key: cord-0887429-nav87qdg authors: Mehta, Sudhir; Bhandari, Sudhir; Mehta, Shaurya title: Cautious interpretation of antiphospholipid antibodies in COVID-19 date: 2020-06-15 journal: Clin Chim Acta DOI: 10.1016/j.cca.2020.06.024 sha: 291d11c3d1fd06ef5d13e34d60fcf1f135331dbe doc_id: 887429 cord_uid: nav87qdg nan Clinica Chimica Acta journal homepage: www.elsevier.com/locate/cca Letter to the editor To the Editor: Currently, there are few data on Antiphospholipid antibodies (aPL Ab) in COVID-19 and it is unclear if they represent an epiphenomenon or are involved in pathogenesis of COVID-19 disease. The presence of aPL Ab alone is not a specific indication for anticoagulation and nor does the presence of aPL Ab represent a clinical diagnosis of antiphospholipid syndrome (APS) Bowles et al. [1] performed coagulation screening in 216 Covid-19 patients, out of which 44(20%) had increased activated partial thromboplastin time (aPTT). 91% of patients with prolonged aPTT tested positive for lupus anticoagulant (LAC). Clinical characteristics and laboratory findings did not suggest diagnosis of APS. In a recent study, Zhang et al. [2] described three severely ill COVID-19 patients with multisystem thrombosis and ischemic strokes, prior risk factors for cardiovascular disease and positive aPL Abs, anticardiolipin IgA and anti-beta-2 glycoprotein-1 IgG and IgA antibodies. The titer of antibody positivity was not reported. Two of the three reported cases with aPL Abs had disseminated intravascular coagulation as per the criteria of the International Society on Hemostasis and Thrombosis (ISTH) [3] . Moreover, criteria for diagnosis of APS were not met in terms of high titres of IgG and IgM of anticardiolipin and antibeta-2-glycoprotein-1which preclude any role in the thrombotic episodes. During the COVID-19 outbreak in Mulhouse, France, Harzallah et al. [4] studied 56 Covid-19 patients for the presence of LAC with dilute Russell's viper venom time and sensitive activated partial thromboplastin time tests. Twenty-five cases (45%) were LAC positive, whereas anticardiolipin or anti-β2GlycoproteinI was detected in only 5 of 50 tested patients (10%, three associated to LAC) but titers of IgM & IgG were not reported. Helms et al. [5] reported the occurrence of thrombotic events among 150 patients with Covid-19 and acute respiratory distress syndrome (ARDS) admitted to the ICU. Lupus anticoagulants were detected in 50 of 57 patients tested (87.7%) due to prolonged aPTT. None of the patients developed disseminated intravascular coagulation (DIC). Anticardiolipin and anti-β2-glycoprotein-1 antibodies were not determined. Above observations suggest that aPL antibodies may have little clinical relevance to thrombosis occurring in COVID-19. Moreover, analytical variations in detection of LAC should be borne in mind. Caution should be exercised when interpreting LAC results on patients receiving anticoagulants [6] . Given common use of low molecular weight heparin (LMWH) for thromboprophylaxis in COVID-19 patients, false positive results due to interference of LMWH may be an important reason for the high positivity of LAC. It has been suggested that the blood should be drawn for LAC testing at least 12 h since the last dose of LMWH. False positive LAC testing might also be expected in patients with COVID-19 because of elevated C-reactive protein (CRP) levels. Many assays to detect LAC are sensitive to the presence of CRP, resulting in false positive results, further limiting interpretation of this test [7] . COVID-19 induces a hypercoagulable state due to poorly understood mechanisms, with increase of fibrinogen and minimal prolongation in PT and aPTT. COVID-19 coagulopathy is pathophysiologically different from DIC, APS and thrombotic microangiopathy. Hence, presence of aPL Abs in Covid-19 patients should be cautiously interpreted. Further studies are required to determine the role, if any, of lupus anticoagulant in the pathogenesis of Covid-19 thrombosis. Lupus Anticoagulant and Abnormal Coagulation Tests in Patients with Covid-19 Coagulopathy and antiphospholipid antibodies in patients with Covid-19 Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation Lupus anticoagulant is frequent in patients with Covid-19 High risk of thrombosis in patients in severe SARS-CoV-2 infection: a multicenter propspective cohort study Update of the guidelines for lupus anticoagulant detection Lupus Anticoagulant (LAC) testing in patients with inflammatory status: does C-reactive protein interfere with LAC test results?