Article Text
Abstract
Background Von 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.
Methods We 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.
Results REAADS 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.
Discussion Trauma 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 evidence Prospective case cohort study.
- coagulopathy
- venous thromboembolism
- thromboembolism
- multiple trauma
Data availability statement
Data are available upon reasonable request. De-identified data used in this study are summarized in this article. Raw data or further de-identified information can be obtained via inquiry to the corresponding author: MP, Division of Trauma, Critical Care and General Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905; Tel: (507) 255-6960, Fax: (507) 255-9872, Park.Myung@mayo.edu.
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Data availability statement
Data are available upon reasonable request. De-identified data used in this study are summarized in this article. Raw data or further de-identified information can be obtained via inquiry to the corresponding author: MP, Division of Trauma, Critical Care and General Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905; Tel: (507) 255-6960, Fax: (507) 255-9872, Park.Myung@mayo.edu.
Footnotes
Contributors TAM, JG: data analysis and interpretation, article writing and critical revision. LMT: sample analysis, data acquisition, analysis and interpretation, critical revision of article. AT: study design and conduct, data analysis and interpretation, critical revision of article. KRB, GMS, J-FD: study planning, conception and design, data analysis and interpretation, critical revision of article. MA: study planning, conception and design, study conduct, data acquisition, analysis and interpretation, critical revision of article. RK: study planning, conception and design, data interpretation, critical revision of article. MP: study planning, conception and design, study conduct, sample and data acquisition, data interpretation, critical revision of article.
Funding This project was supported by R38HL150086 Stimulating Access to Research in Residency (TAM) from the National Heart, Lung, and Blood Institute (NHLBI), HL146508 from the NHLBI (MA), T32 AG049672 from the National Institute on Aging (NIA) and Robert and Arlene Kogod Center on Aging, Mayo Clinic (JG), R01 GM 1 26 086–03 (MP) from the National Institute of General Medical Sciences (NIGMS), UM1 HL120877-06 (MP) by the Trans-Agency Consortium for Trauma-Induced Coagulopathy (TACTIC), 1 UL1 RR024150 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), the NIH Roadmap for Medical Research, and by Grant Number UL1 TR000135 from the National Center for Advancing Translational Sciences (NCATS).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.