Safety and efficacy of prophylactic anticoagulation versus therapeutic anticoagulation in hospital-admitted COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: COVID-19 disease-related coagulopathy and thromboembolic complication, an important aspect of the disease pathophysiology, are frequent and associated with poor outcomes, particularly significant in hospitalized patients. Undoubtedly, anticoagulation forms a cornerstone for the management of hospitalized COVID-19 patients, but the appropriate dosing has been inconclusive and a subject of research. We aim to review existing literature and compare safety and efficacy outcomes of prophylactic and therapeutic dose anticoagulation in such patients. METHODS: We did a systematic review and meta-analysis to compare the efficacy and safety of prophylactic dose anticoagulation when compared with therapeutic dosing in hospitalized COVID-19 patients. We searched PubMed, Google Scholar, EMBASE and COCHRANE databases from 2019 to 2021, without any restriction by language. We screened records, extracted data and assessed the risk of bias in the studies. RCTs that directly compare therapeutic and prophylactic anticoagulants dosing and are not placebo-controlled trials were included. Analyses of data were conducted using the Mantel-Haenszel random-effects model (DerSimonian-Laird analysis). The study is registered with PROSPERO (CRD42021265948). RESULTS: We included three studies in the final quantitative analysis. The incidence of thromboembolic events in therapeutic anticoagulation was lower in comparison with prophylactic anticoagulation in hospitalized COVID-19 patients and reached statistical significance [RR 1·45, 95% CI (1.07, 1.97) I2 -0%], whereas major bleeding as an adverse event was found lower in prophylactic anticoagulation in comparison with therapeutic anticoagulation that was statistically significant [RR 0·42, 95% CI(0.19, 0.93) I2 -0%]. CONCLUSION: Our study shows that therapeutic dose anticoagulation is more effective in preventing thromboembolic events than prophylactic dose but significantly increases the risk of major bleeding as an adverse event. So, the risk-benefit ratio must be considered while using either of them.

Effects of Different Anticoagulation Doses on Moderate-to-Severe COVID-19 Pneumonia With Hypoxemia.

Background COVID-19 is a prothrombotic disease that can cause thromboembolism and microthrombi, which could lead to multiorgan failure and death. Since COVID-19 is a relatively new disease, there are guidelines for anticoagulation dosing for COVID-19 patients without consensus on the dosing. We studied the effects of different doses of anticoagulation in hospitalized patients with COVID-19 pneumonia and hypoxemia on any differences in need for high-flow oxygen, mechanical ventilation, and mortality. We also analyzed the patient population who benefited most from anticoagulation. Methodology We performed a retrospective chart review of all patients who were admitted with the diagnosis of COVID-19 infection with positive polymerase chain reaction, pneumonia (confirmed either by chest X-ray or CT chest), and hypoxemia (oxygen saturation of <94%, while on room air). These patients were studied for outcomes (the need for high-flow oxygen, the requirement for mechanical ventilation, and overall mortality) for different doses of anticoagulation (prophylactic, escalated, and therapeutic). Results The sample consists of 132 subjects, predominantly males (116, 87%), with a mean age of 59 years and a standard deviation of 15. About one-third of the participants had diabetes, and more than 50% had hypertension. Additionally, 27 (20.3%) had a history of heart disease, and 70 (53%) of the subjects were admitted to the intensive care unit (ICU) at some point during the study. Among those admitted to the ICU, about 11 (8%) subjects required mechanical ventilation and 16 (12%) passed away during the study. Those who died had higher use of high-flow oxygen, noninvasive mechanical ventilation, and invasive mechanical ventilation and had a longer stay on mechanical ventilation. There was no significant difference in mortality or need for mechanical ventilation for any strategy of anticoagulation. Conclusions Different doses of anticoagulation did not show any statistically significant relationship between the need for mechanical ventilation and mortality. More patients on high-flow oxygen had received escalated doses of anticoagulation as compared to those who were not on high-flow oxygen. Anticoagulation levels did not have any statistically significant effect on overall survival of patients.

Therapeutic considerations for prevention and treatment of thrombotic events in COVID-19.

Thrombosis is a known complication of SARS-CoV-2 infection, particularly within a severely symptomatic subset of patients with COVID-19 disease, in whom an aggressive host immune response leads to cytokine storm syndrome (CSS). The incidence of thrombotic events coinciding with CSS may contribute to the severe morbidity and mortality observed in association with COVID-19. This review provides an overview of pharmacologic approaches based upon an emerging understanding of the mechanisms responsible for thrombosis across a spectrum of COVID-19 disease involving an interplay between immunologic and pro-thrombotic events, including endothelial injury, platelet activation, altered coagulation pathways, and impaired fibrinolysis.