Role of Therapeutic Anticoagulation in COVID-19: The Current Situation
Abstract
:1. Introduction
2. How Does the Omicron Variant Compare to the Other COVID-19 Variants with Hyper-Coagulopathy?
3. Therapeutic-Dose Thromboprophylaxis
The Study, Author (Year) | Study Type | Patients | Study Drug 1 | Comparator | Efficacy Outcomes | Safety Outcomes |
---|---|---|---|---|---|---|
HESACOVID trial, Lemos et al. (2020) [15] | Phase II randomized, controlled trial | 20 patients requiring mechanical ventilation | Therapeutic-dose enoxaparin | Standard anticoagulant prophylaxis | Statistically significant increase in P/F ratio at 7 days and 14 days. A higher proportion of successful extubation and more ventilator-free days in the therapeutic anticoagulation group. | No major or minor bleeding events. No difference in bleeding events requiring medical attention between the groups. |
The REMAP-CAP, ACTIV-4a, ATTACC trial, Goligher et al. (2021) [19] | Open-label, adaptive, multiplatform randomized, controlled trial | 1098 critically ill patients with severe COVID-19 pneumonia | Therapeutic-dose anticoagulation | Standard of care thromboprophylaxis | Median organ-support-free days were 1 vs. 4 in the standard care group. A similar proportion of patients in both groups survived hospital discharge (62.7% vs. 64.5%). | Major bleeding rates were 3.8% in the intervention group and 2.3% in the standard-of-care group. |
The ATTACC, ACTIV-4a, REMAP-CAP trial, Lawler et al. (2021) [18] | Open-label, adaptive, multiplatform randomized, controlled trial | 2219 non-critically-ill (moderately ill, not requiring ICU level of care) patients | Therapeutic-dose anticoagulation (n = 1190) | Standard of care thromboprophylaxis (n = 1054) | The probability of increasing OSFD with therapeutic-dose anticoagulation was 98.6% compared with standard-of-care thromboprophylaxis (Adjusted OR 1.27, 95% CI 1.03 to 1.58). The therapeutic AC arm had a higher probability of survival until hospital discharge. | Major bleeding was not statistically significant in the two groups (1.9% vs. 0.9%). |
RAPID trial, Sholzberg et al. (2021) [21] | Open-label, adaptive, randomized, controlled trial | 465 moderately ill patients (not in ICU) and increased D-dimer levels | Therapeutic-dose heparin (n = 228) | Prophylactic dose (standard or intermediate dosing) heparin (n = 237) | The primary outcome was a composite of death, invasive and noninvasive mechanical ventilation, or ICU admission up to day 28, which occurred in 16.2% of patients in the experimental arm and 21.9% in the control arm (OR 0.69, 95% CI 0.43 to 1.10; p = 0.12). Death occurred in 1.8% vs. 7.6% in the control group (OR 0.22, 95% CI 0.07 to 0.65; p = 0.006). VTE rates were not different. | Major bleeding rates were not statistically significant in the two groups (0.9% vs. 1.7%). |
HEP-COVID trial, Spyropoulos et al. (2021) [31] | Multicenter, randomized, controlled trial | 253 patients hospitalized with COVID-19 and elevated D-dimer levels (>4 × ULN) | Therapeutic-dose enoxaparin (n = 129) | Institutional standard- or intermediate-dose thromboprophylaxis (n = 124) | The primary outcome was a composite of VTE, ATE, or death from any cause, which occurred in 29% in the therapeutic group vs. 42% in the standard of care group (RR 0.68, 95% CI 0.49 to 0.96; p = 0.03). This benefit was not seen in the ICU group of patients. | Major bleeding occurred in 5% vs. 2% in the standard of care group (RR 2.88; 95% CI 0.59 to 14.02; p = 0.17). |
