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According to this study: Thromboprophylaxis with aspirin was noninferior to low-molecular-weight heparin for preventing fatal events in patients with orthopedic trauma.The incidence of deep vein thrombosis, pulmonary embolism, and death at 90 days was low in both groups., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Unfractionated heparin (UFH) remains a frequently utilized agent in the emergency department (ED) for management of acute venous thromboembolism (VTE). While various protocols of UFH dosing have been proposed for patients with obesity, the optimal dosing and monitoring strategy is unclear. Objective: This study aims to compare the time to the first therapeutic anti-Xa level in obese acute VTE patients following the use of either total body weight (TBW) or adjusted body weight-based (AdjBW) dosing of UFH in the ED, and to analyze the impact of different dosing strategies on patient outcomes. Methods: Inclusion criteria included adult patients with a BMI > 30 kg/m 2 , and suspected VTE managed with UFH per institutional protocol utilizing a bolus dose followed by maintenance infusion and anti-Xa monitoring. The primary outcome was time to the first therapeutic anti-Xa level in the group dosed per TBW compared with the group dosed per AdjBW. Safety outcomes included incidence of bleeding events, protamine administration, and mortality. Results: There were 32 patients included in the study. Patients dosed per TBW achieved a median time to first therapeutic anti-Xa level of 14.5 hours compared with 15 hours in the AdjBW group ( P = .613). The median therapeutic UFH infusion rate was 16 units/kg/hr in the TBW group compared with 13.5 units/kg/hr in the AdjBW group ( P < .001). Safety outcomes were not significantly different between groups. Conclusion: Patients presenting to the ED with acute VTE may be managed with UFH using either a TBW or AdjBW dosing strategy.

This study aimed to evaluate whether early antifactor Xa (anti-Xa) achieved the target range when venous thromboembolism (VTE) was treated with low-molecular-weight heparin (LMWH), based on body weight and renal function in patients treated in intensive care units (ICUs). Anti-Xa levels in patients treated with LMWH for VTE in ICU and medical wards between January 1, 2021, and June 30, 2022, were retrospectively assessed. The demographics, laboratory parameters, and early anti-Xa peak levels of patients were collected. All patients were followed up for 3 months to collect VTE recurrence/bleeding events. Univariate and multivariate linear regression analyses were used to identify the factors affecting anti-Xa levels. A total of 108 patients were enrolled in this study, including 70 patients in ICU and 38 patients on medical wards. The early anti-Xa level (0.36 vs 0.61 IU/mL, P < .001) and target achievement rate (21.4% vs 39.5%, P = .015) of patients in ICU were lower than those in medical wards. Multivariate linear regression showed that only antithrombin (AT) significantly affected anti-Xa levels in patients in ICU (β = 0.008, 95%CI 0.005 to 0.011, P < .001). There was no significant difference in VTE recurrence events (11.8% vs 7.5%, P = .628) and bleeding events (29.4% vs 17.0%, P = .304) between the early anti-Xa within-target group and the early anti-Xa below-target group. Low anti-Xa peak levels are common in patients in ICU. AT activity should be monitored when using LMWH in critically ill patients., (© 2023, The American College of Clinical Pharmacology.)

Background: Hepato-pancreatico-biliary (HPB) patients experience competing risk of venous thromboembolism (VTE) and bleeding. We sought to evaluate the effect of anti-Xa levels on VTE and bleeding, and to characterize factors associated with subprophylaxis., Methods: This prospective cohort study evaluated adult HPB surgical patients; cohorts were described by anti-Xa levels as subprophylactic (<0.2 IU/mL), prophylactic (0.2-0.5 IU/mL), and supraprophylactic (>0.5 IU/mL). Primary outcome evaluated bleeding and VTE complications. Secondary outcomes evaluated factors associated with subprophylaxis., Results: We included 157 patients: 68 (43.6%) attained prophylactic anti-Xa and 89 (56.7%) were subprophylactic. Subprophylactic patients experienced more VTE compared to prophylactic patients (6.9% vs 0%; p = 0.028) without differences in bleeding complications (14.6% vs 5.9%; p = 0.081). Factors associated with subprophylactic anti-Xa included female sex (OR 2.90, p = 0.008), and Caprini score (OR 1.30, p = 0.035). Enoxaparin was protective against subprophylaxis compared to tinzaparin (OR 0.43, p = 0.029)., Conclusions: Many HPB patients have subprophylactic anti-Xa levels, placing them at risk of VTE. Enoxaparin may be