Type 3 Von Willebrand International Registries Inhibitor Prospective Study

NCT02460458 | Completed Results DMC

• 1 other identifier: ABB-11-01
• Study Type: observational
• Target: 265
• Locations: 10 countries
• Sites: 25

Brief Summary

International Registries and Prospective Study on Type 3 Von Willebrand's Disease (VWD3), aimed to assess number, types and risk factors for bleeding and the efficacy and safety of plasma-derived and/or recombinant Von Willebrand Factor (VWF) concentrates used to treat VWD patients.

Conditions

Type 3 Von Willebrand's Disease

Keywords

Factor VIII; Hemorrhage; Type 3 Von Willebrand's Disease; Von Willebrand Factor; Von Willebrand's Disease; Hemostasis; Gastro-Intestinal Bleeds

Outcome Measures

Primary Outcomes (10)

• Centralized Factor VIII (FVIII) Procoagulant Activity (FVIII:C) Laboratory Test for Type 3 Von Willebrand's Disease (VWD3) Diagnosis

  Measurement of the Factor VIII (FVIII) Procoagulant Activity (FVIII:C) in the blood through one-stage clotting test. Only patients with FVIII:C less or equal to 5 IU/dL were considered for the analysis.

  12 months (confirmatory phase)

• Centralized Von Willebrand Factor Antigen (VWF:Ag) Laboratory Test for Type 3 Von Willebrand's Disease (VWD3) Diagnosis

  Measurement of the amount of Von Willebrand Factor (VWF) protein in the blood through Von Willebrand Factor Antigen (VWF:Ag) test. Only patients with VWF:Ag less or equal to 5 IU/dL were considered for the analysis.

  12 months (confirmatory phase)

• Centralized Factor VIII (FVIII) Amidolytic Activity (FVIII:Am) Laboratory Test for Type 3 Von Willebrand's Disease (VWD3) Diagnosis

  Measurement of Factor VIII (FVIII) Amidolytic Activity (FVIII:Am) in the blood through chromogenic test. Only patients with FVIII:Am less or equal to 5 IU/dL were considered for the analysis.

  12 months (confirmatory phase)

• Centralized Factor VIII (FVIII) Antigen (FVIII:Ag) Laboratory Test for Type 3 Von Willebrand's Disease (VWD3) Diagnosis

  Measurement of the amount of Factor VIII (FVIII) protein in the blood through FVIII:Ag test. Only patients with FVIII:Ag less or equal to 5 IU/dL were considered for the analysis.

  12 months (confirmatory phase)

• Centralized Von Willebrand Factor (VWF) Multimer Analysis for Type 3 Von Willebrand's Disease (VWD3) Diagnosis

  Multimer analysis of Von Willebrand Factor (VWF) was carried out by electrophoresis of blood samples collected by investigational sites. The number of patients belonging of each multimer profile group (1 - Homozygotes / 2 - Only Protomers / 3 - 2-4 Bands) was calculated. The qualitative evaluation of VWF multimers is part of the diagnostic process of VWD3.

  12 months (confirmatory phase)

• Centralized Von Willebrand Factor (VWF) Propeptide Laboratory Test for Type 3 Von Willebrand's Disease (VWD3) Diagnosis

  Measurement of Von Willebrand Factor (VWF) Propeptide levels in the blood through VWF Propeptide test. This test has been performed according to the most recent methods and the results are important to characterize the molecular aspects of VWD patients.

  12 months (confirmatory phase)

• Centralized Molecular Type 3 Von Willebrand's Disease (VWD3) Diagnosis Through DNA Analysis

  Evaluation of the presence of Von Willebrand Factor (VWF) gene defects (confirmation or screening for the first time).

  12 months (confirmatory phase)

• Record of Bleeding Episodes

  Record of all bleedings occurred during the prospective phase of the study.

  24 months (first prospective phase) + 24 months (second prospective phase)

• Adverse Events

  Record of all adverse events occurred during the prospective phase of the study.

  24 months (first prospective phase) + 24 months (second prospective phase)

• Type of Von Willebrand Factor / Factor VIII (VWF/FVIII)-Containing Concentrates in Use

  Record of any Von Willebrand Factor / Factor VIII (VWF/FVIII)-containing concentrates used and currently in use, including the current schedule type of treatment.

  24 months (first prospective phase) + 24 months (second prospective phase)

Secondary Outcomes (4)

• Patients Experiencing Allergic Reactions During Use of Von Willebrand Factor (VWF)-Containing Concentrates

  24 months (retrospective phase)

• Number of Participants With Previous Use of Blood Products

  24 months (retrospective phase)

• Number of Patients With Available Local Laboratory Test for Anti-Von Willebrand Factor (Anti-VWF) Antibodies

  24 months (retrospective phase)

• Local Laboratory Tests for Type 3 Von Willebrand's Disease (VWD3) Diagnosis (Composite)

  24 months (retrospective phase)

Study Arms (1)

Type 3 Von Willebrand's Disease (VWD3)

Patients with diagnosis of Type 3 Von Willebrand's Disease

Drug: Von Willebrand Factor

Interventions

Von Willebrand Factor DRUG

Replacement therapy with plasma-derived and/or recombinant VWF concentrates on-demand or under prophylaxis therapeutic scheme.

Also known as: Plasma-derived and/or recombinantVon Willebrand Factor (VWF) concentrates

Type 3 Von Willebrand's Disease (VWD3)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

A large cohort of patients with diagnosis of Type 3 Von Willebrand's Disease (VWD3), enrolled in Europe and in Iran using homogeneous and standardized criteria.

You may qualify if:

• Male and female of any age, including infants, children, adolescent and adults
• Informed Consent obtained (parents should sign for patients \< 18 y.o.)
• Previous Diagnosis of VWD3 (VWF Antigen: undetectable or \<5 U/dL)
• Detailed information on inherited pattern, history of bleeding, previous exposure to blood products
• Availability of plasma and DNA samples

You may not qualify if:

• VWD3 patients who may not be available for follow-up

Sponsors & Collaborators

• Fondazione Angelo Bianchi Bonomi: lead
• Sintesi Research Srl: collaborator

Study Sites (25)

Helsinki University Central Hospital, Department Internal Medicine, Coagulation Disorders, at Haematology and Laboratory Services

Helsinki, FIN-00029 HUS, Finland

Location

Institut d'Hématologie - Hôpital Cardiologique - University of Lille - Haematology Department

Lille, 59037, France

Location

Centre Régional de Traitement de l'Hémophilie - Laboratoire d'Hématologie

Nantes, 44093, France

Location

University Clinic Bonn - Institute of Experimental Haematology & Transfusion Medicine

Bonn, 53127, Germany

Location

University Children's Hospital - Department of Pediatric Hematology and Oncology

Hamburg, 20246, Germany

Location

Department of Haematology, Haemostasis, Oncology and Stem Cell Transplantation - Hannover Medical School - Haemophilia Care Centre

Hanover, 30625, Germany

Location

St. Istvan & St. Laszlo Hospital of Budapest - Hematology and Stem Cell Transplantation

Budapest, 1097, Hungary

Location

Ahvaz Jundishpur University of Medical Sciences - Research Center for Thalassemia & Hemoglobinopathy - Division of Hematology & Oncology

Ahvāz, Iran

Location

Seid-ol-Shohada Hospital - Hemophilia Center - Esfahan University of Medical Science

