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.

Risk and Management of Bleeding Complications with Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Venous Thromboembolism: a Narrative Review.

Atrial fibrillation (AF) and venous thromboembolism (VTE) are highly prevalent conditions with a significant healthcare burden, and represent the main indications for anticoagulation. Direct oral anticoagulants (DOACs) are the first choice treatment of AF/VTE, and have become the most prescribed class of anticoagulants globally, overtaking vitamin K antagonists (VKAs). Compared to VKAs, DOACs have a similar or better efficacy/safety profile, with reduced risk of intracerebral hemorrhage (ICH), while the risk of major bleeding and other bleeding harms may vary depending on the type of DOAC. We have critically reviewed available evidence from randomized controlled trials and observational studies regarding the risk of bleeding complications of DOACs compared to VKAs in patients with AF and VTE. Special patient populations (e.g., elderly, extreme body weights, chronic kidney disease) have specifically been addressed. Management of bleeding complications and possible resumption of anticoagulation, in particular after ICH and gastrointestinal bleeding, are also discussed. Finally, some suggestions are provided to choose the optimal DOAC to minimize adverse events according to individual patient characteristics and bleeding risk.

Left Ventricular Thrombosis: Current Perspective and Use of Direct Oral Anticoagulants br

Left ventricular thrombus (LVT) is a serious risk factor for systemic embolism development. Despite the evident danger of this condition, currentguidelines describe management of patients with this potentially fatal complication very briefly. LVT can complicate myocardial infarction where its in-cidence is around 10%, as well as various forms of cardiomyopathies and novel coronavirus infection. According to clinical guidelines vitamin K antag-onists (VKAs) should be used as treatment of choice for thrombus resolution. However, experts point out that this therapy lacks necessary evidentialbase and bears certain difficulties because of pharmacokinetic and pharmacodynamical properties of VKAs. These drawbacks are absent in direct oralanticoagulants (DOACs), the possibility of using which in LVT is being actively studied. As for now, published results of 3 randomised clinical trialshave demonstrated similar safety and efficacy profiles of DOACs and VKAs. Similarly, the majority of retrospective cohort studies did not observesignificant differences between two groups, where some of them have shown superiority of DOACs especially in terms of earlier thrombus resolution.Nevertheless, some studies have found DOACs ineffective and even potentially unsafe regarding systemic embolism. Existing data does not allow toform an unambiguous conclusion about the equivalence of DOACs and VKAs for LVT resolution. Large randomised clinical trials are needed todetermine efficacy and safety of such treatment in these patients.

Give full play to the role of pharmacists in the safety management of direct oral anticoagulants.

Direct oral anticoagulants (DOACs) are recommended as first-line therapy in patients with atrial fibrillation and venous thromboembolic diseases in relevant guidelines at home and abroad. Compared with warfarin, DOACs have relatively fixed dose, fewer drug interactions, and no need of routine therapeutic drug monitoring in clinic. DOACs bring much convenience to anticoagulant therapy, but they also raise a series of new medication safety challenges. Pharmacists should ensure the safe use of DOAC through improving corresponding pharmaceutical care mechanism, such as assisting doctors to improve the suitability of dose in prescription, standardizing laboratory monitoring process, setting up early warning of potential drug interaction, and strengthening anticoagulant conversion and perioperative anticoagulant therapy management. In the post-coronavirus disease 2019 era, incorporating DOACs into the standardized manage- ment at anticoagulation clinics is an important work extension of the traditional anticoagulation clinics and may reduce the risk of exposure to the novel coronavirus. In addition, considering the limit in labour and work energy of clinical pharmacists, the application of DOAC-related clinical decision support system may help improve the appropriateness of prescription and reduce the adverse drug events.Copyright © 2020 Chinese Medical Journals Publishing House Co.Ltd. All rights reserved.

Analysis of Pharmacy Cardiac Optimization Clinic for Patients with New Onset Atrial Fibrillation Detected via Cardiac Implantable Electronic Device Clinic.

