Improving guideline-concordant thromboprophylaxis prescribing for children admitted to hospital with COVID-19.

BACKGROUND: The incidence of venous thrombo-embolism (VTE) in hospitalized children has increased by 130%-200% over the last two decades. Given this increase, many centers utilize electronic clinical decision support (CDS) to prognosticate VTE risk and recommend prophylaxis. SARS-CoV-2 infection (COVID-19) is a risk factor for VTE; however, CDS developed before the COVID-19 pandemic may not accurately prognosticate VTE risk in children with COVID-19. This study's objective was to identify areas to improve thromboprophylaxis recommendations for children with COVID-19. METHODS: Inpatients with a positive COVID-19 test at admission were identified at a quaternary-care pediatric center between March 1, 2020 and January 20, 2022. The results of the institution's automated CDS thromboprophylaxis recommendations were compared to institutional COVID-19 thromboprophylaxis guidelines and to the actual thromboprophylaxis received. CDS optimization was performed to improve adherence to COVID-19 thromboprophylaxis recommendations. RESULTS: Of the 329 patients included in this study, 106 (28.2%) were prescribed pharmaco-prophylaxis, 167 (50.8%) were identified by the institutional COVID-19 guidelines as requiring pharmaco-prophylaxis, and 45 (13.2%) were identified by the CDS as needing pharmaco-prophylaxis. On univariate analysis, only age 12 years or more was associated with recipient of appropriate prophylaxis (OR 1.78, 95% CI: 1.13-2.82, p = .013). Five patients developed VTEs; three had symptoms at presentation, two were identified as high risk for VTE by both the automated and best practice assessments but were not prescribed pharmaco-prophylaxis. CONCLUSION: Automated thromboprophylaxis recommendations developed prior to the COVID-19 pandemic may not identify all COVID-19 patients needing pharmaco-prophylaxis. Existing CDS tools need to be updated to reflect COVID-19-specific risk factors for VTEs.

Case of acute vision loss after injectable remdesivir with anticoagulants and overdose of antibiotics: A late report.

A woman reported decreased vision in the right eye since hospitalization for COVID-19. Vision in the right eye was 6/18 and in the left eye was counting fingers. Her left eye had cataract and right eye was pseudophakic with earlier documented good recovery. In the right eye, she had branch retinal vein occlusion (BRVO) with macular edema documented on optical coherence tomography (OCT). It was suspected that it might be an ocular manifestation of COVID-19 which had not been reported and had worsened. An overdose of antibiotics or remdesivir might also be responsible for the same. She was advised anti-VEGF injections and was kept under treatment.

Serotonin Release Assay: Functional Assay for Heparin- and Vaccine-Induced (Immune) Thrombotic Thrombocytopenia.

The serotonin release assay (SRA) has been the gold-standard assay for detection of heparin-dependent platelet-activating antibodies and integral for the diagnosis for heparin-induced thrombotic thrombocytopenia (HIT). In 2021, a thrombotic thrombocytopenic syndrome was reported after adenoviral vector COVID-19 vaccination. This vaccine-induced thrombotic thrombocytopenic syndrome (VITT) proved to be a severe immune platelet activation syndrome manifested by unusual thrombosis, thrombocytopenia, very elevated plasma D-dimer, and a high mortality even with aggressive therapy (anticoagulation and plasma exchange). While the platelet-activating antibodies in both HIT and VITT are directed toward platelet factor 4 (PF4), important differences have been found. These differences have required modifications to the SRA to improve detection of functional VITT antibodies. Functional platelet activation assays remain essential in the diagnostic workup of HIT and VITT. Here we detail the application of SRA for the assessment of HIT and VITT antibodies.

Thrombosis Occurrence in COVID-19 Compared With Other Infectious Causes of ARDS: A Contemporary Cohort.