Isfahan, Iran

Location

Hemophilia- Thalassaemia Center of Mashhad (Sarvar Clinic) - Mashad University of Medical Science

Mashhad, Iran

Location

Nemazee Hospital Hemophilia Center - Shiraz University of Medical Science

Shiraz, Iran

Location

Iranian Hemophilia Comprehensive Treatment Centre - Iranian Hemophilia Society

Tehran, Iran

Location

Mofid Comprehensive Care Centre for Children with Hemophilia - Shahid Beheshti University of Medical Science

Tehran, Iran

Location

Thrombosis Hemostasis Research Center - Vali-Asr Hospital - Emam Khmeini Complex Hospital - Tehran University of Medical Science

Tehran, Iran

Location

Azienda Ospedaliera Policlinico Consorziale di Bari - Unità Operativa Semplice di Emostasi e Trombosi

Bari, 70124, Italy

Location

Azienda Ospedaliera Universitaria Careggi - Agenzia per l'Emofilia - Centro di Riferimento Coagulopatie Congenite

Florence, 50141, Italy

Location

Centro Emofilia e Trombosi - Fondazione Angelo Bianchi Bonomi - IRCCS Ospedale Ca' Granda - Dip. di Medicina Interna - Università degli Studi di Milano

Milan, 20122, Italy

Location

Dipartimento di Biotecnologie Cellulari ed Ematologia - Università "Sapienza" di Roma - Policlinico Umberto I

Roma, 00161, Italy

Location

Dipartimento di Terapie Cellulari ed Ematologia - Centro Malattie Emorragiche e Trombotiche - Ospedale San Bortolo

Vicenza, 36100, Italy

Location

Leiden University Medical Center - Department of Hematology - Hemostasis and Thrombosis Center

Leiden, 2333, Netherlands

Location

Erasmus Medical Center - Department of Hematology

Rotterdam, 3015, Netherlands

Location

Complejo Hospitalario Universitario de A Coruña - Servicio de Hematología y Hemoterapia

A Coruña, 15006, Spain

Location

Hospital Universitari General Vall d'Hebron - Unidad de Hemofilia

Barcelona, 08035, Spain

Location

Lund University - Centre for Thrombosis and Haemostasis - Skane University Hospital

Malmo, 205 02, Sweden

Location

Central Manchester University Hospital NHS Foundation Trust - Manchester Royal Infirmary - Manchester Royal Eye Hospital

Manchester, M13 9WL, United Kingdom

Location

Related Publications (128)

• Eikenboom JC. Congenital von Willebrand disease type 3: clinical manifestations, pathophysiology and molecular biology. Best Pract Res Clin Haematol. 2001 Jun;14(2):365-79. doi: 10.1053/beha.2001.0139.

  PMID: 11686105 BACKGROUND

• Sadler JE, Budde U, Eikenboom JC, Favaloro EJ, Hill FG, Holmberg L, Ingerslev J, Lee CA, Lillicrap D, Mannucci PM, Mazurier C, Meyer D, Nichols WL, Nishino M, Peake IR, Rodeghiero F, Schneppenheim R, Ruggeri ZM, Srivastava A, Montgomery RR, Federici AB; Working Party on von Willebrand Disease Classification. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. J Thromb Haemost. 2006 Oct;4(10):2103-14. doi: 10.1111/j.1538-7836.2006.02146.x. Epub 2006 Aug 2.

  PMID: 16889557 BACKGROUND

• Nilsson IM. Commentary to Erik von Willebrand's original paper from 1926 'Hereditar pseudohemofili'. Haemophilia. 1999 May;5(3):220-1. doi: 10.1046/j.1365-2516.1999.0320a.x. No abstract available.

  PMID: 10444292 BACKGROUND

• NILSSON IM, BLOMBACK M, BLOMBACK B. v. Willebrand's disease in Sweden; its pathogenesis and treatment. Acta Med Scand. 1959 Jun 30;164:263-78. No abstract available.

  PMID: 14427267 BACKGROUND

• Mannucci PM, Bloom AL, Larrieu MJ, Nilsson IM, West RR. Atherosclerosis and von Willebrand factor. I. Prevalence of severe von Willebrand's disease in western Europe and Israel. Br J Haematol. 1984 May;57(1):163-9. doi: 10.1111/j.1365-2141.1984.tb02876.x.

  PMID: 6609712 BACKGROUND

• Weiss HJ, Ball AP, Mannucci PM. Incidence of severe von Willebrand's disease. N Engl J Med. 1982 Jul 8;307(2):127. doi: 10.1056/NEJM198207083070222. No abstract available.

  PMID: 6979706 BACKGROUND

• Berliner SA, Seligsohn U, Zivelin A, Zwang E, Sofferman G. A relatively high frequency of severe (type III) von Willebrand's disease in Israel. Br J Haematol. 1986 Mar;62(3):535-43. doi: 10.1111/j.1365-2141.1986.tb02966.x.

  PMID: 3082350 BACKGROUND

• Iorio A, Oliovecchio E, Morfini M, Mannucci PM; Association of Italian Hemophilia Centres Directors. Italian Registry of Haemophilia and Allied Disorders. Objectives, methodology and data analysis. Haemophilia. 2008 May;14(3):444-53. doi: 10.1111/j.1365-2516.2008.01679.x. Epub 2008 Mar 18.

  PMID: 18355268 BACKGROUND

• Federici AB, Mannucci PM. Management of inherited von Willebrand disease in 2007. Ann Med. 2007;39(5):346-58. doi: 10.1080/07853890701513738.

  PMID: 17701477 BACKGROUND

• Silwer J. von Willebrand's disease in Sweden. Acta Paediatr Scand Suppl. 1973;238:1-159. No abstract available.

  PMID: 4550005 BACKGROUND

• 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 Dec;111(4):1236-9. doi: 10.1046/j.1365-2141.2000.02507.x.

  PMID: 11167767 BACKGROUND

• Federici AB, Castaman G, Mannucci PM; Italian Association of Hemophilia Centers (AICE). Guidelines for the diagnosis and management of von Willebrand disease in Italy. Haemophilia. 2002 Sep;8(5):607-21. doi: 10.1046/j.1365-2516.2002.00672.x.

  PMID: 12199668 BACKGROUND

• Rodeghiero F, Castaman G, Tosetto A, Batlle J, Baudo F, Cappelletti A, Casana P, De Bosch N, Eikenboom JC, Federici AB, Lethagen S, Linari S, Srivastava A. The discriminant power of bleeding history for the diagnosis of type 1 von Willebrand disease: an international, multicenter study. J Thromb Haemost. 2005 Dec;3(12):2619-26. doi: 10.1111/j.1538-7836.2005.01663.x.

  PMID: 16359502 BACKGROUND

• Tosetto A, Rodeghiero F, Castaman G, Goodeve A, Federici AB, Batlle J, Meyer D, Fressinaud E, Mazurier C, Goudemand J, Eikenboom J, Schneppenheim R, Budde U, Ingerslev J, Vorlova Z, Habart D, Holmberg L, Lethagen S, Pasi J, Hill F, Peake I. A quantitative analysis of bleeding symptoms in type 1 von Willebrand disease: results from a multicenter European study (MCMDM-1 VWD). J Thromb Haemost. 2006 Apr;4(4):766-73. doi: 10.1111/j.1538-7836.2006.01847.x.

