Haematology, Sydney Centres for Thrombosis and Haemostasis, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, New South Wales, Australia.
School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, New South Wales, Australia.
Semin Thromb Hemost. 2021 Jun;47(4):400-418. doi: 10.1055/s-0041-1727282. Epub 2021 Apr 23.
von Willebrand factor (VWF) is a large adhesive multimeric protein involved in hemostasis. The larger the size (or number of VWF multimers), the greater the functionality of the protein. A deficiency or defect of VWF can lead to von Willebrand disease (VWD) and cause bleeding. Conversely, an increase in VWF may create an environment that promotes thrombosis. ADAMS-13 ( isintegrin nd etalloproteinase with a hrombopondin type 1 motif, member ), sometimes called VWF-cleaving protease, is primarily responsible for controlling the size of VWF. The most severe deficiency (<10% of normal levels) of ADAMTS-13 arises in thrombotic thrombocytopenic purpura, a condition characterized by the presence of ultralarge VWF and clinically resulting in enhanced risk of thrombosis. However, ADAMTS-13 deficiency may result from other pathological processes. Of relevance is the recent finding that COVID-19 (coronavirus disease 2019) is associated with both increased levels and activity of VWF as well as generally decreased (or occasionally normal) activity levels of ADAMTS-13. Thus, in COVID-19 there is an alteration in the VWF/ADAMTS-13 axis, most often described by increased VWF/ADAMTS-13 ratio (or reduced ADAMTS-13/VWF ratio). COVID-19 is also associated with high prothrombotic risk. Thus, the imbalance of VWF and ADAMTS-13 in COVID-19 may be providing a milieu that promotes (micro)thrombosis, in a clinical picture resembling a secondary thrombotic microangiopathy in some patients. This review therefore assesses the literature on VWF, ADAMTS-13, and COVID-19. Whenever reported in COVID-19, VWF has always been identified as raised (compared with normal reference ranges or control populations). Reports have included VWF level (i.e., VWF antigen) and in some cases one or more VWF "activity" (e.g., collagen binding; platelet glycoprotein Ib [GPIb] binding, using ristocetin cofactor or more modern versions including VWF:GPIbR [recombinant] and VWF:GPIbM [mutant]). Whenever reported, ADAMTS-13 has been reported as "normal" or reduced; however, it should be recognized that "normal" levels may still identify a relative reduction in individual cases. Some reports also discuss the raised VWF/ADAMTS-13 (or reduced ADAMTS-13/VWF) ratio, but very few provide actual numerical data.
血管性血友病因子（VWF）是一种参与止血的大型黏附性多聚体蛋白。VWF 多聚体的大小（或数量）越大，蛋白的功能就越大。VWF 的缺乏或缺陷可导致血管性血友病（VWD）并引起出血。相反，VWF 的增加可能会产生促进血栓形成的环境。ADAMS-13（整合素和金属蛋白酶与血栓素 1 型基序，成员），有时称为 VWF 切割蛋白酶，主要负责控制 VWF 的大小。ADAMTS-13 的最严重缺乏（<正常水平的 10%）发生在血栓性血小板减少性紫癜中，其特征是存在超大 VWF，并且临床上会增加血栓形成的风险。然而，ADAMTS-13 缺乏可能是由其他病理过程引起的。值得注意的是，最近的发现表明，COVID-19（2019 年冠状病毒病）与 VWF 水平升高和活性增强以及 ADAMTS-13 活性水平普遍降低（或偶尔正常）相关。因此，在 COVID-19 中，VWF/ADAMTS-13 轴发生改变，通常描述为 VWF/ADAMTS-13 比值升高（或 ADAMTS-13/VWF 比值降低）。COVID-19 还与高血栓形成风险相关。因此，COVID-19 中 VWF 和 ADAMTS-13 的失衡可能提供了促进（微）血栓形成的环境，在某些患者中类似于继发性血栓性微血管病。因此，本综述评估了 VWF、ADAMTS-13 和 COVID-19 的文献。在 COVID-19 中报告的 VWF 始终高于（与正常参考范围或对照人群相比）。报告包括 VWF 水平（即 VWF 抗原），在某些情况下还包括一种或多种 VWF“活性”（例如，胶原结合；血小板糖蛋白 Ib [GPIb] 结合，使用瑞斯托霉素辅因子或更现代的版本，包括 VWF：GPIbR [重组]和 VWF：GPIbM [突变]）。只要报告，ADAMTS-13 就被报告为“正常”或降低；但是，应该认识到，“正常”水平在某些情况下仍然可以识别个体病例中的相对降低。一些报告还讨论了升高的 VWF/ADAMTS-13（或降低的 ADAMTS-13/VWF）比值，但很少提供实际的数值数据。
