Post–COVID-19 Arterial Thrombosis: A Systematic Review

Abstract

COVID-19 (coronavirus disease 2019) is associated with coagulation defects, including endothelial dysfunction, inflammation, hypoxia, cytokine release, and hypercoagulability. We aimed to summarize the available cases of arterial peripheral thrombosis in the setting of post–COVID-19 infection and the use of biomarkers and related pharmacologic therapies to describe the better medical and surgical treatments based on the reported outcomes. We executed a systematic review following the 2020 PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. We searched PubMed, Embase, Scopus, and the Cochrane Library for studies reported from March 2020 to September 2021 with serologic confirmation of a resolved SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. Related questions regarding high-yield end points included the location of the thrombosis, amputation, reintervention rates, mortality, anticoagulant therapy, and biomarkers. Of the 398 matching results, 23 reports met the inclusion criteria of post–COVID-19 thrombosis, arterial, venous, peripheral, and cured. The literature review included 12 case reports, 3 incidence reports, 3 literature reviews, 2 meta-analyses, 1 observational cohort study, and 2 prospective analyses. The overall presentation consisted of peripheral arterial thrombosis (33.3%), venous thrombosis (63.2%), and mixed events (3.5%). Most of the studies had used low-molecular-weight heparin monotherapy as a part of the medical management. There was no difference in the use of clopidogrel and aspirin as antiplatelet agents. Other pharmacologic alternatives were nonfractionated heparin, enoxaparin, warfarin, rivaroxaban, and apixaban. Open thrombectomy was the most common procedure used for COVID-19 thrombosis complications (40%), with mortality of 27.2%, followed by endovascular thrombectomy (15%), amputation (12.5%), exploratory laparotomy (5%), and endarterectomy (2.5%). We found 38 reported biomarkers, which were classified into seven categories related to an inflammatory process, coagulation time, clotting factors, cardiorespiratory function, kidney function, metabolic profile, and autoimmunity. An initial D-dimer level >1.250 ng/mL might identify COVID-19 patients at risk of arterial thrombotic events. Additional end points were associated with increased creatinine, interleukin-6, interferon gamma-induced protein-10, D-dimer, and C-reactive protein levels. COVID-19 infection is associated with a high risk of arterial and venous post-thrombotic complications, with a variable clinical and anatomic presentation, high mortality, and high amputation risk. Microcirculatory alterations can be reflected by a panel of biomarkers. The medical and surgical management of these patients could depend on the availability of resources regarding the context of medical attention. Nevertheless, considering the highly inflammatory context, endovascular interventions with less systemic stress should be considered in addition to thromboprophylaxis measures.