Lupus anticoagulant in patients with COVID‐19

Abstract

Patients with COVID-19 are at increased risk of thromboembolism. In a recent study of 184 patients with COVID-19, there was a cumulative incidence of venous thromboembolism of 27% and arterial thrombotic events of 3.7%.1 Abnormal coagulation parameters, particularly elevated D-dimer and fibrinogen, have been shown to be associated with poor prognosis in these patients,2 and anticoagulation is associated with decreased mortality in severe COVID-19.3 Antiphospholipid antibodies, mainly lupus anticoagulant (LAC) and anticardiolipin antibodies (aCL), contribute to an acquired prothrombotic state. They are associated with significantly increased risk of arterial, venous, and microvascular thrombosis. The prevalence of LAC or aCL in healthy individuals is 1%-5% with a predominance among females though it may increase in elderly and with chronic disease. Many infections have been shown to be accompanied by an increase in antiphospholipid antibodies, which is often transient, but can persist and trigger thromboembolic events.4 The purpose of this retrospective study at the Shaare Zedek Medical Center (SZMC) in Jerusalem was to determine whether patients with COVID-19 have elevated antiphospholipid antibodies and whether there is a correlation between the level of antiphospholipid antibodies and the severity of the disease. The study was approved by the Ethics Committee of SZMC (approval no. 0139-20-SZMC). Forty-three consecutive patients, 27 male and 16 female, were evaluated for LAC, using the HemosIL dilute Russell viper venom time (dRVVT) screen and HemosIL dRVVT confirm assay and the HemosIL Silica clotting (SCT) screen and HemosIL SCT confirm assay in citrated peripheral blood. The tests were described in ratio and considered positive as follows: dRVVT ratio above 1.22 and SCT ratio above 1.2. Anticardiolipin IGM/IGG and anti-beta-2-glycoprotein IGM/IGG were performed by enzyme-linked immunosorbent assays using ORGENTEC test kits. Incidence of lupus Anticoagulants: 16 of 43 patients (37%) were positive for LAC, 6 of 11 (54%) with mild disease, 2 of 13 (15%) with moderate disease, and 8 of 19 (42%) with severe disease. aCL and anti-β2-glycoprotein I were negative in all patients. All LAC-positive patients were on low molecular weight heparin. Eight patients received prophylactic dose (enoxaparin 40 mg once daily), and eight patients received full anticoagulation (seven patients enoxaparin 1mg/kg twice daily and one patient enoxaparin 1 mg/kg once daily due to renal failure). There was no significant difference in D-dimer, fibrinogen, C-reactive protein, or platelet count between patients positive or negative for LAC (Table 1). Interestingly, in our cohort, LAC was more prevalent in male patients. There is no obvious explanation, though it may be related to male patients being more seriously affected by COVID-19. The occurrence of vascular events was not higher in LAC-positive patients although such events were clinically diagnosed in only three patients. This may have been underdiagnosed as patients were not systematically evaluated for thrombotic complications. Microvascular thromboses are difficult to evaluate as they can manifest as organ dysfunction, often impossible to differentiate from other causes without tissue biopsy. An unexpected high incidence of lupus anticoagulant was observed in patients with COVID-19. These results are similar to recently published findings by Bowles et al,5 Harzallah et al6 and de Chambrun et al7 LAC has been reported in 4 out of 21 children suffering from SARS without correlation to thromboembolic events.8 Although intuitively there is a pathophysiologic relationship of APLA with vasculopathy in COVID-19, such an association could not be demonstrated in this cohort of 43 patients, in whom the overall incidence of proven thrombosis was low. Larger studies are needed. The authors have no competing interests. AT, EA, and YH conceived the original idea. EB-C, FSZ, and YH collected data. EB-C and YH performed the analysis. AT wrote the manuscript with the support of EB-C, FSZ, EF, and YH

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