|Year : 2021 | Volume
| Issue : 1 | Page : 44-46
Thromboembolism and anticoagulation therapy among the COVID-19 patients
Tarun Kumar Suvvari1
, Satwik Kuppili2
, LV Simhachalam Kutikuppala2
1 Dr. NTR University of Health Sciences, Vijayawada, Andhra Pradesh, India
2 Konaseema Institute of Medical Sciences and Research Foundation, Amalapuram, Andhra Pradesh, India
|Date of Submission||26-Dec-2020|
|Date of Decision||23-Jan-2021|
|Date of Acceptance||01-Mar-2021|
|Date of Web Publication||28-Apr-2021|
Tarun Kumar Suvvari
Dr. NTR University of Health Sciences, Vijayawada, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Coronavirus disease 2019 (COVID-19), which is caused due to severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), can be complicated with coagulopathy through disseminated intravascular coagulation (DIC) in severe stages leading to profuse morbidity and mortality. The prothrombotic character of DIC can potentiate a higher risk of venous thromboembolism (VTE), whose incidence among COVID-19 patients in intensive care units appears to be a bit higher and severe. The prevalence of VTE was high in the COVID-19 patients due to inflammation and stasis of blood vessel endothelium resulting from viral infection. D-dimer monitoring can help in early recognition, proper treatment, and better prognosis in the high-risk COVID-19 patients. Recent studies show that anticoagulant therapy reduces the mortality in severe COVID-19 patients with sepsis-induced coagulopathy or markedly elevated d-dimer. Direct oral anticoagulants or low-molecular-weight-heparin can be administrated in hospitalized COVID-19 patients to minimize thrombosis risk. However, constant observation on anticoagulant therapy and post-discharge thromboprophylaxis in COVID-19 patients is recommended.
Keywords: Anticoagulation, coronavirus disease 2019, D-dimer, severe acute respiratory syndrome coronavirus 2, thrombosis
|How to cite this article:|
Suvvari TK, Kuppili S, Simhachalam Kutikuppala L V. Thromboembolism and anticoagulation therapy among the COVID-19 patients. Ann Clin Cardiol 2021;3:44-6
|How to cite this URL:|
Suvvari TK, Kuppili S, Simhachalam Kutikuppala L V. Thromboembolism and anticoagulation therapy among the COVID-19 patients. Ann Clin Cardiol [serial online] 2021 [cited 2021 Aug 5];3:44-6. Available from: http://www.onlineacc.org/text.asp?2021/3/1/44/317112
| Introduction|| |
Coronavirus disease 2019 (COVID-19) has led to an unavoidable global pandemic caused by severe acute respiratory corona virus-2 (SARS COV-2). Till date, >2.497 million deaths were recorded due to the COVID-19. Across the globe, patients suffering from COVID-19 were found to develop severe cardiovascular manifestations. In the hypercoagulable state, various changes in circulating prothrombotic factors have been identified in patients with severe COVID-19, which leads to venous thromboembolism (VTE), including pulmonary embolism and extensive deep vein thrombosis (DVT). Arterial thrombosis has also been reported in critically ill COVID-19 patients., According to some research studies, male sex, older age, history of coronary artery disease, hispanic ethnicity, and D-dimer level >230 ng/mL on presentation are the major risk factors for developing arterial thrombosis.
COVID-19 can cause severe inflammatory response and cytokine storm that can lead to end-organ damage to the heart, which increases the risk of mortality. Few studies reported that in COVID-19 patients, cytokine storm leads to rapid onset formation of new coronary plaques, destabilization of pre-existing plaques, and a direct myocardial injury due to acute systemic viral infection., Systemic viral infections also trigger vasoconstriction resulting in narrowing of vascular lumen and platelet activation stimulation through shear stress. The resultant cytokine storm promotes hypercoagulable tissue factor secretion, leading to the development of new-onset thrombi, which can propagate in size, causing myocardial ischemia. In such patients, respiratory viral infections induced severe hypoxemia, elevated cardiac metabolic demands triggered by the subsequent cytokine storm, and the eventual decline in mean arterial pressure due to sepsis caused further development of myocardial ischemia.,
| Thrombo-Embolism and Coronavirus Disease 2019|| |
Among COVID-19 patients, VTE incidence was ranged differently according to the study population. A higher incidence was noticed among patients admitted in intensive care units (ICU), and considerable incidence was also reported among non-ICU patients. In a systematic review and meta-analysis by Nopp S et al., 22.7% of COVID-19 patients admitted in ICU suffered from VTE, and 8% of VTE was noticed in non-ICU patients. Higher incidence of VTE was also observed in patients with a low rate of pharmacologic thromboprophylaxis, and VTE assessment was strongly recommended. Essential precautions and efficacious thromboprophylaxis should be implemented for COVID-19 patients at high risk of VTE.