ACTION trial, Lopes et al. (2021) [17] | Open-label, pragmatic, randomized, controlled trial | 615 patients with COVID-19 and elevated D-dimer | Therapeutic-dose rivaroxaban in stable patients or heparin (UFH or LMWH) followed by rivaroxaban to day 30 (n = 311) | Institutional prophylactic anticoagulation with heparin (UFH or LMWH) (n = 304) | The primary outcome of the time of death, duration of hospitalization, or duration of supplemental oxygen to day 30 was not different in the two groups. | Higher major or CRNMB was seen in the therapeutic group at 8% vs. 2% in the standard group (RR 3.64, 95% CI 1.61 to 8.27; p = 0.0010). |
4. Management Recommendations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Asakura, H.; Ogawa, H. COVID-19-associated coagulopathy and disseminated intravascular coagulation. Int. J. Hematol. 2021, 113, 45–57. [Google Scholar] [CrossRef]
- Rahi, M.S.; Jindal, V.; Reyes, S.-P.; Gunasekaran, K.; Gupta, R.; Jaiyesimi, I. Hematologic disorders associated with COVID-19: A review. Ann. Hematol. 2021, 100, 309–320. [Google Scholar] [CrossRef] [PubMed]
- Tritschler, T.; Le Gal, G.; Brosnahan, S.; Carrier, M. POINT: Should Therapeutic Heparin Be Administered to Acutely Ill Hospitalized Patients with COVID-19? Yes. Chest 2022, 161, 1446–1448. [Google Scholar] [CrossRef]
- Conzelmann, C.; Müller, J.A.; Perkhofer, L.; Sparrer, K.M.; Zelikin, A.N.; Münch, J.; Kleger, A. Inhaled and systemic heparin as a repurposed direct antiviral drug for prevention and treatment of COVID-19. Clin. Med. Lond 2020, 20, e218–e221. [Google Scholar] [CrossRef] [PubMed]
- Cassinelli, G.; Naggi, A. Old and new applications of non-anticoagulant heparin. Int. J. Cardiol. 2016, 212 (Suppl. 1), S14–S21. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, S.Y.; Jin, W.; Sood, A.; Montgomery, D.W.; Grant, O.C.; Fuster, M.M.; Fu, L.; Dordick, J.S.; Woods, R.J.; Zhang, F.; et al. Characterization of heparin and severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) spike glycoprotein binding interactions. Antivir. Res. 2020, 181, 104873. [Google Scholar] [CrossRef] [PubMed]
- Saithong, S.; Saisorn, W.; Tovichayathamrong, P.; Filbertine, G.; Torvorapanit, P.; Wright, H.L.; Edwards, S.W.; Leelahavanichkul, A.; Hirankarn, N.; Chiewchengchol, D. Anti-Inflammatory Effects and Decreased Formation of Neutrophil Extracellular Traps by Enoxaparin in COVID-19 Patients. Int. J. Mol. Sci. 2022, 23, 4805. [Google Scholar] [CrossRef]
- Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern. Available online: https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern (accessed on 1 February 2023).
- SARS-CoV-2 Variant Classifications and Definitions. Available online: https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-classifications.html#anchor_1632154493691 (accessed on 1 February 2023).
- Halfmann, P.J.; Iida, S.; Iwatsuki-Horimoto, K.; Maemura, T.; Kiso, M.; Scheaffer, S.M.; Darling, T.L.; Joshi, A.; Loeber, S.; Singh, G.; et al. SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters. Nature 2022, 603, 687–692. [Google Scholar] [CrossRef]
- Maslo, C.; Friedland, R.; Toubkin, M.; Laubscher, A.; Akaloo, T.; Kama, B. Characteristics and Outcomes of Hospitalized Patients in South Africa during the COVID-19 Omicron Wave Compared with Previous Waves. JAMA 2022, 327, 583–584. [Google Scholar] [CrossRef]
- Grobbelaar, L.M.; Kruger, A.; Venter, C.; Burger, E.M.; Laubscher, G.J.; Maponga, T.G.; Kotze, M.J.; Kwaan, H.C.; Miller, J.B.; Fulkerson, D.; et al. Relative Hypercoagulopathy of the SARS-CoV-2 Beta and Delta Variants when Compared to the Less Severe Omicron Variants Is Related to TEG Parameters, the Extent of Fibrin Amyloid Microclots, and the Severity of Clinical Illness. Semin. Thromb. Hemost. 2022, 48, 858–868. [Google Scholar] [CrossRef]
