|Year : 2018 | Volume
| Issue : 4 | Page : 136-139
Prevalence of von willebrand disease among university students in Riyadh, Saudi Arabia
Esraa Abu-Douleh1, Nouf Al-Numair2, Abdulmajeed Albanyan3, Ayman Alsuliman4, Nirvana Bayoumi3, Tarek Owaidah5
1 Department of Clinical Laboratories Sciences, King Saud University, Riyadh, Saudi Arabia
2 Department of Genetics, Research Centre, King Faisal Specialist Hospital and Research Centre; Department of Genetics, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
3 Center of Excellence in Thrombosis and Hemostasis, King Saud University, Riyadh, Saudi Arabia
4 Department of Genetics, Research Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
5 Center of Excellence in Thrombosis and Hemostasis, King Saud University; Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
|Date of Web Publication||4-Feb-2019|
Dr. Nouf Al-Numair
Department of Genetics, Research Centre, King Faisal Specialist Hospital and Research Centre, Riyadh
Source of Support: None, Conflict of Interest: None
BACKGROUND: von Willebrand disease (vWD) is the most common hereditary bleeding disorder, affecting up to 1% of the general population.
OBJECTIVES: Estimating the prevalence of vWD among adolescents.
DESIGN: This study was conducted between February 2014 and January 2016 on Saudi students in Riyadh.
SETTINGS: We conducted an epidemiological survey on university students, using the standardized questionnaire based on molecular and clinical markers for the diagnosis and management of type 1 VWD.
MATERIALS AND METHODS: All blood samples were tested for complete blood count, prothrombin time, partial thromboplastin time (PTT), and platelet function analyzer (PFA-100).
MAIN OUTCOME MEASURES: Samples had an abnormal result of PTT and/or PFA-100 were tested for von Willebrand factor (vWF) antigen and factor VIII (FVIII) activity.
SAMPLE SIZE: 2000 university students aged between 17 and 22 years were included.
RESULTS: Of these students, 730 (36.5%) had reported bleeding symptoms, 326 (44.6%) had agreed to give blood samples, 116 (35.5%) samples had prolonged PTT (>41 s), 48 (14.7%) had prolonged PFA-100 adenosine diphosphate, 39 (11.9%) had prolonged PFA-100 epinephrine, and 72 (22.0%) had abnormal results in both PTT and PFA-100. Out of 275 samples tested for vWF (Ag and activity) and FVIII, 13 (3.9%) had reduced levels or nonfunction of vWF and 5 (1.6%) had reduced FVIII levels. After correlation with ABO blood group, only 5 (1.6%) cases were confirmed for vWD. The prevalence of vWD among Saudi adolescents in the selected student population was 1.5%.
CONCLUSION: In this study, we report for the first time epidemiological survey of bleeding disorders in Arab ethnicity.
LIMITATIONS: As this is a prevalence study, we have no limitations to discuss.
Keywords: Adolescents, Arabs, bleeding disorders, epidemiology, survey
|How to cite this article:|
Abu-Douleh E, Al-Numair N, Albanyan A, Alsuliman A, Bayoumi N, Owaidah T. Prevalence of von willebrand disease among university students in Riyadh, Saudi Arabia. J Appl Hematol 2018;9:136-9
|How to cite this URL:|
Abu-Douleh E, Al-Numair N, Albanyan A, Alsuliman A, Bayoumi N, Owaidah T. Prevalence of von willebrand disease among university students in Riyadh, Saudi Arabia. J Appl Hematol [serial online] 2018 [cited 2019 Feb 22];9:136-9. Available from: http://www.jahjournal.org/text.asp?2018/9/4/136/251492
| Introduction|| |
von Willebrand disease (vWD) was first described in 1926 by Dr. Eric von Willebrand from Finland. vWD has been reported worldwide as one of the most common hereditary bleeding disorders. It is associated with a quantitative or a qualitative defect in von Willebrand factor (vWF). vWF is essential for platelet adhesion to damaged endothelium as well as platelet interactions at high shear stress. It is a multifunctional adhesive protein that plays an important role in both primary and secondary hemostasis.,, vWF has a direct role in thrombin and fibrin generation, acting as a carrier molecule for the cofactor, factor VIII (FVIII). Patients are classified as type 1, type 2, or type 3, depending on the qualitative and quantitative defects in the vWF antigen. The laboratory diagnosis of vWD can be difficult as the disease is heterogeneous. This heterogeneity stems from different molecular defects that can occur in more than one of the functional domains of the multimeric glycoprotein, so an array of assays is required to characterize the phenotype.,
The method used to estimate the prevalence of vWD is of major importance to the accuracy of the estimation, the referral-based prevalence method based on the number of symptomatic patients seen at hemostasis centers or hospitals, and is dependent on several factors, such as diagnostic facilities, the subtyping of vWD based on laboratory evaluation, severity of bleeding patients in those centers. The alternative method of population-based prevalence (i.e., prevalence of vWD in the general population) employs standard criteria for assessing bleeding symptoms, family history, and laboratory values. In such a survey, asymptomatic subjects and those with less severe bleeding (such as bruises or ecchymosis and menorrhagia which is generally considered as familial), are more likely to be detected. In this study, our purpose was to estimate the prevalence of vWD among university students at Saudi Arabia and identify students with bleeding who are either not diagnosed or misdiagnosed of vWD.