  PMID: 16634745 BACKGROUND

• Cattaneo M, Federici AB, Lecchi A, Agati B, Lombardi R, Stabile F, Bucciarelli P. Evaluation of the PFA-100 system in the diagnosis and therapeutic monitoring of patients with von Willebrand disease. Thromb Haemost. 1999 Jul;82(1):35-9.

  PMID: 10456451 BACKGROUND

• Mannucci PM, Lattuada A, Castaman G, Lombardi R, Colibretti ML, Ciavarella N, Rodeghiero F. Heterogeneous phenotypes of platelet and plasma von Willebrand factor in obligatory heterozygotes for severe von Willebrand disease. Blood. 1989 Nov 15;74(7):2433-6.

  PMID: 2804373 BACKGROUND

• Mannucci PM, Federici AB. Antibodies to von Willebrand factor in von Willebrand disease. Adv Exp Med Biol. 1995;386:87-92. doi: 10.1007/978-1-4613-0331-2_7. No abstract available.

  PMID: 8851017 BACKGROUND

• Federici AB. Clinical and molecular markers of inherited von Willebrand disease type 3: are deletions of the VWF gene associated with alloantibodies to VWF? J Thromb Haemost. 2008 Oct;6(10):1726-8. doi: 10.1111/j.1538-7836.2008.03146.x. No abstract available.

  PMID: 18853484 BACKGROUND

• Veltkamp JJ, van Tilburg NH. Detection of heterozygotes for recessive von Willebrand's disease by the assay of antihemophilic-factor-like antigen. N Engl J Med. 1973 Oct 25;289(17):882-5. doi: 10.1056/NEJM197310252891703. No abstract available.

  PMID: 4542316 BACKGROUND

• Shelton-Inloes BB, Chehab FF, Mannucci PM, Federici AB, Sadler JE. Gene deletions correlate with the development of alloantibodies in von Willebrand disease. J Clin Invest. 1987 May;79(5):1459-65. doi: 10.1172/JCI112974.

  PMID: 3033024 BACKGROUND

• Ngo KY, Glotz VT, Koziol JA, Lynch DC, Gitschier J, Ranieri P, Ciavarella N, Ruggeri ZM, Zimmerman TS. 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 Apr;85(8):2753-7. doi: 10.1073/pnas.85.8.2753.

  PMID: 3258663 BACKGROUND

• Schneppenheim R, Krey S, Bergmann F, Bock D, Budde U, Lange M, Linde R, Mittler U, Meili E, Mertes G, et al. Genetic heterogeneity of severe von Willebrand disease type III in the German population. Hum Genet. 1994 Dec;94(6):640-52. doi: 10.1007/BF00206958.

  PMID: 7989040 BACKGROUND

• Eikenboom JC, Castaman G, Vos HL, Bertina RM, Rodeghiero F. Characterization of the genetic defects in recessive type 1 and type 3 von Willebrand disease patients of Italian origin. Thromb Haemost. 1998 Apr;79(4):709-17.

  PMID: 9569178 BACKGROUND

• Schneppenheim R, Castaman G, Federici AB, Kreuz W, Marschalek R, Oldenburg J, Oyen F, Budde U. A common 253-kb deletion involving VWF and TMEM16B in German and Italian patients with severe von Willebrand disease type 3. J Thromb Haemost. 2007 Apr;5(4):722-8. doi: 10.1111/j.1538-7836.2007.02460.x. Epub 2007 Feb 26.

  PMID: 17371490 BACKGROUND

• Peake IR, Liddell MB, Moodie P, Standen G, Mancuso DJ, Tuley EA, Westfield LA, Sorace JM, Sadler JE, Verweij CL, et al. Severe type III von Willebrand's disease caused by deletion of exon 42 of the von Willebrand factor gene: family studies that identify carriers of the condition and a compound heterozygous individual. Blood. 1990 Feb 1;75(3):654-61.

  PMID: 2297569 BACKGROUND

• Mancuso DJ, Tuley EA, Castillo R, de Bosch N, Mannucci PM, Sadler JE. Characterization of partial gene deletions in type III von Willebrand disease with alloantibody inhibitors. Thromb Haemost. 1994 Aug;72(2):180-5.

  PMID: 7831648 BACKGROUND

• Baronciani L, Cozzi G, Canciani MT, Peyvandi F, Srivastava A, Federici AB, Mannucci PM. Molecular characterization of a multiethnic group of 21 patients with type 3 von Willebrand disease. Thromb Haemost. 2000 Oct;84(4):536-40.

  PMID: 11057846 BACKGROUND

• Mohl A, Marschalek R, Masszi T, Nagy E, Obser T, Oyen F, Sallai K, Bodo I, Schneppenheim R. An Alu-mediated novel large deletion is the most frequent cause of type 3 von Willebrand disease in Hungary. J Thromb Haemost. 2008 Oct;6(10):1729-35. doi: 10.1111/j.1538-7836.2008.03107.x. Epub 2008 Jul 28.

  PMID: 18665926 BACKGROUND

• Xie F, Wang X, Cooper DN, Chuzhanova N, Fang Y, Cai X, Wang Z, Wang H. A novel Alu-mediated 61-kb deletion of the von Willebrand factor (VWF) gene whose breakpoints co-locate with putative matrix attachment regions. Blood Cells Mol Dis. 2006 May-Jun;36(3):385-91. doi: 10.1016/j.bcmd.2006.03.003. Epub 2006 May 11.

  PMID: 16690331 BACKGROUND

• Cooper DN, Krawczak M. The mutational spectrum of single base-pair substitutions causing human genetic disease: patterns and predictions. Hum Genet. 1990 Jun;85(1):55-74. doi: 10.1007/BF00276326.

  PMID: 2192981 BACKGROUND

• Zhang ZP, Lindstedt M, Falk G, Blomback M, Egberg N, Anvret M. Nonsense mutations of the von Willebrand factor gene in patients with von Willebrand disease type III and type I. Am J Hum Genet. 1992 Oct;51(4):850-8.

  PMID: 1415226 BACKGROUND

• Eikenboom JC, Ploos van Amstel HK, Reitsma PH, Briet E. Mutations in severe, type III von Willebrand's disease in the Dutch population: candidate missense and nonsense mutations associated with reduced levels of von Willebrand factor messenger RNA. Thromb Haemost. 1992 Oct 5;68(4):448-54.

  PMID: 1448779 BACKGROUND

• Bahnak BR, Lavergne JM, Rothschild C, Meyer D. A stop codon in a patient with severe type III von Willebrand disease. Blood. 1991 Aug 15;78(4):1148-9. No abstract available.

  PMID: 1868248 BACKGROUND

• Zhang ZP, Falk G, Blomback M, Egberg N, Anvret M. Identification of a new nonsense mutation in the von Willebrand factor gene in patients with von Willebrand disease type III. Hum Mol Genet. 1992 Apr;1(1):61-2. doi: 10.1093/hmg/1.1.61. No abstract available.

  PMID: 1301136 BACKGROUND

• Zhang ZP, Blomback M, Egberg N, Falk G, Anvret M. Characterization of the von Willebrand factor gene (VWF) in von Willebrand disease type III patients from 24 families of Swedish and Finnish origin. Genomics. 1994 May 1;21(1):188-93. doi: 10.1006/geno.1994.1241.

  PMID: 8088787 BACKGROUND

• Hagiwara T, Inaba H, Yoshida S, Nagaizumi K, Arai M, Hanabusa H, Fukutake K. A novel mutation Gly 1672-->Arg in type 2A and a homozygous mutation in type 2B von Willebrand disease. Thromb Haemost. 1996 Aug;76(2):253-7.