For patients with cardiac implantable electronic devices (CIEDs), arrythmias such as atrial fibrillation (AF) can be detected and actions taken to rapidly assess and initiate treatment where appropriate. Actions include timely initiation of anticoagulation, review of blood pressure, and optimization of cholesterol/lipids to prevent unfavorable outcomes, such as stroke and other cardiovascular complications. Delays to initiating anticoagulation can have devastating consequences. We sought to implement a virtual clinic, where a pharmacist reviews patient referrals from a CIED clinic after detecting AF from the CIED. Anticoagulation choice is determined by patient-specific factors, and a shared patient-provider decision to start oral anticoagulation is made. In addition, blood pressure readings and medications are assessed with lipid-lowering therapies for optimization. A total of 315 patients have been admitted through this clinic and anticoagulated over a two-year span; in addition, 322 successful interventions were made for optimization of cardiac therapy. Rapid initiation of anticoagulation within five days of referral was likely to have reduced unfavorable outcomes, such as stroke and other cardiovascular optimizations, leading to improved patient outcomes.

Single-Dose Bioequivalence Study of Rivaroxaban-Containing Medicinal Products in Healthy Volunteers.

Therapeutically, new oral anticoagulants (NOACs) are considered to be non-inferior or superior to vitamin K antagonists (warfarin). NOACs are included in current guidelines for the treatment of various cardiovascular diseases. Rivaroxaban medicinal products have been shown to effectively fight thrombotic complications of the new coronavirus infection, COVID-19. The wide clinical use of rivaroxaban products motivates the development of generics. The aim of the study was to compare the pharmacokinetics and safety of rivaroxaban medicinal products in a single-dose bioequivalence study in healthy volunteers under fasting conditions. Material(s) and Method(s): the bioequivalence study compared single-dose oral administration of Rivaroxaban, 10 mg film-coated tablets (NovaMedica Innotech LLC, Russia), and the reference product Xarelto, 10 mg film-coated tablets (Bayer AG, Germany), in healthy volunteers under fasting conditions. The open, randomised, crossover trial included 46 healthy volunteers. Each of the medicinal products (the test product and the reference product) was administered once;blood samples were collected during the 48 h after the administration. The washout between the study periods lasted 7 days. Rivaroxaban was quantified in plasma samples of the volunteers by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Result(s): no adverse events or serious adverse events were reported for the test and reference products during the study. The following pharmacokinetic parameters were obtained for Rivaroxaban and Xarelto, respectively: Cmax of 134.6 +/- 58.0 ng/mL and 139.9 +/- 49.3 ng/mL, AUC0-48 of 949.7 +/- 354.5 ngxh/mL and 967.6 +/- 319.9 ngxh/mL, AUC0- of 986.9 +/- 379.7 ngxh/mL and 1003.6 +/- 320.4 ngxh/mL, T1/2 of 8.2 +/- 3.2 h and 7.8 +/- 3.3 h. The 90% confidence intervals for the ratios of Cmax, AUC0-48, and AUC0- geometric means were 88.04-108.67%, 89.42-104.92% and 89.44-104.81%, respectively. Conclusion(s): the test product Rivaroxaban and the reference product Xarelto were found to have similar rivaroxaban pharmacokinetics and safety profiles. The study demonstrated bioequivalence of the medicinal products.Copyright © 2022 Obstetrics, Gynecology and Reproduction. All rights reserved.

Unexpected Pulmonary Embolism Late After Recovery from Mild COVID-19?

SARS-CoV-2 infection is associated with an increased risk of venous thromboembolism (VTE), which is common during active illness but unusual in milder cases and after healing. We describe a case of bilateral acute pulmonary embolism occurring 3 months after recovery from a paucisymptomatic SARS-CoV-2 infection. The only VTE risk factor demonstrable was a history of previous SARS-CoV-2 infection, with laboratory signs of residual low-grade inflammation. Clinicians should be aware of VTE as a potential cause of sudden dyspnoea after COVID-19 resolution, especially in the presence of persistent systemic inflammation. LEARNING POINTS: Venous thromboembolism may occur after COVID-19, even in milder SARS-CoV-2 infections and late after coronavirus clearance.Laboratory signs of systemic inflammation are clues for suspecting venous thromboembolism as a cause of sudden dyspnoea in patients with low risk scores for pulmonary embolism but with previous COVID-19 infection.

Management, control, and decision making in unexpected recurrent venous thromboembolism in COVID-19: a case report.