preferential, however, studies evaluating optimized prophylaxis are needed., Competing Interests: Declaration of competing interest AMJS serves as a consultant to ViaCyte Inc., Diagon Inc., Protokinetix Inc. and Pelican Therapeutics Inc. The remaining authors have no conflicts to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background Context: Complications such as pressure sores, pulmonary infection, urinary tract infection (UTI), and venous thromboembolism (VTE) are common after spinal cord injury (SCI). These have serious consequences for patients' physical, social, and vocational well-being. Several authoritative organizations have developed guidelines for managing these complications after SCI., Purpose: We aim to systematically review and appraise guidelines on the management of four common complications (pressure sores, pulmonary infection, UTI, and VTE) after SCI as well as to summarize relevant recommendations and assess the quality of their supporting evidence., Design: Systematic review., Methods: We searched Medline, Embase, Cochrane, and Web of Science, as well as guideline-specific databases (eg, National Guideline Clearinghouse) and Google Scholar, from January 2000 to January 2022. We included the most updated guidelines developed by specific authoritative organizations. We evaluated the included guidelines using the Appraisal of Guidelines for Research and Evaluation 2nd edition instrument, which measures six domains (eg, applicability). Recommendations extracted from guidelines were categorized as for, against, or neither for nor against. An evidence assessment was adopted to classify the quality of supporting evidence as poor, fair, or good., Results: Eleven guidelines from 2005 to 2020 were included, all of which, among the six domains, scored lowest in the domain of applicability. For pressure sores, guidelines recommended for skin inspection, repositioning, and the use of pressure reduction equipment as preventive measures and dressings, debridement, and surgery as treatment measures. For pulmonary infection, guidelines recommended for physical (eg, the use of an insufflation-exsufflation device) and pharmacological measures (eg, the use of bronchodilators). For UTI, guidelines recommended for antibiotics as a treatment measure but recommended against cranberries, methenamine salts, and acidification or alkalinization agents as preventive measures. For VTE prophylaxis, five guidelines recommended for low molecular weight heparin (LMWH). Three guidelines recommended against unfractionated heparin, whereas one guideline recommended for it. Most of the supporting evidence was of poor quality (130/139), and the rest was of fair quality (9/139)., Conclusions: For pressure sores, pulmonary infection, and UTI, evidence of poor to fair quality indicated consistent recommendations for prevention and treatment measures. For VTE, LMWH was consistently recommended, whereas recommendations on the use of unfractionated heparin were controversial., Competing Interests: Declarations of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Direct oral anticoagulants (DOACs), such as apixaban, edoxaban, rivaroxaban, or dabigatran, are an effective treatment for atrial fibrillation (AF) and deep venous thromboembolism. We hope to evaluate the safety of DOACs versus warfarin/low molecular weight heparin (LMWH) in improving bleeding events in patients with different severity of the liver disease., Methods: We systematically searched the Cochrane Library, PubMed, and Embase databases for studies reporting the effects of DOACs in patients with liver cirrhosis. A random-effects model or fixed-effects model was selected to pool risk ratios (RR) and 95% confidence intervals (CI)., Results: A total of 18 studies involving 41,447 participants was included in this meta-analysis. Compare with warfarin/ LMWH, the use of DOACs significantly reduced the incidence of all bleeding (RR: 0.76; 95%CI: 0.66 to 0.87), major bleeding (RR: 0.51; 95%CI: 0.28 to 0.91), intracranial hemorrhage (RR: 0.50; 95%CI: 0.31 to 0.81), and gastrointestinal bleeding (RR: 0.76, 95% CI: 0.60 to 0.97), and all-cause death in patients with liver disease (RR: 0.77; 95%CI: 0.62 to 0.95). Similar results were observed in atrial fibrillation patients with liver disease and cirrhosis subgroups. Furthermore, the pooled estimates of the Child-Turcotte-Pugh (CTP) class indicated that DOACs reduced the incidence of all bleeding (RR: 0.61; 95%CI: 0.45 to 0.82), gastrointestinal bleeding (RR 0.55; 95%CI: 0.37 to 0.83), and all-cause death (RR: 0.62; 95%CI: 0.49 to 0.79) in patients with mild to moderate cirrhosis., Conclusions: Our study demonstrates that DOACs significantly reduce the risk of bleeding in patients with liver disease compared with warfarin/LMWH.

