Quantification of von Willebrand factor and ADAMTS-13 after traumatic injury: a pilot study

Abstract

BackgroundVon Willebrand factor (VWF) is an acute phase reactant synthesized in the megakaryocytes and endothelial cells. VWF forms ultra-large multimers (ULVWF) which are cleaved by the metalloprotease ADAMTS-13, preventing spontaneous VWF–platelet interaction. After trauma, ULVWF is released into circulation as part of the acute phase reaction. We hypothesized that trauma patients would have increased levels of VWF and decreased levels of ADAMTS-13 and that these patients would have accelerated thrombin generation.MethodsWe assessed plasma concentrations of VWF antigen and ADAMTS-13 antigen, the Rapid Enzyme Assays for Autoimmune Diseases (REAADS) activity of VWF, which measure exposure of the platelet-binding A1 domain, and thrombin generation kinetics in 50 samples from 30 trauma patients and an additional 21 samples from volunteers. Samples were analyzed at 0 to 2 hours and at 6 hours from the time of injury. Data are presented as median (IQR) and Kruskal-Wallis test was performed between trauma patients and volunteers at both time points.ResultsREAADS activity was greater in trauma patients than volunteers both at 0 to 2 hours (190.0 (132.0–264.0) vs. 92.0 (71.0–114.0), p<0.002) and at 6 hours (167.5 (108.0–312.5.0) vs. 92.0 (71.0–114.0), p<0.001). ADAMTS-13 antigen levels were also decreased in trauma patients both at 0 to 2 hours (0.84 (0.51–0.94) vs. 1.00 (0.89–1.09), p=0.010) and at 6 hours (0.653 (0.531–0.821) vs. 1.00 (0.89–1.09), p<0.001). Trauma patients had accelerated thrombin generation kinetics, with greater peak height and shorter time to peak than healthy volunteers at both time points.DiscussionTrauma patients have increased exposure of the VWF A1 domain and decreased levels of ADAMTS-13 compared with healthy volunteers. This suggests that the VWF burst after trauma may exceed the proteolytic capacity of ADAMTS-13, allowing circulating ULVWF multimers to bind platelets, potentially contributing to trauma-induced coagulopathy.Level of evidenceProspective case cohort study.

Prognostic value of von Willebrand factor and ADAMTS13 in patients with COVID-19: A systematic review and meta-analysis

“…CAC do not resemble a classic TTP since there is lack of severe ADAMTS13 deficiency (activity levels <10 %), major thrombocytopenia, or hemolytic anemia [22] , [54] , [64] , [68] , [70] , [80] , [81] . However, the imbalanced VWF-ADAMTS13 axis combined with clinical and pathologic findings of widespread microvascular thrombi in multi-organs may suggest a secondary TMA-like phenomenon [62] , which can also be seen in other forms of TMA (drug, cancer, or hematopoietic stem cell transplant induced TMA [159] ) and thrombotic disorders (e.g., severe sepsis, malaria, trauma, and preeclampsia) [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] . Here, we speculate the mechanisms that link VWF-ADAMTS13 axis, endotheliopathy, and CAC: SARS-CoV-2 direct invasion and/or indirect pathophysiologic conditions induce endotheliopathy and subsequent overwhelming ULVWF release.…”

“…Journal Pre-proof levels less than 10%), major thrombocytopenia, or hemolytic anemia [22,54,64,68,70,80,81]. However, the imbalanced VWF-ADAMTS13 axis combined with clinical and pathologic findings of widespread microvascular thrombi in multi-organs may suggest a secondary TMA-like phenomenon [62], which can also be seen in other forms of TMA (drug, cancer, or hematopoietic stem cell transplant induced TMA [159]) and thrombotic disorders (e.g., severe sepsis, malaria, trauma, and preeclampsia) [29][30][31][32][33][34][35][36][37][38][39]. Here, we speculate the mechanisms that link Journal Pre-proof ULVWF [161,162].…”

“…von Willebrand factor (VWF) and its cleaving protease ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) play important roles in primary and secondary thrombotic, and inflammatory response to vascular injury [26] , [27] , [28] . An imbalanced VWF-ADAMTS13 axis has been implicated in pathologies like trauma [29] , [30] , [31] , [32] , sepsis [33] , [34] , malaria [35] , preeclampsia [36] , [37] , and ischemic stroke and myocardial infarction [38] , [39] . This imbalance has also been increasingly recognized for the development of complications of COVID-19 with increasing plasma VWF antigen and activity, and a generally reduction (or occasionally normal) of ADAMTS-13 activity [40] , [41] , leading to kinetic deficiency of VWF cleavage.…”

Early lyophilized cryoprecipitate enhances the ADAMTS13/VWF ratio to reduce systemic endotheliopathy and lessen lung injury in a mouse multiple-trauma hemorrhage model

“…12,13 In addition, ADAMTS13, the metalloprotease that cleaves VWF to reduce its hyperadhesive activity, is low in injured patients. 12,[14][15][16] We hypothesized that the early use of cryoprecipitate would be effective as an endothelial protector by both supplementing physiologic ADAMTS13 to reduce pathologic VWF and to reverse the EoT. Using an animal model, we evaluated a pathogen-reduced lyophilized cryoprecipitate (LPRC) that could expedite the early administration of cryoprecipitate to wounded warfighters in the battlefield.…”

“…Recent clinical evidence suggests that this hyperadhesive form of VWF may contribute to endothelial cell dysfunction and organ injury 12,13 . In addition, ADAMTS13, the metalloprotease that cleaves VWF to reduce its hyperadhesive activity, is low in injured patients 12,14–16 . We hypothesized that the early use of cryoprecipitate would be effective as an endothelial protector by both supplementing physiologic ADAMTS13 to reduce pathologic VWF and to reverse the EoT.…”