Von Willebrand disease among women of African descent attending the Aga Khan University Hospital Nairobi, with menorrhagia
Date of Award
Master of Medicine (MMed)
Dr. Nancy Okinda
Dr. Patricia Muthaura
Dr. Charles Muriuki
Pathology (East Africa)
Introduction: Von Willebrand Disease (VWD) is the most common heritable bleeding disorder with equal prevalence reported across the races. Women are more likely to present with excessive bleeding due to menstruation and child bearing. Studies have found that 5-24% of women presenting with menorrhagia have VWD.
Women of African descent are under-represented in studies carried out on Von Willebrand disease and lower prevalence has been reported in this population. VWD has variable penetrance and racial differences in genetic mutations may influence presentation and disease severity. It was predicted that the standardization of the study conditions (case definition of menorrhagia, use of a standardized bleeding assessment tool, and evaluation of lack of a pelvic pathology, and having a homogenous sample in both the cases and controls) would minimize any confounders and consequently give a clearer picture on Von Willebrand disease among women of African descent.
Objectives: The aim of this study was to determine if there was a difference in Von Willebrand factor levels between women of African descent with menorrhagia and those without menorrhagia. Furthermore, the study proposed to determine the proportion of participants in each arm with VWD and Low VWF, the association between VWF activity and the bleeding score and to determine the appropriateness of the BSCH recommendation against the use of blood group specific cut-offs. In addition, the study described participant characteristics; hemoglobin, peripheral blood film findings and APTT and PT levels.
Methodology: The study was designed as an unmatched case control study with a final 1:2 ratio. Cases were recruited from the Aga Khan University Hospital data base and directly from clinics whereas controls were recruited from the Blood donation unit and out-patient clinics. The participants filled out pictorial bleeding assessment charts and MCMDM-1- Von Willebrand disease bleeding questionnaire and subsequently underwent laboratory testing (complete blood count and prothrombin time, activated partial thromboplastin time and Von Willebrand factor Activity testing). Diagnoses of Von Willebrand disease and Low von Willebrand factor were made based on a cut off of Von Willebrand activity of less than 30IU/dL and 30 – 50 IU/dL respectively.
Data management and analysis: Data were collected using MCMDM-1 Bleeding questionnaire and Pictorial bleeding assessment charts. Preliminary data entry was carried out on MS Excel and subsequent analysis done using IBM version 23.0 (IBM Corp. in Armonk, NY).
Chi -square/ Fisher’s exact test carried out to determine associations for categorical variables (p ≤ 0.05). Associations between categorical and continuous variables was carried out using the Mann-Whitney U statistical test and Pearson’s correlation was used to assess for correlations between continuous variables.
Results: The study recruited 19 cases and 49 controls. The was no difference in the VWF levels between cases and controls. The proportion of participants with Von Willebrand disease was 0% among cases and 4.1% among controls; the overall proportion of participants with VWD was 2.9%. 5.3% of cases were classified as having Low Von Willebrand factor compared to 10.2% of controls; overall, 8.8% of participants had Low VWF. There was no correlation between bleeding score and Von Willebrand Ristocetin co-factor activity. Pictorial bleeding assessment chart and bleeding scores were higher among cases than controls and cases had a higher likelihood of having features of Iron deficiency anemia on peripheral blood film. Blood group had no effect on the likelihood of being classified as VWD, Low VWF or normal VWF levels.
Conclusion: The lack of a statistically significant difference in the levels of VWF and the proportions of VWD and Low VWF between cases and controls as well as the poor correlation between the bleeding score and VWF activity levels, may indicate the presence of another clinically significant bleeding disorder among women of African descent with menorrhagia. Demonstration of VWD in patients with normal bleeding scores indicates the varied clinical presentations of VWD and the limitations of a bleeding score in the young or those without a previous bleeding challenge. In addition, findings suggest that diagnosis of VWD should not be based on blood group specific cut-offs.
Munoko, A. N. (2020). Von Willebrand disease among women of African descent attending the Aga Khan University Hospital Nairobi, with menorrhagia (Unpublished master's dissertation). Aga Khan University, East Africa.