  PMID: 8865541 BACKGROUND

• Gupta PK, Saxena R, Adamtziki E, Budde U, Oyen F, Obser T, Schneppenheim R. Genetic defects in von Willebrand disease type 3 in Indian and Greek patients. Blood Cells Mol Dis. 2008 Sep-Oct;41(2):219-22. doi: 10.1016/j.bcmd.2008.03.004. Epub 2008 May 16.

  PMID: 18485763 BACKGROUND

• Casana P, Martinez F, Haya S, Lorenzo JI, Espinos C, Aznar JA. Q1311X: a novel nonsense mutation of putative ancient origin in the von Willebrand factor gene. Br J Haematol. 2000 Nov;111(2):552-5. doi: 10.1046/j.1365-2141.2000.02410.x.

  PMID: 11122100 BACKGROUND

• Surdhar GK, Enayat MS, Lawson S, Williams MD, Hill FG. Homozygous gene conversion in von Willebrand factor gene as a cause of type 3 von Willebrand disease and predisposition to inhibitor development. Blood. 2001 Jul 1;98(1):248-50. doi: 10.1182/blood.v98.1.248. No abstract available.

  PMID: 11439975 BACKGROUND

• Baronciani L, Cozzi G, Canciani MT, Peyvandi F, Srivastava A, Federici AB, Mannucci PM. Molecular defects in type 3 von Willebrand disease: updated results from 40 multiethnic patients. Blood Cells Mol Dis. 2003 May-Jun;30(3):264-70. doi: 10.1016/s1079-9796(03)00033-0.

  PMID: 12737944 BACKGROUND

• Gupta PK, Adamtziki E, Budde U, Jaiprakash M, Kumar H, Harbeck-Seu A, Kannan M, Oyen F, Obser T, Wedekind I, Saxena R, Schneppenheim R. Gene conversions are a common cause of von Willebrand disease. Br J Haematol. 2005 Sep;130(5):752-8. doi: 10.1111/j.1365-2141.2005.05660.x.

  PMID: 16115133 BACKGROUND

• Eikenboom JC, Vink T, Briet E, Sixma JJ, Reitsma PH. Multiple substitutions in the von Willebrand factor gene that mimic the pseudogene sequence. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2221-4. doi: 10.1073/pnas.91.6.2221.

  PMID: 8134377 BACKGROUND

• Zhang ZP, Falk G, Blomback M, Egberg N, Anvret M. A single cytosine deletion in exon 18 of the von Willebrand factor gene is the most common mutation in Swedish vWD type III patients. Hum Mol Genet. 1992 Dec;1(9):767-8. doi: 10.1093/hmg/1.9.767. No abstract available.

  PMID: 1302613 BACKGROUND

• Xie F, Wang X, Cooper DN, Lan F, Fang Y, Cai X, Wang Z, Wang H. Compound heterozygosity for two novel mutations (1203insG/Y1456X) in the von Willebrand factor gene causing type 3 von Willebrand disease. Haemophilia. 2007 Sep;13(5):645-8. doi: 10.1111/j.1365-2516.2007.01514.x.

  PMID: 17880457 BACKGROUND

• Wetzstein V, Budde U, Oyen F, Ding X, Herrmann J, Liebig B, Schneppenheim R. Intracranial hemorrhage in a term newborn with severe von Willebrand disease type 3 associated with sinus venous thrombosis. Haematologica. 2006 Dec;91(12 Suppl):ECR60.

  PMID: 17194666 BACKGROUND

• Krawczak M, Cooper DN. Gene deletions causing human genetic disease: mechanisms of mutagenesis and the role of the local DNA sequence environment. Hum Genet. 1991 Mar;86(5):425-41. doi: 10.1007/BF00194629.

  PMID: 2016084 BACKGROUND

• Efstratiadis A, Posakony JW, Maniatis T, Lawn RM, O'Connell C, Spritz RA, DeRiel JK, Forget BG, Weissman SM, Slightom JL, Blechl AE, Smithies O, Baralle FE, Shoulders CC, Proudfoot NJ. The structure and evolution of the human beta-globin gene family. Cell. 1980 Oct;21(3):653-68. doi: 10.1016/0092-8674(80)90429-8.

  PMID: 6985477 BACKGROUND

• Zhang ZP, Blomback M, Nyman D, Anvret M. Mutations of von Willebrand factor gene in families with von Willebrand disease in the Aland Islands. Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7937-40. doi: 10.1073/pnas.90.17.7937.

  PMID: 8367445 BACKGROUND

• Mohlke KL, Nichols WC, Rehemtulla A, Kaufman RJ, Fagerstrom HM, Ritvanen KL, Kekomaki R, Ginsburg D. A common frameshift mutation in von Willebrand factor does not alter mRNA stability but interferes with normal propeptide processing. Br J Haematol. 1996 Oct;95(1):184-91. doi: 10.1046/j.1365-2141.1996.7572377.x.

  PMID: 8857958 BACKGROUND

• Eikenboom JC, Reitsma PH, van der Velden PA, Briet E. Instability of repeats of the von Willebrand factor gene variable number tandem repeat sequence in intron 40. Br J Haematol. 1993 Jul;84(3):533-5. doi: 10.1111/j.1365-2141.1993.tb03114.x.

  PMID: 8105872 BACKGROUND

• Antonarakis SE. Recommendations for a nomenclature system for human gene mutations. Nomenclature Working Group. Hum Mutat. 1998;11(1):1-3. doi: 10.1002/(SICI)1098-1004(1998)11:13.0.CO;2-O. No abstract available.

  PMID: 9450896 BACKGROUND

• Mertes G, Ludwig M, Finkelnburg B, Krawczak M, Schwaab R, Brackmann HH, Olek K. A G+3-to-T donor splice site mutation leads to skipping of exon 50 in von Willebrand factor mRNA. Genomics. 1994 Nov 1;24(1):190-1. doi: 10.1006/geno.1994.1602. No abstract available.

  PMID: 7896280 BACKGROUND

• Zhang Z, Lindstedt M, Blomback M, Anvret M. Effects of the mutant von Willebrand factor gene in von Willebrand disease. Hum Genet. 1995 Oct;96(4):388-94. doi: 10.1007/BF00191794.

  PMID: 7557958 BACKGROUND

• Allen S, Abuzenadah AM, Hinks J, Blagg JL, Gursel T, Ingerslev J, Goodeve AC, Peake IR, Daly ME. A novel von Willebrand disease-causing mutation (Arg273Trp) in the von Willebrand factor propeptide that results in defective multimerization and secretion. Blood. 2000 Jul 15;96(2):560-8.

  PMID: 10887119 BACKGROUND

• Castaman G, Lattuada A, Mannucci PM, Rodeghiero F. Factor VIII:C increases after desmopressin in a subgroup of patients with autosomal recessive severe von Willebrand disease. Br J Haematol. 1995 Jan;89(1):147-51. doi: 10.1111/j.1365-2141.1995.tb08921.x.

  PMID: 7833254 BACKGROUND

• Tjernberg P, Castaman G, Vos HL, Bertina RM, Eikenboom JC. Homozygous C2362F von Willebrand factor induces intracellular retention of mutant von Willebrand factor resulting in autosomal recessive severe von Willebrand disease. Br J Haematol. 2006 May;133(4):409-18. doi: 10.1111/j.1365-2141.2006.06055.x.

