DISCOVERY OF TYPE 3 VON WILLEBRAND DISEASE IN A COHORT OF PATIENTS WITH SUSPECTED HEMOPHILIA A IN CÔTE D’IVOIRE

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Adia Eusèbe Adjambri *
Sylvie Bouvier
Roseline N'guessan
Emma N’draman-Donou
Mireille Yayo-Ayé
Marie-France Meledje
Missa Louis Adjé
Duni Sawadogo
(*) Corresponding Author:
Adia Eusèbe Adjambri | eusebeadjambri@yahoo.fr

Abstract

Abstract


Aim : Type 3 von Willebrand disease (VWD) is the most severe form of VWD, characterized by a near-total absence of von Willebrand factor (vWF) leading to a huge deficiency in plasmatic factor VIII (FVIII). VWD may be confused with hemophilia A, sometimes leading to misdiagnosis. The purpose of this work was to finalize the biological diagnosis of patients with FVIII activity deficiency in Abidjan, in order to guide the best type of management. Methods: We conducted a cross-sectional descriptive study from June 2018 to April 2019. Forty-nine patients, all of whom had lower FVIII levels or had been referred for bleeding disorder, were monitored in the clinical hematology service. Pro-coagulant activity of coagulation factors was performed in Abidjan. The assays for von Willebrand antigen and activity were performed at Nîmes University Hospital in France. Results: The mean age of patients was 13.8 years (1 – 65) and 86% were Ivorian. FVIII deficiency was discovered during a biological checkup, circumcision or post-traumatic bleeding, in 33%, 31% and 29% respectively. The FVIII level of patients was classified as severe (89.8%), moderate (8.2%) and mild (2%). Only one patient had a quantitative deficiency of von Willebrand factor (vWF: Ag <3%) with undetectable von Willebrand factor activity (vWF: Ac) and an FVIII level <1%. Conclusion: Not all of the constitutive deficits of FVIII are hemophilia A. It was very important to assess the Willebrand factor of these patients followed in Côte d'Ivoire for whom hemophilia A had been suspected.


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References

[1] Mannucci PM, Tuddenham EG. The hemophilias - from royal genes to gene therapy. N
Engl J Med. 2001;344(23):1773–1779.
https://doi.org/10.1056/NEJM200106073442307
[2] Castaman G and Linari S. Diagnosis and Treatment of von Willebrand Disease and Rare
Bleeding Disorders. J. Clin. Med. 2017; 6(4). pii: E45.
https://doi.org/10.3390/jcm6040045
[3] Lehner S, Ekhlasi-Hundrieser M, Detering C, Allerkamp H, Pfarrer C, von Depka
Prondzinski M. A 12.3-kb Duplication Within the VWF Gene in Pigs Affected by Von
Willebrand Disease Type 3. G3 (Bethesda). 2018; 8(2) : 577-585.
https://doi.org/10.1534/g3.117.300432
[4] 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. Update on the pathology and classification of von Willebrand disease : a report of the
subcommittee on von Willebrand Factor. J Thromb Haemost 2006 ; 4(10) : 2103-2114.
https://doi.org/10.1111/j.1538-7836.2006.02146.x
[5] Srivastava A, Rodeghiero F. Epidemiology of von Willebrand disease in developing
countries. Semin Thromb Hemost. 2005; 31(5) : 569‐576.
https://doi.org/10.1055/s-2005-922229
[6] Elayaperumal S, Fouzia NA, Biswas A, Nair SC, Viswabandya A, George B, Abraham A,
Oldenburg J, Edison ES, Srivastava A. Type-3 von Willebrand disease in India-Clinical
spectrum and molecular profile. Haemophilia. 2018; 24(6): 930–940.
https://doi.org/10.1111/hae.13542
[7] Qachouh M., Harif M., Benchekroun S. La maladie de willebrand. Journal Marocain des
Sciences Médicales 2009 ; 16(3) : 7-11.
https://revues.imist.ma/index.php?journal=JMSM&page=article&op=view&path%5B%5D=639&path%5B%5D=523
[8] Gillham A, Greyling B, Wessels TM, Mbele B, Schwyzer R, Krause A, Mahlangu J.
Uptake of genetic counseling, knowledge of bleeding risks and psychosocial impact in a south African cohort of female relatives of people with hemophilia. J Genet Couns. 2015; 24(6) : 978–86.
https://doi.org/10.1007/s10897-015-9834-8
[9] Naicker T, Aldous C, Thejpal R. Haemophilia: a disease of women as well. S. Afr. J.
Child Health. 2016; 10(1) : 29–32.
https://doi.org/10.7196/SAJCH.2016.v10i1.961
[10] Seck M, Faye BF, Sall A, Sy D, Touré SA, Dieng N, Guéye YB, Gadji M, Touré AO,
Costa C, Lasne D, Rothschild C, Diop S. Bleeding risk assessment in hemophilia a
carriers from Dakar, Senegal. Blood Coagul Fibrinolysis. 2017; 28(8) : 642-645.
https://doi.org/10.1097/MBC.0000000000000653
[11] Lambert C, Meité N, Sanogo I, Lobet S, Adjambri E, Eeckhoudt S, Hermans C.
Haemophilia in Côte d’Ivoire (Ivory Coast) in 2017 : extensives data collection as part of
the World Federation of Haemophilia’s twnning program. Haemophilia. 2019;00 :1-8.
https://doi.org/10.1111/hae.13682

