Variable bleeding phenotype in an Amish pedigree with von Willebrand disease

Through a cross-sectional study design, the bleeding phenotype in the Amish in Indiana (IN) and Wisconsin (WI) was described using two different bleeding scores. von Willebrand factor (VWF) testing was performed and bleeding questionnaires from Centers for Disease Control and Prevention (CDC) and European MCMDM-1 (Tosetto bleeding score (BS)) were administered to the IN and WI cohort respectively. Seven hundred and seventy nine subjects were recruited, 17% were diagnosed with VWD based on Ristocetin cofactor, VWF:RCo < 30 IU/dl. Majority of the affected (AF), 67%, were tested and had a common mutation c.4120 C > T. The WI AF were much younger at a mean age 15 years vs 26 years in IN AF cohort. The AF subjects had a median VWF:RCo of 13IU/dl with a statistically significant higher median BS 1 versus 0 in the WI AF vs WI Unaffected (UA), 2 vs 1 in the IN AF vs IN UA, P < 0.01. Adults had a higher median BS compared to children in the WI and IN cohort, 2 vs 1 and 3 vs 1 respectively (P < 0.05) but there was no statistically significant difference in the BS between males and females in either cohort. The common symptoms reported were epistaxis and gingival oozing. BS ≥ 3 and BS ≥ 4 were observed in 46% of AF IN and 16.6% of AF WI, respectively. There was significant variability in the bleeding phenotype, with an overall low BS in the affected Amish with VWD, despite a unifying mutation. Am. J. Hematol. 91:E431–E435, 2016.