  PMID: 16643449 BACKGROUND

• Castaman G, Eikenboom JC, Lattuada A, Mannucci PM, Rodeghiero F. Heightened proteolysis of the von Willebrand factor subunit in patients with von Willebrand disease hemizygous or homozygous for the C2362F mutation. Br J Haematol. 2000 Jan;108(1):188-90. doi: 10.1046/j.1365-2141.2000.01807.x.

  PMID: 10651743 BACKGROUND

• Baronciani L, Federici AB, Cozzi G, La Marca S, Punzo M, Rubini V, Canciani MT, Mannucci PM. Expression studies of missense mutations p.D141Y, p.C275S located in the propeptide of von Willebrand factor in patients with type 3 von Willebrand disease. Haemophilia. 2008 May;14(3):549-55. doi: 10.1111/j.1365-2516.2008.01682.x. Epub 2008 Mar 4.

  PMID: 18328061 BACKGROUND

• Voorberg J, Fontijn R, Calafat J, Janssen H, van Mourik JA, Pannekoek H. Assembly and routing of von Willebrand factor variants: the requirements for disulfide-linked dimerization reside within the carboxy-terminal 151 amino acids. J Cell Biol. 1991 Apr;113(1):195-205. doi: 10.1083/jcb.113.1.195.

  PMID: 2007623 BACKGROUND

• Peake IR, Bowen D, Bignell P, Liddell MB, Sadler JE, Standen G, Bloom AL. Family studies and prenatal diagnosis in severe von Willebrand disease by polymerase chain reaction amplification of a variable number tandem repeat region of the von Willebrand factor gene. Blood. 1990 Aug 1;76(3):555-61.

  PMID: 2378985 BACKGROUND

• Federici AB, Mazurier C, Berntorp E, Lee CA, Scharrer I, Goudemand J, Lethagen S, Nitu I, Ludwig G, Hilbert L, Mannucci PM. Biologic response to desmopressin in patients with severe type 1 and type 2 von Willebrand disease: results of a multicenter European study. Blood. 2004 Mar 15;103(6):2032-8. doi: 10.1182/blood-2003-06-2072. Epub 2003 Nov 20.

  PMID: 14630825 BACKGROUND

• Castaman G, Lethagen S, Federici AB, Tosetto A, Goodeve A, Budde U, Batlle J, Meyer D, Mazurier C, Fressinaud E, Goudemand J, Eikenboom J, Schneppenheim R, Ingerslev J, Vorlova Z, Habart D, Holmberg L, Pasi J, Hill F, Peake I, Rodeghiero F. 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 Apr 1;111(7):3531-9. doi: 10.1182/blood-2007-08-109231. Epub 2008 Jan 29.

  PMID: 18230755 BACKGROUND

• Cattaneo M, Moia M, Delle Valle P, Castellana P, Mannucci PM. DDAVP shortens the prolonged bleeding times of patients with severe von Willebrand disease treated with cryoprecipitate. Evidence for a mechanism of action independent of released von Willebrand factor. Blood. 1989 Nov 1;74(6):1972-5.

  PMID: 2508791 BACKGROUND

• Mannucci PM, Chediak J, Hanna W, Byrnes J, Ledford M, Ewenstein BM, Retzios AD, Kapelan BA, Schwartz RS, Kessler C; Alphanate Study Group. Treatment of von Willebrand disease with a high-purity factor VIII/von Willebrand factor concentrate: a prospective, multicenter study. Blood. 2002 Jan 15;99(2):450-6. doi: 10.1182/blood.v99.2.450.

  PMID: 11781224 BACKGROUND

• Federici AB, Baudo F, Caracciolo C, Mancuso G, Mazzucconi MG, Musso R, Schinco PC, Targhetta R, Mannuccio Mannucci P. Clinical efficacy of highly purified, doubly virus-inactivated factor VIII/von Willebrand factor concentrate (Fanhdi) in the treatment of von Willebrand disease: a retrospective clinical study. Haemophilia. 2002 Nov;8(6):761-7. doi: 10.1046/j.1365-2516.2002.00688.x.

  PMID: 12410644 BACKGROUND

• Bello IF, Yuste VJ, Molina MQ, Navarro FH. Fanhdi, efficacy and safety in von Willebrand's disease: prospective international study results. Haemophilia. 2007 Dec;13 Suppl 5:25-32. doi: 10.1111/j.1365-2516.2007.01570.x.

  PMID: 18078394 BACKGROUND

• Federici AB, Barillari G, Zanon E, Mazzucconi MG, Musso R, Targhetta R, Mannucci PM. Efficacy and safety of highly purified, doubly virus-inactivated VWF/FVIII concentrates in inherited von Willebrand's disease: results of an Italian cohort study on 120 patients characterized by bleeding severity score. Haemophilia. 2010 Jan;16(1):101-10. doi: 10.1111/j.1365-2516.2009.02088.x. Epub 2009 Oct 6.

  PMID: 19811543 BACKGROUND

• Dobrkovska A, Krzensk U, Chediak JR. Pharmacokinetics, efficacy and safety of Humate-P in von Willebrand disease. Haemophilia. 1998;4 Suppl 3:33-9. doi: 10.1046/j.1365-2516.1998.0040s3033.x.

  PMID: 10028316 BACKGROUND

• Lillicrap D, Poon MC, Walker I, Xie F, Schwartz BA; Association of Hemophilia Clinic Directors of Canada. Efficacy and safety of the factor VIII/von Willebrand factor concentrate, haemate-P/humate-P: ristocetin cofactor unit dosing in patients with von Willebrand disease. Thromb Haemost. 2002 Feb;87(2):224-30.

  PMID: 11858481 BACKGROUND

• Franchini M, Rossetti G, Tagliaferri A, Pattacini C, Pozzoli D, Lippi G, Manzato F, Bertuzzo D, Gandini G. Efficacy and safety of factor VIII/von Willebrand's factor concentrate (Haemate-P) in preventing bleeding during surgery or invasive procedures in patients with von Willebrand disease. Haematologica. 2003 Nov;88(11):1279-83.

  PMID: 14607757 BACKGROUND

• Federici AB, Castaman G, Franchini M, Morfini M, Zanon E, Coppola A, Tagliaferri A, Boeri E, Mazzucconi MG, Rossetti G, Mannucci PM. Clinical use of Haemate P in inherited von Willebrand's disease: a cohort study on 100 Italian patients. Haematologica. 2007 Jul;92(7):944-51. doi: 10.3324/haematol.11124.

  PMID: 17606445 BACKGROUND

• Gill JC, Ewenstein BM, Thompson AR, Mueller-Velten G, Schwartz BA; Humate-P Study Group. Successful treatment of urgent bleeding in von Willebrand disease with factor VIII/VWF concentrate (Humate-P): use of the ristocetin cofactor assay (VWF:RCo) to measure potency and to guide therapy. Haemophilia. 2003 Nov;9(6):688-95. doi: 10.1046/j.1351-8216.2003.00816.x.

  PMID: 14750934 BACKGROUND

• Thompson AR, Gill JC, Ewenstein BM, Mueller-Velten G, Schwartz BA; Humate-P Study Group. Successful treatment for patients with von Willebrand disease undergoing urgent surgery using factor VIII/VWF concentrate (Humate-P). Haemophilia. 2004 Jan;10(1):42-51. doi: 10.1046/j.1351-8216.2003.00809.x.