The rise in the D-dimer levels and inflammation markers were observed among hospitalized COVID-19 patients, but after receiving treatment, a decline in D-dimer and C-reactive protein was observed with a good prognosis. It indicates that the abnormal D-dimer changes suggest the immediate requirement of anticoagulant therapy. Physiologically, D-dimer is generated during fibrin breakdown and hence is considered as an indication for fibrinolytic activity. Elevated levels of D-dimer are an indication of increased risk for aggressive thrombosis.
A study in China reported atypical coagulation in 99 Chinese patients that include the rise in D-dimer levels among 36 patients, decline in prothrombin time in thirty patients, and incline in activated partial prothrombin time in 16 patients, which is an indication for the surge for risk of thrombosis among severe COVID-19 patients. In a study by Julie Helms et al., among the thromboembolic complications, pulmonary embolism was most reported in COVID-19 patients with acute respiratory distress syndrome (ARDS). It could be due to the systemic inflammatory response syndrome, determined by large amounts of fibrinogen found in all patients, and can be led to the activation of blood coagulation. The same coagulation activation pattern was not observed in the cohort study of non-COVID-19 ARDS patients., Few research studies reported that thrombosis and microangiopathy in vessels and capillaries of lungs with significant hemorrhage, individual cell necrosis in cardiac tissue without lymphocytic myocarditis was observed among a group of autopsies in African American patients who died from COVID-19. In a prospective cohort study by Witchman et al., autopsy findings reported deep venous thrombosis in 7 out of 12 COVID-19 patients (58%), and VTE was not expected before the death in those patients.
| Prevention and Treatment|| |
Because of viral infection, VTE could be quite common in COVID-19 patients, directly due to endothelialitis, indirectly due to stasis and inflammation. All severe and adult COVID-19 patients were recommended to administrate low-molecular-weight heparin (LMWH) over unfractionated heparin (UFH) as thromboprophylaxis to minimize thrombosis risk. Fondaparinux was recommended in a heparin-induced thrombocytopenia setting., In the scenario of contraindications or unavailability, mechanical thromboprophylaxis such as pneumatic compression devices can be preferred, and a combination of mechanical and pharmacological thromboprophylaxis was usually not recommended. According to the American Society of Hematology (ASH) guidelines, they suggested using prophylactic-intensity anticoagulation rather than therapeutic-intensity/intermediate-intensity in severe COVID-19 patients with no suspension confirmation of VTE.,
In COVID-19 patients with acute respiratory distress syndrome (ARDS), there could be involvement of microvascular thrombosis, and similar observations (pulmonary hemorrhage and high incidence of VTE) were reported in autopsy studies., Although few research studies have been published on empirical anticoagulation therapy, ASH has not recommended it for severe COVID-19 patients with no suspension or confirmation of VTE due to bias in research data, lack of strong evidence…etc., Up to 90 days postdischarge, hospitalized COVID-19 patients are at increased risk for developing VTE. 0.6% VTE incidence was reported at 30–42 days discharge in symptomatic COVID-19 patients. Regarding postdischarge thromboprophylaxis for COVID-19 patients, the decision should be based on individual risk factors (bleeding risk, co-morbidities…etc.,) to VTE. Aspirin as a potential postdischarge thromboprophylaxis was still under clinical trials and educating patients regarding the possible signs/symptoms of VTE at hospital discharge and advice to visiting hospital if developed VTE postdischarge.
Multiple therapeutics such as dexamethasone, corticosteroids, and monoclonal antibodies are using for COVID-19.,, Cytochrome P450 3A4 (CYP3A4) was induced by dexamethasone, and CYP3A4 activity can be increased due to tocilizumab and sarilumab. Hence, they were not administrated with rivaroxaban and apixaban due to the possibility of drug-drug interactions.,, LMWH and UFH were most preferred among severe COVID-19 patients and pregnant people than direct oral anticoagulants due to shorter half-life and less drug-drug interactions. Regular Warfarin therapy was suggested for patients with valvular atrial fibrillation, ventricular assist devices, and mechanical heart valves.,
Novel oral anticoagulants (NOACs) include rivaroxaban, apixaban, edoxaban and dabigatran...etc. NOACs were a good alternative to warfarin therapy for high-risk out-patient COVID-19 patients and out-patients with pre-existing heart diseases. NOACs mainly inhibit Factor Xa (whereas dabigatran is a direct thrombin inhibitor). Compared to warfarin, rivaroxaban, apixaban and dabigatran showed significant results in the prevention of embolism and stroke in out-patient COVID-19 patients. Special care should be taken while prescribing NOAC combined with anti-viral drugs as it may increase blood levels.
