ABSTRACT
von Willebrand disease (VWD) in all developing countries including India is considered a rare coagulation disorder, contrary to many reports from Western countries. Prevalence data based on hospital referrals identifies type 3 VWD as the most common subtype followed by type 1 and type 2. Approximately 60 to 70% cases of type 3 VWD are reportedly born of consanguineous marriages. The discriminatory diagnostic tests mainly include assays for factor (F)VIII:C and ristocetin-induced platelet agglutination and von Willebrand factor (VWF) antigen either by immunoelectrophoresis or by enzyme-linked immunosorbent assay. VWD-type assisting tests like VWF collagen binding, VWF ristocetin cofactor assay, VWF-FVIII binding assay, and multimer analysis are occasionally used but not routinely applied in many laboratories. Among women, menorrhagia is an important presenting manifestation. Except for a handful of centers mainly in metropolitan cities, most laboratories in the remote parts of the country have no facilities for VWD-related investigations, resulting in occasional misdiagnoses of VWD as hemophilia A. Genetic diagnosis is being offered in two or three centers using the indirect linkage method in type 3 VWD, and efforts are continuing to implementing a direct mutation detection technique for routine practice in a few laboratories. Depending on the subtype or the severity of VWD, desmopressin, cryoprecipitate, fresh-frozen plasma, and factor VIII/VWF concentrates are used for management. Antifibrinolytic agents like epsilon-aminocaproic acid and tranexamic acid are widely used as an adjuvant therapy. In women with menorrhagia, oral contraceptives as a supplementary treatment are also being widely advocated to reduce bleeding. Products like danazol, ethenyl estradiol, thalidomide, and atorvastatin have been used in individual patients; acquired VWD associated with hypothyroidism has been managed successfully with thyroid hormone treatment. Both minor and major surgical procedures are performed in a few centers with judicious use of cryoprecipitate or FVIII concentrate containing VWF along with other supplementary therapeutic products to achieve adequate hemostasis. Awareness about the disease, establishment of the comprehensive coagulation laboratory, and treatment centers will be successful in increasing diagnosis of VWD and consequently better management of affected patients. This is likely to tilt the ratios of different VWD types, and VWD is likely to emerge as the most common of all coagulation disorders in the near future.
KEYWORDS
von Willebrand disease - diagnosis - management - epidemiology - India
REFERENCES
-
1
Sadler JE, Mannucci PM, Berntorp E et al.
Impact, diagnosis and treatment of von Willebrand disease.
Thromb Haemost.
2000;
84
(2)
160-174
-
2
Mehta BC, Agarwal MB.
Inherited coagulation disorders in India.
Indian J Pediatr.
1981;
48
(393)
525-531
-
3
Kumar S, Kishore R, Gupta V, Jain M, Shukla J.
Prevalence and spectrum of von Willebrand disease in Eastern Uttar Pradesh.
Indian J Pathol Microbiol.
2010;
53
(3)
486-489
-
4
Ahmad F, Kannan M, Ranjan R, Bajaj J, Choudhary VP, Saxena R.
Inherited platelet function disorders versus other inherited bleeding disorders: an Indian overview.
Thromb Res.
2008;
121
(6)
835-841
-
5
Trasi S, Shetty S, Ghosh K, Mohanty D.
Prevalence and spectrum of von Willebrand disease from western India.
Indian J Med Res.
2005;
121
(5)
653-658
-
6
Srivastava A, Rodeghiero F.
Epidemiology of von Willebrand disease in developing countries.
Semin Thromb Hemost.
2005;
31
(5)
569-576
-
7
Mehta BC, Agarwal MB.
Inherited disorders of coagulation in India.
The Ind J Paediatrics.
1981;
48
525-531
-
8 Chandy M Indian Council for Medical Research ed.. Collaborative Study on Haemophilia: An ICMR Task Force Project. New Delhi, India: ICMR; 1990
-
9
Cabrera ME, Artigas CG, Páez E et al.
von Willebrand's disease in the IX Region of Chile.
Rev Med Chil.
1989;
117
(4)
423-430
-
10
Diez-Ewald M, Vizcaíno G, Arteaga-Vizcaíno M, Fernández N, Weir-Medina J, Gómez O.
Epidemiology of von Willebrand's disease in the state of Zulia, Venezuela.
Invest Clin.
1991;
32
(4)
187-199
-
11
Karimi M, Yarmohammadi H, Ardeshiri R, Yarmohammadi H.
Inherited coagulation disorders in southern Iran.
Haemophilia.
2002;
8
(6)
740-744
-
12
Islam SI, Quadri MI.
Spectrum of hereditary coagulation factor deficiencies in eastern province, Saudi Arabia.
East Mediterr Health J.
1999;
5
(6)
1188-1195
-
13
Gupta PK, Ahmed RP, Sazawal S, Choudhry VP, Saxena R.
Relatively high frequency of VWD types 3 and 2 in a cohort of Indian patients: the role of multimeric analysis.
J Thromb Haemost.
