Therapeutic Doses Of Anticoagulants Research Articles

Efficacy of therapeutic-dose heparin for severe COVID-19 patients at COVID-19 Emergency Hospital Jakarta.

Arterial and venous thrombotic events in COVID-19 cause significant morbidity and mortality. For optimal thromboprophylaxis treatment for hospitalized patients, especially those with severe COVID-19 symptoms, it is still unclear whether to use full- or therapeutic-dose versus prophylactic-dose anticoagulation therapy. The study aim was to evaluate the efficacy and safety of unfractionated heparin (UFH) for thromboprophylaxis in severe degree of COVID-19. In this cross-sectional study, the medical records of 160 COVID-19 patients at the COVID-19 Emergency Hospital Wisma Atlet, Jakarta, from March to August 2021, were collected. The predetermined inclusion criteria for patients were severe COVID-19 infection; age > 18 years; positive D-dimer level > 400 ng/mL; high-flow nasal cannula (HFNC) oxygenation; IMPROVE bleeding risk score < 7; and willingness to participate in the study. The primary outcome was activated partial thromboplastin time (APTT) target achievement, oxygenation changed to nasal cannula or ended with room air, mortality rate, and the principal safety criterion was presence of bleeding. Of 160 subjects, 63.8% were male and 45.6% were aged 45-59 years old. Obesity was the most common comorbidity at 45.6% Among all subjects, 9.4% experienced bleeding, with hematuria being the most frequent type at 66.7%. All subjects released HFNC, and no deaths were reported. It can be concluded that administration of therapeutic doses of heparin in patients with severe COVID-19 had a low risk of bleeding and no patients were reported to have died. However, further investigation is needed to determine the long-term effects of therapeutic doses of anticoagulants.

Ophthalmic assessment of an intensive care ward patients in the first and last wave of the COVID-19. Do they have a difference?

BACKGROUND: The new coronavirus infection (COVID-19) gained the pandemic status in 2020, and despite the fact that since then the virus has become less pathogenic, its virulence has increased by 2023. Well-vascularized organs and tissues, including the retina, represent the target for coronavirus. The etiopathogenesis of COVID-associated retinopathy, first described in 2021, still remains poorly understood, and its forms and occurrence frequency during different periods of the infectious process vary greatly. AIM: To identify the main characteristics of the COVID-associated retinopathy in patients with moderate and severe COVID-19 course during the acute period of the disease. MATERIALS AND METHODS: The study, conducted in 2021 (group 1) and 2023 (group 2), included patients with confirmed COVID-19 of moderate to severe course during the first 7 days from the onset of symptoms. Group 1 included 46 people, mean age 65.5 years, and group 2 included 55 people, mean age 69.3 years. The ophthalmologic examination was carried out in the “red zone” and intensive care unit, and included examination of the anterior segment of the eye, indirect ophthalmoscopy, and fundus photography using a portable hand-held digital fundus camera (Smartscope M5, Optomed, Finland). Hypertension, diabetes mellitus, volume of lung damage, invasive mechanical ventilation, and anticoagulant therapy were considered as conditions affecting retinal microcirculation. RESULTS: The observation groups were homogeneous in terms of gender, age, and concomitant diseases. The incidence of ophthalmoscopic findings in group 1 was 17.3%, and in group 2 — 12.7%. Most often, during the first 7 days of the disease, signs of angiopathy were observed: dilatation of blood vessels, irregularity of their diameter and tortuosity. Among focal changes, there were multiple retinal hemorrhages (6.5% and 3.6%) and cotton wool spots (4.3% and 5.4%). In patients with fundus changes, diabetes mellitus was significantly less common (in group 1, 25% vs. 39%, p 0.001; in group 2, 28% vs. 44%, p 0.001), as well as arterial hypertension (in group 1, 55% vs. 66%, p = 0.003; in group 2 28% vs. 83%, p 0.001). In group 1, there was a higher proportion of patients treated in intensive care unit, as in group 2 (37% vs. 17%, p 0.001), but in group 2, patients with identified retinal changes were more likely to receive therapeutic doses of anticoagulants (33% vs. 12%, p 0.001). CONCLUSION: The main characteristics of COVID-associated retinopathy in patients with moderate to severe COVID-19 during the acute period of the disease are dilatation and pathological tortuosity of the retinal arteries and veins, intraretinal hemorrhages and cotton wool spots. The connection between COVID-associated retinopathy and concomitant to the infectious process cardiovascular conditions has not been established. Retinopathy associated with coronavirus infection, with absolute similarity of clinical manifestations, was significantly more common in 2021 than in 2023.

