Reiter Rosemarie A, Varadi Katalin, Turecek Peter L, Jilma Bernd, Knöbl Paul
Department of Clinical Pharmacology, Medical University of Vienna, Austria.
Thromb Haemost. 2005 Mar;93(3):554-8. doi: 10.1160/TH04-08-0467.
Von Willebrand factor (VWF) is synthesized in endothelial cells, stored in the form of high molecular weight multimers and released after stimulation. After release, the multimers are cleaved by ADAMTS13 (von-Willebrand-factor-cleaving protease). We studied healthy volunteers in a double-blind, placebo controlled inflammation model. Ten male volunteers received 2 ng/kg endotoxin intravenously, and 5 volunteers placebo. Endotoxin infusion induced systemic inflammation and coagulation activation. After 4 hours the observed increase in neutrophils reached a maximum (273+/-34% of baseline; mean+/-SEM) and the platelet count dropped (81+/-2%). These parameters returned to baseline values after 24 hours. VWF antigen increased to 259+/-16% of baseline after 4 hours, remained elevated (192+/-15%) after 24 hours and returned to baseline after 7 days. Unusually large VWF multimers occurred in the plasma 4 hours after endotoxin infusion. ADAMTS13 activity (measured with a collagen-binding assay) decreased to 64+/-5% of baseline (P<0.001) after 4 hours, was still reduced after 24 hours (86+/- %; P=0.008) and returned to normal after 7 days. VWF multimer analysis showed pronounced satellite bands in the 4-hour samples, indicating cleavage of VWF by ADAMTS13. No apparent changes of the analyzed parameters were observed in the placebo group. The reciprocal course of ADAMTS13 and VWF after short-term VWF release induced by systemic inflammation is similar to that observed after induction of VWF release by desmopressin.
血管性血友病因子（VWF）在内皮细胞中合成，以高分子量多聚体的形式储存，并在受到刺激后释放。释放后，这些多聚体被ADAMTS13（血管性血友病因子裂解蛋白酶）裂解。我们在一个双盲、安慰剂对照的炎症模型中研究了健康志愿者。10名男性志愿者静脉注射2 ng/kg内毒素，5名志愿者注射安慰剂。内毒素输注引发全身炎症和凝血激活。4小时后，观察到的中性粒细胞增加达到最大值（为基线的273±34%；平均值±标准误），血小板计数下降（81±2%）。这些参数在24小时后恢复到基线值。VWF抗原在4小时后增加到基线的259±16%，24小时后仍保持升高（192±15%），并在7天后恢复到基线。内毒素输注4小时后，血浆中出现异常大的VWF多聚体。4小时后，ADAMTS13活性（用胶原结合试验测量）降至基线的64±5%（P<0.001），24小时后仍降低（86±%；P=0.008），并在7天后恢复正常。VWF多聚体分析显示4小时样本中有明显的卫星带，表明ADAMTS13对VWF进行了裂解。在安慰剂组中未观察到分析参数的明显变化。全身炎症诱导的VWF短期释放后，ADAMTS13和VWF的相反变化过程与去氨加压素诱导VWF释放后观察到的相似。