[12] Seck M, Sagna A, Guéye MS, Faye BF, Sy D, Touré SA, Sall A, Touré AO, Diop S.
Circumcision in haemophilia using low quantity of factor concentrates : experience from
Dakar, Senegal. BMC Hematol. 2017 ;17(1) :4-9.
https://doi.org/10.1186/s12878-017-0080-1
[13] Diop S., Touré AO., Thiam D, Dièye M, Diakhaté L. Profil évolutif de l'hémophilie A au
Sénégal: étude prospective réalisée chez 54 patients. Transfus Clin Biol. 2003; 10(1) :
37-40.
https://doi.org/10.1016/S1246-7820(02)00002-2
[14] Zhang ZP, Lindstedt M, Falk G, Blombäck 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; 51(4) : 850-858.
https://www.ncbi.nlm.nih.gov/pubmed/1415226
[15] 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; 89(1) : 147-151.
https://doi.org/10.1111/j.1365-2141.1995.tb08921.x
[16] de Wee EM, Sanders YV, Mauser-Bunschoten EP, van der Bom JG, Degenaar-Dujardin
ME, Eikenboom J, de Goede-Bolder A, Laros-van Gorkom BA, Meijer K, Hamulyák K,
Nijziel MR, Fijnvandraat K, Leebeek FW. : Determinants of bleeding phenotype in adult
patients with moderate or severe von Willebrand disease. Thromb Haemost 2012 ;
108(4) : 683-692.
https://doi.org/10.1160/TH12-04-0244
[17] Lee AC, Li CH, Wong LG : A case of von Willebrand disease type 3 misdiagnosed as
hemophilia A. Zhonghua Er Ke Za Zhi 2007 ; 45(12) : 950.
https://www.ncbi.nlm.nih.gov/pubmed/18339291
[18] Boylan B, Rice AS, De Staercke C, Eyster ME, Yaish HM, Knoll CM, Bean CJ, Miller
CH. Evaluation of von Willebrand factor phenotypes and genotypes in Hemophilia A
patients with and without identified F8 mutations. J Thromb Haemost 2015 ; 13(6) :
1036-1042.
https://doi.org/10.1111/jth.12902
[19] Echahdi H, El Hasbaoui B, El Khorassani M, Agadr A, Khattab M. Von Willebrand's
disease: case report and review of literature. Pan Afr Med J. 2017; 27 :147.
https://doi.org/10.11604/pamj.2017.27.147.12248
[20] Benlaldj D, Moueden MA, Seghier F. Maladie de von Willebrand type 3 faussement
diagnostiquée en hémophilie A modérée: à propos d’une observation. Rev Med Brux
2017 ; 38(1) : 36-38.
https://www.ncbi.nlm.nih.gov/pubmed/28525200
[21] Eikenboom JC. Congenital von Willebrand disease type 3: Clinical manifestations,
pathophysiology and molecular biology. Best Pract Res Clin Haematol. 2001; 14(2)
:365-79.
https://doi.org/10.1053/beha.2001.0139
[22] Bowman M, Tuttle A, Notley C, Brown C, Tinlin S, Deforest M, Leggo J, Blanchette
VS, Lillicrap D, James P. The Genetics of Canadian Type 3 von Willebrand Disease
(VWD): Further Evidence for Co-dominant Inheritance of Mutant Alleles. J Thromb
Haemost. 2013; 11(3): 512–520.
https://doi.org/10.1111/jth.12130
[23] 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; 57(1) : 163-169.
https://doi.org/10.1111/j.1365-2141.1984.tb02876.x
[24] Hussain, R, Bittles AH. The prevalence and demographic characteristics of
consanguineous marriages in Pakistan. J Biosoc Sci 1998, 30 (2): 261-275.
https://doi.org/10.1017/s0021932098002612
[25] Denic, S. Consanguinity as risk factor for cervical carcinoma. Med Hypotheses 2003; 60
(3): 321-324.
https://doi.org/10.1016/s0306-9877(02)00389-4
[26] Talbi J, Khadmaoui AE, Soulaymani AEM, Chafik AEA. Etude de la consanguinité dans
la population marocaine. Impact sur le profil de la santé. Antropo. 2007, 15: 1-11.
http://www.didac.ehu.es/antropo/15/15-1/Talbi.pdf
[27] Castaman G, Federici AB, Rodeghiero F, Mannucci PM: Von Willebrand’s disease in the
year 2003: towards the complete identification of gene defects for correct diagnosis and
treatment. Haematologica 2003; 88(1) : 94-108.
https://www.ncbi.nlm.nih.gov/pubmed/12551832
[28] Federici AB, Castaman G, Franchini M. Clinical use of Haemate P in inherited von
Willebrand’s disease: a cohort study on 100 Italian patients. Haematologica 2007; 92(7):
944-951.
https://doi.org/10.3324/haematol.11124
[29] Federici AB, James P. Current Management of Patients with Severe von Willebrand
Disease Type 3: A 2012 Update. Acta Haematol. 2012; 128(2): 88–99.
https://doi.org/10.1159/000338208