Location of metastasis and complications in patients with venous thromboembolism and cancer: systematic review

According to current guidelines, patients with venous thromboembolism (VTE) and active cancer should receive prolonged anticoagulant treatment (&gt;6 months). In patients with cancer-associated thrombosis (CAT), metastasis is a factor in recurrent VTE and bleeding; however, the function of metastasis location remains unclear. In order to assess the risk of complications (such as bleeding or recurrent VTE) based on the location of metastases in patients with CAT, we conducted a systematic review. The PubMed database search was used to perform a systematic review. MESH terms pertaining to metastasis, VTE, and neoplasms were employed. Patients with CAT who were at least eighteen years old and receiving therapeutic doses of anticoagulants were included, as were details regarding the locations of metastases and the availability of patients who had complications (bleeding or recurrent VTE). Among the 1,447 articles found by the search, 7 retrospective studies met all eligibility requirements and were added to the analysis. The majority of these studies addressed brain metastases. Studies found that intracranial hemorrhage occurred between 4% and 19% of the time. In the context of brain metastases and VTE, other studies examined the safety and effectiveness of direct oral anticoagulants in comparison to low-molecular-weight heparin. This systematic review draws attention to the paucity of data regarding the impact of metastasis location on complications in CAT patients. Further research is required to assess the effect of metastasis location on the risk of VTE complications in patients with CAT.

Venous thromboembolism in patients with isolated moderate to severe traumatic brain injury

Background. Traumatic brain injury (TBI) remains a big problem of modern neurosurgery, accompanied by high rates of disability and lethality. Venous thromboembolism (VTE) including venous thrombosis and pulmonary embolism (PE) plays a significant role in the structure of mortality in this pathology. Regimens and schemes of pharmacological prevention of VTE in TBI as well as corresponding preventative measures are not yet determined completely.Aim. To identify the frequency of VTE in patients with isolated moderate and severe TBI, and to evaluate the results of prevention and treatment of these complications in patients of this category.Materials and methods. Over a 3‑year period (from 2020 to 2023) 73 patients with isolated moderate and severe TBI (51 men and 22 women, mean age 61.0 ± 13.0 years) were treated in the V. M. Buyanov City Clinical Hospital. Of these, 31 patients received only conservative therapy, and 42 patients underwent surgery (craniotomy with hematoma removal, closed external hematoma drainage, and installation of intracranial pressure sensor). Ultrasound examination of the lower limb veins was performed at patient admission, then every 7 days until discharge from the hospital. Pharmacological prevention of VTE using low molecular weight heparin in non‑surgical patients was started after 1–2 days if computed tomography of the brain 24 h after admission showed no negative hematoma dynamics. Surgical patients were prescribed preventive medications 24 h after surgery if computed tomography confirmed intracranial hemostasis.Results. Venous thrombosis was detected in 22 (30.1 %) of 73 patients. PE complicated the underlying disease in 1 (1.4 %) case and was non‑fatal. There was no fatal PE in the study group. An increase of the initial intracranial hematoma volume occurred in 3 (4.1 %) patients, in 2 (2.8 %) patients the recurrence of hemorrhage occurred before the beginning of heparin administration, and in 1 (1.4 %) case against the background of therapeutic doses of anticoagulants prescribed for venous thrombosis. In the majority of cases (82.0 %; 18 of 22 patients) thromboses were localized in deep veins of the lower leg and were asymptomatic. Intrahospital mortality was 23.3 % (17 patients), all lethal outcomes were due to the course of traumatic brain disease.Conclusion. VTE is a frequent complication of TBI with intracranial hemorrhage. Regular ultrasound diagnostics makes it possible to diagnose asymptomatic distal venous thrombosis in a timely manner and to prescribe therapeutic doses of low molecular weight heparin in time which in turn allows to avoid fatal PE. Currently, there are no clear domestic recommendations for the prevention and, most importantly, for the treatment of these complications in patients with isolated moderate and severe TBI, which requires further active study of this problem.