The Food and Drug Administration (FDA) approved the use of rivaroxaban 10 mg daily for 31 to 39 days in COVID-19 patients. The inclusion criteria are VTE risk score ≥4 or VTE risk score ≥2 and D-dimer level >2 times the upper limit of normal. Physicians should consider patients' individual risk factors before prescribing NOAC as post-discharge VTE prophylaxis for COVID-19 patients. Patients receiving NOACs don't require constant blood profile monitoring, and it reduces their travel to the hospital, which lowers the risk for COVID-19 transmission. So, NOAC would be preferred in out-patients requiring anticoagulation therapy for thrombosis and related cardiovascular diseases due to COVID-19. So, NOAC can be an ideal VTE prophylaxis post-discharge for COVID-19 patients.
In conclusion, the prevalence of VTE was high among severe and hospitalized COVID-19 patients. Direct oral anticoagulants or LMWH can be administrated in hospitalized COVID-19 patients to minimize thrombosis risk. For severe COVID-19 patients with a previous history of heart diseases, antiplatelet therapy is indicated. Hence, constant observation on anticoagulant therapy and postdischarge thromboprophylaxis in COVID-19 patients is recommended.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Pal M, Berhanu G, Desalegn C, Kandi V. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): An Update. Cureus 2020;12:e7423.
Sheth AR, Grewal US, Patel HP, Thakkar S, Garikipati S, Gaddam J, et al
. Possible mechanisms responsible for acute coronary events in COVID-19. Med Hypotheses 2020;143:110125.
Helms J, Tacquard C, Severac F, Leonard-Lorant I, Ohana M, Delabranche X, et al
. High risk of thrombosis in patients with severe SARS-CoV-2 infection: A multicenter prospective cohort study. Intensive Care Med 2020;46:1089-98.
Nopp S, Moik F, Jilma B, Pabinger I, Ay C. Risk of venous thromboembolism in patients with COVID-19: A systematic review and meta-analysis. Res Pract Thromb Haemost 2020;4:1178-91.
Zhang C, Shen L, Le KJ, Pan MM, Kong LC, Gu ZC, et al.
Incidence of venous thromboembolism in hospitalized coronavirus disease 2019 patients: A systematic review and meta-analysis. Front Cardiovasc Med 2020;7:151.
Yu B, Li X, Chen J, Ouyang M, Zhang H, Zhao X, et al
. Evaluation of variation in D-dimer levels among COVID-19 and bacterial pneumonia: A retrospective analysis. J Thromb Thrombolysis 2020;50:548-57.
Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al
. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 2020;395:507-13.
Fox SE, Akmatbekov A, Harbert JL, Li G, Quincy Brown J, Vander Heide RS. Pulmonary and cardiac pathology in African American patients with COVID-19: An autopsy series from New Orleans. Lancet Respir Med 2020;8:681-6.
Wichmann D, Sperhake JP, Lütgehetmann M, Steurer S, Edler C, Heinemann A, et al
. autopsy findings and venous thromboembolism in patients with COVID-19: A prospective cohort study. Ann Intern Med 2020;173:268-277.
Tritschler T, Mathieu ME, Skeith L, Rodger M, Middeldorp S, Brighton T, et al
. International Network of VENous Thromboembolism Clinical Research Networks INVENT-VTE. Anticoagulant interventions in hospitalized patients with COVID-19: A scoping review of randomized controlled trials and call for international collaboration. J Thromb Haemost 2020;18:2958-67.
Costa A, Weinstein ES, Sahoo DR, Thompson SC, Faccincani R, Ragazzoni L. How to build the plane while flying: VTE/PE thromboprophylaxis clinical guidelines for COVID-19 patients. Disaster Med Public Health Prep 2020;14:391-405.
Burugu HR, Kandi V, Kutikuppala LV, Suvvari TK. Activities of serum ferritin and treatment outcomes among covid-19 patients treated with vitamin c and dexamethasone: An uncontrolled single-center observational study. Cureus 2020;12:e11442.
Edara L, Suvvari T, Kutikuppala L. High Dose steroid therapy to prevent severe hypoxia in COVID-19 patients: A potential solution for low resource clinical setting. Cureus 2020;12:E12330.
Suvvari TK. Therapeutic uses of monoclonal antibodies for COVID-19. Biomed Res J 2020;7:60-1. [Full text]
Doganci S, Yildirim AK. Problems related with anticoagulant usage during COVID-19 outbreak. J Vasc Surg Venous Lymphat Disord 2020;8:695-6. doi: 10.1016/j.jvsv.2020.04.022.