Thrombosis occurrence in coronavirus disease 2019 (COVID-19) has been mostly compared to historical cohorts of patients with other respiratory infections. We retrospectively evaluated the thrombotic events that occurred in a contemporary cohort of patients hospitalized between March and July 2020 for acute respiratory distress syndrome (ARDS) according to the Berlin Definition and compared those with positive and negative real-time polymerase chain reaction results for wild-type severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) using descriptive analysis. The association between COVID-19 and thrombotic risk was evaluated using logistic regression. 264 COVID-19-positive (56.8% male, 59.0 years [IQR 48.6-69.7], Padua score on admission 3.0 [2.0-3.0]) and 88 COVID-19-negative patients (58.0% male, 63.7 years [51.2-73.5], Padua score 3.0 [2.0-5.0]) were included. 10.2% of non-COVID-19 and 8.7% of COVID-19 patients presented ≥ 1 clinically relevant thrombotic event confirmed by imaging exam. After adjustment for sex, Padua score, intensive care unit stay, thromboprophylaxis, and hospitalization length, the odds ratio for thrombosis in COVID-19 was 0.69 (95% CI, 0.30-1.64). We, therefore, conclude that infection-induced ARDS carries an inherent thrombotic risk, which was comparable between patients with COVID-19 and other respiratory infections in our contemporary cohort.

Acute pulmonary embolism in times of SARS-CoV-2: Diagnostic and therapeutic management / Tromboembolismo pulmonar agudo en tiempos de SARS-CoV-2: diagnóstico y tratamiento

There is a clear association between novel coronavirus 2 infection and the diagnosis of venous thromboembolic disease, as a cosequence of the development of a systemic inflammatory response syndrome due to the activation of the coagulation cascade. It occurs in 90% of patients with severe forms of the infection, evidencing the presence of pulmonary endovascular micro and macro thrombosis. This suggests a possible clinical benefit of thromboprophylaxis according to the patient's clinical risk. The suspicion of venous thromboembolic disease in the context of this pandemic represents a diagnostic challenge due to the co-existence of similarities between both conditions in several different aspects. It should be noted that the diagnosis of acute pulmonary embolism does not exclude the possibility of simultaneous viral infection. The evaluation of patients with suspected acute pulmonary embolism in the context of the pandemic should be optimized in order to implement a rapid diagnosis and treatment to reduce the associated morbidity and mortality. This will help reducing infectious risk for health-care professionals and other patients.

Existe una clara relación entre la infección por el nuevo coronavirus 2 y el diagnóstico de enfermedad tromboembólica venosa, como consecuencia del desarrollo de un síndrome de respuesta inflamatoria sistémica debido a la activación de la cascada de la coagulación. Se presenta en el 90% de los pacientes con formas graves de la infección, lo que revela la presencia de microtrombosis y macrotrombosis intravascular pulmonar. Esto sugiere un posible beneficio clínico de la aplicación de una tromboprofilaxis adecuada al riesgo clínico de cada paciente. Asimismo, la sospecha de enfermedad tromboembólica venosa en el contexto de esta pandemia representa un reto diagnóstico debido a la existencia de similitudes entre ambas alteraciones en varios aspectos. Debe tenerse en cuenta que el diagnóstico de tromboembolismo pulmonar agudo no excluye la posibilidad de infección viral. La valoración de pacientes con sospecha de tromboembolismo pulmonar agudo en el contexto de la pandemia debe ser eficaz para establecer un diagnóstico y tratamiento con rapidez, a fin de reducir la morbilidad y mortalidad adjuntas, sin que ello eleve el riesgo de infección para los profesionales de la salud y otros pacientes.

Guidelines for prophylaxis and anti-thrombotic treatment for patients with COVID-19. Consensus of the Latin American Cooperative Group on Hemostasis and Thrombosis (CLAHT) / Guía de profilaxia y tratamiento antitrombótico para pacientes con COVID-19. Consenso del Grupo Cooperativo Latinoamericano en Hemostasia y Trombosis (CLAHT)

