Research output: Contribution to journal › Article › Academic › peer-review
Dynamics of von Willebrand factor reactivity in sickle cell disease during vaso-occlusive crisis and steady state. / Sins, J. W. R.; Schimmel, M.; Luken, B. M. et al.
In: Journal of thrombosis and haemostasis, Vol. 15, No. 7, 2017, p. 1392-1402.Research output: Contribution to journal › Article › Academic › peer-review
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TY - JOUR
T1 - Dynamics of von Willebrand factor reactivity in sickle cell disease during vaso-occlusive crisis and steady state
AU - Sins, J. W. R.
AU - Schimmel, M.
AU - Luken, B. M.
AU - Nur, E.
AU - Zeerleder, S. S.
AU - van Tuijn, C. F. J.
AU - Brandjes, D. P. M.
AU - Kopatz, W. F.
AU - Urbanus, R. T.
AU - Meijers, J. C. M.
AU - Biemond, B. J.
AU - Fijnvandraat, K.
PY - 2017
Y1 - 2017
N2 - Background: Endothelial activation plays a central role in the pathophysiology of vaso-occlusion in sickle cell disease (SCD), facilitating adhesive interactions with circulating blood cells. Upon activation, various adhesive molecules are expressed, including von Willebrand factor (VWF). Increased VWF levels have been observed in patients with SCD during steady state. However, the role of VWF in the pathogenesis of SCD vasoocclusion is unclear. Objectives: To longitudinally assess the quantity and reactivity of VWF and its regulating protease ADAMTS-13 during vaso-occlusive crisis (VOC). Methods: In this observational study, we obtained sequential blood samples in adult SCD patients during VOC. Results: VWF reactivity was significantly higher during VOC (active VWF, VWF glycoprotein Ib-binding activity, and high molecular weight multimers), whereas platelet count and levels of ADAMTS-13 antigen and ADAMTS-13 activity were concomitantly lower than during steady state. Levels of VWF antigen, VWF propeptide (VWF: pp) and ADAMTS-13 specific activity did not change during VOC. VWF reactivity correlated strongly with markers of inflammation and neutrophil activation, and was inversely correlated with the platelet count. In patients who developed acute chest syndrome, levels of VWF, VWF: pp and active, hyperadhesive VWF were significantly higher, whereas ADAMTS-13 activity was lower, than in patients without this complication. Conclusions: We provide the first evidence that VOC in SCD is associated with increased reactivity of VWF, without a pronounced ADAMTS-13 deficiency. This hyper-reactivity may be explained by resistance of VWF to proteolysis, secondary to processes such as inflammation and oxidative stress. Hyperadhesive VWF, scavenging blood cells in the microcirculation, may thereby amplify and sustain VOC in SCD
AB - Background: Endothelial activation plays a central role in the pathophysiology of vaso-occlusion in sickle cell disease (SCD), facilitating adhesive interactions with circulating blood cells. Upon activation, various adhesive molecules are expressed, including von Willebrand factor (VWF). Increased VWF levels have been observed in patients with SCD during steady state. However, the role of VWF in the pathogenesis of SCD vasoocclusion is unclear. Objectives: To longitudinally assess the quantity and reactivity of VWF and its regulating protease ADAMTS-13 during vaso-occlusive crisis (VOC). Methods: In this observational study, we obtained sequential blood samples in adult SCD patients during VOC. Results: VWF reactivity was significantly higher during VOC (active VWF, VWF glycoprotein Ib-binding activity, and high molecular weight multimers), whereas platelet count and levels of ADAMTS-13 antigen and ADAMTS-13 activity were concomitantly lower than during steady state. Levels of VWF antigen, VWF propeptide (VWF: pp) and ADAMTS-13 specific activity did not change during VOC. VWF reactivity correlated strongly with markers of inflammation and neutrophil activation, and was inversely correlated with the platelet count. In patients who developed acute chest syndrome, levels of VWF, VWF: pp and active, hyperadhesive VWF were significantly higher, whereas ADAMTS-13 activity was lower, than in patients without this complication. Conclusions: We provide the first evidence that VOC in SCD is associated with increased reactivity of VWF, without a pronounced ADAMTS-13 deficiency. This hyper-reactivity may be explained by resistance of VWF to proteolysis, secondary to processes such as inflammation and oxidative stress. Hyperadhesive VWF, scavenging blood cells in the microcirculation, may thereby amplify and sustain VOC in SCD
U2 - 10.1111/jth.13728
DO - 10.1111/jth.13728
M3 - Article
C2 - 28457019
VL - 15
SP - 1392
EP - 1402
JO - Journal of thrombosis and haemostasis
JF - Journal of thrombosis and haemostasis
SN - 1538-7933
IS - 7
ER -
ID: 3788786