Semin Thromb Hemost 2005; 31(5): 569-576
DOI: 10.1055/s-2005-922229
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Epidemiology of von Willebrand Disease in Developing Countries

Alok Srivastava1 , Francesco Rodeghiero2
  • 1Professor, Department of Haematology, Christian Medical College, Vellore, India
  • 2Department of Haematology, San Bortolo Hospital, Vicenza, Italy
Further Information

Publication History

Publication Date:
08 November 2005 (online)


There is limited information on von Willebrand disease (vWD) in developing countries. A questionnaire survey in 1998 showed that overall, less than one third of the expected number of patients with vWD in the population had been detected. Among those registered, the proportion with the severe form of the disease was relatively higher, forming up to 50% of the total, particularly in those countries with high prevalence of consanguineous marriages. Diagnosis was based on von Willebrand factor antigen (vWF:Ag) assays, vWF ristocetin cofactor (vWF:Rco) activity, and ristocetin-induced platelet aggregation (RIPA) at the reporting centers, but vWF multimer analysis was not widely available. Responsiveness to desmopressin acetate (DDAVP), which could be very significant clinically, was not often assessed. An attempt was made to assess accuracy of reporting of the prevalence of vWD by conducting a second survey aimed at normalizing the reported numbers with that of severe hemophilia A in a defined population on the presumption that the latter is less likely to be missed. These data showed that in most countries, the ratio of patients with vWD to severe hemophilia varied between 0.1 to 0.6 with a mean of approximately 0.4, as opposed to an expected ratio of approximately 1 (based on population-based data from Italy), confirming the underdiagnosis of vWD even within the same health-care system. A system for collecting more extensive and detailed data on vWD from developing countries (where 80% of the world’s population lives) is required. Efforts are needed to develop national registries and make at least basic services for diagnosis and treatment widely available.