Coagulopathy and thrombosis associated with coronavirus disease 2019 (COVID-19) represent a major issue in the management of this disease. In the past months, clinical studies have demonstrated that COVID-19 patients present with a particular hypercoagulable state, in which a markedly increased D-dimer concomitant with increased levels of fibrinogen are observed. This hypercoagulable state leads to an increased risk of thrombosis, which seems to be higher among those patients with critical symptoms of COVID-19. The best therapeutic approach to prevent thrombotic events in COVID-19 has not been determined yet and several questions regarding thromboprophylaxis therapy, such as the time to initiate anticoagulation, type of anticoagulant and dose regimen, have emerged among physicians. To address these concerns, several medical societies have published position papers to provide the opinion of thrombosis experts on the management of coagulopathy and thrombosis associated with COVID-19. In line with this, the Latin America Cooperative Group of Hemostasis and Thrombosis (Grupo CLAHT) has constituted a panel of experts in thrombosis and hemostasis to discuss the available data on this topic. The aim of this review is to summarize the current evidence regarding hemostatic impairment and thrombotic risk in COVID-19 and to provide a carefully revised opinion of Latin American experts on the thromboprophylaxis and management of thrombotic events and coagulopathy in patients with suspected COVID-19.

La coagulopatía y la trombosis asociadas a la enfermedad por coronavirus 2019 (COVID-19) representan un problema importante en el manejo de esta enfermedad. Los estudios clínicos de los últimos meses han demostrado que los pacientes con COVID-19 presentan un estado de hipercoagulabilidad particular, en el que se observa un aumento notable del dímero D concomitante con niveles elevados de fibrinógeno. El estado de hipercoagulabilidad conduce a un mayor riesgo de trombosis, que parece ser mayor entre aquellos pacientes con síntomas críticos de COVID-19. El mejor enfoque terapéutico para prevenir los eventos trombóticos en esta nueva enfermedad aún no se ha determinado y han surgido varias preguntas con respecto a la tromboprofilaxia, como el momento adecuado para iniciar la anticoagulación, el tipo de anticoagulante y el régimen de dosis. Para abordar estas preocupaciones, varias sociedades médicas han publicado artículos de posición para brindar la opinión de expertos en trombosis sobre el manejo de la coagulopatía y trombosis asociadas a COVID-19. Grupo Cooperativo Latinoamericano de Hemostasia y Trombosis (Grupo CLAHT) ha convocado a un panel de expertos en trombosis y hemostasia para discutir los datos disponibles sobre este tema. El objetivo de esta revisión es resumir la evidencia actual con respecto al deterioro hemostático y el riesgo trombótico en el COVID-19 y proporcionar una opinión cuidadosamente revisada de los expertos latinoamericanos sobre la tromboprofilaxis y el manejo de eventos trombóticos y coagulopatía en pacientes con sospecha de COVID-19.

COVID in obstetrics: labor analgesia and cesarean section.

PURPOSE OF REVIEW: This review is based on the latest evidence to provide a good standard of care for COVID-19 parturients and protection to healthcare givers. RECENT FINDINGS: COVID-19 by itself is not an indication for cesarean section. Different publications demonstrated the efficacy of neuraxial analgesia/anesthesia for delivery. Although SARS-CoV-2 was associated with a certain neurotropism, neuraxial block was not associated with neurological damage in COVID-19 parturients, and seems as safe and effective as in normal situations. It permits to avoid a general anesthesia in case of intrapartum cesarean section. Epidural failure is a concern: it may lead to a general anesthesia in case of emergency cesarean section. Local protocols and well-trained anesthesiologists will be helpful. COVID-19 patients require special circuits and every step (transfer to and from theatre, recovery, analgesia, and so on) should be planned in advance. For cesarean section under general anesthesia, personal protection equipment must be enhanced. Postoperative analgesia with neuraxial opioids, NSAIDs, or regional blocks are recommended. COVID-19 and pregnancy increase the risk of thrombosis, so thromboprophylaxis has to be considered and protocolized. SUMMARY: Anesthetic care for delivery in COVID-19 parturients should include neuraxial blocks. Special attention should be paid on the risk of thrombosis.

Clinically stable covid-19 patients presenting to acute unscheduled episodic care venues have increased risk of hospitalization: secondary analysis of a randomized control trial.