BACKGROUND: Coronavirus disease 2019 was spread worldwide, as a pandemic, from December 2019. Venous thromboembolism events can inflict patients with coronavirus disease 2019 during the hospitalization or convalescent period. Therefore, monitoring of these patients, in terms of venous thromboembolism events signs and symptoms, and timely management of antithrombotic agents are of great importance. CASE REPORT: A 45-year-old Iranian man, who is the first author of this case report, was infected by severe acute respiratory syndrome coronavirus 2 and displayed the typical signs and symptoms of coronavirus disease 2019. Although reverse transcription polymerase chain reaction for coronavirus disease 2019, and specific immunoglobulin M and immunoglobulin G against severe acute respiratory syndrome coronavirus 2, were negative at first, chest computed tomography scan showed the characteristic pattern of lung involvement of a coronavirus disease 2019 infection including bilateral and multilobar ground-glass opacities. At that time, there were no signs or symptoms of deep-vein thrombosis or pulmonary thromboembolism, so these were not investigated. About 30 hours after hospital discharge, the patient presented back to the hospital with acute-onset chest pain. We instantly tested his blood for D-dimer, and sent him to take a Doppler sonography of his lower legs and a chest computed tomography angiography in search of pulmonary thromboembolism and deep-vein thrombosis. Although we could confirm pulmonary thromboembolism with computed tomography angiography in our patient, there were no signs or symptoms of venous thromboembolism in his lower legs, and color Doppler sonography of lower limbs was normal. So, the patient was treated with rivaroxaban as an antithrombotic agent. After some days, he was discharged in good condition. About 1 month later, he was referred to our hospital because of left lower limb edema. Although he was under antithrombotic therapy, color Doppler sonography of lower limbs revealed acute deep-vein thrombosis of the left leg. Hence, we decided to shift antithrombotic therapy from rivaroxaban to warfarin, as it is more potent than rivaroxaban in recurrent venous thromboembolism and when taking new oral anticoagulants. Unlike rivaroxaban, which needs no blood test to monitor its efficacy but has a warning for signs and symptoms of bleeding, warfarin therapy must be monitored carefully by regular blood tests for prothrombin time and international normalized ratio to maintain them in the therapeutic range. The patient was informed about the bleeding cautions, and required regular check of prothrombin time and international normalized ratio to maintain them in the proper and advised range of treatment (international normalized ratio therapeutic range 2-3). CONCLUSION: In the case of unexpected recurrent venous thromboembolism in coronavirus disease 2019, especially when patients are taking rivaroxaban or other new oral anticoagulants, such drugs should be substituted by warfarin, with routine follow-up, to maintain the value of prothrombin time and international normalized ratio within the therapeutic range.

Impact of drug interactions with direct oral anticoagulants on mortality in elderly with atrial fibrillation during the COVID-19 pandemic.

OBJECTIVE: To evaluate the effect of drug interactions with chronic direct oral anticoagulants (DOAC) on mortality in older atrial fibrillation (AF) patients during the Coronavirus disease 2019(COVID-19) pandemic. METHODS: We followed a total of 601 elderly patients (65 years of age) from the NOEL-Drug Registry cohort who were referred to a tertiary outpatient clinic between 9 March 2020 and 1 March 2021. We recorded clinical characteristics and medications for the last 3 months. In addition, all drug interactions were identified using Lexicomp®. Finally, we recorded retrospectively all death events, COVID-19 diagnosis, and relevant deaths from the database at the end of the study. According to logistic regression, we performed propensity score (PS) matching to reduce potential bias. Factors associated with total mortality in the 12 months were analyzed using multivariable Cox proportion hazard analysis. RESULTS: The mean age [standard deviation (SD)] was 74.5 (±6.9), and the male/female ratio was 337/264. The prevalence of total mortality was 16.9% (n=102). A total of 4472 drugs were analyzed for DOAC interaction. 81.8% of older AF patients were not at risk in terms of potential interaction. In the Cox proportional hazard model after PS-matching, previous DOAC use with class X interaction was associated with significantly higher mortality risk (adjusted hazard ratio: 2.745, 95% confidence interval: 1.465-5.172, p=0.004). CONCLUSIONS: Our study showed that while most co-medications do not have significant interactions with DOACs, few serious drug interactions contribute to mortality in elderly patients with AF during the pandemic.

