van den Born Bert-Jan H, van der Hoeven Niels V, Groot Evelyn, Lenting Peter J, Meijers Joost C M, Levi Marcel, van Montfrans Gert A
Department of Internal and Vascular Medicine, Academic Medical Centre, Meibergdreef 9, Room F4-222, PO Box 22660, 1100 DD, Amsterdam, the Netherlands.
Hypertension. 2008 Apr;51(4):862-6. doi: 10.1161/HYPERTENSIONAHA.107.103127. Epub 2008 Mar 10.
The thrombotic microangiopathy observed in malignant hypertension is similar to that of thrombotic thrombocytopenic purpura, which is associated with a deficiency of ADAMTS13, a von Willebrand factor (VWF)-cleaving protease that cleaves large prothrombogenic multimers. We hypothesized that ADAMTS13 is deficient in malignant hypertension and that the severity of thrombotic microangiopathy is associated with decreased ADAMTS13 activity. We included 20 patients with malignant and 20 patients with severe hypertension, and 20 matched normotensive individuals served as control subjects. VWF, active VWF, and free hemoglobin were assessed to explore predictors of ADAMTS13 activity. Patients with malignant hypertension had lower ADAMTS13 activity (80%; interquartile range: 53% to 130%) compared with control subjects (99% interquartile range: 82% to 129%; P<0.01) but not compared with patients with severe hypertension (P=0.14). ADAMTS13 activity negatively correlated with lactic dehydrogenase levels after logarithmic transformation (r=-0.65; P<0.001) and was associated with platelet count (r=0.34; P=0.04) and the presence of schistocytes (r=-0.37; P=0.02). Apart from the association with thrombotic microangiopathy, ADAMTS13 was inversely associated with creatinine (r=-0.42; P=0.008). Increasing levels of VWF were associated with a decrease in ADAMTS13 activity (r=-0.34; P=0.03). There was no significant association between ADAMTS13 activity and other parameters, including blood pressure. In conclusion, ADAMTS13 is decreased in malignant hypertension and associated with the severity of thrombotic microangiopathy, likely because of the release of VWF after endothelium stimulation. A severe deficiency could not be demonstrated. More studies are needed to identify the role of ADAMTS13 in the thrombotic microangiopathy and ischemic complications of malignant hypertension.
恶性高血压中观察到的血栓性微血管病与血栓性血小板减少性紫癜相似，后者与ADAMTS13缺乏有关，ADAMTS13是一种切割血管性血友病因子（VWF）的蛋白酶，可切割大型促血栓形成多聚体。我们假设ADAMTS13在恶性高血压中缺乏，并且血栓性微血管病的严重程度与ADAMTS13活性降低有关。我们纳入了20例恶性高血压患者、20例重度高血压患者，20例匹配的血压正常个体作为对照。评估VWF、活性VWF和游离血红蛋白以探索ADAMTS13活性的预测因素。与对照受试者（四分位间距99%：82%至129%；P<0.01）相比，恶性高血压患者的ADAMTS13活性较低（80%；四分位间距：53%至130%），但与重度高血压患者相比无差异（P=0.14）。对数转换后，ADAMTS13活性与乳酸脱氢酶水平呈负相关（r=-0.65；P<0.001），并与血小板计数（r=0.34；P=0.04）和裂体细胞的存在（r=-0.37；P=0.02）相关。除了与血栓性微血管病有关外，ADAMTS13与肌酐呈负相关（r=-0.42；P=0.008）。VWF水平升高与ADAMTS13活性降低有关（r=-0.34；P=0.03）。ADAMTS13活性与包括血压在内的其他参数之间无显著关联。总之，ADAMTS13在恶性高血压中降低，并与血栓性微血管病的严重程度有关，可能是因为内皮刺激后VWF的释放。未证实存在严重缺乏。需要更多研究来确定ADAMTS13在恶性高血压的血栓性微血管病和缺血性并发症中的作用。
