC, Morateck PA, et al. Common VWF exon 28 polymorphisms in African Americans affecting the VWF activity assay by ristocetin cofactor. Blood 2010; 116:280.
  48. Mammen EF, Comp PC, Gosselin R, et al. PFA-100 system: a new method for assessment of platelet dysfunction. Semin Thromb Hemost 1998; 24:195.
  49. Fressinaud E, Veyradier A, Truchaud F, et al. Screening for von Willebrand disease with a new analyzer using high shear stress: a study of 60 cases. Blood 1998; 91:1325.
  50. Posan E, McBane RD, Grill DE, et al. Comparison of PFA-100 testing and bleeding time for detecting platelet hypofunction and von Willebrand disease in clinical practice. Thromb Haemost 2003; 90:483.
  51. Castaman G, Tosetto A, Goodeve A, et al. The impact of bleeding history, von Willebrand factor and PFA-100(®) on the diagnosis of type 1 von Willebrand disease: results from the European study MCMDM-1VWD. Br J Haematol 2010; 151:245.
  52. Quiroga T, Goycoolea M, Muñoz B, et al. Template bleeding time and PFA-100 have low sensitivity to screen patients with hereditary mucocutaneous hemorrhages: comparative study in 148 patients. J Thromb Haemost 2004; 2:892.
  53. Nichols WL, Hultin MB, James AH, et al. von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA). Haemophilia 2008; 14:171.
  54. Ratnoff OD, Saito H. Letter: Bleeding in von Willebrand's disease. N Engl J Med 1974; 290:1089.
  55. Gralnick HR, Rick ME, McKeown LP, et al. Platelet von Willebrand factor: an important determinant of the bleeding time in type I von Willebrand's disease. Blood 1986; 68:58.
  56. Peterson P, Hayes TE, Arkin CF, et al. The preoperative bleeding time test lacks clinical benefit: College of American Pathologists' and American Society of Clinical Pathologists' position article. Arch Surg 1998; 133:134.
  57. Hoyer LW, Shainoff JR. Factor VIII-related protein circulates in normal human plasma as high molecular weight multimers. Blood 1980; 55:1056.
  58. Krizek DR, Rick ME. A rapid method to visualize von willebrand factor multimers by using agarose gel electrophoresis, immunolocalization and luminographic detection. Thromb Res 2000; 97:457.
  59. 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; 306:326.
  60. Miller JL, Kupinski JM, Castella A, Ruggeri ZM. von Willebrand factor binds to platelets and induces aggregation in platelet-type but not type IIB von Willebrand disease. J Clin Invest 1983; 72:1532.
  61. Scott JP, Montgomery RR. The rapid differentiation of type IIb von Willebrand's disease from platelet-type (pseudo-) von Willebrand's disease by the "neutral" monoclonal antibody binding assay. Am J Clin Pathol 1991; 96:723.
  62. López JA, Andrews RK, Afshar-Kharghan V, Berndt MC. Bernard-Soulier syndrome. Blood 1998; 91:4397.
  63. Roberts JC, Morateck PA, Christopherson PA, et al. Rapid discrimination of the phenotypic variants of von Willebrand disease. Blood 2016; 127:2472.
  64. Sadler JE. Von Willebrand disease type 1: a diagnosis in search of a disease. Blood 2003; 101:2089.
  65. Bellissimo DB, Christopherson PA, Flood VH, et al. VWF mutations and new sequence variations identified in healthy controls are more frequent in the African-American population. Blood 2012; 119:2135.
  66. Abildgaard CF, Suzuki Z, Harrison J, et al. Serial studies in von Willebrand's disease: variability versus "variants". Blood 1980; 56:712.
  67. Gill JC, Endres-Brooks J, Bauer PJ, et al. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood 1987; 69:1691.
  68. O'Donnell J, Boulton FE, Manning RA, Laffan MA. Genotype at the secretor blood group locus is a determinant of plasma von Willebrand factor level. Br J Haematol 2002; 116:350.
  69. Nitu-Whalley IC, Lee CA, Griffioen A, et al. Type 1 von Willebrand disease - a clinical retrospective study of the diagnosis, the influence of the ABO blood group and the role of the bleeding history. Br J Haematol 2000; 108:259.
  70. Baumgartner-Parzer SM, Wagner L, Reining G, et al. Increase by tri-iodothyronine of endothelin-1, fibronectin and von Willebrand factor in cultured endothelial cells. J Endocrinol 1997; 154:231.
  71. Harrison RL, McKee PA. Estrogen stimulates von Willebrand factor production by cultured endothelial cells. Blood 1984; 63:657.