2005;
3
(6)
1321-1322
-
14
Ghosh K, Trasi S, Shetty S, Mohanty D.
Use of a new enzyme-linked immunosorbent assay for the detection of type 2N von Willebrand disease and its prevalence in an Indian population.
Blood Coagul Fibrinolysis.
2006;
17
(1)
7-11
-
15
Giangrande PL, Black C.
World Federation of Haemophilia programs in developing countries.
Semin Thromb Hemost.
2005;
31
(5)
555-560
-
16
Edlund M, Blombäck M,
von Schoultz B, Andersson O.
On the value of menorrhagia as a predictor for coagulation disorders.
Am J Hematol.
1996;
53
(4)
234-238
-
17
Kadir RA, Economides DL, Sabin CA, Owens D, Lee CA.
Frequency of inherited bleeding disorders in women with menorrhagia.
Lancet.
1998;
351
(9101)
485-489
-
18
Kouides P, Phatak P, Sham R et al.
The prevalence of subnormal von Willebrand factor levels in menorrhagia patients in Rochester, NY: final analysis.
Haemophilia.
2000;
6
240-247
-
19
Goodman-Gruen D, Hollenbach K.
The prevalence of von Willebrand disease in women with abnormal uterine bleeding.
J Womens Health Gend Based Med.
2001;
10
(7)
677-680
-
20
Saxena R, Gupta M, Gupta PK, Kashyap R, Choudhry VP, Bhargava M.
Inherited bleeding disorders in Indian women with menorrhagia.
Haemophilia.
2003;
9
(2)
193-196
-
21
Trasi SA, Pathare AV, Shetty SD, Ghosh K, Salvi V, Mohanty D.
The spectrum of bleeding disorders in women with menorrhagia: a report from Western India.
Ann Hematol.
2005;
84
(5)
339-342
-
22
Trasi S, Mohanty D, Pathare A, Shetty S, Ghosh K.
von Willebrand factor 1 and factor 2 alleles (intron 40) are suitable markers for carrier detection in von Willebrand disease families in the Indian population.
Acta Haematol.
2006;
115
(1–2)
64-67
-
23
Gupta PK, Kannan M, Saxena R.
Carrier detection in severe von Willebrand's disease.
Ann Hematol.
2004;
83
(10)
625-627
-
24
Trasi S, Mohanty D, Shetty S, Ghosh K.
Prenatal diagnosis of von Willebrand disease in a family.
Natl Med J India.
2005;
18
(4)
187-188
-
25
Shetty S, Ghosh K.
Robustness of factor assays following cordocentesis in the prenatal diagnosis of haemophilia and other bleeding disorders.
Haemophilia.
2007;
13
(2)
172-177
-
26
Gupta PK, Saxena R, Adamtziki E et al.
Genetic defects in von Willebrand disease type 3 in Indian and Greek patients.
Blood Cells Mol Dis.
2008;
41
(2)
219-222
-
27
Baronciani L, Cozzi G, Canciani MT et al.
Molecular defects in type 3 von Willebrand disease: updated results from 40 multiethnic patients.
Blood Cells Mol Dis.
2003;
30
(3)
264-270
-
28
Gupta PK, Adamtziki E, Budde U et al.
Gene conversions are a common cause of von Willebrand disease.
Br J Haematol.
2005;
130
(5)
752-758
-
29
Kasatkar P, Shetty S, Ghosh K.
VWF pseudogene: mimics, masks and spoils.
Clin Chim Acta.
2010;
411
(7-8)
607-609
-
30
Nomikou E, Tsevrenis V, Gafou A, Bellia M, Theodossiades G.
Type IIb von Willebrand disease with angiodysplasias and refractory gastrointestinal bleeding successfully treated with thalidomide.
Haemophilia.
2009;
15
(6)
1340-1342
-
31
Sohal M, Laffan M.
von Willebrand disease and angiodysplasia responding to atorvastatin.
Br J Haematol.
2008;
142
(2)
308-309
-
32
Viswabandya A, Mathews V, George B et al.
Successful surgical haemostasis in patients with von Willebrand disease with Koate DVI.
Haemophilia.
2008;
14
(4)
763-767
-
33
Mathews V, Srivastava A, Nair SC, Chandy M.
Haemostasis with cryoprecipitate in patients undergoing surgery for severe von Willebrand disease.
Natl Med J India.
2000;
13
(4)
188-190
-
34
Shanthala Devi AM, Sitalakshmi S, Anuradha S.
Profile of inherited bleeding disorders in a teaching hospital.
Ind J Hematol Blood Transf.
1999;
17
17-19
-
35
Mohanty D, Ghosh K, Das K.
Inherited disorders of blood coagulation in North Western India.
Thromb Haemost.
1983;
50
(Suppl 1)
272
Abstract 0853
Kanjaksha GhoshM.D.
National Institute of Immunohaematology (ICMR)
KEM Hospital, Parel, Mumbai, India
Email: kanjakshaghosh@hotmail.com