  • 1 Sadler J E, Mannucci P M, Berntorp E et al.. Impact, diagnosis and treatment of von Willebrand disease.  Thromb Haemost. 2000;  84 160-174
  • 2 Mannucci P M. Desmopressin (DDAVP) in the treatment of bleeding disorder in the first 20 years.  Blood. 1997;  90 2515-2521
  • 3 Rodeghiero F, Castman G, Dini E. Epidemiological investigations of the prevalence of von Willebrand’s disease.  Blood. 1987;  69 454-459
  • 4 Sadler J E. A revised classification of von Willebrand disease.  Thromb Haemost. 1994;  71 520-525
  • 5 Mazurier C, Meyer D. Molecular basis of von Willebrand disease.  Baillieres Clin Haematol. 1996;  9 229-241
  • 6 The University of Sheffield ISTH SSC vWF data base. Available at: Accessed September 23, 2005
  • 7 Scott J P, Montgomery R R. Therapy of von Willebrand disease.  Semin Thromb Hemost. 1993;  19 37-47
  • 8 von Willebrand Working Party . Treatment and management of von Willebrand Disease.  Haemophilia. 1997;  3(suppl 2) 4-8
  • 9 Plaimauer B, Schlokat U, Turecek P L et al.. Recombinant von Willebrand factor: preclinical development.  Semin Thromb Hemost. 2001;  27 395-403
  • 10 The World Development Report, 2002. Geneva; United Nations Development Program 2002
  • 11 Werner E J, Broxson E H, Tucker E L, Dgiroux D S, Shults J, Abshire T C. Prevalence of von Willebrand disease in children: a multiethnic study.  J Pediatr. 1993;  123 893-898
  • 12 Shoa’i I, Lavergne J M, Ardaillou N, Obert B, Ala F, Meyer D. Heterogeneity of von Willebrand’s disease: study of 40 Iranian cases.  Br J Haematol. 1977;  37 67-83
  • 13 Bird A R, Shuttleworth M, Anderson C, Karabus C. von Willebrand disease in the Western Cape.  S Afr Med J. 1996;  86 261-263
  • 14 Cabrera M E, Artigas C G, Paez E et al.. von Willebrand’s disease in the IX region of Chile.  Rev Med Chil. 1989;  117 423-430
  • 15 Diez-Ewald M, Vizcaino G, Arteaga-Vizcaino M, Fernandez N, Weir-Medina J, Gomez O. Epidemiology of von Willebrand’s disease in the state of Zulia, Venezuela.  Invest Clin. 1991;  32 187-199
  • 16 Srivastava A, Chuansumrit A, Chandy M, Duraiswamy G D, Karabus C. Management of hemophilia in the developing world.  Haemophilia. 1998;  4 474-480
  • 17 Zhang L, Li H, Zhao H, Zhang X, Ji L, Yang R. Retrospective analysis of 1312 patients with haemophilia and related disorders in a single Chinese institute.  Haemophilia. 2003;  9 696-702
  • 18 Islam S I, Quadri M I. Spectrum of hereditary coagulation factor deficiencies in eastern province, Saudi Arabia.  East Mediterr Health J. 1999;  5 1188-1195
  • 19 Karimi M, Yarmohammadi H, Ardeshiri R, Yarmohammadi H. Inherited coagulation disorders in southern Iran.  Haemophilia. 2002;  8 740-744
  • 20 Mannucci P M, Bloom A L, Larrieu M J, Nilsson I M, West R R. Atherosclerosis and von Willebrand factor 1. Prevalence of severe von Willebrand’s disease in Western Europe and Israel.  Br J Haematol. 1984;  57 163-169
  • 21 Mueller R F, Cook J. Mendelian inheritance. In: Rimoin DL, Connor JM, Pyeritz RE Principles and Practice of Medical Genetics. 3rd ed. New York; Churchill Livingstone 1997: 87-102
  • 22 Berliner S A, 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;  62 535-543
  • 23 Fischer R R, Lerner C, Bandinelli E, Fonseca A S, Roisenberg I. Inheritance and prevalence of von Willebrand’s disease severe form in a Brazilian population.  J Inherit Metab Dis. 1989;  12 293-301
  • 24 Awidi A S. A study of von Willebrand’s disease in Jordon.  Ann Hematol. 1992;  64 299-302
  • 25 Quiroga T, Perez M, Pereira J, Mezzano D. Diagnosis of von Willebrand’s disease subtypes by analysis of multimeric composition of plasma von Willebrand factor.  Rev Med Chil. 1993;  121 987-993
  • 26 Mahasandana C, Suvatte V, Pung-amrit P, Tuchinda S. von Willebrand’s disease: Studies of platelet functions, factor VIII procoagulant activity (F VIII C) and factor VIII-related antigen (F VIII Rag) in three families.  Southeast Asian J Trop Med Public Health. 1979;  10 243-247
  • 27 Mehta B C, Agarwal M B. Inherited coagulation disorders in India.  Indian J Pediatr. 1981;  48 525-531
  • 28 Kulkarni M L, Nanda G. Hemophiliacs-a picture from a developing country: Karnataka, a south Indian state.  Southeast Asian J Trop Med Public Health. 1993;  24(suppl 1) 270-273
  • 29 A1-Fawaz I M, Gader A MA, Bahakim H M, Al-Momen A K, Harakati M S. Hereditary bleeding disorders in Riyadh, Saudi Arabia.  Ann Saudi Med. 1996;  16 257-261
  • 30 Quiroga T, Perez M, Rodriguez S et al.. Skin and mucous membrane hemorrhages: clinical assessment, study sequence and relative frequency of hereditary diseases of hemostasis in a Chilean population.  Rev Med Chil. 1997;  125 409-418
  • 31 Mehta B C, Agarwal M B, Bhanotre P C, Rao S M. Inheritance pattern of von Willebrand’s disease-a study of 26 cases.  Indian Pediatr. 1982;  19 665-668
  • 32 Almaani W S, Awidi A S. Spontaneous intracranial haemorrhage secondary to von Willebrand’s disease.  Surg Neurol. 1986;  26 457-460
  • 33 Tsay W, Shen M C. Experience of desmopressin (DDAVP) administration in patients with congenital and acquired bleeding disorders.  J Formos Med Assoc. 1992;  91 962-969
  • 34 Chuansumrit A, Hathirat P, Pintadit P, Isarangkura P. Response of patients with bleeding disorder to DDAVP administration.  Southeast Asian J Trop Med Public Health. 1993;  24(suppl 1) 174-179
  • 35 Sivasankaran P, Prasad H S, Nalini P. von Willebrand’s disease in identical twins.  Indian J Pediatr. 1989;  56 435-437
  • 36 Grand B, Blanco A, Riveros D et al.. Congenital factor XIII deficiency associated with von Willebrand disease.  Am J Hematol. 1990;  35 208-209
  • 37 Paul B, Nkrumah F K, Bird A R, Kossew B P, Jacobs P. von Willebrand’s disease in Zimbabwe.  S Afr Med J. 1991;  80 153-155
  • 38 Dharnidharka V R, Bichile S K, Vaidya S S. von Willebrand’s disease with gastrointestinal telangiectasia.  J Assoc Physicians India. 1993;  41 395-396
  • 39 Ahuja R, Kripalani A, Choudhary V P, Takkar D. von Willebrand disease: a rare cause of puberty menorrhagia.  Aust N Z J Obstet Gynaecol. 1995;  35 337-338
  • 40 Nathwani A C, Tuddenham EGD. Epidemiology of coagulation disorders.  Baillieres Clin Haematol. 1992;  5 383-439
  • 41 World Federation of Haemophilia .Status and Atlas of Hemophilia Worldwide, 1984. Munich, Germany; World Federation of Haemophilia Clearing House 1984
  • 42 Anonymous. World Economic and Social Survey 1997. New York; United Nations 1997
  • 43 Scientific Subcommittee Reports .1999 Minutes and Annual Reports: Scientific Subcommittees of the Scientific and Standardization Committee International Society on Thrombosis and Haemostasis. Accessed September 23, 2005
  • 44 Soucie J R, Evatt B, Jackson D. and the Hemophilia Surveillance System Project Investigators. . Occurrence of hemophilia in the United States.  Am J Hematol. 1998;  59 288-294
  • 45 Anonymous. Report on the World Social Situation, 1997. New York; United Nations 1997
  • 46 Anonymous. Control of Haemophilia: Haemophilia Care in Developing Countries. Report of a joint WHO/World Federation of Haemophilia meeting. Geneva; World Health Organisation 1997
  • 47 Srivastava A. The delivery of haemophilia care in the developing world.  Haemophilia. 1998;  4(suppl 2) 33-40

Alok SrivastavaM.D. 

Department of Haematology, Christian Medical College Vellore-632004, India