BACKGROUND: Assessment for risks associated with acute stable COVID-19 is important to optimize clinical trial enrollment and target patients for scarce therapeutics. To assess whether healthcare system engagement location is an independent predictor of outcomes we performed a secondary analysis of the ACTIV-4B Outpatient Thrombosis Prevention trial. METHODS: A secondary analysis of the ACTIV-4B trial that was conducted at 52 US sites between September 2020 and August 2021. Participants were enrolled through acute unscheduled episodic care (AUEC) enrollment location (emergency department, or urgent care clinic visit) compared to minimal contact (MC) enrollment (electronic contact from test center lists of positive patients).We report the primary composite outcome of cardiopulmonary hospitalizations, symptomatic venous thromboembolism, myocardial infarction, stroke, transient ischemic attack, systemic arterial thromboembolism, or death among stable outpatients stratified by enrollment setting, AUEC versus MC. A propensity score for AUEC enrollment was created, and Cox proportional hazards regression with inverse probability weighting (IPW) was used to compare the primary outcome by enrollment location. RESULTS: Among the 657 ACTIV-4B patients randomized, 533 (81.1%) with known enrollment setting data were included in this analysis, 227 from AUEC settings and 306 from MC settings. In a multivariate logistic regression model, time from COVID test, age, Black race, Hispanic ethnicity, and body mass index were associated with AUEC enrollment. Irrespective of trial treatment allocation, patients enrolled at an AUEC setting were 10-times more likely to suffer from the adjudicated primary outcome, 7.9% vs. 0.7%; p < 0.001, compared with patients enrolled at a MC setting. Upon Cox regression analysis adjustment patients enrolled at an AUEC setting remained at significant risk of the primary composite outcome, HR 3.40 (95% CI 1.46, 7.94). CONCLUSIONS: Patients with clinically stable COVID-19 presenting to an AUEC enrollment setting represent a population at increased risk of arterial and venous thrombosis complications, hospitalization for cardiopulmonary events, or death, when adjusted for other risk factors, compared with patients enrolled at a MC setting. Future outpatient therapeutic trials and clinical therapeutic delivery programs of clinically stable COVID-19 patients may focus on inclusion of higher-risk patient populations from AUEC engagement locations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04498273.

Efficacy and Safety of Direct Oral Anticoagulants Compared With Heparin for Preventing Thromboembolism in Hospitalized Patients With COVID-19: A Systematic Review and Meta-Analysis.

A high rate of thromboembolism and a high risk of death have been reported regarding hospitalized patients with coronavirus disease 2019 (COVID-19). Recently, we noticed that clinicians in some comparative studies used direct oral anticoagulants (DOACs) to prevent thromboembolism in patients with COVID-19. However, it is uncertain whether DOACs are better than recommended heparin for hospitalized patients with COVID-19. Therefore, a direct comparison of the prophylactic effects and safety between DOACs and heparin is needed. We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library from 2019 to December 1, 2022. Randomized controlled trials or retrospective studies comparing the efficacy or safety of DOACs with that of heparin in preventing thromboembolism for hospitalized patients with COVID-19 were included. We assessed endpoints and publication bias using Stata 14.0. Five studies comprising 1360 hospitalized COVID-19 patients with mild to moderate cases were identified in the databases. Comparing the embolism incidence, we found that DOACs had a better effect than heparin, mainly low-molecular-weight heparin (LMWH), in preventing thromboembolism (risk ratio [RR] = 0.63, 95% confidence interval [CI] [0.43-0.91], P = 0.014). Considering safety, DOACs resulted in less bleeding than heparin during hospitalization (RR = 0.52, 95% CI [0.11-2.44], P = 0.411). Similar mortality was discovered in the 2 groups (RR = 0.94, 95% CI [0.59-1.51], P = 0.797). In noncritically hospitalized patients with COVID-19, DOACs are superior to heparin, even LMWH, in preventing thromboembolism. Compared with heparin, DOACs have a lower trend of bleeding and yield a similar mortality rate. Therefore, DOACs may be a better alternative for patients with mild to moderate COVID-19.

The clinical manifestation and outcome of COVID-19 in patients with a history of ischemic heart disease; a retrospective case-control study.