Direct Oral Anticoagulants for Stroke and Systemic Embolism Prevention in Patients with Left Ventricular Thrombus.

In recent years, direct oral anticoagulants (DOAC) have accumulated evidence of efficacy and safety in various clinical scenarios and are approved for a wide spectrum of indications. Still, they are currently used off-label for left ventricular thrombus owing to a paucity of evidence. For the same reason, there is a lack of guideline indication as well. Our work is based on an exhaustive analysis of the available literature and provides a structured and detailed update on the use of DOACs in patients with left ventricle thrombus. The safety and efficacy of DOACs were analyzed in particular clinical scenarios. As far as we know, this is the first paper that analyzes DOACs in this approach.

Single-Dose Bioequivalence Study of Rivaroxaban-Containing Medicinal Products in Healthy Volunteers

Therapeutically, new oral anticoagulants (NOACs) are considered to be non-inferior or superior to vitamin K antagonists (warfarin). NOACs are included in current guidelines for the treatment of various cardiovascular diseases. Rivaroxaban medicinal products have been shown to effectively fight thrombotic complications of the new coronavirus infection, COVID-19. The wide clinical use of rivaroxaban products motivates the development of generics. The aim of the study was to compare the pharmacokinetics and safety of rivaroxaban medicinal products in a single-dose bioequivalence study in healthy volunteers under fasting conditions. Material(s) and Method(s): the bioequivalence study compared single-dose oral administration of Rivaroxaban, 10 mg film-coated tablets (NovaMedica Innotech LLC, Russia), and the reference product Xarelto, 10 mg film-coated tablets (Bayer AG, Germany), in healthy volunteers under fasting conditions. The open, randomised, crossover trial included 46 healthy volunteers. Each of the medicinal products (the test product and the reference product) was administered once;blood samples were collected during the 48 h after the administration. The washout between the study periods lasted 7 days. Rivaroxaban was quantified in plasma samples of the volunteers by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Result(s): no adverse events or serious adverse events were reported for the test and reference products during the study. The following pharmacokinetic parameters were obtained for Rivaroxaban and Xarelto, respectively: Cmax of 134.6 +/- 58.0 ng/mL and 139.9 +/- 49.3 ng/mL, AUC0-48 of 949.7 +/- 354.5 ngxh/mL and 967.6 +/- 319.9 ngxh/mL, AUC0- of 986.9 +/- 379.7 ngxh/mL and 1003.6 +/- 320.4 ngxh/mL, T1/2 of 8.2 +/- 3.2 h and 7.8 +/- 3.3 h. The 90% confidence intervals for the ratios of Cmax, AUC0-48, and AUC0- geometric means were 88.04-108.67%, 89.42-104.92% and 89.44-104.81%, respectively. Conclusion(s): the test product Rivaroxaban and the reference product Xarelto were found to have similar rivaroxaban pharmacokinetics and safety profiles. The study demonstrated bioequivalence of the medicinal products. Copyright © 2022 Obstetrics, Gynecology and Reproduction. All rights reserved.

The Occurrence of Thrombotic Complications Due to Combat Trauma Against the Background of the COVID-19 Pandemic