Abstract WP110: DEVIATING: Determining Variability in Antiplatelet Timing in Stroke by Gender

Background: Antiplatelet administration within 48 hours of acute stroke presentation is standardized as it reduces mortality and recurrent ischemic stroke rate. Gender disparities have been noted in acute stroke care, including IV tPA and thrombectomy. Limited data exists for gender disparities in antiplatelet administration by day 2 of hospitalization. Methods: In an IRB-approved analysis, we retrospectively assessed patients admitted with acute ischemic strokes from the prospectively collected UC San Diego Stroke Registry from 2013 to 2023. We reviewed baseline demographics, whether an antiplatelet agent was initiated by hospital day 2, and choice of antiplatelet agent. We grouped patients based on their gender identification: male versus female. Patients who transitioned to comfort care, had an embolic source, were treated with a therapeutic dose of anticoagulation, had hemorrhagic conversion of infarct, or had a contraindication to antiplatelet use were excluded. Chi-squared, Kruskal-Wallis and Fisher tests were utilized. Results: 471 patients were included in this analysis (179 female, 292 male). We found no significant differences in medical history except diabetes (60 female, 69 male, p = 0.03). We found a significant difference in age (female 69.3 years, male 64.3 years, p &lt; 0.01). We found a significant difference in patient race (p = 0.01). There was no significant difference in antiplatelet administration by hospital day 2 (171 female, 287 male, p = 0.14) or choice of antiplatelet (aspirin p = 0.29, clopidogrel p = 0.12, ticagrelor p = 0.67, dual antiplatelet p = 0.22). Conclusions: These findings suggest equality of care in antiplatelet administration for acute ischemic stroke between genders, which is reassuring. This data was collected at an academic comprehensive stroke center. Further studies should be completing including patients who were treated at various levels of stroke centers.

Case report of a Pulmonary embolism in a patient with Inferior vena cava compression by a 11x28 cm abdominal benign tumor

ABSTRACT Background: Pulmonary embolism is a life-threatening condition causing abrupt reduction in blood flow in the pulmonary vasculature due to a migrating thrombus. The most cases are related to thromboembolism events originating in the lower limbs. However alternate etiologies should be suspected in certain clinical cases mainly in young patients with no risk factors. Case: We present a case of young patient with proximal pulmonary embolism caused by compression on the inferior vena cava by an abdominal benign tumour measuring 11x28cm. The patient was treated surgically and started on therapeutic dose of Anticoagulation. The etiology of pulmonary embolism in this case was attributed to large vein compression promoting blood stasis and leading to thrombus formation Conclusion: In short, acute pulmonary embolism in young female patients, is unusual and should raise the suspicion for miscellaneous causes including vascular compression by tumors.

Prognostic value of D-dimers in patients with COVID-19: narrative synthesis

Introduction. Contemporary researchers have suggested and demonstrated the hypothesis that the elevated level of D-dimers, which is a valuable marker of coagulation and fibrinolysis activation, can predict the severity of COVID-19, pulmonary complications, and thromboembolic events before they occur. Material and methods. The bibliographic resources were analyzed and selected from databases such as PubMed, Hinari, SpringerLink, and Google Search using keywords such as “COVID-19,” “SARS-CoV-2,” “coronavirus,” “D-dimers,” “biomarkers,” and “severity prediction,” which were used in various combinations to maximize search efficiency. Therefore, the manuscript contains 51 representative articles for the purpose of this synthesis article. Results. The D-dimer levels are significantly higher in patients with severe forms of COVID-19 compared to those with non-severe forms, in patients with acute respiratory distress syndrome compared to those without acute respiratory distress syndrome, and in deceased patients compared to those who have survived. D-dimers positively correlate with the degree of severity and the increased risk of progression to severe disease, inversely proportional to the survival rate. They can predict prognosis, determine therapeutic strategies, prevent complications, positively influence the disease’s course, and monitor the prognosis. Conclusions. D-dimers should be used as a pre-radiographic screening tool as early as possible after admission and as an indicator for risk stratification of venous thromboembolism in hospitalized patients with COVID-19. Based on the increase in D-dimer levels, adjusting therapeutic doses of anticoagulants is more beneficial for patients compared to administering prophylactic doses.

Safety and Efficacy of Different Anticoagulant Doses for Patients with COVID-19 in the ICU: A Systematic Review and Meta-Analysis.

