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[This corrects the article DOI: 10.3389/fphar.2025.1588846.].

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

Abstract BACKGROUND Venous thromboembolism (VTE) represents a rare but preventable postoperative complication. Unfractionated heparin (UH) and low-molecular-weight heparin (LMWH) are used to prevent VTE, but comparative studies of their safety and efficacy in the neurosurgical context are limited. OBJECTIVE To determine the relative safety and efficacy of UH and LMWH for prophylaxis after cranial surgery. METHODS We performed a retrospective analysis of 3204 elective intracranial surgical admissions in 2901 patients over the period 2013 to 2018. From chart review, we extracted demographic and clinical features, including diagnosis and procedure, drugs administered, and the occurrence of VTE events. To compare postoperative outcomes, we performed propensity score matching of patients receiving different drugs, and reviewed postoperative cranial imaging. To contextualize our results, we selected 14 prior neurosurgical studies of VTE prophylaxis to compare our outcomes to the existing literature. RESULTS In our sample of 3204 admissions, the overall rate of VTE was 0.8% (n = 27). Rates of VTE were not statistically different in matched cohorts receiving UH and LMWH (1.7% vs 1.0%, respectively); however, LMWH was associated with a higher rate of clinically significant intracranial hemorrhage (ICH) (3.4% vs 0.5%, P = .008). Literature review and meta-analysis supported these findings. Across studies, UH and LMWH were associated with similar rates of VTE. Studies in which patients received LMWH reported significantly higher rates of ICH (4.9% higher, P = .005). CONCLUSION We find that LMWH and UH show similar efficacy in preventing VTE; however, LMWH is associated with higher rates of ICH.

Background Withholding prophylactic anticoagulation from patients with aneurysmal subarachnoid hemorrhage (aSAH) before external ventricular drain (EVD) removal or replacement remains controversial. This study analyzed whether prophylactic anticoagulation was associated with hemorrhagic complications related to EVD removal. Method All aSAH patients treated from January 1, 2014, to July 31, 2019, with an EVD placed were retrospectively analyzed. Patients were compared based on the number of prophylactic anticoagulant doses withheld for EVD removal (> 1 vs. ≤ 1). The primary outcome analyzed was deep venous thrombosis (DVT) or pulmonary embolism (PE) after EVD removal. A propensity-adjusted logistic-regression analysis was performed for confounding variables. Results A total of 271 patients were analyzed. For EVD removal, > 1 dose was withheld from 116 (42.8%) patients. Six (2.2%) patients had a hemorrhage associated with EVD removal, and 17 (6.3%) patients had a DVT or PE. No significant difference in EVD-related hemorrhage after EVD removal was found between patients with  > 1 versus ≤ 1 dose of anticoagulant withheld (4 of 116 [3.5%] vs. 2 of 155 [1.3%]; p  = 0.41) or between those with no doses withheld compared to ≥ 1 dose withheld (1 of 100 [1.0%] vs. 5 of 171 [2.9%]; p  = 0.32). After adjustment, withholding > 1 dose of anticoagulant versus ≤ 1 dose was associated with the occurrence of DVT or PE (OR 4.8; 95% CI, 1.5–15.7; p  = 0.009). Conclusions In aSAH patients with EVDs, withholding > 1 dose of prophylactic anticoagulant for EVD removal was associated with an increased risk of DVT or PE and no reduction in catheter removal–associated hemorrhage.