- Tang, N.; Bai, H.; Chen, X.; Gong, J.; Li, D.; Sun, Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J. Thromb. Haemost. 2020, 18, 1094–1099. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Paranjpe, I.; Fuster, V.; Lala, A.; Russak, A.J.; Glicksberg, B.S.; Levin, M.A.; Charney, A.W.; Narula, J.; Fayad, Z.A.; Bagiella, E.; et al. Association of Treatment Dose Anticoagulation with In-Hospital Survival Among Hospitalized Patients With COVID-19. J. Am. Coll. Cardiol. 2020, 76, 122–124. [Google Scholar] [CrossRef] [PubMed]
- Lemos, A.C.B.; do Espírito Santo, D.A.; Salvetti, M.C.; Gilio, R.N.; Agra, L.B.; Pazin-Filho, A.; Miranda, C.H. Therapeutic versus prophylactic anticoagulation for severe COVID-19: A randomized phase II clinical trial (HESACOVID). Thromb. Res. 2020, 196, 359–366. [Google Scholar] [CrossRef]
- Yu, B.; Gutierrez, V.P.; Carlos, A.; Hoge, G.; Pillai, A.; Kelly, J.D.; Menon, V. Empiric use of anticoagulation in hospitalized patients with COVID-19: A propensity score-matched study of risks and benefits. Biomark. Res. 2021, 9, 29. [Google Scholar] [CrossRef]
- Lopes, R.D.; de Barros E Silva, P.G.M.; Furtado, R.H.M.; Macedo, A.V.S.; Bronhara, B.; Damiani, L.P.; Barbosa, L.M.; de Aveiro Morata, J.; Ramacciotti, E.; de Aquino Martins, P.; et al. Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): An open-label, multicentre, randomised, controlled trial. Lancet 2021, 397, 2253–2263. [Google Scholar] [CrossRef]
- Lawler, P.R.; Goligher, E.C.; Berger, J.S.; Neal, M.D.; McVerry, B.J.; Nicolau, J.C.; Gong, M.N.; Carrier, M.; Rosenson, R.S.; Reynolds, H.R.; et al. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with COVID-19. N. Engl. J. Med. 2021, 385, 790–802. [Google Scholar] [CrossRef] [PubMed]
- Goligher, E.C.; Bradbury, C.A.; McVerry, B.J.; Lawler, P.R.; Berger, J.S.; Gong, M.N.; Carrier, M.; Reynolds, H.R.; Kumar, A.; Turgeon, A.F.; et al. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with COVID-19. N. Engl. J. Med. 2021, 385, 777–789. [Google Scholar] [CrossRef]
- Jimenez, D.; Rali, P.; Doerschug, K. COUNTERPOINT: Should Therapeutic Heparin Be Administered to Acutely Ill Hospitalized Patients with COVID-19? No. Chest 2022, 161, 1448–1451. [Google Scholar] [CrossRef]
- Sholzberg, M.; Tang, G.H.; Rahhal, H.; AlHamzah, M.; Kreuziger, L.B.; Áinle, F.N.; Alomran, F.; Alayed, K.; Alsheef, M.; AlSumait, F.; et al. Effectiveness of therapeutic heparin versus prophylactic heparin on death, mechanical ventilation, or intensive care unit admission in moderately ill patients with COVID-19 admitted to hospital: RAPID randomised clinical trial. Bmj 2021, 375, n2400. [Google Scholar] [CrossRef]
- Ortega-Paz, L.; Galli, M.; Capodanno, D.; Franchi, F.; Rollini, F.; Bikdeli, B.; Mehran, R.; Montalescot, G.; Gibson, C.M.; Lopes, R.D.; et al. Safety and efficacy of different prophylactic anticoagulation dosing regimens in critically and non-critically ill patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials. Eur. Heart J. Cardiovasc. Pharmacother. 2021, 8, 677–686. [Google Scholar] [CrossRef]
- Parisi, R.; Costanzo, S.; Di Castelnuovo, A.; de Gaetano, G.; Donati, M.B.; Iacoviello, L. Different Anticoagulant Regimens, Mortality, and Bleeding in Hospitalized Patients with COVID-19: A Systematic Review and an Updated Meta-Analysis. Semin. Thromb. Hemost. 2021, 47, 372–391. [Google Scholar] [CrossRef] [PubMed]
- Sadeghipour, P.; Talasaz, A.H.; Rashidi, F.; Sharif-Kashani, B.; Beigmohammadi, M.T.; Farrokhpour, M.; Sezavar, S.H.; Payandemehr, P.; Dabbagh, A.; Moghadam, K.G.; et al. Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality among Patients with COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial. JAMA 2021, 325, 1620–1630. [Google Scholar] [CrossRef] [PubMed]