Critically ill COVID-19 patients have a high incidence of thromboembolic events, which significantly influence the risk of mortality. Anticoagulant therapy is generally recommended to these patients but the optimal dosing regimens require further investigations. The objective of this systematic review and meta-analysis was to assess the efficacy and safety of prophylactic, intermediate and therapeutic dose anticoagulation in COVID-19 patients admitted to the ICU. A systematic search for original prospective observational studies and clinical trials was performed in online databases from 2020 to 2022. A total of 13 studies (3239 patients) were included. The type of anticoagulant dosing showed no significant influence on short-term mortality (p = 0.84), deep vein thrombosis (p = 0.66), arterial thrombosis (p = 0.44), major bleeding (p = 0.35) and minor bleeding incidence (p = 0.46). An anticoagulation regimen significantly influenced pulmonary embolism occurrence (16% for prophylactic dose vs. 4% for therapeutic dose, p = 0.02), but the number of studies in the analysis was relatively low. In conclusion, the results of this meta-analysis suggest that critically ill COVID-19 patients admitted in the ICU have no benefit from therapeutic doses of anticoagulants and that all three thromboprophylaxis regimes have a comparable effect on short term mortality and venous thromboembolism incidence but for pulmonary embolism, for which the results were inconclusive.

The effect of anti-coagulation dosage on the outcome of hospitalized COVID-19 patients in Ethiopia: a multi-center retrospective cohort study

BackgroundStudies have indicated that hospitalized COVID-19 patients benefit from anticoagulation therapy in terms of survival; however, there is an ongoing controversy over the optimum anticoagulant dosage. This study aimed to compare clinical outcomes between patients who received prophylactic anticoagulation and those who received therapeutic anticoagulation.MethodsA multi-center retrospective cohort study was conducted to determine the impact of anticoagulation dosage in hospitalized COVID-19 patients in Ethiopia. The primary outcome measure was in-hospital mortality, and it was assessed using multivariable binary logistic regression and covariate-adjusted Cox Proportional Hazard model. For critical and severe COVID-19 patients, subgroup analyses were performed using multivariable binary logistic regression model and multivariable Cox regression models.ResultA total of 472 hospitalized COVID-19 patients were included in this study, of whom 235 (49.8%) received therapeutic anticoagulation and 237 (50.2%) received prophylactic dose. The demographic and baseline clinical characteristics were roughly similar between the groups. After adjustment for several confounders, in critical COVID-19 subgroup, therapeutic dose of anticoagulation was significantly associated with a higher inpatient mortality (AOR 2.27, 95% CI, 1.18—4.35, p = 0.013), whereas in severe COVID-19 subgroup, anticoagulation dosage was not associated with inpatient mortality (OR, 1.02, 95% CI, 0.45 – 2.33, p = 0.958). In severe COVID-19 patient group however, the incidence of thrombosis was slightly lower in the therapeutic group as compared with prophylactic group although the difference was not statistically significant (AOR 0.15, 95% CI, 0.02 – 1.20, p = 0.073). Although there were only six major bleeding events in this study, all these were recorded from patients in the therapeutic subgroup, making the difference statistically significant (p = 0.013).ConclusionAlthough this study is limited by its observational design, our results are not consistent with current recommendations on anti-coagulation dose for hospitalized patients with COVID-19, necessitating the need for RCT in resource limited settings.

Role of Genetic Thrombophilia Markers in Thrombosis Events in Elderly Patients with COVID-19

Thrombosis is an extremely dangerous complication in elderly patients with COVID-19. Since the first months of the pandemic, anticoagulants have been mandatory in treatment protocols for patients with COVID-19, unless there are serious contraindications. We set out to discover if genetic thrombophilia factors continue to play a triggering role in the occurrence of thrombosis in patients with COVID-19 with prophylactic or therapeutic anticoagulants. We considered the following genetic markers as risk factors for thrombophilia: G1691A in the FV gene, C677T and A1298C in the MTHFR gene, G20210A and C494T in the FII gene, and (-675) 4G/5G in the PAI-I gene. In a cohort of 176 patients, we did not obtain a reliable result indicating a higher risk of thrombotic complications when taking therapeutic doses of anticoagulants in carriers of genetic markers for thrombophilia except the C494T mutation in the FII gene. However, there was still a pronounced tendency to a higher incidence of thrombosis in patients with markers of hereditary thrombophilia, such as FV G1691A and FII G20210A mutations. The presence of the C494T (Thr165Met) allele in the FII gene in this group of patients showed a statistically significant effect of the mutation on the risk of thrombotic complications despite anticoagulant therapy.