| Materials and Methods|| |
This study was conducted between February 2014 and January 2016. This study was performed as a part of a big project, which studies the prevalence of bleeding disorders among adolescents in Capital city, Saudi Arabia. Each student had signed consent after approval by the ethical committees of participating institutes.
We conducted an epidemiological survey on a randomly selected Saudi national adolescent sample of 2000 preparatory and 1st-year university students (male and female) at King Saud University (KSU) in Riyadh city, Saudi Arabia. The age range of students was between 17 and 22 years. The questionnaire was developed using the molecular and clinical markers for the diagnosis and management of type 1 (MCMDM-1 VWD) questionnaire. Process of translation into Arabic and adaptation of MCMDM-1 through an expert committee for implementation has been published elsewhere.
A total of 730 (36.5%) of the 2000 students interviewed have been confirmed as Arab ethnicity and identified as potential candidates for bleeding disorders with at least two positive answer “YES” to any bleeding symptoms questions. The potential candidates identified in the Phase I were contacted for collecting sample; only 326 (44.6%) had agreed to have blood testing to investigate for the bleeding tendency and the other 404 (55.4%) students did not participate: 217 (54%) of them refused sampling, and 187 did not respond (46%) [Graph 1].
Venous blood collection was collected at students' locations and samples arrived at the Center of Excellence in Thrombosis and Hemostasis laboratory within 4 h of collection. For each candidate, 2 ml of blood was collected in a 3.2% sodium citrate tube and centrifuged at 3500 rpm for 10 min to obtain plasma. Prothrombin time (PT) and partial thromboplastin time (PTT) was performed by plasma (STAGO Compact® System, France) according to the manufacturer's recommendation. A sample of EDTA was collected for complete blood count (CBC, UniCel® DxH 800 COULTER) and ABO grouping. PFA-100 testing (Siemens-Dade International, USA) by both cartridge epinephrine (EPI) and adenosine diphosphate (ADP), which was performed immediately, and the results were reported as closure time in seconds. Each candidate who had abnormal results for PFA-100 EPI or ADP or PTT or both was tested for vWF profile (Vwf: Ag, activity, and FVIII) using STAGO Compact® system and reagents.
Data were analyzed using IBM Statistical Package for the Social Sciences (IBM-SPSS for Windows Ver. 20). Median with minimum and maximum values is preferred over mean and standard deviation where data were not in conformity with the normality assumptions tested using Shapiro–Wilk test. P < 0.05 was considered statistically significant.
| Results|| |
Of 2000 students interviewed, 730 (36.5%) suspected to have bleeding disorders because they answered two or more questions in our servey with “yes,”, of which 550 (75%) female and 180 (25%) male. Only 326 from suspected subjects agreed to continue in the study. This studied group consisted of 120 (37%) males and 206 (63%) females with a median age of 19 years whereas minimum age was 17 years and maximum age was 22 years. The most common symptom of the responders was mucocutaneous bleeding, whereas 128 (39.7%) had minor gum bleeding when brushing or flossing, 100 (30.3%) had epistaxis, and 98 (30.0%) had ecchymosis [Table 1].