- Perepu, U.S.; Chambers, I.; Wahab, A.; Ten Eyck, P.; Wu, C.; Dayal, S.; Sutamtewagul, G.; Bailey, S.R.; Rosenstein, L.J.; Lentz, S.R. Standard prophylactic versus intermediate dose enoxaparin in adults with severe COVID-19: A multi-center, open-label, randomized controlled trial. J. Thromb. Haemost. 2021, 19, 2225–2234. [Google Scholar] [CrossRef] [PubMed]
- Kumar, D.; Kaimaparambil, V.; Chandralekha, S.; Lalchandani, J. Oral Rivaroxaban in the Prophylaxis of COVID-19 Induced Coagulopathy. J. Assoc. Physicians India 2022, 70, 11–12. [Google Scholar]
- Connors, J.M.; Brooks, M.M.; Sciurba, F.C.; Krishnan, J.A.; Bledsoe, J.R.; Kindzelski, A.; Baucom, A.L.; Kirwan, B.A.; Eng, H.; Martin, D.; et al. Effect of Antithrombotic Therapy on Clinical Outcomes in Outpatients with Clinically Stable Symptomatic COVID-19: The ACTIV-4B Randomized Clinical Trial. JAMA 2021, 326, 1703–1712. [Google Scholar] [CrossRef]
- Ramacciotti, E.; Barile Agati, L.; Calderaro, D.; Aguiar, V.C.R.; Spyropoulos, A.C.; de Oliveira, C.C.C.; Lins Dos Santos, J.; Volpiani, G.G.; Sobreira, M.L.; Joviliano, E.E.; et al. Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): An open-label, multicentre, randomised, controlled trial. Lancet 2022, 399, 50–59. [Google Scholar] [CrossRef]
- Cools, F.; Virdone, S.; Sawhney, J.; Lopes, R.D.; Jacobson, B.; Arcelus, J.I.; Hobbs, F.D.R.; Gibbs, H.; Himmelreich, J.C.L.; MacCallum, P.; et al. Thromboprophylactic low-molecular-weight heparin versus standard of care in unvaccinated, at-risk outpatients with COVID-19 (ETHIC): An open-label, multicentre, randomised, controlled, phase 3b trial. Lancet Haematol. 2022, 9, e594–e604. [Google Scholar] [CrossRef]
- Wang, T.Y.; Wahed, A.S.; Morris, A.; Kreuziger, L.B.; Quigley, J.G.; Lamas, G.A.; Weissman, A.J.; Lopez-Sendon, J.; Knudson, M.M.; Siegal, D.M.; et al. Effect of Thromboprophylaxis on Clinical Outcomes after COVID-19 Hospitalization. Ann. Intern. Med. 2023, 176, 515–523. [Google Scholar] [CrossRef]
- Spyropoulos, A.C.; Goldin, M.; Giannis, D.; Diab, W.; Wang, J.; Khanijo, S.; Mignatti, A.; Gianos, E.; Cohen, M.; Sharifova, G.; et al. Efficacy and Safety of Therapeutic-Dose Heparin vs. Standard Prophylactic or Intermediate-Dose Heparins for Thromboprophylaxis in High-risk Hospitalized Patients with COVID-19: The HEP-COVID Randomized Clinical Trial. JAMA Intern. Med. 2021, 181, 1612–1620. [Google Scholar] [CrossRef]
- Smith, K.; Krajewski, K.C.; Krajewski, M.P. Practical considerations in prevention and treatment of venous thromboembolism in hospitalized patients with COVID-19. Am. J. Health Syst. Pharm. 2020, 77, 1739–1745. [Google Scholar] [CrossRef]
- Gunasekaran, K.; Rajasurya, V.; Devasahayam, J.; Singh Rahi, M.; Chandran, A.; Elango, K.; Talari, G. A Review of the Incidence Diagnosis and Treatment of Spontaneous Hemorrhage in Patients Treated with Direct Oral Anticoagulants. J. Clin. Med. 2020, 9, 2984. [Google Scholar] [CrossRef] [PubMed]
- Rahi, M.S.; Pednekar, P.; Parmar, G.; Keibel, L.; Gunasekaran, K.; Amoah, K.; Winterbottom, C. Spontaneous intercostal artery bleeding in a patient with alcohol-induced liver cirrhosis. Clin. Case Rep. 2021, 9, e04613. [Google Scholar] [CrossRef] [PubMed]
- Cuker, A.; Tseng, E.K.; Nieuwlaat, R.; Angchaisuksiri, P.; Blair, C.; Dane, K.; DeSancho, M.T.; Diuguid, D.L.; Griffin, D.O.; Kahn, S.R.; et al. American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: January 2022 update on the use of therapeutic-intensity anticoagulation in acutely ill patients. Blood Adv. 2022, 6, 4915–4923. [Google Scholar] [CrossRef] [PubMed]