Chronic obstructive pulmonary disease (COPD) is a major contributor to global morbidity and mortality, particularly during acute exacerbations that frequently require intensive care unit (ICU) admissions. Considering the hypercoagulability associated with COPD, which intensifies during acute episodes, prophylactic anticoagulation therapy may help reduce ICU mortality. However, this potential has not been explored specifically in this population of patients. We conducted a retrospective cohort study using data from the Medical Information Mart for Intensive Care IV, spanning patient records from 2008 to 2019 at the Beth Israel Deaconess Medical Center in Boston. This study focused on critically ill patients with COPD, employing feature selection methods, to identify key variables influencing clinical outcomes. The impact of prophylactic enoxaparin on prognosis was assessed using logistic regression models and Kaplan-Meier survival analysis. Our analysis included 4,433 critically ill patients with COPD, of whom 446 received enoxaparin within the first 72 h of ICU admission. The primary analysis showed that patients treated with enoxaparin experienced a 48% lower ICU mortality (odds ratio 0.52 [95% confidence interval 0.31-0.86]) than that of those not treated with enoxaparin, with an E-value of 3.26. This association between enoxaparin use and lower ICU mortality persisted across all subgroups examined. Additionally, a visual analysis of patients with varying Oxford acute severity of illness score (OASIS) indicated that early enoxaparin use was linked to an improved prognosis in critically ill patients with COPD who had higher OASIS than in those without. Early initiation of prophylactic enoxaparin therapy was significantly associated with low ICU mortality in critically ill patients with COPD, especially in high-risk subgroups. These findings support the need for randomized controlled trials to confirm the effectiveness of thromboprophylaxis in this specific patient population and to evaluate the potential bleeding risks.

BackgroundVenous thromboembolism (VTE) is a common morbidity in trauma patients. Standard VTE chemoprophylaxis is often inadequate. We hypothesized that weight-based dosing would result in appropriate prophylaxis more reliably than fixed dosing.MethodsAll patients admitted to a Level 1 trauma center over a 6-month period were included unless contra-indications for VTE prophylaxis existed. A prospective adjusted-dosing group was compared to a retrospective uniform-dosing group. The adjusted-dosing approach consisted of initial weight-based dosing of 0.5 mg/kg subcutaneously (subQ) every 12 h (q12h). Peak anti-factor Xa was measured. Patients outside of the prophylactic range had their dose adjusted by ± 10 mg. The uniform-dosing group received 30 mg subQ q12h, without adjustments.ResultsEighty-four patients were included: 44 in the retrospective control cohort and 40 in the prospective experimental cohort. More patients were sub-prophylactically dosed in the uniform-dosing group relative to the adjusted-dosing group (25% vs 5%, p = 0.03). There was no difference in overall prophylactic range targeting, because the supra-prophylactically dosed patients in the adjusted-dosing group eliminated the effect (p = 0.173). However, after a single dose adjustment, zero patients were outside of prophylactic range (25% versus 0%, RR = infinite, p = 0.003). In the uniform-dosing group, anti-Xa level correlated with body surface area (BSA; R2 = 0.33, p < 0.0001) and weight (R2 = 0.26, p = 0.0005). Weight-based dosing both pre- and post-readjustment normalized the correlation of anti-Xa with BSA (R2 = 0.07, p = 0.1) and weight (R2 = 0.07, p = 0.1).ConclusionsWeight-based VTE prophylaxis with anti-Xa-based dose adjustment improves prophylactic range targeting relative to uniform dosing and eliminates variances secondary to BSA and weight in trauma patients.

Background Nephrotic syndrome (NS) is associated with increased risk of thromboembolic events (TE) adding to the morbidity and mortality. International guidelines recommend prophylactic anticoagulation in patients with NS and high risk of TE, but no studies have identified the optimal type of anticoagulation in NS. We aimed to assess the effectiveness and safety of direct oral anticoagulant (DOAC) by analyzing the thromboembolic and bleeding events in NS patients prescribed DOAC as primary prophylaxis to prevent TE or as treatment for TE occurring in relation to NS. Methods We performed a single-center, retrospective study including patients with NS, a plasma albumin less than 25 g/L and prophylactic anticoagulation treatment with DOAC at the Department of Renal Medicine at Aarhus University Hospital, Denmark from July 2016 to June 2021. Patients treated with DOAC as thromboprophylaxis for other indications than NS were excluded. Baseline characteristics and outcomes, including TE, bleeding and other adverse effects associated with DOAC were obtained from medical records. Results We identified 268 patients treated with DOAC of which 21 patients with NS were included in the study. Nineteen patients were prescribed DOAC as thromboprophylaxis and two patients received DOAC due to previous TE, which was considered associated with the NS. The type of DOAC prescribed was apixaban ( n  = 10) and rivaroxaban ( n  = 11). No patients experienced TE during DOAC treatment, while five patients had a minor bleeding episode. Patients who experienced bleeding episodes were older (median 62 vs 51 years), more often female (80%) and had been on DOAC for a longer period (204 days vs 47 days). Neither the HAS-BLED score nor GN-risk-score predicted the risk of minor bleedings in this population. Conclusions In this case series, no new TE and only minor bleeding complications were observed among adult NS patients treated with DOAC.