  PMID: 14962219 BACKGROUND

• Lethagen S, Kyrle PA, Castaman G, Haertel S, Mannucci PM; HAEMATE P Surgical Study Group. von Willebrand factor/factor VIII concentrate (Haemate P) dosing based on pharmacokinetics: a prospective multicenter trial in elective surgery. J Thromb Haemost. 2007 Jul;5(7):1420-30. doi: 10.1111/j.1538-7836.2007.02588.x. Epub 2007 Apr 16.

  PMID: 17439628 BACKGROUND

• Stadler M, Gruber G, Kannicht C, Biesert L, Radomski KU, Suhartono H, Pock K, Neisser-Svae A, Weinberger J, Romisch J, Svae TE. Characterisation of a novel high-purity, double virus inactivated von Willebrand Factor and Factor VIII concentrate (Wilate). Biologicals. 2006 Dec;34(4):281-8. doi: 10.1016/j.biologicals.2005.11.010. Epub 2006 Feb 23.

  PMID: 16500114 BACKGROUND

• Favaloro EJ, Lloyd J, Rowell J, Baker R, Rickard K, Kershaw G, Street A, Scarff K, Barrese G, Maher D, McLachlan AJ. Comparison of the pharmacokinetics of two von Willebrand factor concentrates [Biostate and AHF (High Purity)] in people with von Willebrand disorder. A randomised cross-over, multi-centre study. Thromb Haemost. 2007 Jun;97(6):922-30.

  PMID: 17549293 BACKGROUND

• Shortt J, Dunkley S, Rickard K, Baker R, Street A. Efficacy and safety of a high purity, double virus inactivated factor VIII/von Willebrand factor concentrate (Biostate) in patients with von Willebrand disorder requiring invasive or surgical procedures. Haemophilia. 2007 Mar;13(2):144-8. doi: 10.1111/j.1365-2516.2006.01430.x.

  PMID: 17286766 BACKGROUND

• Menache D, Aronson DL, Darr F, Montgomery RR, Gill JC, Kessler CM, Lusher JM, Phatak PD, Shapiro AD, Thompson AR, White GC 2nd. Pharmacokinetics of von Willebrand factor and factor VIIIC in patients with severe von Willebrand disease (type 3 VWD): estimation of the rate of factor VIIIC synthesis. Cooperative Study Groups. Br J Haematol. 1996 Sep;94(4):740-5. doi: 10.1046/j.1365-2141.1996.d01-1860.x.

  PMID: 8826903 BACKGROUND

• Goudemand J, Scharrer I, Berntorp E, Lee CA, Borel-Derlon A, Stieltjes N, Caron C, Scherrmann JM, Bridey F, Tellier Z, Federici AB, Mannucci PM. Pharmacokinetic studies on Wilfactin, a von Willebrand factor concentrate with a low factor VIII content treated with three virus-inactivation/removal methods. J Thromb Haemost. 2005 Oct;3(10):2219-27. doi: 10.1111/j.1538-7836.2005.01435.x.

  PMID: 16194199 BACKGROUND

• Borel-Derlon A, Federici AB, Roussel-Robert V, Goudemand J, Lee CA, Scharrer I, Rothschild C, Berntorp E, Henriet C, Tellier Z, Bridey F, Mannucci PM. Treatment of severe von Willebrand disease with a high-purity von Willebrand factor concentrate (Wilfactin): a prospective study of 50 patients. J Thromb Haemost. 2007 Jun;5(6):1115-24. doi: 10.1111/j.1538-7836.2007.02562.x.

  PMID: 17403090 BACKGROUND

• Bergamaschini L, Mannucci PM, Federici AB, Coppola R, Guzzoni S, Agostoni A. Posttransfusion anaphylactic reactions in a patient with severe von Willebrand disease: role of complement and alloantibodies to von Willebrand factor. J Lab Clin Med. 1995 Mar;125(3):348-55.

  PMID: 7897302 BACKGROUND

• Ciavarella N, Schiavoni M, Valenzano E, Mangini F, Inchingolo F. Use of recombinant factor VIIa (NovoSeven) in the treatment of two patients with type III von Willebrand's disease and an inhibitor against von Willebrand factor. Haemostasis. 1996;26 Suppl 1:150-4. doi: 10.1159/000217258.

  PMID: 8904191 BACKGROUND

• Boyer-Neumann C, Dreyfus M, Wolf M, Veyradier A, Meyer D. Multi-therapeutic approach to manage delivery in an alloimmunized patient with type 3 von Willebrand disease. J Thromb Haemost. 2003 Jan;1(1):190-2. doi: 10.1046/j.1538-7836.2003.00009.x. No abstract available.

  PMID: 12871560 BACKGROUND

• Berntorp E, Petrini P. Long-term prophylaxis in von Willebrand disease. Blood Coagul Fibrinolysis. 2005 Apr;16 Suppl 1:S23-6. doi: 10.1097/01.mbc.0000167659.23262.18.

  PMID: 15849523 BACKGROUND

• De Meyer SF, Vanhoorelbeke K, Chuah MK, Pareyn I, Gillijns V, Hebbel RP, Collen D, Deckmyn H, VandenDriessche T. Phenotypic correction of von Willebrand disease type 3 blood-derived endothelial cells with lentiviral vectors expressing von Willebrand factor. Blood. 2006 Jun 15;107(12):4728-36. doi: 10.1182/blood-2005-09-3605. Epub 2006 Feb 14.

  PMID: 16478886 BACKGROUND

• von Willebrand EA. (1926) Hereditär Pseudohemofili. Finska Läkaresällskapets Handlingar 68, 87-112.

  BACKGROUND

• Federici AB, Bucciarelli P, Castaman G et al. (2007) Incidence and determinants of bleeding in different types of von Willebrand disease:results of the first prospective multicenter study on 814 Italian patients Blood 110, 713

  BACKGROUND

• Abuzenadah AM, Gursel T, Ingerslev J et al. (1999) Mutational analysis of the von Willebrand factor gene in 27 families from Turkey with von Willebrand disease Thromb Haemost 82 (Suppl), 283

  BACKGROUND

• Castaman G, Giacomelli SH, Coppola A et al. (2008) Molecular bases of type 3 von Willebrand disease in Italy: report on 12 families Blood Transfus Suppl 3, 44

  BACKGROUND

• Gazda H, Budde U, Krey S et al. (1997) Delta C in exon 18 of the von Willebrand factor gene is the most common mutation in patients with severe von Willebrand disease type 3 in Poland Blood 90 (Suppl 1), 94b

  BACKGROUND

• Titapiwatanakun R, Guenther JC, Asmann YW et al. (2007) Novel Mutations in Types 2 & 3 von Willebrand Disease and Correlation with von Willebrand Factor Multimer Patterns. Blood 110, 2136

  BACKGROUND

• Montgomery RR, Jozwiak MA, Hutter JJ et al. (1999) A homozygous variant of the von Willebrand factor (VWF) that fails to c-terminal dimerize resulting in loss of VWF multimers larger than dimer Blood 94 (Suppl 1), 443a

  BACKGROUND

• Schneppenheim R, Budde U, Drewke E et al. (1999) Cysteine mutations of von Willebrand factor correlate with different types of von Willebrand disease Thromb Haemost 82 (Suppl), 283

  BACKGROUND

• Enayat MS, Guilliatt AM, Surdhar GK et al. (2001) Identification of five novel mutations in families with type 3 von Willebrand's disease Thromb Haemost 86 (Suppl), P1810

  BACKGROUND

• Mannucci PM. Treatment of von Willebrand's Disease. N Engl J Med. 2004 Aug 12;351(7):683-94. doi: 10.1056/NEJMra040403. No abstract available.

