key: cord-0902133-c9auung8 authors: Jizzini, Mazen; Shah, Mohsin; Zhou, Kehua title: SARS-CoV-2 and Anti-Cardiolipin Antibodies date: 2020-12-08 journal: Clin Med Insights Case Rep DOI: 10.1177/1179547620980381 sha: c45f170558d985dd32b2b88a461d38a3939a7862 doc_id: 902133 cord_uid: c9auung8 The current COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to distinct diagnostic and management challenges for front-line healthcare workers. The risk of excessive coagulation activation leading to a cascade of thrombotic events in critically ill patients with SARS-CoV-2 is now well reported. We discuss a recent case of COVID-19 with concurrent acute pulmonary embolism and a positive cardiolipin antibody (IgM). The presence of antiphospholipid antibodies is key to diagnosing antiphospholipid syndrome (APS). However, their presence can be transient or persistent after viral infections. Serial inflammatory markers in conjunction with anti-phospholipid antibody testing is critical for the diagnosis of APS in this emerging patient population. Our case report reviews details suggestive of APS in the setting of SARS-CoV-2 and aims to provide clinical diagnostic clues that could help warrant further workup and assist with management strategies. Patients hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are at risk for excessive coagulation activation leading to thrombotic events and poor prognosis. [1] [2] [3] Recently, Harzallah et al 4 reported on antiphospholipid antibody testing in 56 patients with confirmed or suspected SARS-CoV-2. Of these, 25 patients were found to be positive for lupus anticoagulants, while 5 patients had either anticardiolipin or anti-β2-glycoprotein 1 antibodies. Similarly, Zhang et al 5 described 3 SARS-CoV-2 patients with coagulopathy, thrombocytopenia, and the presence of anticardiolipin IgA who developed multiple cerebral infarcts. A Dutch observational study found a remarkably high incidence (49%) of thrombotic events in patients with SARS-Cov-2 after adjusting for the competing risk of death. 6 Based on a review of literature, it appears that SARS-CoV-2 induces a hypercoagulable state; theorized to be associated with hypoxia, immobilization, or disseminated coagulopathy. [4] [5] [6] [7] [8] [9] [10] [11] Further, elevated levels of antiphospholipid antibodies may contribute to between SARS-Cov-2 and an acquired coagulopathy. 8 However, the exact mechanisms remain unclear. We report a case of COVID-19 with concurrent acute pulmonary embolism and a positive cardiolipin antibody (IgM). Our patient is a 64-year-old male with chronic obstructive pulmonary disease (not on home oxygen), asthma, obstructive sleep apnea, hypertension, obesity, and a previous history of hepatitis C who originally presented on with complaints of shortness of breath, loss of appetite, fatigue, and diarrhea for 1 week. His oxygen saturation was 86% on room air. Nasopharyngeal swab testing by RT-PCR for SARS-CoV-2 was positive and the patient was then admitted to the intensive care unit. Despite worsening respiratory status, he refused intubation; he was started on hydroxychloroquine, azithromycin, ceftriaxone, and prednisone, as at that time the existing data supported their use in this patient population. Two days later, he was transferred to floor on a non-rebreather. The patient continued to improve and required only 2 liters of oxygen and was discharged home. The following week, the patient returned to the hospital complaining of severe right-sided pleuritic chest pain. His vital signs included a heart rate of 120's and a respiratory rate of 30's while on 2 liters/minute of oxygen with good saturations. The patient was re-admitted for COVID-19 pneumonia. The next day, he remained tachycardic requiring 4 liters of oxygen. D-dimer was 3404 and a subsequent computed tomography angiogram of chest revealed multifocal pneumonia and multiple bilateral pulmonary emboli with right heart strain ( Figure 1 ). Intravenous (IV) heparin treatment was planned but delayed for 36 hours because of persistently elevated partial thromboplastin time (PTT) while off any anticoagulation medication. IV heparin was eventually started without referencing PTT, and the dosing of heparin was rather adjusted based on anti-factor Xa. Three days later, the patient was discharged home on rivaroxaban. His labs revealed positive titers for cardiolipin antibody IgM while IgG was not detected. Additionally, a hereditary hypercoagulable workup was negative, ruling out other potential of coagulation (Table 1 ). The presence of antiphospholipid antibodies is key to diagnosing antiphospholipid syndrome (APS). However, their presence can be transient or persistent after viral infections. 12 According to the International Society of Thrombosis and Hemostasis criteria for APS it is necessary to determine anti-ß2-glycoprotein 1antibodies and 2 positive antibody tests separated by 12 weeks are required for diagnosis (because the phenomenon is often transient). This proves increasingly difficult during the current pandemic as many patients are lost to follow up. Furthermore, we don't have enough long term follow up data to know if these patients truly have antiphospholipid syndrome, or if the antiphospholipid antibodies are transient and in response to the septic phase of SARS-CoV-2. Currently, the risk factors, prevalence, and timing of the development of antiphospholipid antibodies in SARS-CoV-2 is not yet understood. Additional prospective clinical epidemiologic studies are warranted to explore the coagulopathy patterns in these patients. In our opinion and in the current pandemic, these suspected patients should be further worked up for APS and clinicians should not withhold the use of anticoagulation therapies due to an increase in PTT alone nor should they withhold thrombolytic therapy in the event of a high-risk pulmonary embolism solely on the basis of a prolonged PTT. 13 We believe doing so may ultimately delay treatment and possibly lead to worse outcomes. Finally, once APS is confirmed, we suggest switching to subcutaneous low molecular weight heparin as opposed to a direct oral anticoagulant based on its increased risk of thrombotic events in the setting of APS. 14 This basis for such a modification of therapy must be based on repeated measurements of positive antibodies. In summary, the risk of developing thromboembolism in patients with SARS-Cov-2 is a growing concern. This coupled with the paradoxical prolongation of PTT in APS makes management challenging. We suggest patients who are hypercoaguable who are found to have features suggestive of APS (ie, prolonged PTT, IgM cardiolipin antibodies) should be closely monitored with a full APS workup and followedup after hospital discharge as the optimal treatment plan may differ. MJ, MS and KZ wrote and edited the paper. The patient gave consent for publication of this manuscript. Dr. Shah is supported by the National Institutes of Health T-32 post-doctoral fellowship (NIH/NIGMS T32GM-075766) Mazen Jizzini https://orcid.org/0000-0002-9575-6876 Thromboembolic risk and anticoagulant therapy in COVID-19 patients: emerging evidence and call for action Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia Severe COVID-19 infection associated with endothelial activation Lupus anticoagulant is frequent in patients with Covid-19 Coagulopathy and antiphospholipid antibodies in patients with Covid-19 Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: an updated analysis Incidence of thrombotic complications in critically ill ICU patients with COVID-19 Clinically significant anticardiolipin antibodies associated with COVID-19 Incidence of venous thromboembolism in hospitalized patients with COVID-19 High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study Autopsy findings and venous thromboembolism in patients with COVID-19: a prospective cohort study Viral infections and antiphospholipid antibodies Lupus anticoagulant and abnormal coagulation tests in patients with Covid-19 Rivaroxaban versus vitamin K antagonist in antiphospholipid syndrome: a randomized noninferiority trial