  72. van den Burg PJ, Hospers JE, van Vliet M, et al. Changes in haemostatic factors and activation products after exercise in healthy subjects with different ages. Thromb Haemost 1995; 74:1457.
  73. Rickles FR, Hoyer LW, Rick ME, Ahr DJ. The effects of epinephrine infusion in patients with von Willebrand's disease. J Clin Invest 1976; 57:1618.
  74. McGill SN, Ahmed NA, Christou NV. Increased plasma von Willebrand factor in the systemic inflammatory response syndrome is derived from generalized endothelial cell activation. Crit Care Med 1998; 26:296.
  75. van der Poll T, van Deventer SJ, Pasterkamp G, et al. Tumor necrosis factor induces von Willebrand factor release in healthy humans. Thromb Haemost 1992; 67:623.
  76. Bennett B, Ratnoff OD. Changes in antihemophilic factor (AHF, factor 8) procoagulant activity and AHF-like antigen in normal pregnancy, and following exercise and pneumoencephalography. J Lab Clin Med 1972; 80:256.
  77. Sié P, Caron C, Azam J, et al. Reassessment of von Willebrand factor (VWF), VWF propeptide, factor VIII:C and plasminogen activator inhibitors 1 and 2 during normal pregnancy. Br J Haematol 2003; 121:897.
  78. Cumming A, Grundy P, Keeney S, et al. An investigation of the von Willebrand factor genotype in UK patients diagnosed to have type 1 von Willebrand disease. Thromb Haemost 2006; 96:630.
  79. Goodeve A, Eikenboom J, Castaman G, et al. Phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD). Blood 2007; 109:112.
  80. Schooten CJ, Tjernberg P, Westein E, et al. Cysteine-mutations in von Willebrand factor associated with increased clearance. J Thromb Haemost 2005; 3:2228.
  81. James PD, Notley C, Hegadorn C, et al. The mutational spectrum of type 1 von Willebrand disease: Results from a Canadian cohort study. Blood 2007; 109:145.
  82. Haberichter SL, Castaman G, Budde U, et al. Identification of type 1 von Willebrand disease patients with reduced von Willebrand factor survival by assay of the VWF propeptide in the European study: molecular and clinical markers for the diagnosis and management of type 1 VWD (MCMDM-1VWD). Blood 2008; 111:4979.
  83. Castaman G, Lethagen S, Federici AB, et al. Response to desmopressin is influenced by the genotype and phenotype in type 1 von Willebrand disease (VWD): results from the European Study MCMDM-1VWD. Blood 2008; 111:3531.
  84. Gézsi A, Budde U, Deák I, et al. Accelerated clearance alone explains ultra-large multimers in von Willebrand disease Vicenza. J Thromb Haemost 2010; 8:1273.
  85. Haberichter SL, Balistreri M, Christopherson P, et al. Assay of the von Willebrand factor (VWF) propeptide to identify patients with type 1 von Willebrand disease with decreased VWF survival. Blood 2006; 108:3344.
  86. Haberichter SL. von Willebrand factor propeptide: biology and clinical utility. Blood 2015; 126:1753.
  87. Lyons SE, Bruck ME, Bowie EJ, Ginsburg D. Impaired intracellular transport produced by a subset of type IIA von Willebrand disease mutations. J Biol Chem 1992; 267:4424.
  88. Gralnick HR, Williams SB, McKeown LP, et al. In vitro correction of the abnormal multimeric structure of von Willebrand factor in type IIa von Willebrand's disease. Proc Natl Acad Sci U S A 1985; 82:5968.
  89. Ruggeri ZM, Pareti FI, Mannucci PM, et al. Heightened interaction between platelets and factor VIII/von Willebrand factor in a new subtype of von Willebrand's disease. N Engl J Med 1980; 302:1047.
  90. Grainick HR, Williams SB, McKeown LP, et al. Von Willebrand's disease with spontaneous platelet aggregation induced by an abnormal plasma von Willebrand factor. J Clin Invest 1985; 76:1522.
  91. Casari C, Du V, Wu YP, et al. Accelerated uptake of VWF/platelet complexes in macrophages contributes to VWD type 2B-associated thrombocytopenia. Blood 2013; 122:2893.
  92. Federici AB, Canciani MT, Forza I, et al. A sensitive ristocetin co-factor activity assay with recombinant glycoprotein Ibalpha for the diagnosis of patients with low von Willebrand factor levels. Haematologica 2004; 89:77.
  93. Caron C, Hilbert L, Vanhoorelbeke K, et al. Measurement of von Willebrand factor binding to a recombinant fragment of glycoprotein Ibalpha in an enzyme-linked immunosorbent assay-based method: performances in patients with type 2B von Willebrand disease. Br J Haematol 2006; 133:655.