To investigate the association between early prophylactic anticoagulation and in-hospital mortality in ICU patients with severe acute pancreatitis. This retrospective cohort study used data from the MIMIC-IV database (v3.1), including adult ICU patients diagnosed with SAP between 2008 and 2019. Patients receiving therapeutic anticoagulation were excluded. Early prophylactic anticoagulation was defined as subcutaneous heparin or enoxaparin administered within 24 hours of ICU admission. The primary outcome was in-hospital mortality. Multivariable Cox regression models with multiple imputation and propensity score matching were used to adjust for confounding. Among 1341 eligible patients, 286 (21.3%) received early prophylactic anticoagulation. While crude in-hospital mortality was not significantly different between groups, patients receiving early anticoagulation had significantly lower in-hospital mortality (Log-rank P = 0.015). Multivariable Cox models confirmed a consistent protective association across imputed datasets (HRs ranging from 0.60 to 0.62; all P < 0.05). Subgroup analysis showed no significant interaction across age, gender, or comorbidity status. After 1:1 propensity score matching (n = 284 pairs), the mortality benefit persisted (HR = 0.51; 95% CI: 0.32-0.82; P = 0.005). Additional sensitivity analyses yielded similar results. Early prophylactic anticoagulation within 24 hours of ICU admission was associated with reduced in-hospital mortality in patients with severe acute pancreatitis. These findings suggest potential benefits of early anticoagulation in this high-risk population and warrant further prospective validation.

Patients with cancer, both hematologic and solid malignancies, are at increased risk for thrombosis and thromboembolism. In addition to general risk factors such as immobility and major surgery, shared by non-cancer patients, cancer patients are exposed to specific thrombotic risk factors. These include, among other factors, cancer-induced hypercoagulation, and chemotherapy-mediated endothelial dysfunction as well as tumor-cell-derived microparticles. After an episode of thrombosis in a cancer patient, secondary thromboprophylaxis to prevent recurrent thromboembolism has long been established and is typically continued as long as the cancer is active or actively treated. On the other hand, primary prophylaxis, even though firmly established in hospitalized cancer patients, has only recently been studied in ambulatory patients. This recent change is mostly due to the emergence of direct oral anticoagulants (DOACs). DOACs have a shorter half-life than vitamin K antagonists (VKA), and they overcome the need for parenteral application, the latter of which is associated with low-molecular-weight heparins (LMWH) and can be difficult for the patient to endure in the long term. Here, first, we discuss the clinical trials of primary thromboprophylaxis in the population of cancer patients in general, including the use of VKA, LMWH, and DOACs, and the potential drug interactions with pre-existing medications that need to be taken into account. Second, we focus on special situations in cancer patients where primary prophylactic anticoagulation should be considered, including myeloma, major surgery, indwelling catheters, or immobilization, concomitant diseases such as renal insufficiency, liver disease, or thrombophilia, as well as situations with a high bleeding risk, particularly thrombocytopenia, and specific drugs that may require primary thromboprophylaxis. We provide a novel algorithm intended to aid specialists but also family practitioners and nurses who care for cancer patients in the decision process of primary thromboprophylaxis in the individual patient.

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