Background: Recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) during in vitro fertilization (IVF) treatment are still tough problems without effective treatments; thus, they are important research topics. There is controversy on whether low molecular weight heparin (LMWH) improves pregnancy outcomes in women with unexplained RPL and RIF. Moreover, currently, there is a paucity of reports on the role of LMWH in the entire population undergoing frozen-thawed embryo transfer (FET) cycles. This study aimed to estimate the effects of LMWH on pregnancy outcomes in women undergoing FET cycles., Methods: There were 1881 female patients included in the study. Of the 1881 patients, 107 underwent preimplantation genetic diagnosis cycles, which were analyzed individually. The patients were divided into two groups: the LMWH group received injections of 4100 IU/d LMWH from the day of transfer until 14 ± 2 days posttransplant, the control group was the comparison group (without LMWH use). The baseline characteristics and reproductive outcomes of the patients were reviewed., Results: Of the 1774 women with normal FET cycles, no significant differences were found in the number of embryos implanted (1.31 ± 0.02 vs. 1.28 ± 0.02), embryo implantation rate, biochemical pregnancy rate, clinical pregnancy rate, live birth rate, late abortion rate, and ectopic pregnancy rate between the two groups. The LMWH group had a higher early abortion (17.8% [76/427] vs. 12.5% [55/439], p = 0.030). In the sub-group analysis, among the patients who underwent more than four transfers, the LMWH group had a lower late abortion rate (1.7% [1/60] vs. 13.2% [7/53], p = 0.043). Similarly, of the 107 women who underwent preimplantation genetic diagnosis cycles, the reproductive outcomes were comparable between the two groups., Conclusion: In the general population and PGD patients, LMWH did not improve pregnancy outcomes. Therefore, the routine use of LMWH is not recommended for early treatment., (© 2023. The Author(s).)

Venous thromboembolism (VTE) is a common complication in hospitalized patients. Pharmacologic prophylaxis is used in order to reduce the risk of VTE events. The main purpose of this study is to compare the prevalence of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients admitted to the intensive care unit (ICU) who received unfractionated heparin (UFH) versus enoxaparin as VTE prophylaxis. Mortality was evaluated as a secondary outcome. This was a Propensity Score Adjusted Analysis. Patients admitted to neurology, surgical, or medical ICUs and screened with venous doppler ultrasonography or computed tomography angiography for detection of VTE were included in the analysis. We identified 2228 patients in the cohort, 1836 (82.4%) patients received UFH and 392 (17.6%) patients received enoxaparin. Propensity score matching yielded a well-balanced cohort of 950 (74% UFH, 26% enoxaparin) patients. After matching, there was no difference in prevalence of DVT (RR 1.05; 95% CI 0.67-1.64, p = 0.85) and PE (RR 0.76; 95% CI, 0.44-1.30, p = 0.31). No significant differences in location and severity of DVT and PE between the two groups were detected. Hospital and intensive care unit stay was similar between the two groups. Unfractionated heparin was associated with a higher rate of mortality, (HR 2.04; 95% CI, 1.13-3.70; p = 0.019). The use of UFH as VTE prophylaxis in ICU patients was associated with a similar prevalence of DVT and PE compared with enoxaparin, and the site and degree of occlusion were similar. However, a higher mortality rate was seen in the UFH group., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Neurosurgeons often face this dilemma. Brain neoplasm patients undergoing neurosurgery are at a high risk of venous thrombosis. However, antithrombotic drugs may induce bleeding complications. Therefore, we compared the efficacy and safety of prophylaxis for venous thromboembolism (VTE) in brain neoplasm patients undergoing neurosurgery. We searched Cochrane Central Register of Controlled Trials, Ovid MEDLINE(R), and Embase from inception to January 2022 for randomized controlled trials (RCTs) comparing the prophylactic measures efficacy and safety for VTE in brain neoplasm patients undergoing neurosurgery. The main efficacy outcome was symptomatic or asymptomatic VTE. The safety outcomes included major bleeding, minor bleeding, all occurrences of bleeding, and all-cause mortality. We used (Log) odds ratio (OR) of various chemoprophylaxis regimens to judge the safety and effectiveness of VTE. Additionally, all types of intervention were ranked by the Surface Under the Cumulative Ranking (SUCRA) value. We included 10 RCTs with 1128 brain neoplasm patients undergoing neurosurgery. For symptomatic or asymptomatic VTE and proximal DVT or PE, DOACs, compared with placebo, can significantly reduce the events. DOACs were superior to all other interventions in the rank plot of these events. For major bleeding reduction, unfractionated heparin (SUCRA value = 0.21) demonstrated better safety efficacy than others. For minor bleeding reduction, DOACs had a significantly higher risk of minor bleeding compared with placebo [Log OR 16.76, 95% CrI (1.53, 61.13)], LMWH [Log OR 15.68, 95% CrI (0.26, 60.10)] and UFH [Log OR 15.93, 95% CrI (0.22, 60.16)] respectively. Except for placebo (SUCRA values of 0.13), UFH (SUCRA values of 0.37) depicted better safety efficacy than others. For all-cause mortality, we found UFH always had significantly lower all-cause mortality compared with low-molecular-weight heparin (LMWH) [Log OR = 14.17, 95% CrI (0.05, 48.35)]. UFH plus intermittent pneumatic compression (IPC) (SUCRA value of 0.12) displayed the best safety for all-cause mortality. In our study, DOACs were more effective as prophylaxis for VTE in brain neoplasm patients undergoing neurosurgery. Regarding the safety of prophylaxis for VTE, UFH of chemoprophylaxis consistently demonstrated better safety efficacy, involving either major bleeding, minor bleeding, bleeding, or all-cause mortality., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Preeclampsia is a common disease during pregnancy that leads to fetal and maternal adverse events. Few head-to-head clinical trials are currently comparing the effectiveness of prophylactic strategies for preeclampsia. In this network meta-analysis, we aimed to compare the efficacy of prophylactic strategies for preventing preeclampsia in pregnant women at risk., Data Sources: Articles published in or before September 2021 from PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov, references of key articles, and previous meta-analyses were manually searched., Study Eligibility Criteria: Randomized controlled trials comparing prophylactic strategies preventing preeclampsia with each other or with negative controls were included., Methods: Two reviewers independently extracted data, assessed the risk of bias, and assessed evidence certainty. The efficacy of prophylactic strategies was estimated by frequentist and Bayesian network meta-analysis models. The primary composite outcome was preeclampsia/ pregnancy-induced hypertension., Results: In total, 130 trials with a total of 112,916 patients were included to assess 13 prophylactic strategies. Low-molecular-weight heparin (0.60; 95% confidence interval, 0.42-0.87), vitamin D supplementation (0.65; 95% confidence interval, 0.45-0.95), and exercise (0.68; 95% confidence interval, 0.50-0.92) were as efficacious as calcium supplementation (0.71; 95% confidence interval, 0.62-0.82) and aspirin (0.79; 95% confidence interval, 0.72-0.86) in preventing preeclampsia/pregnancy-induced hypertension, with a P score ranking of 85%, 79%, 76%, 74%, and 61%, respectively. In the head-to-head comparison, no differences were found between these effective prophylactic strategies for preventing preeclampsia and pregnancy-induced hypertension, except with regard to exercise, which tended to be superior to aspirin and calcium supplementation in preventing pregnancy-induced hypertension. Furthermore, the prophylactic effects of aspirin and calcium supplementation were robust across subgroups. However, the prophylactic effects of low-molecular-weight heparin, exercise, and vitamin D supplementation on preeclampsia and pregnancy-induced hypertension varied with different risk populations, dosages, areas, etc. The certainty of the evidence was moderate to very low., Conclusion: Low-molecular-weight heparin, vitamin D supplementation, exercise, calcium supplementation, and aspirin reduce the risk of preeclampsia/pregnancy-induced hypertension. No significant differences between effective prophylactic strategies were found in preventing preeclampsia. These findings raise the necessity to reevaluate the prophylactic effects of low-molecular-weight heparin, vitamin D supplementation, and exercise on preeclampsia., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Trauma patients are at high risk of venous thromboembolism (VTE). We summarize the comparative efficacy and safety of anti-Xa-guided versus fixed dosing for low molecular weight heparin (LMWH) for the prevention of VTE in adult trauma patients., Methods: We searched Medline and Embase from inception through June 1, 2022. We included randomized controlled trials or observational studies comparing anti-Xa-guided versus fixed dosing of LMWH for thromboprophylaxis in adult trauma patients. We incorporated primary data from 2 large observational cohorts. We pooled effect estimates using a random-effects model. We assessed risk of bias using the ROBINS-I tool for observational studies and assessed certainty of findings using GRADE methodology., Results: We included 15 observational studies involving 10,348 patients. No randomized controlled trials were identified. determined that, compared to fixed LMWH dosing, anti-Xa-guided dosing may reduce deep vein thrombosis [adjusted odds ratio (aOR); 0.52, 95% CI: 0.40-0.69], pulmonary embolism (aOR: 0.48, 95% CI: 0.30-0.78) or any VTE (aOR: 0.54, 95% CI: 0.42-0.69), though all estimates are based on low certainty evidence. There was an uncertain effect on mortality (aOR: 1.06, 95% CI: 0.85-1.32) and bleeding events (aOR: 0.84, 95% CI: 0.50-1.39), limited by serious imprecision. We used several sensitivity and subgroup analyses to confirm the validity of our