High-Dose Prophylactic Anticoagulation for COVID-19 Pneumonia: A Review of Benefits and Risks.

The COVID-19 pandemic has had a devastating impact on a global scale, causing significant morbidity and mortality. The virus affects multiple organ systems, including the respiratory, cardiovascular, and coagulation systems, leading to severe pneumonia in some patients. Moreover, COVID-19 patients with severe pneumonia have a high incidence of thrombotic events, which can result in significant morbidity and mortality. Given the potential benefits of anticoagulation therapy in COVID-19 patients with thrombotic complications, recent studies have proposed high-dose prophylactic anticoagulation (HD-PA) therapy as a potential treatment option. In fact, some studies have suggested that HD-PA therapy may be more effective in reducing thrombotic events and mortality rates than other treatment options. This review aims to provide a comprehensive overview of the benefits and risks of HD-PA therapy for COVID-19 pneumonia patients. By synthesizing and analyzing the latest available research, we highlight patient selection criteria and discuss the optimal dosage, duration, and timing of therapy. Additionally, we review the potential risks associated with HD-PA therapy and provide recommendations for clinical practice. Ultimately, this review provides valuable insights into the use of HD-PA therapy in COVID-19 pneumonia patients and paves the way for further research in this critical area. By exploring the benefits and risks of this treatment option, we hope to provide healthcare professionals with the information they need to make informed decisions about the best course of treatment for their patients.

A case report on uneventful anticoagulation and persistence of Type 1 Respiratory Failure post severe COVID-19 infection in a patient of Osler-Weber-Rendu syndrome.

The SARS-CoV-2 pandemic has led researchers worldwide to study the patterns of association of SARS-CoV-2 with different diseases, which have been a prime focus of medical literature. Osler-Weber-Rendu syndrome, also known as hereditary hemorrhagic telangiectasia (HHT), is a rare genetic disorder in which patients present with recurrent epistaxis, nostril manipulations, and multiple arteriovenous malformations (AVMs) along with telangiectasias involving internal organs and mucocutaneous areas. In addition, these AVMs are prone to bleeding or act as a nidus for thrombus formation, apart from other serious complications, such as chronic hypoxemia, anemia, pulmonary artery hypertension, heart failure, and cerebrovascular accidents. Here, we present a case report of a patient who presented with acute onset respiratory complaints, had multiple episodes of epistaxis in the past, and was later diagnosed with HHT as per Curaçao criteria in our hospital. Doppler ultrasound over the left calf region showed an AVM. Contrast-enhanced computed tomography (CECT) angiography of the chest and abdomen revealed multiple pulmonary and hepatic AVMs along with splenic and uterine telangiectasias and malformations, who on acquiring severe COVID-19 infection developed complications such as anemia, pulmonary artery hypertension, sepsis, acute kidney injury, and post-COVID-19 persistence of Type 1 respiratory failure. Furthermore, the risk-benefit ratio of anticoagulation therapy in such patients with COVID-19 infection is tricky and challenging. However, our patient was prophylactically anti-coagulated with enoxaparin for 12 days with an uneventful outcome.

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.

The Comparison of Therapeutic With Prophylactic Anticoagulation on Mortality, Risk of Bleeding, and Thromboembolism in Hospitalized Patients With COVID-19: A Systematic Review.

Thromboembolism is one of the most severe manifestations of coronavirus disease 2019 (COVID-19). Thrombotic complications have been reported even with the administration of thromboprophylaxis. This has led many experts to have variable opinions on the most effective prophylactic strategy and to anticipate the discovery of the ideal dosing of anticoagulation to reduce thromboembolic events and related mortality. We performed a systematic review to evaluate whether therapeutic-dose anticoagulation is superior to prophylactic-dose anticoagulation by comparing mortality rates, bleeding risks, and rates of thromboembolism. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to create our systematic review. Twenty-two records were collected from PubMed, PubMed Central (PMC), and Medical Literature Analysis and Retrieval System Online (MEDLINE), after which they undertook quality appraisals. A total of 124 studies were analyzed in six systematic reviews and meta-analyses, one pooled analysis, two multicenter retrospective cohort studies, one observational study, one retrospective chart review, one evidence-based protocol, and four narrative reviews.