INTRODUCTION: Coronary artery disease (CAD) is considered an independent risk factor for COVID-19. However, no study has specifically examined the clinical manifestations and outcomes of COVID-19 in patients with ischemic heart disease (IHD). METHODS: In a retrospective case-control study between 20 March 2020 to 20 May 2020, the medical record of 1611 patients with laboratory-confirmed SARS-CoV-2 infection was reviewed. IHD was defined as a history of an abnormal coronary angiography, coronary angioplasty, coronary artery bypass graft (CABG), or chronic stable angina. Demographic data, past medical history, drug history, symptoms, vital signs, laboratory findings, outcome, and death were investigated from medical records. RESULTS: 1518 Patients (882 men (58.1%)) with a mean age of 59.3 ± 15.5 years were included in the study. Patients with IHD (n = 300) were significantly less likely to have fever (OR: 0.170, 95% CI: 0.34-0.81, P < 0.001), and chills (OR: 0.74, 95% CI: 0.45-0.91, P < 0.001). Patients with IHD were 1.57 times more likely to have hypoxia (83.3% vs. 76%, OR: 1.57, 95% CI: 1.13-2.19, P = 0.007). There was no significant difference in terms of WBC, platelets, lymphocytes, LDH, AST, ALT, and CRP between the two groups (P > 0.05). After adjusting for demographic characteristics, comorbidities and vital signs, the risk factors for mortality of these patients were older age (OR: 1.04 and 1.07) and cancer (OR: 1.03, and 1.11) in both groups. In addition, in the patients without IHD, diabetes mellitus (OR: 1.50), CKD (OR: 1.21) and chronic respiratory diseases (OR: 1.48) have increased the odds of mortality. In addition, the use of anticoagulants (OR: 2.77) and calcium channel blockers (OR: 2.00) has increased the odds of mortality in two groups. CONCLUSION: In comparison with non-IHD, the symptoms of SARS-CoV-2 infection such as fever, chills and diarrhea were less common among patients with a history of IHD. Also, older age, and comorbidities (including cancer, diabetes mellitus, CKD and chronic obstructive respiratory diseases) have been associated with a higher risk of mortality in patients with IHD. In addition, the use of anticoagulants and calcium channel blockers has increased the chance of death in two groups without and with IHD.

Antiphospholipid syndrome, antiphospholipid antibodies, and stroke.

Antiphospholipid syndrome (APS) is a prothrombotic autoimmune disease with heterogeneous clinicopathological manifestations and is a well-established cause of acute ischemic stroke (AIS) and transient ischemic attack (TIA), particularly in younger patients. There is growing recognition of a wider spectrum of APS-associated cerebrovascular lesions, including white matter hyperintensities, cortical atrophy, and infarcts, which may have clinically important neurocognitive sequalae. Diagnosis of APS-associated AIS/TIA requires expert review of clinical and laboratory information. Management poses challenges, given the potential for substantial morbidity and recurrent thrombosis, additional risk conferred by conventional cardiovascular risk factors, and limited evidence base regarding optimal antithrombotic therapy for secondary prevention. In this review, we summarize key features of APS-associated cerebrovascular disorders, with focus on clinical and laboratory aspects of diagnostic evaluation. The current status of prognostic markers is considered. We review the evidence base for antithrombotic treatment in APS-associated stroke and discuss uncertainties, including the optimal intensity of anticoagulation and efficacy of direct oral anticoagulants. Clinical practice recommendations are provided, covering antithrombotic treatment, supportive management, and options for anticoagulant-refractory cases, and we highlight the benefits of adopting a considered, multidisciplinary team approach.

Structural requirements of Holothuria floridana fucosylated chondroitin sulfate oligosaccharides in anti-SARS-CoV-2 and anticoagulant activities.