Venous Thromboembolism in COVID-19 Patients: A Single-Center Case Series

: Since thrombosis occurrence among coronavirus disease 2019 (COVID-19) patients is a critical complication, this study aimed to describe the clinical characteristics and outcomes of COVID-19-associated pulmonary thromboembolism (PTE). This case series of 39 venous thromboembolism (VTE) patients represents clinical characteristics, laboratory data, imaging data, and outcomes. The mean age of the patients was 55 ± 15 years. Moreover, 25 patients (64.10%) were male. The most frequent COVID-19 clinical presentations were dyspnea and cough in 22 (56.41%) and 19 (48.71%) patients, respectively. Additionally, the most frequent PTE clinical presentations were palpitation and anxiety in 28 (71.79%) and dyspnea in 24 (61.53%) patients. Additionally, eight patients (20.51%) showed deep vein thrombosis in color Doppler ultrasound. The mean measures of D-dimer, erythrocyte sedimentation rate and C-reactive protein were 3680 ng/mL, 53 mm/hour, and 44 mg/L, respectively. Supplemental oxygen and a ventilator were required in 29 (74.35%) and 2 (5.12%) patients, respectively. One patient died from PTE complications, and others improved without any complications. The VTE is a potentially life-threatening complication that frequently occurs in patients with COVID-19. Therapeutic doses of anticoagulants, extended thromboprophylaxis, meticulous assessments, follow-up, and high clinical suspicion to the early detection of PTE are necessary in this regard.

Post COVID Thrombotic Sequelae: Once Bitten, Twice Shy!

Introduction Long Covid has been recognized as a distinct entity with thrombotic sequelae [1]. Persistent systemic vascular inflammation caused by thrombosis drives the complications associated with long COVID. The risks of arterial and venous thrombosis after COVID-19 extend well beyond the hospitalization period. Early prophylactic anticoagulation has been shown to reduce the incidence of post-covid thrombotic sequelae [2]. Some evidence suggests the use of a higher than prophylactic dose for primary venous thromboembolism prophylaxis, especially in patients with a history of venous thromboembolism (VTE) [1]. We present a case of long Covid who developed recurrent thrombosis despite being on a therapeutic dose of anticoagulation. Case Presentation A 55-year-old male was brought to our Emergency Department with complaints of diffuse abdominal pain and black-coloured stools for three days. Contrast-enhanced CT abdomen (CECT) showed distal superior mesenteric artery (SMA) thrombosis and splenic infarct (Figure 1). He was treated for mild Covid-19 infection three months back. History also revealed he was hospitalized two months ago with a diagnosis of non-ST segment elevated myocardial infarction (NSTEMI) and acute ischemic stroke (Figure 2), which was managed with antiplatelets, statins and anticoagulants. He was discharged on oral anticoagulants (Tab Rivaroxaban 15 mg twice daily) for three months and was on regular follow-up. There was no history of smoking or hypertension. Protein C, Protien S, homocysteine levels were normal. After the diagnosis of SMA thrombosis, his anti-coagulation was increased to Tab Rivaroxaban 20 mg twice daily. No further thrombotic episodes have been noted as of date. Discussion This case suggests that unexplained repeat thrombotic events at multiple sites may have been a consequence of Covid-19 infection. Covid-19 patients experience both arterial and venous thromboembolism [3]. Most commonly, the former presents as myocardial infarction and ischemic stroke, whereas the latter as deep venous thrombosis and pulmonary embolism. Mechanisms include changes in lung structure secondary to chronic hypoxia, persistent immune dysfunction, and endothelial damage [1]. Risks of thrombotic events after mild Covid-19 are less clear, with the need and intensity of prophylactic anti-coagulation in this subset of patients being a matter of future research [4]. Shabaka et al. have shown that patients with a history of Covid-19 infection and previous thromboembolic events were at higher risk of developing a repeat thrombotic event [5]. Physicians need to be vigilant about the thrombotic events in patients with long Covid, even in patients receiving therapeutic anti-coagulation. Such patients require more frequent monitoring for signs of thrombotic events, risk factor management, and adherence to preventive therapies [3].

