Abstract

Objectives: The incidence of acute limb ischemia (ALI) has increased since the emergence of coronavirus disease 2019 (COVID-19) and has been linked to the serum level of cross-linked fibrin degradation products (D-dimer). The purpose of this study is to understand arterial thromboembolic architecture in patients with ALI and how this is altered by COVID-19 infection. Methods: Arterial thromboembolic specimens were prospectively collected at a single institution, stored in an IRB-approved tissue bank at -80°C for preservation of architecture. Liquid chromatography mass spectrometry (LC-MS/MS) was used to identify in-vivo Factor XIII (FXIII) generated cross-links, critical determinants of clot stability and strength. Protein composition of thromboemboli was compared between COVID and non-COVID patients. Results: Arterial thromboemboli were obtained from four patients. Patient #1 had COVID pneumonia and a D-dimer of 14,690 ng/mL FEU and developed ALI secondary to embolization of an aortic thrombus. Patients #2-4 did not have COVID and developed ALI secondary to synthetic graft thrombosis, septic embolization from endocarditis, and embolization during aortic arch replacement. COVID thromboemboli demonstrated a higher abundance of immune response proteins compared to non-COVID thromboemboli. Eighty-one cross-links were identified across the four specimens (Fig 1). A six-fold greater degree of Fibrinogen Alpha Chain (FibA-FibA) cross-linking was present in the COVID specimen (Mean: 295,100) compared to the mean of the three non-COVID specimens (Mean: 52,973) (Figure 2). Conclusions: A higher degree of cross-linking and increased levels of innate and adaptive immune response proteins appear to be features of arterial thromboemboli in COVID-induced ALI. This supports a virus-associated hypercoagulable state in COVID-19 patients with ALI.

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