- Schulman, S.; Sholzberg, M.; Spyropoulos, A.C.; Zarychanski, R.; Resnick, H.E.; Bradbury, C.A.; Broxmeyer, L.; Connors, J.M.; Falanga, A.; Iba, T.; et al. ISTH guidelines for antithrombotic treatment in COVID-19. J. Thromb. Haemost. 2022, 20, 2214–2225. [Google Scholar] [CrossRef]
- Barnes, G.D.; Burnett, A.; Allen, A.; Ansell, J.; Blumenstein, M.; Clark, N.P.; Crowther, M.; Dager, W.E.; Deitelzweig, S.B.; Ellsworth, S.; et al. Thromboembolic prevention and anticoagulant therapy during the COVID-19 pandemic: Updated clinical guidance from the anticoagulation forum. J. Thromb. Thrombolysis 2022, 54, 197–210. [Google Scholar] [CrossRef] [PubMed]
- COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institue of Health. Available online: https://www.covid19treatmentguideliines.nih.gov/ (accessed on 1 February 2023).
- Moores, L.K.; Tritschler, T.; Brosnahan, S.; Carrier, M.; Collen, J.F.; Doerschug, K.; Holley, A.B.; Iaccarino, J.; Jimenez, D.; LeGal, G.; et al. Thromboprophylaxis in Patients With COVID-19: A Brief Update to the CHEST Guideline and Expert Panel Report. Chest 2022, 162, 213–225. [Google Scholar] [CrossRef]
Society (Year of Publication) | Recommendations | Level of Recommendation and Evidence |
---|---|---|
American Society of Hematology (2022) [35] | Recommends using therapeutic-intensity over prophylactic-intensity anticoagulation in patients with non-critically-ill COVID-19 infection who do not have suspected or confirmed VTE or another indication for anticoagulation. | Conditional recommendation, very low certainty in evidence |
International Society on Thrombosis and Haemostasis (2022) [36] | In select non-critically-ill patients hospitalized for COVID-19, therapeutic-dose LMWH or UFH is beneficial in preference to low- (prophylactic) or intermediate-dose LMWH or UFH to reduce the risk for thromboembolism and end-organ failure. | Strong, high-quality evidence |
In critically ill patients hospitalized with COVID-19, therapeutic-dose LMWH/UFH is not recommended over the usual care or prophylactic-dose LMWH/UFHs. | No benefit, moderate-quality evidence | |
The Anticoagulation Forum (2022) [37] | Suggests considering therapeutic intensity anticoagulation (LMWH or UFH) in non-critically-ill patients at increased risk of disease progression (hypoxic, elevated D-dimer) and not at increased risk of bleeding. | Less strong evidence |
Recommends using standard-dose thromboprophylaxis instead of intermediate or therapeutic intensity thromboprophylaxis in critically ill patients. | Strong evidence | |
National Institutes of Health (2022) [38] | Recommends therapeutic-dose heparin for hospitalized patients with COVID-19 pneumonia who require supplemental oxygen through low-flow nasal cannula and are non-pregnant, with elevated D-dimer, and not at increased bleeding risk. | Weak recommendation and level IIa quality of evidence |
Recommends prophylactic-dose heparin in critically ill patients with COVID-19 pneumonia (those requiring supplemental oxygen through a high-flow device or NIV, requiring MV). | Strong recommendation and level I quality of evidence | |
American College of Chest Physicians (2022) [39] | Suggests therapeutic-dose heparin (LMWH or UFH) over standard-dose anticoagulant thromboprophylaxis in acutely ill patients with COVID-19 pneumonia and low risk of bleeding. | Conditional recommendation, Ungraded Consensus-Based Statement |
Suggests standard-dose anticoagulant thromboprophylaxis over therapeutic- or intermediate-dose anticoagulation in critically ill patients with COVID-19 pneumonia. | Conditional recommendation, Ungraded Consensus-Based Statement |