  PMID: 15306670 BACKGROUND

• Federici AB, Gianniello F, Canciani MT et al. (2005) Secondary long-term prophylaxis in severe patients with von Willebrand disease: an Italian cohort study Blood 106, 507a

  BACKGROUND

• Marchese M, De Cristofaro R, Federici AB, Biondi A, Petruzziello L, Tringali A, Spada C, Mutignani M, Ronconi P, Costamagna G. Duodenal and gastric Dieulafoy's lesions in a patient with type 2A von Willebrand's disease. Gastrointest Endosc. 2005 Feb;61(2):322-5. doi: 10.1016/s0016-5107(04)02636-7. No abstract available.

  PMID: 15729257 BACKGROUND

• Tosetto A, Rodeghiero F, Castaman G, Bernardi M, Bertoncello K, Goodeve A, Federici AB, Batlle J, Meyer D, Mazurier C, Goudemand J, Eikenboom J, Schneppenheim R, Budde U, Ingerslev J, Vorlova Z, Habart D, Holmberg L, Lethagen S, Pasi J, Hill F, Peake I. Impact of plasma von Willebrand factor levels in the diagnosis of type 1 von Willebrand disease: results from a multicenter European study (MCMDM-1VWD). J Thromb Haemost. 2007 Apr;5(4):715-21. doi: 10.1111/j.1538-7836.2007.02444.x.

  PMID: 17408405 BACKGROUND

• Federici AB. Highly purified VWF/FVIII concentrates in the treatment and prophylaxis of von Willebrand disease: the PRO. WILL Study. Haemophilia. 2007 Dec;13 Suppl 5:15-24. doi: 10.1111/j.1365-2516.2007.01573.x.

  PMID: 18078393 BACKGROUND

• Federici AB, Mannucci PM, Castaman G, Baronciani L, Bucciarelli P, Canciani MT, Pecci A, Lenting PJ, De Groot PG. Clinical and molecular predictors of thrombocytopenia and risk of bleeding in patients with von Willebrand disease type 2B: a cohort study of 67 patients. Blood. 2009 Jan 15;113(3):526-34. doi: 10.1182/blood-2008-04-152280. Epub 2008 Sep 19.

  PMID: 18805962 BACKGROUND

• Gritti G, Cortelezzi A, Bucciarelli P, Rezzonico F, Lonati S, La Marca S, Silvestris I, Federici AB. Circulating and progenitor endothelial cells are abnormal in patients with different types of von Willebrand disease and correlate with markers of angiogenesis. Am J Hematol. 2011 Aug;86(8):650-6. doi: 10.1002/ajh.22070. Epub 2011 May 31.

  PMID: 21630316 BACKGROUND

• Abshire TC, Federici AB, Alvarez MT, Bowen J, Carcao MD, Cox Gill J, Key NS, Kouides PA, Kurnik K, Lail AE, Leebeek FW, Makris M, Mannucci PM, Winikoff R, Berntorp E; VWD PN. Prophylaxis in severe forms of von Willebrand's disease: results from the von Willebrand Disease Prophylaxis Network (VWD PN). Haemophilia. 2013 Jan;19(1):76-81. doi: 10.1111/j.1365-2516.2012.02916.x. Epub 2012 Jul 23.

  PMID: 22823000 BACKGROUND

• Castaman G, Goodeve A, Eikenboom J; European Group on von Willebrand Disease. Principles of care for the diagnosis and treatment of von Willebrand disease. Haematologica. 2013 May;98(5):667-74. doi: 10.3324/haematol.2012.077263.

  PMID: 23633542 BACKGROUND

• Federici AB, Bucciarelli P, Castaman G, Mazzucconi MG, Morfini M, Rocino A, Schiavoni M, Peyvandi F, Rodeghiero F, Mannucci PM. The bleeding score predicts clinical outcomes and replacement therapy in adults with von Willebrand disease. Blood. 2014 Jun 26;123(26):4037-44. doi: 10.1182/blood-2014-02-557264. Epub 2014 Apr 30.

  PMID: 24786773 BACKGROUND

• Abdul-Kadir R, McLintock C, Ducloy AS, El-Refaey H, England A, Federici AB, Grotegut CA, Halimeh S, Herman JH, Hofer S, James AH, Kouides PA, Paidas MJ, Peyvandi F, Winikoff R. Evaluation and management of postpartum hemorrhage: consensus from an international expert panel. Transfusion. 2014 Jul;54(7):1756-68. doi: 10.1111/trf.12550. Epub 2014 Mar 12.

  PMID: 24617726 BACKGROUND

• Makris M, Federici AB, Mannucci PM, Bolton-Maggs PHB, Yee TT, Abshire T, Berntorp E. The natural history of occult or angiodysplastic gastrointestinal bleeding in von Willebrand disease. Haemophilia. 2015 May;21(3):338-342. doi: 10.1111/hae.12571. Epub 2014 Nov 7.

  PMID: 25381842 BACKGROUND

• Federici AB. Clinical and laboratory diagnosis of VWD. Hematology Am Soc Hematol Educ Program. 2014 Dec 5;2014(1):524-30. doi: 10.1182/asheducation-2014.1.524. Epub 2014 Nov 18.

  PMID: 25696905 BACKGROUND

• Holm E, Abshire TC, Bowen J, Alvarez MT, Bolton-Maggs P, Carcao M, Federici AB, Gill JC, Halimeh S, Kempton C, Key NS, Kouides P, Lail A, Landorph A, Leebeek F, Makris M, Mannucci P, Mauser-Bunschoten EP, Nugent D, Valentino LA, Winikoff R, Berntorp E. Changes in bleeding patterns in von Willebrand disease after institution of long-term replacement therapy: results from the von Willebrand Disease Prophylaxis Network. Blood Coagul Fibrinolysis. 2015 Jun;26(4):383-8. doi: 10.1097/MBC.0000000000000257.

  PMID: 25688461 BACKGROUND

• Randi AM, Laffan MA. Von Willebrand factor and angiogenesis: basic and applied issues. J Thromb Haemost. 2017 Jan;15(1):13-20. doi: 10.1111/jth.13551.

  PMID: 27778439 BACKGROUND

• Federici AB. Current and emerging approaches for assessing von Willebrand disease in 2016. Int J Lab Hematol. 2016 May;38 Suppl 1:41-9. doi: 10.1111/ijlh.12540.

  PMID: 27426859 BACKGROUND

• De Jong A, Eikenboom J. Developments in the diagnostic procedures for von Willebrand disease. J Thromb Haemost. 2016 Mar;14(3):449-60. doi: 10.1111/jth.13243. Epub 2016 Feb 12.

  PMID: 26714181 BACKGROUND

• Abshire T, Cox-Gill J, Kempton CL, Leebeek FW, Carcao M, Kouides P, Donfield S, Berntorp E. Prophylaxis escalation in severe von Willebrand disease: a prospective study from the von Willebrand Disease Prophylaxis Network. J Thromb Haemost. 2015 Sep;13(9):1585-9. doi: 10.1111/jth.12995. Epub 2015 Jul 14.