assumptions., Conclusion: Anti-Xa-guided dosing may be more effective than fixed dosing for prevention of deep vein thrombosis, pulmonary embolism, and VTE for adult trauma patients. These promising findings justify the need for a high-quality randomized study with the potential to deliver practice changing results., Competing Interests: M.C. is supported by a Tier 2 Research Chair in Venous Thrombosis and Cancer from the Department of Medicine at the University of Ottawa. M.C. reports research funding from Leo Pharma, Pfizer, and Bristol-Myers Squibb and honoraria from Pfizer, Bayer, Bristol-Myers Squibb, Sanofi, Leo Pharma, and Servier. B.R. is supported by a McMaster Department of Medicine Mid-Career Award. The remaining authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: This review aims to assess the treatment options for cancer-associated venous thromboembolism (VTE) based on the most robust level of evidence recommendations and suggestions based on expert opinion., Recent Findings: Several classes of anticoagulants have been studied in the treatment of cancer-associated thrombosis (CAT). Since the CLOT trial, guidelines recommend the use of low-molecular-weight heparin (LMWH) for the treatment of this condition. However, since 2018, some direct oral anticoagulants became an alternative first-line treatment for CAT. Three Xa antagonists (rivaroxaban, apixaban, and edoxaban) proved to be at least as effective as the LMWH strategy for the short-term prevention of VTE recurrence. The right choice of treatment in the context of anticoagulation strategy, thrombo-hemorrhagic risk management, and a patient's comorbidities represents a challenge. The correct management of CAT and a more individualized approach are needed to identify risk factors and offer the best treatment for each patient., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Venous thromboembolism (VTE) in the Intensive Care Unit (ICU) is associated with significant morbidity and mortality therefore prevention is imperative to reduce its burden. VTE prophylaxis in ICU patients is primarily pharmacological using low molecular weight heparin (LMWH). Plasma anti-factor Xa (anti-FXa) levels may be used to measure LMWH activity. This study aims to determine the proportion of acutely ill patients in a general ICU receiving standard VTE prophylaxis that achieve adequate peak or trough anti-FXa prophylactic levels and to determine the effect of LMWH dose adjustment in patients not achieving adequate anti-FXa prophylactic levels., Methods: Peak and trough anti-FXa levels were measured at four and 23 hours respectively after receiving the second consecutive daily enoxaparin 40 mg sc injection. Patients in whom peak anti-FXa levels were found to be sub-prophylactic (<0.2 IU/mL), were dose escalated to enoxaparin 60 mg once daily. Peak and trough levels were repeated as above., Results: Sixty-one percent of study patients (N.=46) were found to have sub-prophylactic peak anti-FXa levels. Twenty-seven patients received an increased enoxaparin dose of 60 mg/d. Of these, nine patients (33.3%) still failed to achieve the target prophylactic peak anti-FXa level (0.2-0.4 IU/mL). Male gender and high body mass index (BMI) were significantly and strongly correlated with sub-prophylactic anti-FXa levels., Conclusions: Most ICU patients in this study did not achieve recommended prophylactic anti-FXa levels while receiving a standard dose of enoxaparin and these levels failed to increase after enoxaparin dose escalation in a significant proportion of patients. High BMI and male gender are associated with sub-prophylactic levels of anti-FXa in critically ill patients.

Purpose of Review: Antiphospholipid syndrome (APS) is an acquired thrombo-inflammatory disease that has morbid and sometimes devastating effects on patients and their families. This review will discuss the most recent international societal treatment guidelines and propose practical management algorithms for various APS sub-types., Recent Findings: APS represents a disease spectrum. Although thrombosis and pregnancy morbidities are traditional hallmarks of APS, a variety of extra-criteria clinical phenotypes can often be seen, which makes clinical management more challenging. Primary APS thrombosis prophylaxis should take a risk-stratified approach. Although vitamin K antagonists (VKAs) or heparin/low molecular weight heparin (LMWH) remain the preferred treatment for secondary APS thrombosis prophylaxis, some international society guidelines support the use of direct oral anticoagulants (DOACs) in certain circumstances. Careful monitoring and individualized obstetric care with the use of aspirin and heparin/LMWH will improve pregnancy outcomes among pregnant individuals with APS. Treatment of microvascular and catastrophic APS remains challenging. While the addition of various immunosuppressive agents is often utilized, further systemic evaluations of their use are warranted before definitive recommendations can be made. Several new therapeutic strategies are on the horizon that might enable more personalized and targeted APS management in the near future., Summary: Although the knowledge of APS