|Table 1: Distribution of gender, ABO, and the most common symptom observed on suspected cases who agreed to continue in the study|
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Of 326 blood samples tested for CBC, PT, PTT, and PFA-100, 275 samples had abnormal results whereas 116 (35.5%) samples had prolonged PTT (>41 s), 48 (14.7%) had abnormal PFA-100 ADP, 39 (11.9%) had abnormal PFA-100 EPI, and 72 (22.0%) had prolonged results in both PTT and PFA-100 by both cartridge EPI and ADP. Out of 275 samples that have abnormal results (PTT, PT, and PFA-100) tested for vWF (Ag and activity) and FVIII, 13 (3.9%) had reduced levels or nonfunction of vWF and 5 (1.6%) had reduced level of FVIII. After correlation with ABO blood group, only 5 (1.6%) cases were confirmed for vWD. The medians (normal ranges) of vWF antigen, vWF activity, and FVIII activity were 101.5 (25–178 (U dL)-1), 102.5 927–178 (U dL)-1) and 183 (31%–335%), respectively [Table 2].
|Table 2: Laboratory evaluation of 5 cases who confirmed diagnosis to von Willebrand disease|
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| Discussion|| |
vWD was reported worldwide as one of the most common hereditary bleeding disorders. This study was made to estimate the prevalence of vWD among Saudi adolescents in the selected student population. Our results showed that 13 (3.9%) cases met criteria for possible vWD, and they had reduced levels or nonfunction of vWF. Many studies revealed that levels of vWF correlate with ABO blood type O individuals have significantly (approximately 25%) lower than those of people with non-O blood groups.,
After correlation with ABO blood group, only 5 (1.6%) cases were confirmed for vWD, so the prevalence of vWD was 1.5%. This study, which is, to the best of our knowledge, the first epidemiological screening study of bleeding disorders based on a validated questionnaire and confirmed by specialized tests for suspected cases. The prevalence of vWD in our study is likely to other global studies., Two pediatrics studies, one involving the screening of 1218 otherwise healthy Italian children and another involving 600 American children, found 10 (0.82%) Italian and 8 (1.3%) American children with vWD. All affected children had at least one significant bleeding symptom and a family member with bleeding symptoms, in addition to fulfilling the laboratory criteria.
Various investigations have been conducted on the prevalence of vWD in Turkey. The prevalence was found in two separate investigations to be 0.7% in the Ankara region and 0.9% in the Edirne region. New study was conducted on adolescents in Izmir between October 2006 and March 2007. A total of approximately 1339 high-school students were vWD type 1 was diagnosed in 14 individuals for a prevalence of 1.04%. Compared to a previous study in the Izmir region, the prevalence of vWD was 0.4%.
The prevalence of vWD has also been studied in other ethnic groups (A total of 315 subjects were White, 212 were Black, 16 were Hispanic, 10 were from other groups, and 47 were biracial. Eight subjects [four Black and four White] met the criteria for vWD, for a prevalence of 1.3%).
Unfortunately, no other similar local studies were evaluated for comparison because they are not available. There are few old reports from Saudi Arabia and the Middle East which conducted either in hospitals or on small population sizes, such studies not large enough to establish an accurate prevalence estimate of vWD in Saudi Arabia. Zaher and Adam did an 11-year retrospective analysis in the Western Province of the KSA. They found that 18 out of 64 studied patients where they already suspected to have vWD. Al-Fawaz et al. reported clinical characteristics and types of hereditary bleeding disorder in one institute of KSA. Of 168 patients where they already suspected to have vWD, 25 (14.8%) from 15 different families had vWD. Kumar et al. reported a vWD prevalence of 40 (17.4%) in 230 patients with known inherited bleeding disorders. Type 2 and 3 were the most common. Other findings have been reported from Iran: 39 (7%) of 545 patients with inherited bleeding disorders had vWD with a greater predominance of type 2 and 3.
| Conclusion|| |
The data presented herein will serve as a basic reference that can help to establish the prevalence of vWD in Saudi Arabia and will facilitate the way for further research into diagnosing and treating these disorders.
We would like to acknowledge King Abdul-Aziz City for Science and Technology for their grant for this research, Riyadh, Saudi Arabia.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Von Willebrand EA. Hereditary pseudohamofili. Finska Lakaresallsk. Handl 1926;67:87-112.
Favaloro EJ. Von willebrand disease: Local diagnosis and management of a globally distributed bleeding disorder. Semin Thromb Hemost 2011;37:440-55.