An important point in the provision of highly specialized cardiac surgical care for combat trauma is deter-mination of the optimal time, method and volume of surgical intervention, taking into account the persisting threat of infection with the SARS-COV-2 virus and associated thrombotic complications. The aim. To investigate the mechanism of development and methods of prevention of thrombotic complications re-sulting from combat trauma against the background of the COVID-19 pandemic. Materials and methods. We analyzed clinical case of patient R., a 37-year-old soldier with a postinfarction throm-bosed aneurysm of the left ventricle. The patient underwent standard clinical and laboratory tests, electrocardiography, echocardiography, coronary angiography, computed tomography of the chest, duplex scanning of carotid arteries, arteries and veins of the upper and lower extremities. It was established that 4 months ago, during a combat mission, the service-man received a mine-explosive injury, shrapnel wounds of lower extremities, multifragmentary fracture of the right fibula and a gunshot wound to the right chest. The causes of post-traumatic myocardial infarction are mine-explosive injury, intramural course of the left anterior descending artery, young age, poorly developed collaterals of coronary arteries, long-term transportation during the stages of medical evacuation and post-traumatic stress disorder. A month ago, the patient was diagnosed with COVID-19, thromboembolism of the right main branch of the pulmonary artery, for which thrombolytic therapy was performed. Follow-up computed tomography showed the signs of thromboembolism of the pulmonary arteries. Ultrasound examination revealed thromboses of upper and lower limbs. Thrombotic complications against the background of combat polytrauma are the result of hypercoagulation, acute inflammation with the release of proinflammatory cytokines and damage of the endothelium. SARS-COV-2 infection triggers a state of hypercoagulation and creates additional conditions for the occurrence of arterial and venous thrombosis. Considering the nature of the thrombotic lesions, a decision was made to postpone the cardiosurgical intervention for 3 months. Conclusions. Thrombotic complications are an urgent problem after combat trauma. COVID-19 is an additional risk factor for hypercoagulation and a reason for delaying elective cardiac surgery. Conducting an electrocardiography to the wounded, regardless of age, is crucial for timely diagnosis and treatment of acute coronary events. It is important to initi-ate anticoagulant therapy after eliminating all possible sources of bleeding due to the high risk of thrombotic complications against the background of chest trauma and limb fractures. © 2022, Professional Edition Eastern Europe. All rights reserved.

Age and gender-associated radiological findings in COVID-19 infection

Objectives: At present, the novel coronavirus disease 2019 (COVID-19) pandemic is the most important infectious disease worldwide. Due to false positives and false negatives of PCR results in the diagnosis of coronavirus infection, Computed Tomography (CT) is especially important in the initial diagnosis and assessment of the intensity of COVID-19 infection. According to the stage and intensity of COVID-19 infection chest CT scan findings display different features. Although men, women, and different age groups may be equally affected, different epidemiological studies have shown differences in gender and age in intensity and mortality. Although there are many studies on radiological findings in COVID-19 infection, however limited literature reviews have been stated on the relationship between age and gender with radiological finding. Methods: This reviews summarized studies that evaluated the association age and gender with radiologic CT fndings. Results: In general, the findings of these studies show that different age and gender groups have different characteristics which can role in primary diagnosis, facilitate the classification of the initial prognosis in COVID-19 pneumonia. Conclusions: As an indicator for outcome, treatment, determining the intensity of the disease as well as the prognosis, nevertheless studies with higher sample sizes and multicenter are required.

Impact of drug interactions with direct oral anticoagulants on mortality in elderly with atrial fibrillation during the COVID-19 pandemic.

Objective: To evaluate the effect of drug interactions with chronic direct oral anticoagulants (DOAC) on mortality in older atrial fibrillation (AF) patients during the Coronavirus disease 2019(COVID-19) pandemic. Methods: We followed a total of 601 elderly patients (65 years of age) from the NOEL-Drug Registry cohort who were referred to a tertiary outpatient clinic between 9 March 2020 and 1 March 2021. We recorded clinical characteristics and medications for the last 3 months. In addition, all drug interactions were identified using Lexicomp®. Finally, we recorded retrospectively all death events, COVID-19 diagnosis, and relevant deaths from the database at the end of the study. According to logistic regression, we performed propensity score (PS) matching to reduce potential bias. Factors associated with total mortality in the 12 months were analyzed using multivariable Cox proportion hazard analysis. Results: The mean age [standard deviation (SD)] was 74.5 (±6.9), and the male/female ratio was 337/264. The prevalence of total mortality was 16.9% (n = 102). A total of 4472 drugs were analyzed for DOAC interaction. 81.8% of older AF patients were not at risk in terms of potential interaction. In the Cox proportional hazard model after PS-matching, previous DOAC use with class X interaction was associated with significantly higher mortality risk (adjusted hazard ratio: 2.745, 95% confidence interval: 1.465-5.172, p = 0.004). Conclusions: Our study showed that while most co-medications do not have significant interactions with DOACs, few serious drug interactions contribute to mortality in elderly patients with AF during the pandemic.

