Management, control, and decision making in unexpected recurrent venous thromboembolism in COVID-19: a case report.

BACKGROUND: Coronavirus disease 2019 was spread worldwide, as a pandemic, from December 2019. Venous thromboembolism events can inflict patients with coronavirus disease 2019 during the hospitalization or convalescent period. Therefore, monitoring of these patients, in terms of venous thromboembolism events signs and symptoms, and timely management of antithrombotic agents are of great importance. CASE REPORT: A 45-year-old Iranian man, who is the first author of this case report, was infected by severe acute respiratory syndrome coronavirus 2 and displayed the typical signs and symptoms of coronavirus disease 2019. Although reverse transcription polymerase chain reaction for coronavirus disease 2019, and specific immunoglobulin M and immunoglobulin G against severe acute respiratory syndrome coronavirus 2, were negative at first, chest computed tomography scan showed the characteristic pattern of lung involvement of a coronavirus disease 2019 infection including bilateral and multilobar ground-glass opacities. At that time, there were no signs or symptoms of deep-vein thrombosis or pulmonary thromboembolism, so these were not investigated. About 30 hours after hospital discharge, the patient presented back to the hospital with acute-onset chest pain. We instantly tested his blood for D-dimer, and sent him to take a Doppler sonography of his lower legs and a chest computed tomography angiography in search of pulmonary thromboembolism and deep-vein thrombosis. Although we could confirm pulmonary thromboembolism with computed tomography angiography in our patient, there were no signs or symptoms of venous thromboembolism in his lower legs, and color Doppler sonography of lower limbs was normal. So, the patient was treated with rivaroxaban as an antithrombotic agent. After some days, he was discharged in good condition. About 1 month later, he was referred to our hospital because of left lower limb edema. Although he was under antithrombotic therapy, color Doppler sonography of lower limbs revealed acute deep-vein thrombosis of the left leg. Hence, we decided to shift antithrombotic therapy from rivaroxaban to warfarin, as it is more potent than rivaroxaban in recurrent venous thromboembolism and when taking new oral anticoagulants. Unlike rivaroxaban, which needs no blood test to monitor its efficacy but has a warning for signs and symptoms of bleeding, warfarin therapy must be monitored carefully by regular blood tests for prothrombin time and international normalized ratio to maintain them in the therapeutic range. The patient was informed about the bleeding cautions, and required regular check of prothrombin time and international normalized ratio to maintain them in the proper and advised range of treatment (international normalized ratio therapeutic range 2-3). CONCLUSION: In the case of unexpected recurrent venous thromboembolism in coronavirus disease 2019, especially when patients are taking rivaroxaban or other new oral anticoagulants, such drugs should be substituted by warfarin, with routine follow-up, to maintain the value of prothrombin time and international normalized ratio within the therapeutic range.

Non-vitamin K antagonist oral anticoagulants for COVID-19 thrombosis

Thrombotic complications appear to be a major predictor of death in COVID-19 patients, and multiple studies have shown that anticoagulants can help to improve the outcome. The Food and Drug Administration's acceptance of non-vitamin K antagonist oral anticoagulants (NOACs) has sparked much excitement about their potential as a replacement for existing oral anticoagulants. NOACs target a single clotting factor, often activated factor X or thrombin, and involve the coagulation factor Xa inhibitors including apixaban, edoxaban, and rivaroxaban, and the thrombin inhibitor dabigatran. COVID-19 is an infectious disease that causes thrombotic events by inducing a pro-inflammatory and prothrombotic condition. This article provides a comprehensive overview of the mechanism behind enhanced thrombogenicity accompanying COVID-19, the clinical range of NOACs, and the role of NOACs in treatment of COVID-19 based on recent investigations and clinical trials. Copyright ©2022 Journal of Acute Disease Produced by Wolters Kluwer-Medknow.

The pharmacology of anticoagulant drug treatment options in COVID-19 patients: reviewing real-world evidence in clinical practice.