pathogenesis has grown in recent years, the management principles and strategies are largely unchanged. There is an unmet need for evaluating pharmacological agents, beyond anticoagulants, that target diverse thromboinflammatory pathways., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The management of patients who are receiving chronic oral anticoagulation therapy and require an elective surgery or an invasive procedure is a common clinical scenario., Research Question: What is the best available evidence to support the development of American College of Chest Physicians guidelines on the perioperative management of patients who are receiving long-term vitamin K agonist (VKA) or direct oral anticoagulant (DOAC) and require elective surgery or procedures?, Study Design and Methods: A literature search including multiple databases from database inception through July 16, 2020, was performed. Meta-analyses were conducted when appropriate., Results: In patients receiving VKA (warfarin) undergoing elective noncardiac surgery, shorter (< 3 days) VKA interruption is associated with an increased risk of major bleeding. In patients who required VKA interruption, heparin bridging (mostly with low-molecular-weight heparin [LMWH]) was associated with a statistically significant increased risk of major bleed, representing a very low certainty of evidence (COE). Compared with DOAC interruption 1 to 4 days before surgery, continuing DOACs may be associated with higher risk of bleeding demonstrated in some, but not all studies. In patients who needed DOAC interruption, bridging with LMWH may be associated with a statistically significant increased risk of bleeding, representing a low COE., Interpretation: The certainty in the evidence supporting the perioperative management of anticoagulants remains limited. No high-quality evidence exists to support the practice of heparin bridging during the interruption of VKA or DOAC therapy for an elective surgery or procedure, or for the practice of interrupting VKA therapy for minor procedures, including cardiac device implantation, or continuation of a DOAC vs short-term interruption of a DOAC in the perioperative period., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Women with antiphospholipid syndrome (APS) have an increased risk of adverse pregnancy outcomes. To define clinical, serologic, and treatment factors that can predict outcomes in pregnant women with APS. Retrospective cohort study of pregnant women with APS evaluated at a university medical center between January 2006 and August 2021. Demographics, personal and family history of thrombosis, autoimmune disease, antithrombotic use, pregnancy outcomes, maternal and fetal complications were collected. We compared pregnancy outcomes in the presence or absence of lupus anticoagulant (LA), systemic lupus erythematosus (SLE), prior thrombosis or pregnancy losses, and antithrombotic use. There were 169 pregnancies in 50 women; 79 (46.7%) occurred after maternal diagnosis of APS. The most common antithrombotic regimen was aspirin and low molecular weight heparin (LMWH) in 26.6% of pregnancies; 55.0% of all pregnancies and 68.4% of pregnancies post-APS diagnosis resulted in a live birth. In age-adjusted analyses, aspirin plus LMWH regardless of dosage was associated with significantly higher odds of live birth compared with no antithrombotic use (OR = 7.5, p < 0.001) and compared with aspirin alone (OR = 13.2, p = 0.026). SLE increased the risk for preterm birth and preeclampsia. A positive LA did not impact the outcomes evaluated and anticardiolipin IgM decreased the risk of pre-eclampsia. The presence of SLE is a significant risk factor for adverse outcomes in pregnant women with APS. Treatment with LMWH and aspirin was superior to aspirin alone. The creation of a global registry may be useful in improving the management of these patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study investigates the effect of low-molecular-weight heparin (LMWH) on cytokines TNF-α, IFN-γ, IL-2, IL-4, IL-6, and IL-10 in peripheral blood of patients with repeated implantation failure during the implantation window. From May 2019 to March 2021, we enrolled 32 patients with recurrent implantation failure (RIF group) and 30 patients with successful pregnancy after the first frozen embryo transfer (control group) in the Reproductive Medicine Centre of Wuxi Maternity and Child Health Care Hospital. During the implantation window, the following features were compared between two groups and between different time points using ELISA: the status of immune cytokines in peripheral blood; Th1 cytokines (TNF-α, IFN-γ, and IL-2) and Th2 cytokines (IL-4, IL-6, and IL-10) in peripheral blood. The levels of Th1 cytokines in the RIF group before treatment were higher in comparison with the control group. In the RIF group, the LMWH treatment can inhibit the expression of Th1 cytokines and enhance the expression of Th2 cytokines. Using LMWH during the implantation window can improve the immune imbalance of patients with repeated implantation failure, which makes it a potential treatment strategy for patients with abnormal cellular immunity.