Спонтанные гематомы у госпитальных пациентов с новой коронавирусной инфекцией

Treatment of the new coronavirus infection (NCVI) is associated with high risks of hemorrhagic complications. This is due to the use of anticoagulants to prevent coagulopathy and thrombotic complications, which are the most frequent and severe complications of NCVI. The article presents the results of a retrospective analysis of 80 cases of spontaneous hematomas in patients with NCVI who were treated in a temporary infectious diseases hospital of the Republic of Clinical Hospital. Verification of the diagnosis was carried out using clinical data, ultrasound diagnostics, and computed tomography. The mean age of the patients was 62.4 ± 14.47 years. The most common localizations of spontaneous hematoma were: abdominal wall — 31.3%, retroperitoneal hematoma — 26.3%, chest hematoma — 16.3%, lower or upper limb — 8.8%, neck — 3.8%, combined hematomas — 5%. The number of small hematomas was 87.5%, large – 12.5%. The highest incidence of spontaneous hematomas (74%) and mortality (22%) was recorded in the group of patients receiving therapeutic doses of anticoagulants. X-ray endovascular diagnosis of the source of bleeding and its embolization was performed in 15 patients. The use of therapeutic doses in patients with NCVI is accompanied by a high risk of developing spontaneous hematomas and, as a result, increases the risk of death. X-ray endovascular embolization of spontaneous hematomas is an effective and safe method of treatment in patients with NCVI.

Thrombotic and hemorrhagic events in patients with a new coronavirus infection COVID-19 (experience of one center)

Introduction. COVID-associated coagulopathy is an important pathogenetic factor in the development of new coronavirus infection (NCI) complications. Therefore the use of anticoagulants is considered as one of the fundamental components of the therapy of NCI. The aim of the study was to find the optimal anticoagulant therapy regimen in patients with severe NCI. Materials and methods. The study is retrospective and included an analysis of 947 cases of confirmed NCI. A survival analysis was performed with the construction of Kaplan-Meyer curves in order to assess the effect of a particular anticoagulant therapy regimen on the occurrence of thrombosis, bleeding, and death. In order to exclude the influence of cofounders due to the retrospective nature of the study, the pseudorandomization method («propensity score matching») was used, followed by the re-construction of Kaplan-Meyer curves. Results. Among 947 patients with severe COVID-19, 27 thrombotic events were verified in 24 patients and 44 hemorrhagic incidents in 38 patients. The day of the event, regardless of the choice of the starting point (the onset of the disease or the 1st day of hospitalization) and its nature (thrombosis or bleeding), had no statistical differences (p=0.33 and p=0.12, respectively). The use of a particular anticoagulant therapy regimen did not significantly affect the development of thrombosis, bleeding or death, including the use of the propensity score matching method. Conclusion. Thus, using therapeutic doses of anticoagulants in COVID-19 patients does not give advantages over the use of preventive doses concerning the risk of thrombosis, bleeding and death.

Does High-Dose Thromboprophylaxis Improve Outcomes in COVID-19 Patients? A Meta-analysis of Comparative Studies.

Background Thromboembolism remains a detrimental complication of novel coronavirus disease (COVID-19) despite the use of prophylactic doses of anticoagulation Objectives This study aimed to compare different thromboprophylaxis strategies in COVID-19 patients Methods We conducted a systematic database search until June 30, 2022. Eligible studies were randomized (RCTs) and nonrandomized studies that compared prophylactic to intermediate or therapeutic doses of anticoagulation in adult patients with COVID-19, admitted to general wards or intensive care unit (ICU). Primary outcomes were mortality, thromboembolism, and bleeding events. Data are analyzed separately in RCTs and non-RCTs and in ICU and non-ICU patients. Results. We identified 682 studies and included 53 eligible studies. Therapeutic anticoagulation showed no mortality benefit over prophylactic anticoagulation in four RCTs (odds ratio [OR] = 0.67, 95% confidence interval [CI], 0.18–2.54). Therapeutic anticoagulation didn't improve mortality in ICU or non-ICU patients. Risk of thromboembolism was significantly lower among non-ICU patients who received enhanced (therapeutic/intermediate) anticoagulation (OR = 0.21, 95% CI, 0.06–0.74). Two additional RCTs (Multiplatform Trial and HEP-COVID), not included in quantitative meta-analysis, analyzed non-ICU patients, and reported a similar benefit with therapeutic-dose anticoagulation. Therapeutic anticoagulation was associated with a significantly higher risk of bleeding events among non-randomized studies (OR = 3.45, 95% CI, 2.32–5.13). Among RCTs, although patients who received therapeutic-dose anticoagulation had higher numbers of bleeding events, these differences were not statistically significant. Studies comparing prophylactic and intermediate-dose anticoagulation showed no differences in primary outcomes. Conclusion There is a lack of mortality benefit with therapeutic-dose over prophylactic-dose anticoagulation in ICU and non-ICU COVID-19 patients. Therapeutic anticoagulation significantly decreased risk of thromboembolism risk in some of the available RCTs, especially among non-ICU patients. This potential benefit, however, may be counter balanced by higher risk of bleeding. Individualized assessment of patient's bleeding risk will ultimately impact the true clinical benefit of anticoagulation in each patient. Finally, we found no mortality or morbidity benefit with intermediate-dose anticoagulation.

