von Willebrand factor dynamics in trauma managed with extracorporeal life support

Background Extracorporeal life support (ECLS) can cause bleeding via excessive cleavage of multimeric protein von Willebrand Factor (VWF) by protease ADAMTS-13, a bleeding diathesis termed acquired von Willebrand syndrome. VWF high-molecular-weight multimers (HMWM) are more procoagulant than smaller multimers. Acute-phase responses generate high levels of VWF-HMWM and reduced ADAMTS-13 activity. Objectives Assess whether VWF-HMWM degradation is less pronounced and VWF:collagen binding activity (CB)/VWF:antigen (Ag) ratios are lower during ECLS in acute trauma vs noninjury settings. Methods Anesthetized, mechanically ventilated swine (45-60 kg) were randomized to polytrauma (INJ CTRL, n = 14) managed with mechanical ventilation, uninjured receiving veno-venous extracorporeal carbon dioxide removal (ECLS CTRL, n = 20), or polytrauma managed with extracorporeal carbon dioxide removal (ECLS INJ, n = 22). In ECLS groups, 50% of animals received heparin anticoagulation, while 50% received no systemic anticoagulation. VWF:Ag, VWF:CB, VWF multimer size distribution, and ADAMTS-13 activity were evaluated at baseline, post-injury/intervention, and at 6, 24, 48, and 72 hours. Results VWF-HMWM were depleted at 72 hours in ECLS CTRL (−19 ± 3%, P < .0001), but not in ECLS INJ (−10 ± 5%, P = .09). VWF:CB/VWF:Ag ratios relative to baseline were reduced at 48 to 72 hours in ECLS CTRL (0.84 ± 0.04, P = .002) and ECLS INJ (0.69 ± 0.05, P < .001) but not INJ CTRL. ADAMTS-13 activity decreased in all groups. Animals treated with heparin showed less pronounced VWF-HMWM degradation, higher VWF:CB/VWF:Ag ratios, and higher ADAMTS-13 activity vs matched non-anticoagulated animals. Conclusion Trauma managed with ECLS was associated with reduced VWF:CB/VWF:Ag ratios and lower ADAMTS-13 activity, but VWF-HMWM depletion was minimal. Thus, potential for acquired von Willebrand syndrome is a concern for trauma patients undergoing ECLS. Heparin partially countered effects of ECLS on VWF and ADAMTS-13.