Study | Intervention | Number of Patients | Outcomes |
---|---|---|---|
NCT04445935 | Comparing therapeutic-dose anticoagulation with bivalirudin with standard thromboprophylaxis | 100 patients with severe COVID-19 pneumonia requiring mechanical ventilation and with elevated D-dimer (1.2 mg/L) | Change in P/F ratio at 3 days and change in kidney function at 3 days |
NCT04808882 | Comparing low-dose, high-dose prophylactic tinzaparin and therapeutic tinzaparin | 353 patients with severe COVID-19 pneumonia | All-cause mortality and number of days to clinical improvement |
NCT04377997 | Comparing therapeutic-dose anticoagulation with the standard of care | 300 patients with COVID-19 pneumonia and elevated D-dimer (>1.5 g/mL) | Composite efficacy end point of death, cardiac arrest, VTE, MI, and shock in 12 weeks |
NCT04646655 | Comparing therapeutic with prophylactic dosing enoxaparin | 300 patients with COVID-19 pneumonia, moderate-severe ARDS, and elevated D-dimer (>2000 ng/mL) | Mortality and progression of respiratory failure at 30 days; major bleeding episodes |
NCT04584580 | Comparing therapeutic-dose LMWH with D-dimer-adjusted LMWH dosing | 500 patients with severe COVID-19 pneumonia | Mortality and occurrence of arterial and/or venous thrombosis at 4 weeks or discharge |
NCT04406389 | Comparing intermediate-dose prophylaxis with therapeutic-dose anticoagulation | 186 patients with moderate to severe COVID-19 pneumonia and elevated D-dimer (>700 mg/mL) | Mortality at 30 days, ICU length of stay, number of arterial and/or venous thrombotic events, number of bleeding events |
NCT04512079 | Comparing prophylactic-dose and full-dose enoxaparin with full-dose apixaban | 3600 patients admitted with COVID-19 pneumonia and elevated D-dimer | The time to first event rate within 30 days of randomization of the composite of all-cause mortality, intubation requiring mechanical ventilation, and VTE |
NCT04505774 | Comparing therapeutic- and prophylactic-dose anticoagulation alone versus the addition of a P2Y12 inhibitor | 3000 patients with moderate to severe COVID-19 pneumonia | Organ-support-free days and all-cause mortality |
NCT04508023 | Comparing full-dose rivaroxaban with the standard of care | 4000 patients with acute symptomatic COVID-19 infection not requiring hospitalization | Time to first occurrence of a composite endpoint of symptomatic VTE, MI, ischemic stroke, acute limb ischemia, non-CNS systemic embolization, all-cause hospitalization, and all-cause mortality |
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Rahi, M.S.; Parekh, J.; Pednekar, P.; Mudgal, M.; Jindal, V.; Gunasekaran, K. Role of Therapeutic Anticoagulation in COVID-19: The Current Situation. Hematol. Rep. 2023, 15, 358-369. https://doi.org/10.3390/hematolrep15020037
Rahi MS, Parekh J, Pednekar P, Mudgal M, Jindal V, Gunasekaran K. Role of Therapeutic Anticoagulation in COVID-19: The Current Situation. Hematology Reports. 2023; 15(2):358-369. https://doi.org/10.3390/hematolrep15020037
Chicago/Turabian StyleRahi, Mandeep Singh, Jay Parekh, Prachi Pednekar, Mayuri Mudgal, Vishal Jindal, and Kulothungan Gunasekaran. 2023. "Role of Therapeutic Anticoagulation in COVID-19: The Current Situation" Hematology Reports 15, no. 2: 358-369. https://doi.org/10.3390/hematolrep15020037
APA StyleRahi, M. S., Parekh, J., Pednekar, P., Mudgal, M., Jindal, V., & Gunasekaran, K. (2023). Role of Therapeutic Anticoagulation in COVID-19: The Current Situation. Hematology Reports, 15(2), 358-369. https://doi.org/10.3390/hematolrep15020037