Fucosylated chondroitin sulfate (FucCS) is a unique glycosaminoglycan found primarily in sea cucumbers. This marine sulfated glycan is composed of a chondroitin sulfate backbone decorated with fucosyl branches attached to the glucuronic acid. FucCS exhibits potential biological actions including inhibition of blood clotting and severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. These biological effects have been attributed to certain structural features, including molecular weight (MW), and/or those related to fucosylation, such as degrees of fucosyl branches, sulfation patterns and contents. In a previous work, we were able to generate oligosaccharides of the FucCS from Pentacta pygmaea (PpFucCS) with reduced anticoagulant effect but still retaining significant anti-SARS-CoV-2 activity against the delta strain. In this work, we extended our study to the FucCS extracted from the species Holothuria floridana (HfFucCS). The oligosaccharides were prepared by free-radical depolymerization of the HfFucCS via copper-based Fenton reaction. One-dimensional 1H nuclear magnetic resonance spectra were employed in structural analysis. Activated partial thromboplastin time and assays using protease (factors Xa and IIa) and serine protease inhibitors (antithrombin, and heparin cofactor II) in the presence of the sulfated carbohydrates were used to monitor anticoagulation. Anti-SARS-CoV-2 effects were measured using the concentration-response inhibitory curves of HEK-293T-human angiotensin-converting enzyme-2 cells infected with a baculovirus pseudotyped SARS-CoV-2 wild-type and delta variant spike (S)-proteins. Furthermore, the cytotoxicity of native HfFucCS and its oligosaccharides was also assessed. Like for PpFucCS, we were able to generate a HfFucCS oligosaccharide fraction devoid of high anticoagulant effect but still retaining considerable anti-SARS-CoV-2 actions against both variants. However, compared to the oligosaccharide fraction derived from PpFucCS, the average MW of the shortest active HfFucCS oligosaccharide fraction was significantly lower. This finding suggests that the specific structural feature in HfFucCS, the branching 3,4-di-sulfated fucoses together with the backbone 4,6-di-sulfated N-acetylgalactosamines, is relevant for the anti-SARS-CoV-2 activity of FucCS molecules.

Tissue-specific pathway activities: A retrospective analysis in COVID-19 patients.

The ACE2 receptors essential for SARS-CoV-2 infections are expressed not only in the lung but also in many other tissues in the human body. To better understand the disease mechanisms and progression, it is essential to understand how the virus affects and alters molecular pathways in the different affected tissues. In this study, we mapped the proteomics data obtained from Nie X. et al. (2021) to the pathway models of the COVID-19 Disease Map project and WikiPathways. The differences in pathway activities between COVID-19 and non-COVID-19 patients were calculated using the Wilcoxon test. As a result, 46% (5,235) of the detected proteins were found to be present in at least one pathway. Only a few pathways were altered in multiple tissues. As an example, the Kinin-Kallikrein pathway, an important inflammation regulatory pathway, was found to be less active in the lung, spleen, testis, and thyroid. We can confirm previously reported changes in COVID-19 patients such as the change in cholesterol, linolenic acid, and arachidonic acid metabolism, complement, and coagulation pathways in most tissues. Of all the tissues, we found the thyroid to be the organ with the most changed pathways. In this tissue, lipid pathways, energy pathways, and many COVID-19 specific pathways such as RAS and bradykinin pathways, thrombosis, and anticoagulation have altered activities in COVID-19 patients. Concluding, our results highlight the systemic nature of COVID-19 and the effect on other tissues besides the lung.

SARS-CoV-2 induced coagulopathy and potential role of anticoagulation: Scoping review of literature.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can vary on a spectrum of asymptomatic disease to rarer manifestations like hypercoagulability especially among elderly patients admitted in the intensive care unit (ICU) and those with preexisting comorbidities. The exact mechanism behind this phenomenon is still unclear, however studies have shown an association with elevated cytokines and severe inflammatory response which encompasses this disease. Hypercoagulability can be limited to the lungs, or present as systemic manifestations of arterial and venous thrombosis leading to mortal outcomes. Thus, careful evaluation of risk factors should be performed by physicians and treatment with anticoagulants should be modified accordingly. All Coronavirus Disease 2019 (COVID-19) in-patients should receive thromboprophylactic therapy, with increased dosages administered to patients with increased disease severity or those with a high risk. D-dimer levels and sepsis-induced coagulopathy (SIC) score aid in identifying high risk patients and predicting outcome. This article highlights the pathophysiology behind hypercoagulability, its clinical associations and discusses therapeutic modalities to combat this fatal consequence of SARS-CoV-2.