Double Trouble: A Case of Two Simultaneous Thrombotic Events in a Patient With COVID-19.

Coronavirus disease 2019 (COVID-19) is known to primarily have respiratory tract involvement, but thromboembolic complications can occur as well, leading to increased overall mortality seen in these patients. We present a case of a patient infected with COVID-19 who then developed two simultaneous thrombotic events. Our patient is a 57-year-old male who presented to the emergency department with sudden onset dysarthria and left lower extremity weakness. Medical records indicated he recently tested positive for COVID-19 infection 10 days ago. Magnetic resonance imaging (MRI) of the brain revealed an acute right cerebellar infarction as well as acute bilateral thalamic infarcts. Later in the hospital course, computed tomography angiography (CTA) of the chest revealed a right lower lobe segmental pulmonary artery embolism. Patients with COVID-19 have been seen to develop a wide spectrum of thromboembolic manifestations, most commonly being venous thromboembolism. Arterial thrombosis and microvascular disease can be detected as well. Early diagnosis and treatment of clotting disease is essential and may decrease overall mortality in COVID-19-infected patients.

Supraprophylactic Anti-Factor Xa Levels Are Associated with Major Bleeding in Neurosurgery Patients Receiving Prophylactic Enoxaparin.

BACKGROUND: Prior studies demonstrated reduced risk for venous thromboembolism (VTE) in neurosurgical patients secondary to prophylaxis with both heparin and low-molecular-weight heparin. The ability to monitor low-molecular-weight heparin by obtaining anti-factor Xa (anti-Xa) serum levels provides an opportunity to evaluate safety and efficacy. The aim of this study was to describe characteristics of patients who have anti-Xa levels outside of the goal range (0.2-0.4/0.5 IU/mL) and investigate incidence of major bleeding and VTE. METHODS: A single-center, retrospective, observational study was conducted on neurosurgical patients receiving enoxaparin for VTE prophylaxis between August 2019 and December 2020. Significance testing was conducted via Fisher exact test and independent samples t test. RESULTS: The study included 85 patients. Patients were less likely to have an anti-Xa level in the goal range if they were male, had a higher weight, or were morbidly obese. Three neuroendovascular patients (3.5%) experienced a major bleed. Serum anti-Xa levels were significantly higher in patients who experienced major bleeds compared with patients who did not (0.45 ± 0.16 IU/mL vs. 0.28 ± 0.09 IU/mL, P = 0.003). Patients with a supraprophylactic anti-Xa level (>0.5 IU/mL) were more likely to experience a major bleed (P = 0.005). One VTE event occurred: the patient experienced a pulmonary embolism with anti-Xa level at goal. CONCLUSIONS: Anti-Xa-guided enoxaparin dosing for VTE prophylaxis in neurosurgical patients may help prevent major bleeding. These data suggest that a higher anti-Xa level may predispose patients to major bleeding. Further evaluation is needed to identify the goal anti-Xa level for VTE prophylaxis in this population.

Prothrombotic Milieu, Thrombotic Events and Prophylactic Anticoagulation in Hospitalized COVID-19 Positive Patients: A Review.

The Coronavirus Disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality worldwide. Although initial reports concentrated on severe respiratory illness, emerging literature has indicated a substantially elevated risk of thromboembolic events in patients with COVID-19 disease. Pro-inflammatory cytokine release has been linked to endothelial dysfunction and activation of coagulation pathways, as evident by elevated D-dimer levels and deranged coagulation parameters. Both macrovascular and microvascular thromboses have been described in observational cohort and post-mortem studies. Concurrently, preliminary data have suggested the role of therapeutic anticoagulation in preventing major thromboembolic complications in moderately but not critically ill patients. However, pending results from randomized controlled trials, clear guidance is lacking regarding the intensity and duration of anticoagulation in such patients. Herein, we review the existing evidence on incidence and pathophysiology of COVID-19 related thromboembolic complications and guide anticoagulation therapy based on current literature and societal consensus statements.

