Back
Active von Willebrand factor (VWF) in plasma of sickle cell patients is an indicator of disease severity
Abstract number: PP-WE-887
Chen1 J., Hobbs1 W., Le1 J., Lenting2 P., de Groot2 P.G., Lopez1 J.A.
11Research Division, Puget Sound Blood Center, Seattle, WA, USA 22Department of Clinical Chemistry & Haematology, UMC, Utrecht, the Netherlands
How-to-cite Chen J, Hobbs W, Le J, Lenting P, de Groot PG, Lopez JA. Active von Willebrand factor (VWF) in plasma of sickle cell patients is an indicator of disease severity. Journal of Thrombosis and Haemostasis 2009; Volume 7, Supplement 2: Abstract PP-WE-887
Vasoocclusion, hemolysis and oxidative stress are hallmarks of sickle cell anemia (SCA). Oxidants generated in SCA can stimulate endothelial cell release of ultralarge VWF, which is hyperactive in binding platelets and erythrocytes compared to normal plasma VWF, binding sickle erythrocytes especially well. We therefore assessed several parameters of VWF quantity and function in plasma from SCA patients at disease baseline (16 individuals, not acutely ill, some with multiple determinations). Parameters measured included VWF antigen, multimer pattern, and activation factor determined using a llama antibody (nanobody) that detects an active conformation of the VWF A1 domain, which correlates with enhanced platelet binding. Elevated nanobody binding has been demonstrated in patients with type 2B von Willebrand disease, thrombotic thrombocytopenic purpura, HELLP syndrome, and other thrombotic disorders. VWF activation factor is defined as the ratio of nanobody binding of patient plasma to that of pooled normal plasma at a given VWF antigen level. All SCA patients had VWF antigen levels that were higher than in pooled plasma (1.2–3.6 fold) or in ethnically matched control plasma. Activation factors ranged from 0.6 to 4.4 (the activation factor of pooled plasma set at 1). By multiplying the antigen level by the activation factor we determined the total active VWF in the plasma. Total active VWF significantly correlated with chronic disease severity and with plasma lactate dehydrogenase (LDH) level (P = 0.02). In SCA, elevated LDH is associated with increased risk of pulmonary hypertension, leg ulcers, priapism and death. In these patients, total active VWF also correlated with higher VWF multimer composition on agarose gels. These findings suggest that elevated levels of active VWF predispose patients with SCA to vasoocclusive complications.
Disclosure of interest: none declared.
To cite this abstract use the following format:
Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number
Session Details
| Date: |
Unpresented
|
| Time: |
N/A
|
| Session name: |
ISTH2009 |
| Subject: |
|
| Location: |
|
| Presentation type: |
|
| Back to top |