[Practice guidelines of thromboprophylaxis and management of anticoagulation in hospitalized patients with COVID-19].

Corona virus disease 2019 (COVID-19) can lead to thrombotic complications through multiple mechanisms. Venous thromboembolism (VTE) is one of the most important causes of death or poor prognosis in hospitalized patients with COVID-19. The prognosis of thrombosis in COVID-19 patients can be improved with VTE and bleeding risk assessment, as well as appropriate VTE prophylaxis. However, in current clinical practice, there still is much room for progress in choose of appropriate prevention methods, anticoagulant regimens, doses, and courses based on the severity and specific condition of COVID-19 patients and dynamically balancing the risk of thrombosis and bleeding. In the past three years, a series of authoritative guidelines related to VTE and COVID-19 and high-quality, evidence-based medical research evidence have been released both in domestic and internationally. Based on this, in order to better guide the clinical practice in China, multi-discipline expert discussions and Delphi expert demonstrations formulated the"Thromboprophylaxis and management of anticoagulation in hospitalized patients with COVID-19: an update of the CTS guidelines", aiming to address the issues of thrombosis risk and prevention strategies caused by COVID-19, anticoagulant management of hospitalized patients, diagnosis and treatment of thrombosis, anticoagulant management of special populations, interaction and adjustment strategies of antiviral and anti-inflammatory drugs and anticoagulant drugs, follow-up after discharge and many other aspects of clinical situations. Recommendations and clinical guidelines are provided for appropriate thromboprophylaxis and anticoagulation management strategies for VTE in patients with COVID-19.

Randomized Trial of Anticoagulation Strategies for Noncritically Ill Patients Hospitalized With COVID-19.

BACKGROUND: Prior studies of therapeutic-dose anticoagulation in patients with COVID-19 have reported conflicting results. OBJECTIVES: We sought to determine the safety and effectiveness of therapeutic-dose anticoagulation in noncritically ill patients with COVID-19. METHODS: Patients hospitalized with COVID-19 not requiring intensive care unit treatment were randomized to prophylactic-dose enoxaparin, therapeutic-dose enoxaparin, or therapeutic-dose apixaban. The primary outcome was the 30-day composite of all-cause mortality, requirement for intensive care unit-level of care, systemic thromboembolism, or ischemic stroke assessed in the combined therapeutic-dose groups compared with the prophylactic-dose group. RESULTS: Between August 26, 2020, and September 19, 2022, 3,398 noncritically ill patients hospitalized with COVID-19 were randomized to prophylactic-dose enoxaparin (n = 1,141), therapeutic-dose enoxaparin (n = 1,136), or therapeutic-dose apixaban (n = 1,121) at 76 centers in 10 countries. The 30-day primary outcome occurred in 13.2% of patients in the prophylactic-dose group and 11.3% of patients in the combined therapeutic-dose groups (HR: 0.85; 95% CI: 0.69-1.04; P = 0.11). All-cause mortality occurred in 7.0% of patients treated with prophylactic-dose enoxaparin and 4.9% of patients treated with therapeutic-dose anticoagulation (HR: 0.70; 95% CI: 0.52-0.93; P = 0.01), and intubation was required in 8.4% vs 6.4% of patients, respectively (HR: 0.75; 95% CI: 0.58-0.98; P = 0.03). Results were similar in the 2 therapeutic-dose groups, and major bleeding in all 3 groups was infrequent. CONCLUSIONS: Among noncritically ill patients hospitalized with COVID-19, the 30-day primary composite outcome was not significantly reduced with therapeutic-dose anticoagulation compared with prophylactic-dose anticoagulation. However, fewer patients who were treated with therapeutic-dose anticoagulation required intubation and fewer died (FREEDOM COVID [FREEDOM COVID Anticoagulation Strategy]; NCT04512079).