Zimmermann TS, Ruggeni ZM. Von Willebrand's disease. In: Spaet TH, editor. Progress in Hemostasis and Thrombosis. Vol. 6. Orlando, FL: Grune & Stratton; 1982. p. 203.
De Meyer SF, Deckmyn H, Vanhoorelbeke K. Von willebrand factor to the rescue. Blood 2009;113:5049-57.
Sadler JE. A revised classification of von Willebrand disease. For the subcommittee on von Willebrand factor of the scientific and standardization committee of the international society on thrombosis and haemostasis. Thromb Haemost 1994;71:520-5.
Castaman G, Tosetto A, Rodeghiero F, Makris M, O'Shaughnessy D, Lillicrap D, editors. Von Willebrand Disease Practical Hemostasis and Thrombosis. Oxford, UK: Blackwell; 2009. p. 73-87.
Lillicrap D. von Willebrand disease: Advances in pathogenetic understanding, diagnosis, and therapy. Am Soc Hematol Blood 2013;122:3735-40.
Mohanty D, Shetty S. Von Willebrand disease: An update. J Blood Dis Transfuz 2014;5:238.
Owaidah T, Al-Momen AK, Alzahrani HA, Albanyan A, Alsulaiman A, Khawar S, et al
. First report from the Saudi bleeding screening study: Are platelet disorders more common in Arabs? Blood 2015;126:4641.
Bowman M, Mundell G, Grabell J, Hopman WM, Rapson D, Lillicrap D, et al.
Generation and validation of the condensed MCMDM-1VWD bleeding questionnaire for von Willebrand disease. J Thromb Haemost 2008;6:2062-6.
Siddiqui KS, Abu-Riash M, Al-Suliman A. Translation and adaptation of English language questionnaire into Arabic for implimnation of a large survey on assessing the symptoms of bleeding disorder in Saudi Arabia. J Appl Hamatol 2017;8:156-8.
Chen YC, Yang L, Cheng SN, Hu SH, Chao TY. Von Willebrand disease: A clinical and laboratory study of sixty-five patients. Ann Hematol 2011;90:1183-90.
Gill JC, Endres-Brooks J, Bauer PJ, Marks WJ Jr., Montgomery RR. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood 1987;69:1691-5.
Rodeghiero F, Castaman G, Dini E. Epidemiological investigation of the prevalence of von Willebrand's disease. Blood 1987;69:454-9.
Werner EJ, Broxson EH, Tucker EL, Giroux DS, Shults J, Abshire TC, et al.
Prevalence of von Willebrand disease in children: A multiethnic study. J Pediatr 1993;123:893-8.
Gursel T, Bumin C, Ozaltin S. von Willebrand disease The prevalence. Nature Turk J Med Sci 1992; 16: 324-30.
Kundak T, Demir M. von Willebrand in the central villages of Edirne Province disease frequency detection. Trakya Ü.T.F. Internal Diseases A.D. Thesis; 2004. p. 1-55.
Sap F, Kavaklı T, Kavaklı K, Dizdarer C. The prevalence of von Willebrand disease and significance of in vitro
bleeding time (PFA-100) in von Willebrand disease screening in the Izmir region. Turk J Haematol 2013;30:40-7.
Yilmaz D, Karapinar B, Yeniay BS, Balkan C, Bilenoglu B, Kavakli K. İzmir'de von Willebrand Hastalığı sıklığını belirlemeye yönelik epidemiyolojik çalışma. Ege Pediatri Bülteni 2005;12:151-9.
Zaher G, Adam S, Outcomes of congenital bleeding disorders. Bahrain Med Bull 2012;34:P78.
Al-Fawaz IM, Gader AM, Bahakim HM, Al-Mohareb F, Al-Momen AK, Harakati MS. Hereditary bleeding disorders in Riyadh, Saudi Arabia. Ann Saudi Med 1996;16:257-61.
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;53:486-9.
] [Full text]
Karimi M, Haghpanah S, Amirhakimi A, Afrasiabi A, Dehbozorgian J, Nasirabady S. Spectrum of inherited bleeding disorders in Southern Iran, before and after the establishment of comprehensive coagulation laboratory. Blood Coagul Fibrinolysis 2009;20:642-5.
[Table 1], [Table 2]