VPB0835 - Hemoglobin concentration is a determinate of plasma VWF and FVIII levels

Background: Von Willebrand Disease (VWD) is the most common bleeding disorder. Complicating the diagnosis, von Willebrand factor (VWF) and factor VIII (FVIII) are acute phase reactants, and levels fluctuate in response to many stimuli, including physical activity. A common scenario for evaluation of a bleeding disorder is in patients with bleeding symptoms leading to iron deficiency anemia. We therefore sought to determine if anemia leads to elevations in VWF and factor VIII levels.

Aims: Define the impact of hemoglobin levels on VWF and FVIII levels in persons without a known bleeding disorder.

Methods: This is a single-site retrospective review of the electronic health record of patients that had von Willebrand profiles [VWF:Antigen (Ag), VWF:Activity (Act), and FVIII activity] obtained within 24 hours of a hemoglobin level. Data was retrieved from January 1, 2012, through June 1, 2021.

Results: We identified 4899 instances among 4552 patients of a VWF profile that had an associated hemoglobin level in a 24-hour period in individuals that did not carry a diagnosis of VWD. 1134 (30%) of these instances were associated with a hemoglobin < 12 g/dL. Stratifying by hemoglobin, we found that both VWF: Ag (P < 0.0001) and VWF:Act (P < 0.0001) were significantly elevated in patients with anemia (defined as hemoglobin < 12 g/dL). This correlation was strongest in patients with a hemoglobin of < 10 g/dL. FVIII levels also increased in strong association with anemia (P < 0.0001). Interestingly, we also observed that anemia was associated with a significant decrease in the VWF Act:Ag ratio (P < 0.01).

Conclusion(s): Anemia was found to be associated with elevations of VWF:Ag, VWF:Act, and FVIII. As many patients presenting for a bleeding disorder evaluation are anemic, the confounding effect of anemia should be considered during the diagnostic evaluation.