Influence of blood group, von Willebrand factor levels, and age on factor VIII levels in non‐severe haemophilia A

Abstract

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractBackground: Data on the effect of ABO blood group (ABO), von Willebrand factor (VWF) levels, and age on factor VIII (FVIII) in non-severe haemophilia A (HA) is scarce.Objective: To investigate if ABO, VWF levels, and age have an influence on the variability of FVIII levels and consequently on the assessment of severity in non-severe HA. Patients/Methods: Eighty-nine patients with non-severe HA and 82 healthy controls were included. Data on ABO was collected and FVIII clotting activity (FVIII:C) with onestage clotting assay (FVIII:C OSA) and chromogenic substrate assay (FVIII:C CSA), FVIII antigen (FVIII:Ag) and VWF antigen (VWF:Ag) and activity (VWF:Act) were determined. Results: In HA, FVIII:C OSA and CSA and FVIII:Ag were not different between non-O (n = 42, median 15.5, interquartile range 10.4-24.0; 10.0, 6.8-26.0 and 15.2, 10.7-24.9)and O (n = 47, 14.1, 9.0-23.0; 10.0, 5.0-23.0 and 15.2, 9.3-35.5), whereas in healthy controls, non-O individuals had significantly higher FVIII levels. FVIII:C showed no relevant correlation with VWF levels in HA, but we observed strong correlations in healthy controls. Age had only a minor influence in HA, but had a considerable impact on FVIII:C in healthy controls. In multivariable regression analysis ABO, VWF:Ag and age were not associated with FVIII:C in HA, whereas this model explained 61.3% of the FVIII:C variance in healthy controls. Conclusions:We conclude that in non-severe HA ABO and VWF levels do not substantially influence the variability of FVIII levels and age has only minor effects on it, which is important information for diagnostic procedures.

ABO Blood Groups and Their Relationship with Coagulation Factor VIII in Healthy Adults

“…Von Willebrand factor as study subjects. This might be the reason of contrary in findings from present study [23].…”

“…Rejto et al (2020) observed no significant difference among ABO blood groups in case of coagulation factor VIII. They include non severe haemophilia patients…”

Age-Associated Increase in Thrombogenicity and Its Correlation with von Willebrand Factor

“…However, the influence of aging and plasma VWF levels on FVIII level and coagulant activity in mild Hemophilia A patients is scarcely studied. One study reported a significant positive correlation between FVIII coagulant activity and aging without amelioration of bleeding [ 70 ]; whereas another study identified only minor influence of aging on FVIII levels/activity [ 71 ]. A cross-sectional study of 3616 Japanese participants, aged 30 to 79 years reported that VWF levels tend to increase (significantly influenced by ABO blood groups), whereas ADAMTS13 activity was decreased (not significantly influenced by ABO blood groups) with advancing age, leading to an increased ratio of plasma VWF levels -to-ADAMTS13 activity with aging in both men and women [ 72 ].…”

Genomic Analysis for the Detection of Bleeding and Thrombotic Disorders

“…However, if we consider mild hemophilia there is an increasing contribution to phenotype from genetic modifiers (variants in other genes) and environmental or acquired factors. For example, in mild hemophilia A, the factor VIII level is heavily dependent on von Willebrand factor levels and variants in VWF can thus affect the bleeding phenotype 23 (►Fig. 1).…”