INTRODUCTION: The optimal anticoagulation strategy for venous thromboembolism (VTE) prevention among COVID-19 patients, hospitalized or in the community setting, is still challenging and largely based on real-world evidence. AREAS COVERED: We analyzed real-world data regarding the safety and effectiveness of anticoagulant treatment, both parenteral and oral, for VTE prevention or atrial fibrillation (AF)/VTE treatment among COVID-19 patients. EXPERT OPINION: The efficacy of low-molecular-weight heparin (LMWH) doses for VTE prevention correlates with COVID-19 disease status. LMWH prophylactic dose may be useful in COVID-19 patients at the early stage of the disease. LMWH intermediate or therapeutic dose is recommended in COVID-19 patients with an advanced stage of the disease. COVID-19 patients on VKA therapy for atrial fibrillation (AF) and VTE should switch to NOACs in the community setting or LMWH in the hospital setting. No definitive data on de-novo starting of NOACs or VKA therapy for VTE prevention in COVID-19 outpatients are available. In patients at high risk discharged after hospitalization due to COVID-19, thromboprophylaxis with NOACs may be considered.

Pharmacotherapy of atrial fibrillation in COVID-19 patients.

The coronavirus pandemic disease 2019 (COVID-19) has changed the face of contemporary medicine. However, each and every medical practitioner must be aware of potential early and late complications of COVID-19, its impact on chronic diseases - especially ones as common as atrial fibrillation (AF) - and the possible interactions between patients' chronic medications and pharmacotherapy of COVID-19. Patients with AF due to comorbidities and, often, elderly age are assumed to be at a higher risk of a severe course of COVID-19. This expert consensus summarizes the current knowledge regarding the pharmacotherapy of AF patients in the setting of the COVID-19 pandemic. In general, anticoagulation principles in quarantined or asymptomatic individuals remain unchanged. Nevertheless, it is advisable to switch from vitamin K antagonists to non-vitamin K antagonist oral anticoagulants (NOACs) whenever possible due to their consistent benefits and safety with fixed dosing and no monitoring. Additionally, in AF patients hospitalized due to mild or moderate COVID-19 pneumonia, we recommend continuing NOAC treatment or to switching to low-molecular-weight heparin (LMWH). On the other hand, in severely ill patients hospitalized in intensive care units, intravenous or subcutaneous dosing is preferable to oral, which is why the treatment of choice is either LMWH or unfractionated heparin. Finally, particularly in critical scenarios, the treatment strategy in COVID-19 patients with AF should be individualized based on possible interactions between anticoagulants, antiarrhythmics, antivirals, and antibiotics. In this consensus, we also discuss how to safely perform COVID-19 vaccination in anticoagulated AF patients.

Chronic Oral Anticoagulation and Clinical Outcome in Hospitalized COVID-19 Patients.

PURPOSE: The clinical course of COVID-19 may be complicated by acute respiratory distress syndrome (ARDS) and thromboembolic events, which are associated with high risk of mortality. Although previous studies reported a lower rate of death in patients treated with heparin, the potential benefit of chronic oral anticoagulation therapy (OAT) remains unknown. We aimed to investigate the association between OAT with the risk of ARDS and mortality in hospitalized patients with COVID-19. METHODS: This is a multicenter retrospective Italian study including consecutive patients hospitalized for COVID-19 from March 1 to April 22, 2020, at six Italian hospitals. Patients were divided into two groups according to the chronic assumption of oral anticoagulants. RESULTS: Overall, 427 patients were included; 87 patients (19%) were in the OAT group. Of them, 54 patients (13%) were on treatment with non-vitamin k oral anticoagulants (NOACs) and 33 (8%) with vitamin-K antagonists (VKAs). OAT patients were older and had a higher rate of hypertension, diabetes, and coronary artery disease compared to No-OAT group. The rate of ARDS at admission (26% vs 28%, P=0.834), or developed during the hospitalization (9% vs 10%, P=0.915), was similar between study groups; in-hospital mortality (22% vs 26%, P=0.395) was also comparable. After balancing for potential confounders by using the propensity score matching technique, no differences were found in term of clinical outcome between OAT and No-OAT patients CONCLUSION: Oral anticoagulation therapy, either NOACs or VKAs, did not influence the risk of ARDS or death in patients hospitalized with COVID-19.