Venous thromboembolism in patients with COVID-19. A prevalent and a preventable complication of the pandemic.

Coronavirus disease 2019 or most commonly known as COVID-19 is a trending global infectious disease which a few months ago was affirmed as a global health emergency or a pandemic by the WHO Emergency Committee. The common symptoms manifested in this pandemic disease are high grade fever, cough, fatigue, shortness of breath and flu like symptom which can evolve into severe respiratory disorders such as pneumonia, acute respiratory distress syndrome (ARDS) and/or end-organ failure. Factors that contribute to the severity or high mortality rate in COVID-19 include old age, comorbidities like hypertension, diabetes, hyperlipidaemia, neutrophilia, and organ and coagulation dysfunction. Disseminated intravascular coagulation and other various coagulopathies including Venous thromboembolism have known to become a major contributing factor to high mortality rate. Venous thromboembolism is a disease which is a combination of deep vein thrombosis and pulmonary embolism. Prophylactic anticoagulation in patients prone to or with a pre-existing history of venous thromboembolism is associated with decreased mortality in severe COVID-19 pneumonia. This review article focuses upon COVID-19 and increased incidence of venous thromboembolism in patients infected by COVID-19 along with the role it has in high mortality rate in COVID-19 patients.

Central pulmonary embolism in patients with Covid-19.

BACKGROUND: The purpose was to evaluate central pulmonary embolism (PE) in patients with Covid-19. The association with severe radiological pulmonary changes, prophylactic anticoagulation and ICU care was assessed. METHODS: From 1 March until 31 May 2020, all in-hospital patients with a positive PCR for SARS-CoV-2-RNA and PE diagnosed with computed tomography pulmonary angiography were identified through diagnostic codes in medical charts. PE was characterised as central/peripheral and unilateral/bilateral. Covid-19 related lung changes were evaluated scoring the proportion of affected lung (max-score score 25) for all five lobes in both lungs. ICU and non-ICU patients were included and anticoagulant regimens were assessed. RESULTS: Of 1162 patients with Covid-19, 41 were diagnosed with PE (cumulative incidence 3.5%), and of these 63.4% (=overall 2.2%) had central PE. PE on admission was present in 46.3%. No differences were seen in the distribution of central vs. peripheral PE in relation to prophylactic anticoagulation (p=.317). Of ICU patients 82.4% were diagnosed with central PE compared to 50.0% among non-ICU patients (p=.05). No association was observed between the presence of central PE and the extent of radiological Covid-19 changes (p=.451). Mild (0-12 p) and severe (13-25 p) pulmonary changes were seen in 63.4% and 36.6% of patients respectively. CONCLUSIONS: Overall, and especially in ICU-patients, a high proportion of central PE was seen and many were diagnosed at admission. No association between central PE and prophylactic anticoagulation, or the extent of pulmonary Covid-19 changes was observed.

Acute cor pulmonale from saddle pulmonary embolism in a patient with previous COVID-19: should we prolong prophylactic anticoagulation?

Severe coronavirus disease 2019 (COVID-19) is known to be associated with a heightened risk of thromboembolism. However, the risk associated with mild and moderate illness from COVID-19 is unknown, and there is no current recommendation for prophylaxis against thromboembolism in patients after hospital treatment, unless there are established thrombophilic risk factors. We report the case of a 52-year-old woman who presented with massive saddle pulmonary embolism 1 week after initial hospital discharge, which was treated successfully with thrombolysis. This case raises the question of whether extended prophylactic anticoagulation should be considered even in low-risk COVID-19 cases.