Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, the Netherlands.
Thromb Haemost. 2010 Jan;103(1):181-7. doi: 10.1160/TH09-04-0223. Epub 2009 Sep 15.
Severe falciparum malaria remains a major killer in tropical countries. Central in the pathophysiology is mechanical obstruction in the microcirculation caused by cytoadherence and sequestration of parasitized erythrocytes. However, the pathogenesis of many features complicating severe malaria, including coma, renal failure and thrombocytopenia, remains incompletely understood. These disease manifestations are also key features of thrombotic thrombocytopenic purpura, a life-threatening disease strongly associated with a deficiency of the von Willebrand factor (VWF) cleaving protease, ADAMTS13. We measured plasma ADAMTS13 activity, VWF antigen and VWF propeptide levels in 30 patients with severe falciparum malaria, 12 patients with uncomplicated falciparum malaria and 14 healthy Bangladeshi controls. In patients with severe malaria ADAMTS13 activity levels were markedly decreased in comparison to normal controls (mean [95%CI]: 23% [20-26] vs. 64% [55-72]) and VWF antigen and propeptide concentrations were significantly elevated (VWF antigen: 439% [396-481] vs. 64% [46-83]; VWF propeptide: 576% [481-671] vs. 69% [59-78]). In uncomplicated malaria VWF levels were also increased compared to healthy controls but ADAMTS13 activity was normal. The results suggest that decreased ADAMTS13 activity in combination with increased VWF concentrations may contribute to the complications in severe malaria.
严重的恶性疟原虫疟疾仍然是热带国家的主要杀手。在病理生理学中，中心问题是寄生红细胞的细胞粘附和隔离导致微循环的机械阻塞。然而，许多使严重疟疾复杂化的疾病发病机制，包括昏迷、肾衰竭和血小板减少症，仍未完全理解。这些疾病表现也是血栓性血小板减少性紫癜的关键特征，血栓性血小板减少性紫癜是一种与 von Willebrand 因子（VWF）裂解蛋白酶 ADAMTS13 缺乏强烈相关的危及生命的疾病。我们测量了 30 例严重恶性疟原虫疟疾患者、12 例无并发症恶性疟原虫疟疾患者和 14 名健康孟加拉国对照者的血浆 ADAMTS13 活性、VWF 抗原和 VWF 前肽水平。与正常对照组相比，严重疟疾患者的 ADAMTS13 活性水平明显降低（平均[95%CI]：23%[20-26]比 64%[55-72]），VWF 抗原和前肽浓度显著升高（VWF 抗原：439%[396-481]比 64%[46-83]；VWF 前肽：576%[481-671]比 69%[59-78]）。与健康对照组相比，无并发症疟疾患者的 VWF 水平也升高，但 ADAMTS13 活性正常。结果表明，ADAMTS13 活性降低与 VWF 浓度增加相结合可能导致严重疟疾的并发症。