Introducción: Evaluar el efecto de las interacciones farmacológicas con anticoagulantes orales directos (ACOD) crónicos sobre la mortalidad en pacientes mayores con fibrilación auricular (FA) durante la pandemia de la enfermedad por coronavirus 2019 (COVID-19). Métodos: Seguimos a un total de 601 pacientes ancianos (65 años) de la cohorte NOEL-Drug Registry que fueron remitidos a una consulta externa de tercer nivel entre el 9 de marzo de 2020 y el 1 de marzo de 2021. Registramos las características clínicas y los medicamentos durante los últimos tres meses. Además, todas las interacciones medicamentosas se identificaron utilizando Lexicomp®. Finalmente, registramos retrospectivamente todos los eventos de muerte, el diagnóstico de COVID-19 y las muertes relevantes de la base de datos al final del estudio. De acuerdo con la regresión logística, realizamos un emparejamiento por puntaje de propensión (PP) para reducir el posible sesgo. Los factores asociados con la mortalidad total en los 12 meses se analizaron mediante análisis de riesgo de proporción de Cox multivariable. Resultados: La edad media (desviación estándar [DE]) fue de 74,5 (± 6,9) y la relación hombre/mujer, de 337/264. La prevalencia de mortalidad total fue del 16,9% (n = 102). Se analizaron un total de 4.472 fármacos para determinar la interacción con ACOD. El 81,8% de los pacientes mayores con FA no estaban en riesgo en términos de interacción potencial. En el modelo de riesgos proporcionales de Cox después del emparejamiento por PP, el uso previo de ACOD con interacción X clase se asoció con un riesgo de mortalidad significativamente mayor (índice de riesgo ajustado: 2,745; intervalo de confianza del 95%: 1,465-5,172; p = 0,004). Conclusión: Nuestro estudio mostró que, si bien la mayoría de los medicamentos concomitantes no tienen interacciones significativas con los ACOD, pocas interacciones farmacológicas graves contribuyen a la mortalidad en pacientes de edad avanzada con fibrilación auricular durante la pandemia.

Real-World Management of Pharmacological Thromboprophylactic Strategies for COVID-19 Patients in Japan: From the CLOT-COVID Study.

Background: Data on prophylactic anticoagulation are important in understanding the current issues, unmet needs, and optimal management of Japanese COVID-19 patients. Objectives: This study aimed to investigate the clinical management strategies for prophylactic anticoagulation of COVID-19 patients in Japan. Methods: The CLOT-COVID study was a multicenter observational study that enrolled 2,894 consecutive hospitalized patients with COVID-19. The study population consisted of 2,889 patients (after excluding 5 patients with missing data); it was divided into 2 groups: patients with pharmacological thromboprophylaxis (n = 1,240) and those without (n = 1,649). Furthermore, we evaluated the 1,233 patients who received prophylactic anticoagulation-excluding 7 patients who could not be classified based on the intensity of their anticoagulants-who were then divided into 2 groups: patients receiving prophylactic anticoagulant doses (n = 889) and therapeutic anticoagulant doses (n = 344). Results: The most common pharmacological thromboprophylaxis anticoagulant was unfractionated heparin (68.2%). The severity of COVID-19 at admission was a predictor of the implementation of pharmacological thromboprophylaxis in the multivariable analysis (moderate vs mild: OR: 16.6; 95% CI:13.2-21.0; P < 0.001, severe vs mild: OR: 342.6, 95% CI: 107.7-1090.2; P < 0.001). It was also a predictor of the usage of anticoagulants of therapeutic doses in the multivariable analysis (moderate vs mild: OR: 2.10; 95% CI: 1.46-3.02; P < 0.001, severe vs mild: OR: 5.96; 95% CI: 3.91-9.09; P < 0.001). Conclusions: In the current real-world Japanese registry, pharmacological thromboprophylaxis, especially anticoagulants at therapeutic doses, was selectively implemented in COVID-19 patients with comorbidities and severe COVID-19 status at admission.