Hemostatic system and COVID-19 crosstalk: A review of the available evidence.

Since the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant coronavirus disease 2019 (COVID-19) pandemic, respiratory manifestations have been the mainstay of clinical diagnosis, laboratory evaluations, and radiological investigations. As time passed, other pathological aspects of SARS-CoV-2 have been revealed. Various hemostatic abnormalities have been reported since the rise of the pandemic, which was sometimes superficial, transient, or fatal. Mild thrombocytopenia, thrombocytosis, venous, arterial thromboembolism, and disseminated intravascular coagulation are among the many hemostatic events associated with COVID-19. Venous thromboembolism necessitating therapeutic doses of anticoagulants is more frequently seen in severe cases of COVID-19, especially in patients admitted to intensive care units. Hemorrhagic complications rarely arise in COVID-19 patients either due to a hemostatic imbalance resulting from severe disease or as a complication of over anticoagulation. Although the pathogenesis of coagulation disturbance in SARS-CoV-2 infection is not yet understood, professional societies recommend prophylactic antithrombotic therapy in severe cases, especially in the presence of abnormal coagulation indices. The review article discusses the various available evidence on coagulation disorders, management strategies, outcomes, and prognosis associated with COVID-19 coagulopathy, which raises awareness about the importance of anticoagulation therapy for COVID-19 patients to guard against possible thromboembolic events.

Trends in post-discharge prophylactic anticoagulant use among stroke patients in the United States between 2006 and 2019

BackgroundStroke is an independent risk factor for venous thromboembolism (VTE). Although the risk of VTE persists after hospital discharge, information on the utilization of anticoagulants among stroke patients after discharge remains limited. ObjectiveTo evaluate changes in post-discharge thromboprophylaxis among stroke patients between 2006 and 2019. MethodsWe conducted a retrospective repeated cross-sectional analysis using a commercial healthcare insurance database in the United States. We included patients aged ≥ 18 years with incident stroke diagnosis and assessed prophylactic use of anticoagulants in the 30 days following hospital discharge including low-molecular-weight heparin (enoxaparin ≤40 mg/day, dalteparin ≤5000 IU/day), unfractionated heparin ≤5000 IU/ twice daily or 3 times a day, apixaban 2.5 mg twice daily, and rivaroxaban 10 mg/day. Patients with atrial fibrillation, VTE, mechanical heart valves, cancer, antiphospholipid antibody syndrome, and users of therapeutic doses of anticoagulants were excluded. We used the Cochrane-Armitage test to assess changes in the use of anticoagulants across the study period. ResultsThere was a small increase in the overall use of post-discharge prophylactic anticoagulants among stroke patients between 2006 and 2019 from 0.5% to 1.9%. The use of heparin decreased from 0.5% in 2006 to 0.3% in 2019 (P-value for trend = 0.001). In contrast, the use of apixaban or rivaroxaban increased from 0.1% in 2013 to 1.6% in 2019 (P-value for trend < 0.001). Apixaban was more commonly used than rivaroxaban. ConclusionsIn this population-based study of stroke patients, we found that post-discharge anticoagulant use remains low through 2019. Prophylactic use of heparin or rivaroxaban was relatively low but the use of apixaban increased over the study period. Further research is needed to determine if these agents are safe and effective for VTE prevention in stroke patients.

Factors Influencing Disease Stability and Response to Tocilizumab Therapy in Severe COVID-19: A Retrospective Cohort Study.