  94. 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; 139:623.
  95. Hillery CA, Mancuso DJ, Evan Sadler J, et al. Type 2M von Willebrand disease: F606I and I662F mutations in the glycoprotein Ib binding domain selectively impair ristocetin- but not botrocetin-mediated binding of von Willebrand factor to platelets. Blood 1998; 91:1572.
  96. Ciavarella G, Ciavarella N, Antoncecchi S, et al. High-resolution analysis of von Willebrand factor multimeric composition defines a new variant of type I von Willebrand disease with aberrant structure but presence of all size multimers (type IC). Blood 1985; 66:1423.
  97. Lopez-Fernandez MF, Gonzalez-Boullosa R, Blanco-Lopez MJ, et al. Abnormal proteolytic degradation of von Willebrand factor after desmopressin infusion in a new subtype of von Willebrand disease (ID). Am J Hematol 1991; 36:163.
  98. Mannucci PM, Lombardi R, Castaman G, et al. von Willebrand disease "Vicenza" with larger-than-normal (supranormal) von Willebrand factor multimers. Blood 1988; 71:65.
  99. Schneppenheim R, Federici AB, Budde U, et al. Von Willebrand Disease type 2M "Vicenza" in Italian and German patients: identification of the first candidate mutation (G3864A; R1205H) in 8 families. Thromb Haemost 2000; 83:136.
  100. Larsen DM, Haberichter SL, Gill JC, et al. Variability in platelet- and collagen-binding defects in type 2M von Willebrand disease. Haemophilia 2013; 19:590.
  101. Kroner PA, Friedman KD, Fahs SA, et al. Abnormal binding of factor VIII is linked with the substitution of glutamine for arginine 91 in von Willebrand factor in a variant form of von Willebrand disease. J Biol Chem 1991; 266:19146.
  102. Rick ME, Krizek DM. Identification of a His54Gln substitution in von Willebrand factor from a patient with defective binding of factor VIII. Am J Hematol 1996; 51:302.
  103. Kroner PA, Foster PA, Fahs SA, Montgomery RR. The defective interaction between von Willebrand factor and factor VIII in a patient with type 1 von Willebrand disease is caused by substitution of Arg19 and His54 in mature von Willebrand factor. Blood 1996; 87:1013.
  104. Cacheris PM, Nichols WC, Ginsburg D. Molecular characterization of a unique von Willebrand disease variant. A novel mutation affecting von Willebrand factor/factor VIII interaction. J Biol Chem 1991; 266:13499.
  105. Gaucher C, Mercier B, Jorieux S, et al. Identification of two point mutations in the von Willebrand factor gene of three families with the 'Normandy' variant of von Willebrand disease. Br J Haematol 1991; 78:506.
  106. Eikenboom JC, Castaman G, Kamphuisen PW, et al. The factor VIII/von Willebrand factor ratio discriminates between reduced synthesis and increased clearance of von Willebrand factor. Thromb Haemost 2002; 87:252.
  107. Lak M, Peyvandi F, Mannucci PM. Clinical manifestations and complications of childbirth and replacement therapy in 385 Iranian patients with type 3 von Willebrand disease. Br J Haematol 2000; 111:1236.
  108. Ngo KY, Glotz VT, Koziol JA, et al. Homozygous and heterozygous deletions of the von Willebrand factor gene in patients and carriers of severe von Willebrand disease. Proc Natl Acad Sci U S A 1988; 85:2753.
  109. Schneppenheim R, Krey S, Bergmann F, et al. Genetic heterogeneity of severe von Willebrand disease type III in the German population. Hum Genet 1994; 94:640.
  110. Sanders YV, Groeneveld D, Meijer K, et al. von Willebrand factor propeptide and the phenotypic classification of von Willebrand disease. Blood 2015; 125:3006.
  111. Sadler JE, Budde U, Eikenboom JC, et al. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. J Thromb Haemost 2006; 4:2103.
  112. Lipton R. Why make a diagnosis? Blood 2007; 109:4106; author reply 4106.
  113. Lipton R. Why make a diagnosis? Blood 2007; 109:4106; author reply 4106.
  114. Sadler JE. Low von Willebrand factor: sometimes a risk factor and sometimes a disease. Hematology Am Soc Hematol Educ Program 2009; :106.
  115. Rodeghiero F, Castaman G, Tosetto A. Optimizing treatment of von Willebrand disease by using phenotypic and molecular data. Hematology Am Soc Hematol Educ Program 2009; :113.
  116. Tiede A, Rand JH, Budde U, et al. How I treat the acquired von Willebrand syndrome. Blood 2011; 117:6777.