The expediency of long-term anticoagulant therapy in convalescents with severe COVID-19

Background: Venous thrombosis in convalescents after Covid-19 occurs very often. Method(s): The study included 130 people aged 45-75 years who suffered from COVID-19 in the form of severe polysegmental pneumonia (30-63% of lungs). Women-78, men-52. On outpatient treatment, they were divided into 4 groups.1 group (n=32), apixaban was prescribed 5 mg per day, lasting 1 month.2 group (n=32), apixaban was prescribed the same way, but for 6 months.3 group (n=32), sulodexide was prescribed 500TU per day, as well as acetylsalicylic acid 100 mg, lasting 1 month.4 group (n=34), patients took sulodexide and acetylsalicylic acid in the same way, but for 6 months. Result(s): The patients were examined after 1,3,6 months from the beginning of the outpatient stage.Venous thrombotic events were detected in 18(13.8%) patients. Of these, 14(77.8%) people had thrombosis in the lower extremities: Superficial 11(78.6%) cases, deep 3(21.4%). Thrombosis in the veins of the upper extremities was detected in 4(22.2%) patients. All 4 were superficial. TELA not revealed. Attention should be paid to the period of thrombosis formation: In the first month- 4(22.2%) patients, 1-6 months- 14(77.8%) people (who stopped taking anticoagulants). The majority of venous thrombosis was recorded during the first 3 months after the hospital- 13 (72.2%) cases. It should be noted that there was no distinctive difference between patients who were prescribed apixaban and who took sulodexide and acetylsalicylic acid. However, there are differences in the groups who took the same drug treatment, but different in duration.Coagulogram indicators were analyzed and compared, which reflect changes in hemostasis and indicate the likelihood of venous thrombosis and the severity of COVID-19. These are ACTV, INR, fibrinogen, PTI, platelets. These indicators have changed slightly. But the D-dimer significantly decreased in the groups of patients who were prescribed anticoagulant therapy lasting 6 months. This is a positive moment in the prognosis of venous thrombosis.Hemorrhagic complications were recorded in 1(3.1%) patient in group 1 and in 3(9.7%) people in group 2. It should be noted that in 1 month after the start of outpatient anticoagulants, hemorrhages were recorded in 1(3.1%) patient in group 1, and 1(3.1%) in group 2. And in the period 1-6 months- 2(6.2%) in group 2. However, there were no significant and large bleeds. Apixaban was replaced briefly with acetylsalicylic acid, and then the previous anticoagulant therapy was resumed. Please note that there were no hemorrhagic complications in groups 3 and 4. Conclusion(s): In convalescents after a severe course of COVID-19, we consider it appropriate to prescribe anticoagulant therapy: Oral anticoagulants, or a combination of sulodexide with acetylsalicylic acid- for a long time, up to 6 months..

Pulmonary thromboembolism in adults: Experience from a tertiary care center

Background Venous thromboembolism (VTE) includes deep vein thrombosis (DVT) and pulmonary embolism (PE). We aimed to analyze the risk factors, clinical presentations, evaluation and management strategies as well as outcomes of adult pulmonary thromboembolism cases at a tertiary care center. Methods In a retrospective observational study, all consecutive adult pulmonary thromboembolism cases admitted from January 2019 to September 2020 at our center were enrolled in this study. Results Forty-eight patients were included in the present study. The commonest presenting features were dyspnea (93.8%) and cough (79.2%). The risk factors included hypertension 11 (23%), diabetes 6 (12%), recent trauma and recent surgery 3 (6%) each, and malignancy in 2 (4%). DVT was present in 12 (25%) cases while history of smoking was significant, 31 present in (64.6%). Tuberculosis was also found to be an important risk factor for PE in 8 (16.7%). The current COVID-19 pandemic has come up as an important risk factor for PTE which was also true in our case with 13 (27%) patients being cases of moderate to severe COVID-19 pneumonia. Electrocardiogram revealed sinus tachycardia (56.25%), precordial lead T-wave changes (6.3%), and S1Q3T3 pattern (16.67%). Diagnosis was confirmed by computed tomographic pulmonary angiography (CTPA) in 81% of cases. Treatment options included low molecular weight heparin (LMWH) in 91%, newer oral anticoagulants (NOACs) in 2% of the patients and thrombolysis was needed in 12.5% of patients. There was no in-hospital mortality;however one patient had major bleeding. Conclusion The clinical presentation of PE varied from dyspnea to cough, though the commonest feature of dyspnea remains unchanged compared to prior studies. CTPA has been modality of choice for diagnosis, however few patients with high probability for PTE were diagnosed clinically along with suggestive echocardiography and ECG findings. Thus, a high index of suspicion and timely therapeutic anticoagulation with various agents led to effective management and better outcome in the studied patients.