  PMID: 25930155 BACKGROUND

• Engelen ET, van Galen KP, Schutgens RE. Thalidomide for treatment of gastrointestinal bleedings due to angiodysplasia: a case report in acquired von Willebrand syndrome and review of the literature. Haemophilia. 2015 Jul;21(4):419-29. doi: 10.1111/hae.12701. Epub 2015 Apr 30.

  PMID: 25929157 BACKGROUND

• Franchini M, Mannucci PM. Gastrointestinal angiodysplasia and bleeding in von Willebrand disease. Thromb Haemost. 2014 Sep 2;112(3):427-31. doi: 10.1160/TH13-11-0952. Epub 2014 Jun 5.

  PMID: 24898873 BACKGROUND

• Randi AM, Laffan MA, Starke RD. Von Willebrand factor, angiodysplasia and angiogenesis. Mediterr J Hematol Infect Dis. 2013 Sep 2;5(1):e2013060. doi: 10.4084/MJHID.2013.060.

  PMID: 24106610 BACKGROUND

• Thachil J, Hay CR, Campbell S. Tamoxifen for recurrent bleeds due to angiodysplasia in von Willebrand's disease. Haemophilia. 2013 Sep;19(5):e313-5. doi: 10.1111/hae.12196. Epub 2013 Jun 4. No abstract available.

  PMID: 23731407 BACKGROUND

• Castaman G, Federici AB, Tosetto A, La Marca S, Stufano F, Mannucci PM, Rodeghiero F. Different bleeding risk in type 2A and 2M von Willebrand disease: a 2-year prospective study in 107 patients. J Thromb Haemost. 2012 Apr;10(4):632-8. doi: 10.1111/j.1538-7836.2012.04661.x.

  PMID: 22329792 BACKGROUND

• Starke RD, Ferraro F, Paschalaki KE, Dryden NH, McKinnon TA, Sutton RE, Payne EM, Haskard DO, Hughes AD, Cutler DF, Laffan MA, Randi AM. Endothelial von Willebrand factor regulates angiogenesis. Blood. 2011 Jan 20;117(3):1071-80. doi: 10.1182/blood-2010-01-264507. Epub 2010 Nov 3.

  PMID: 21048155 BACKGROUND

• Veyradier A, Balian A, Wolf M, Giraud V, Montembault S, Obert B, Dagher I, Chaput JC, Meyer D, Naveau S. Abnormal von Willebrand factor in bleeding angiodysplasias of the digestive tract. Gastroenterology. 2001 Feb;120(2):346-53. doi: 10.1053/gast.2001.21204.

  PMID: 11159874 BACKGROUND

• Bowers M, McNulty O, Mayne E. Octreotide in the treatment of gastrointestinal bleeding caused by angiodysplasia in two patients with von Willebrand's disease. Br J Haematol. 2000 Mar;108(3):524-7. doi: 10.1046/j.1365-2141.2000.01897.x.

  PMID: 10759709 BACKGROUND

• Van Belle E, Rauch A, Vincent F, Robin E, Kibler M, Labreuche J, Jeanpierre E, Levade M, Hurt C, Rousse N, Dally JB, Debry N, Dallongeville J, Vincentelli A, Delhaye C, Auffray JL, Juthier F, Schurtz G, Lemesle G, Caspar T, Morel O, Dumonteil N, Duhamel A, Paris C, Dupont-Prado A, Legendre P, Mouquet F, Marchant B, Hermoire S, Corseaux D, Moussa K, Manchuelle A, Bauchart JJ, Loobuyck V, Caron C, Zawadzki C, Leroy F, Bodart JC, Staels B, Goudemand J, Lenting PJ, Susen S. Von Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement. N Engl J Med. 2016 Jul 28;375(4):335-44. doi: 10.1056/NEJMoa1505643.

  PMID: 27464202 BACKGROUND

• Susen S, Rauch A, Van Belle E, Vincentelli A, Lenting PJ. Circulatory support devices: fundamental aspects and clinical management of bleeding and thrombosis. J Thromb Haemost. 2015 Oct;13(10):1757-67. doi: 10.1111/jth.13120. Epub 2015 Sep 25.

  PMID: 26302994 BACKGROUND

• Blatchford O, Murray WR, Blatchford M. A risk score to predict need for treatment for upper-gastrointestinal haemorrhage. Lancet. 2000 Oct 14;356(9238):1318-21. doi: 10.1016/S0140-6736(00)02816-6.

  PMID: 11073021 BACKGROUND

• Gerson LB, Fidler JL, Cave DR, Leighton JA. ACG Clinical Guideline: Diagnosis and Management of Small Bowel Bleeding. Am J Gastroenterol. 2015 Sep;110(9):1265-87; quiz 1288. doi: 10.1038/ajg.2015.246. Epub 2015 Aug 25.

  PMID: 26303132 BACKGROUND

• Strate LL, Gralnek IM. ACG Clinical Guideline: Management of Patients With Acute Lower Gastrointestinal Bleeding. Am J Gastroenterol. 2016 Apr;111(4):459-74. doi: 10.1038/ajg.2016.41. Epub 2016 Mar 1.

  PMID: 26925883 BACKGROUND

• Jackson CS, Gerson LB. Management of gastrointestinal angiodysplastic lesions (GIADs): a systematic review and meta-analysis. Am J Gastroenterol. 2014 Apr;109(4):474-83; quiz 484. doi: 10.1038/ajg.2014.19. Epub 2014 Mar 18.

  PMID: 24642577 BACKGROUND

• Martin-Grace J, Tamagno G. Somatostatin analogs in the medical management of occult bleeding of the lower digestive tract. Gastroenterol Res Pract. 2015;2015:702921. doi: 10.1155/2015/702921. Epub 2015 Mar 9.

  PMID: 25838821 BACKGROUND

• Holleran G, Hall B, Breslin N, McNamara D. Long-acting somatostatin analogues provide significant beneficial effect in patients with refractory small bowel angiodysplasia: Results from a proof of concept open label mono-centre trial. United European Gastroenterol J. 2016 Feb;4(1):70-6. doi: 10.1177/2050640614559121. Epub 2015 Nov 5.

  PMID: 26966525 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Venous blood sample, that will be used to obtain both citrated Platelet Poor Plasma for Von Willebrand Factor (VWF) assays and Cell Pellet for DNA extraction.

MeSH Terms

Conditions

von Willebrand Disease, Type 3; Hemophilia A; Hemorrhage; von Willebrand Diseases

Interventions

von Willebrand Factor

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood Platelet Disorders

Intervention Hierarchy (Ancestors)

Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Limitations and Caveats

Lack of data due to issues with samples. Some samples were not collected properly or properly stored, resulting impossible to be analyzed.

Results Point of Contact

• Title: Prof. Augusto B. Federici
• Organization: Hematology and Transfusion Medicine, L. Sacco University Hospital, University of Milan, Via G. B. Grassi, 74 20157 Milan, Italy

augusto.federici@unimi.it

+39-0250319895

Study Officials

• Augusto B. Federici, MD

  Hematology and Transfusion Medicine, L. Sacco University Hospital, University of Milan, Via G. B. Grassi, 74 20157 Milan, Italy

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2015
• First Posted: June 2, 2015
• Study Start: November 5, 2012
• Primary Completion: March 28, 2023
• Study Completion: April 17, 2023
• Last Updated: December 27, 2024
• Results First Posted: April 19, 2016

Record last verified: 2024-12

Locations

DE (3); IT (5); NL (2); HU (1); ES (2); SE (1); FI (1); FR (2); IR (7); GB (1)