key: cord-0870753-i533bvoc
authors: Dumitrascu, Oana M.; Volod, Oksana; Bose, Swaraj; Wang, Yao; Biousse, Valérie; Lyden, Patrick D.
title: Acute ophthalmic artery occlusion in a Covid-19 patient on apixaban
date: 2020-05-23
journal: J Stroke Cerebrovasc Dis
DOI: 10.1016/j.jstrokecerebrovasdis.2020.104982
sha: 3750feb29b09690fcc443c06c2174c5f28d4d7d8
doc_id: 870753
cord_uid: i533bvoc

Abstract We report a case of ophthalmic artery occlusion (OAO) in a young patient with Covid-19 infection that was on therapeutic anticoagulation with apixaban for deep venous thrombosis (DVT). A 48-year-old man with obesity was hospitalized with a severe form of Covid-19 infection, complicated with acute respiratory failure, septic shock, dilated cardiomyopathy and fungemia. Despite treatment with prophylactic enoxaparin (initial D-Dimer 1.14 µg/ml FEU (normal < 0.05 µg/ml FEU), D-Dimer increased to above 20 µg/ml FEU and patient continued to spike high fevers. This prompted further investigations and upper and lower extremities DVTs were confirmed and managed with enoxaparin 1mg/kg twice daily. D-dimer level decreased to 4.98 µg/ml FEU while on therapeutic anticoagulation. Three weeks later pending hospital discharge, the anticoagulation was switched to oral apixaban 10 mg twice daily. Patient developed acute severe right eye visual loss of no light perception and was diagnosed with incomplete OAO. D-Dimer was elevated at 2.13 µg/ml FEU. Stroke etiological work-up found no embolic sources, resolution of the dilated cardiomyopathy and negative antiphospholipid antibodies. Treatment was changed to enoxaparin and no thrombotic events were encountered to date. Ocular vascular complications have not yet been reported in Covid-19. Controversy exists on the best management algorithm for the hypercoagulable state associated to Covid-19. Either direct oral anticoagulants or low-molecular-weight-heparin are considered appropriate at discharge for patients with venous thromboembolism. The optimum regimen for ischemic stroke prevention and the significance of D-Dimer for anticoagulation monitoring in Covid-19 remain unclear..

We report a case of ophthalmic artery occlusion (OAO) in a young patient with infection that was on therapeutic anticoagulation with apixaban for deep venous thrombosis (DVT).

A 48-year-old man with obesity was hospitalized with a severe form of Covid-19 infection, complicated with acute respiratory failure, septic shock, dilated cardiomyopathy and fungemia.

Despite treatment with prophylactic enoxaparin (initial D-Dimer 1.14 µg/ml FEU (normal < 0.05 µg/ml FEU), D-Dimer increased to above 20 µg/ml FEU and patient continued to spike high fevers. This prompted further investigations and upper and lower extremities DVTs were confirmed and managed with enoxaparin 1mg/kg twice daily. D-dimer level decreased to 4.98 A 48-year-old man with a history of obesity (BMI 41 kg/m 2 ) and sleep-disordered breathing (SDB) presented with fever, cough, and progressive dyspnea following a business trip to Florida two weeks before. The chest X-ray showed bilateral patchy middle and lower field MRI of the brain and orbits and CT angiogram head and neck were normal. Transthoracic echocardiogram was unremarkable. Patient was not on medications that could potentially affect apixaban metabolism (e.g. P-glycoprotein and strong CYP3A4 inducers). The anticoagulant regimen was changed to enoxaparin 1 mg/kg twice daily and the patient has had no further thrombotic events to date.

The incidence of thrombotic complications in patients with COVID-19 infection is elevated due to multiple factors and is associated with poorer outcomes 6, 7 . In this case, a cardioembolic etiology of the OAO was unlikely. Although multifactorial cardiomyopathy was described in Covid-19 8 , and our patient had developed right ventricle dilatation initially, the repeat echocardiogram at the time of the OAO showed normal cardiac chambers' sizes, valves and myocardial motility. Telemetry monitoring did not show arrhythmias and transcranial doppler ultrasound with bubble study demonstrated no cardiac shunt. Antiphospholipid antibodies in association with multiple cerebral and systemic infarctions was recently described in 3 COVID-19 patients 9 , however our patient had negative titers of these antibodies. In a recent report of 5 young patients with ischemic strokes and large vessels occlusion, the presumed 6 mechanisms were coagulopathy and vascular endothelial dysfunction and either antiplatelets or apixaban were begun 3 . The coagulopathy that COVID-19 patients develop may be unique and different from other virus-induced or sepsis related coagulopathy and considerable investigation remains to be done. Evidence of venous and arterial thromboembolic events in these patients suggest that pharmacologic anticoagulation prophylaxis for all hospitalized patients with confirmed or highly suspected COVID-19, regardless of venous thromboembolism (VTE) risk should be considered; such prophylaxis is recommended by major societies 10,11 (e.g. American Society of Hematology, International Society of Hemostasis and Thrombosis, Anticoagulation Forum). A systematic review of 26 consecutive patients with severe COVID-19 who were screened for VTE showed 100 % rate of VTE in patients who received prophylactic anticoagulation when compared to 56% rate of VTE in patients receiving therapeutic anticoagulation 7 . Our patient also had evidence of VTE early in the infectious disease process and was treated with a therapeutic dose of low-molecular-weight-heparin (LMWH). One day after switching to therapeutic apixaban, he developed an arterial thrombotic event. D-Dimer was noted to remain mildly elevated despite therapeutic anticoagulation. While D-dimer elevation have been associated with worse outcomes in patients with COVID-19 6 , it is unknown if intensification of anticoagulant therapy based on D-Dimer thresholds alone improve patient outcomes 11 . Current guidelines do not recommend monitoring D-Dimer for the purpose of guiding anticoagulant therapy 11 , even so in our case it provided meaningful information.

Controversy exists on the best management algorithm for the hypercoagulable state associated to Covid-19 12 . Prior reports support anti-inflammatory properties of heparin in other medical conditions 13 , and current anticoagulation guidelines endorse either direct oral anticoagulants or LMWH for Covid-19 patients with VTE at hospital discharge 10, 11 . Hence, the optimum regimen 

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