Proportion of Patients on Warfarin Therapy Who Are Eligible for Conversion to a Direct Oral Anticoagulant in the Setting of COVID-19.

BACKGROUND: Warfarin, a commonly prescribed anticoagulant, requires frequent lab monitoring. Lab monitoring puts patients at risk of COVID-19 exposure and diverts medical resources away from health care systems. Direct oral anticoagulants (DOACs) do not require routine therapeutic monitoring and are indicated first line for nonvalvular atrial fibrillation (NVAF) stroke prevention and venous thromboembolism (VTE) prevention/treatment. OBJECTIVE: The purpose of the study was to determine the proportion of patients who qualify for DOACs and assess for predictors of qualification. METHODS: This cross-sectional study investigated patients on warfarin managed by Michigan Medicine Anticoagulation Service. Direct oral anticoagulant eligibility criteria were established using apixaban, dabigatran, and rivaroxaban package inserts. Patient eligibility was determined through chart review. The primary outcome was the proportion of patients who qualify for DOACs based on clinical factors. Predictors of DOAC qualification were assessed. RESULTS: This study included 3205 patients and found 51.8% (n = 1661) of patients qualified for DOACs. Qualifying patients were older (71.9 vs 59.4 years, P < 0.0001) with a higher CHA2DS2 VASc (3.7 vs 3.4, P < 0.0007). The primary disqualifying factor was extreme weight, high and low. Accounting for a patient's sex and referral source, age > 65 (odds ratio [OR] = 1.9, P < 0.0001) and NVAF indication (OR = 5.6, P < 0.0001) were significant predictors for DOAC qualification. CONCLUSION AND RELEVANCE: Approximately 52% of patients on warfarin were eligible for DOACs. This presents an opportunity to reduce patient exposure to health care settings and health care utilization in the setting of COVID-19. Increased costs of DOACs need to be assessed.

A Case of Renal Vein Thrombosis Associated With COVID-19 Treated With Rivaroxaban.

Renal vein thrombosis (RVT) is a rare form of deep venous thrombosis. It usually involves one or both renal veins and one of their branches. Most cases were reported in patients with nephrotic syndrome or inherited hypercoagulability syndromes. RVT can present with flank pain, hematuria, and acute kidney injury but can also present asymptomatically and be incidentally discovered on abdominal or renal imaging. The management of RVT is usually with warfarin for at least six to 12 months and periodically is continued if the patient is in the nephrotic range. Direct-acting oral anticoagulants (DOACs) have not been well studied in cases of RVT, especially in patients with coronavirus disease 2019 (COVID-19). We present a case of RVT in the setting of COVID-19 that was treated successfully with a DOAC, rivaroxaban, with complete resolution of the thrombus.

Give full play to the role of pharmacists in the safety management of direct oral anticoagulants

Direct oral anticoagulants (DOACs) are recommended as first⁃line therapy in patients with atrial fibrillation and venous thromboembolic diseases in relevant guidelines at home and abroad. Compared with warfarin, DOACs have relatively fixed dose, fewer drug interactions, and no need of routine therapeutic drug monitoring in clinic. DOACs bring much convenience to anticoagulant therapy, but they also raise a series of new medication safety challenges. Pharmacists should ensure the safe use of DOAC through improving corresponding pharmaceutical care mechanism, such as assisting doctors to improve the suitability of dose in prescription, standardizing laboratory monitoring process, setting up early warning of potential drug interaction, and strengthening anticoagulant conversion and perioperative anticoagulant therapy management. In the post⁃coronavirus disease 2019 era, incorporating DOACs into the standardized manage⁃ ment at anticoagulation clinics is an important work extension of the traditional anticoagulation clinics and may reduce the risk of exposure to the novel coronavirus. In addition, considering the limit in labour and work energy of clinical pharmacists, the application of DOAC⁃related clinical decision support system may help improve the appropriateness of prescription and reduce the adverse drug events. © 2020 Chinese Medical Journals Publishing House Co.Ltd. All rights reserved.