(1) Background: The efficacy of tocilizumab in COVID-19 has been doubted. The study aimed to investigate factors affecting disease stability and response to tocilizumab among severe COVID-19 patients. (2) Methods: This was a cohort study of 70 severe COVID-19 patients at NMC Royal Hospital, UAE, from April to June 2020. (3) Results: Elderly patients and those with cardiovascular comorbidities had a higher risk of unstable COVID-19 (p = 0.025). Regarding tocilizumab therapy timing, compared to the critical group receiving tocilizumab, the unstable severe patients receiving tocilizumab had a significantly higher rate of improvement (86%). In contrast, the late critical subgroup showed a significantly increased mortality rate (52.9%). The risk for secondary infection and adverse events following tocilizumab was higher in the late critical group than in the unstable severe and early critical groups (p = 0.024 and p = 0.006, respectively). Therapeutic doses of anticoagulation and high-dose vitamin D were correlated with better outcomes than the prophylactic dose and the treatment dose of vitamin D (p < 0.001 and p = 0.07, respectively). (4) Conclusions: elderly patients and those with cardiovascular disease developed unstable COVID-19. Tocilizumab is a potentially effective choice against severe and critical COVID-19. Early tocilizumab administration combined with therapeutic dose anticoagulation and high vitamin D doses could improve the patients’ outcomes.

Anticoagulation Management and Outcomes in Patients With Covid-19 With Propensity Score Matching: A Multicenter Retrospective Cohort Study.

Therapeutic doses of anticoagulation have been administered to patients with coronavirus-19 disease (Covid-19) without thromboembolism, although there is a lack of robust evidence supporting this practice. To compare outcomes between patients admitted to the hospital for Covid-19 who received full-dose anticoagulation purely for the indication of Covid-19 and patients who received prophylactic doses of anticoagulation. This is a multicenter retrospective cohort study, including 7 community hospitals in Michigan. Patients were >18 years of age, confirmed positive for Covid-19 by polymerase chain reaction, and admitted to the hospital between March 10 and May 3, 2020. Exposed group: Patients receiving therapeutic dose anticoagulation for Covid-19 for any duration excluding clinically evident venous thromboembolism, atrial fibrillation, and myocardial infarction; control group: Patients receiving prophylactic anticoagulation. Propensity score matching was used to adjust for the nonrandomized nature of the study. The primary endpoint: 30-day in-hospital mortality. Secondary endpoints: intubation, length of hospital stay, and readmissions in survivors. A total of 115 exposed and 115 control patients were analyzed. Rates of 30-day in-hospital mortality were similar (exposed: 33.0% vs. control: 28.7%). Controlling for institution, there was no significant association between treatment and 30-day in-hospital mortality (hazard ratio: 0.63; 95% confidence interval: 0.37-1.06). Survivors had statistically similar length of hospital stay and readmission rates. We found no difference in mortality in patients with Covid-19 without clinically evident venous thromboembolism, atrial fibrillation, and myocardial infarction who received therapeutic versus prophylactic doses of anticoagulation.

Host-modifying drugs against COVID-19: some successes, but not yet the breakthrough.

SummaryAfter reviewing antiviral drugs (Brüssow Environmental Microbiology 2021) the present review summarizes the results of clinical trials with host‐modifying drugs in COVID‐19 patients. Clinical benefits were observed with different immunomodulators. The variable outcomes of trials with the interleukin 6 receptor inhibitor tocilizumab demonstrated that treatment benefits might only be present in specific subgroups of patients or in specific infection stages. A meta‐analysis of trials with the interleukin 1 receptor antagonist anakinra showed a survival benefit only in patients with hyperinflammation. The Janus kinase inhibitor baricitinib is an anti‐inflammatory treatment that showed a clinical benefit in hospitalized patients who do not yet need supplementary oxygen. In contrast, the corticosteroid dexamethasone showed mortality reducing effects that were limited to patients on ventilation or in need of supplementary oxygen. Therapeutic dose of anticoagulation met the criteria for inferiority in severe cases, but showed a small survival benefit in non‐severe COVID‐19 patients. Large trials with colchicine showed a small or no survival benefit. Azithromycin, an antibiotic with immunomodulatory activity, showed no effects in numerous clinical trials. The trials showed a clear need for new drugs instead of repurposed drugs and drugs that specifically target the SARS‐CoV‐2 virus or the pathology developing in COVID‐19 patients.