In this study, we investigated the effect of low-molecular-weight heparin combined with pneumatic pressure in preventing lower extremity deep vein thrombosis after cesarean section, as well as on the visual analog scale (VAS) score. 120 women who underwent cesarean sections at full term in our hospital from January 2019 to January 2022 were included and divided into a control group (55 cases) and an observation group (65 cases) based on the different treatment methods: the control group was treated with low-molecular-weight heparin and the observation group was treated with pneumatic compression therapy based on the control group. The 2 groups were analyzed for thrombosis, clinical efficacy of the treatment methods, and VAS scores. The incidence of deep vein thrombosis in the observation group were significantly lower than in the control group (4.62% vs 21.82%, P < .05). There were no statistically significant differences in activated partial thromboplastin time, prothrombin time, and thrombin time between the 2 groups (P > .05) before treatment; however, after treatment, activated partial thromboplastin time, prothrombin time, and thrombin time in the observation group were significantly higher than those in the control group (P < .05). The clinical efficacy was significantly higher in the observation group compared with the control group (95.38% vs 78.18%, respectively). The VAS scores in the observation group were significantly lower than those in the control group (P < .05). Hence, low-molecular-weight heparin combined with pneumatic pressure therapy significantly reduces the incidence of lower limb deep vein thrombosis after cesarean section. It also improves the coagulation index and reduces post-operative pain. Therefore, it should be considered for use in clinical practice., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: Low molecular weight heparins are widely used in various thrombotic diseases and exert a preventive effect on thrombosis in high-risk patients. Umbilical artery thrombosis (UAT) is a rare occurrence that is difficult to detect during routine prenatal visits but can lead to adverse perinatal outcomes., Patient Concerns: The aim of this study was to elucidate the therapeutic effect of low molecular weight heparins on UAT and to provide a new treatment option for the timing of delivery timing., Diagnoses and Interventions: A retrospective study was conducted on cases involving thrombosis of the umbilical cord enrolled from July 2017 to July 2022. Data were acquired and analyzed from medical records and the final diagnosis was confirmed by histopathology. All included patients received LWMHs therapy after initial diagnosis of UAT., Outcomes: The mean age of the 10 pregnant women recruited into this study was 27.9 ± 4.0 year-of-age; 1 (10%) was elderly. The gestational age at diagnosis was 29.9 ± 3.7 weeks, the gestational age at termination was 36.3 ± 2.5 weeks and the mean gestational age of extension was 6.4 ± 4.2 weeks. Low molecular weight heparin sodium was administered after umbilical artery embolism was detected on ultrasound. The LWMHs treatment received by the included patients in this study was subcutaneous injection. The specific usage varies due to the types of LWMHs. Of the 10 cases, 5 (50%) had fetal distress but all fetuses were born alive without neonatal asphyxia. With regards to delivery mode, 9 pregnancies were terminated by cesarean section., Lesson: Early anticoagulant treatment with LWMHs may improve pregnancy outcomes. The timing and mode of termination of pregnancy should be determined according to the condition of the mother and the fetus along with the gestational age., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The issue of how to identify newly diagnosed multiple myeloma (NDMM) patients requiring thromboprophylaxis remains unsolved. Several changes in thrombin generation (TG)-derived parameters have been described in multiple myeloma (MM) patients recently. Assessment of prothrombotic risk with a fully automated TG analyzer could reduce interlaboratory variability. Our objective was to determine whether ST-Genesia ® could reveal a hypercoagulable state in NDMM compared to healthy controls. We conducted a multicenter observational study of NDMM requiring initial treatment to compare TG parameters obtained with ST-Genesia ® analyzer and ST-ThromboScreen ® reagent with a control group. Clinical data were obtained from medical records and blood samples were collected before initial anti-myeloma therapy. A thrombophilia panel was performed in all patients. Compared to age- and sex-matched controls (n = 83), NDMM patients (n = 83) had significantly higher peak height, higher velocity index, shorter time-to-peak and lower percentage of endogenous thrombin potential (ETP) inhibition after adding thrombomodulin (TM) (ETP%inh). NDMM on prophylactic low molecular weight heparin (LMWH) showed reduced both peak height and velocity index compared to NDMM who had not yet started VTE prophylaxis, similar to that of controls. Moreover, partial correction of ETP%inh was observed in MM patients on LMWH. The presence of a thrombophilia did not modify the TG phenotype. Untreated NDMM patients showed an enhanced TG, regardless of their thrombophilia status. They generate a higher peak of thrombin, take less time to produce it, and exhibit resistance to TM inhibition. Our findings suggest that standard prophylactic dose of LMWH may reduce TG at levels of healthy controls., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). The optimal heparin regimen remains unknown and should balance thromboembolic and bleeding risks. The aim of this study was to evaluate the efficacy and safety of standard or higher heparin regimens for the prevention of VTE in patients hospitalized due to COVID-19. We performed a systematic literature search; studies reporting on hospitalized patients with COVID-19 who received standard heparin prophylaxis vs. high (intermediate or therapeutic) heparin regimens were included if outcome events were reported by treatment group and more than 10 patients were included. Primary study outcome was in-hospital VTE. Secondary study outcomes were major bleeding (MB), all-cause death, fatal bleeding and fatal pulmonary embolism. Overall, 33 studies (11,387 patients) were included. Venous thromboembolic events occurred in 5.2% and in 8.2% of patients who received heparin prophylaxis with at high-dose or standard-dose, respectively (RR 0.71, 95% CI 0.55-0.90, I2 48.8%). MB was significantly higher in patients who received high- compared to the standard-dose (4.2% vs 2.2%, RR 1.94, 95% CI 1.47-2.56, I2 18.1%). Sub-analyses showed a slight benefit associated with high-dose heparin in patients admitted to non-intensive care unit (ICU) but not in those to ICU. No significant differences were observed for mortality outcomes. Heparin prophylaxis at high-dose reduces the risk of VTE, but increased the risk of MB compared to the standard-dose. No clinical benefit for heparin high-dose was observed for ICU setting, but its role in the non-ICU deserves further evaluation. PROSPERO registration number: CRD42021252550., (© 2022. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Background: Direct oral anticoagulants (DOACs) are recommended as a possible pharmacologic venous thromboembolism (VTE) prophylaxis in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, current guidelines did not introduce recommendations for administration of DOACs as an option for pharmacologic VTE prophylaxis in patients undergoing hip fracture surgery (HFS). The purpose of this study is to compare the effectiveness and safety of DOACs administered for pharmacologic VTE prophylaxis in patients undergoing HFS to conventional pharmacologic VTE prophylaxis, as well as mortality between these thromboprophylaxis medications., Methods: We performed a systematic review of multiple electronic databases for randomized controlled trials (RCTs) including patients who were subjected to HFS and prescribed either DOACs as pharmacologic VTE prophylaxis or a conventional VTE prophylaxis drug. We conducted a meta-analysis comparing effectiveness, safety and mortality of these agents between the patient groups studied. Three endpoints were studied. The first one regarding the effectiveness of the agents included clinical manifestations of VTE. The second one regarding the safety of the agents included clinical presentation of bleeding. The latter endpoint studied was mortality of patient groups studied. We generated forest plots to depict the relative risk of the above clinical manifestations between the two studied patient groups and to investigate if there is statistical significance for each patient group to present any of these clinical manifestations. Additionally, we calculated the inconsistency (I 2 ) statistic and assessed the risk of bias of RCTs included in our meta-analysis by using the modified Cochrane collaboration tool., Results: We selected 2 RCTs in this review including 279 patients totally. Patients of control groups in both eligible studies were administered enoxaparin, which is a low molecular weight heparin (LMWH). The meta-analysis found no statistically significant difference between patients prescribed DOACs and patients prescribed LMWH for VTE (95% CI 0.19 to 1.13, RR=0.46, p=0.09), deep vein thrombosis (DVT) (95% CI 0.21 to 1.32, RR=0.53, p=0.17) and pulmonary embolism (PE) (95% CI 0.03 to 3.12, RR=0.33, p=0.33), major bleeding events (95% CI 0.57 to 1.78, RR=1.01, p=0.97), minor bleeding events (95% CI 0.72 to 1.64, RR=1.09, p=0.69), all bleeding events (95% CI 0.79 to 1.38, RR=1.05, p=0.74) and mortality (95% CI 0.01 to 8.0, RR=0.33, p=0.5). The major risk of bias of the selected RCTs was the fact that either the researchers or the patients could have knowledge whether the latter were administered DOACs or LMWHs., Discussion: DOACs are not inferior compared to LMWHs regarding their effectiveness, safety and mortality in patients subjected to HFS. Further studies with larger patient samples should be conducted in the future, so that safer results and conclusions could be reached., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: In critically ill (preterm) neonates, catheter-related venous thromboembolism (CVTE) can be a life-threatening complication. Evidence on optimal management in the literature is lacking. In the Netherlands, a consensus-based national management guideline was developed to create uniform CVTE management., Objectives: To evaluate the efficacy and safety of the national guideline., Methods: This prospective, multicenter, observational study included all infants aged ≤6 months with CVTE in the Netherlands between 2014 and 2019. CVTE was divided into thrombosis in veins and that in the right atrium, with their own treatment algorithms. The primary outcomes were recurrent venous thrombotic events (VTEs) and/or death due to CVTE as well as major bleeding., Results: Overall, 115 neonates were included (62% male; 79% preterm). The estimated incidence of CVTE was 4.0 per 1000 neonatal intensive care unit admissions. Recurrent thrombosis occurred in 2 (1.7%) infants and death due to CVTE in 1 (0.9%) infant. Major bleeding developed in 9 (7.8%) infants: 2 of 7 (29%) on recombinant tissue plasminogen activator, which was given for high-risk right-atrium thrombosis, and 7 of 63 (11%) on low-molecular-weight heparin (LMWH). Five of the 7 bleedings because of LMWH were complications of subcutaneous catheter use for LMWH administration., Conclusion: The management of neonatal CVTE according to the Dutch CVTE management guideline led to a low incidence of recurrent VTEs and death due to VTEs. Major bleeding occurred in 7.8% of the infants. Specific guideline adjustments may improve efficacy and, especially, safety of CVTE management in neonates., Competing Interests: Declaration of competing interests C.H.v.O. reports consulting fees paid to the department from Bayer BV, Boehringer Ingelheim, and Daiichi Sankyo; lecture honoraria paid to the department from Boehringer Ingelheim; and an unrestricted grant paid to the department from Octapharma, all outside the submitted work., (Copyright © 2022 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the effectiveness of pharmacologic venous thromboembolism (VTE) prophylaxis in postpartum patients., Data Sources: On February 21, 2022, a literature search was conducted on Embase.com , Ovid-Medline All, Cochrane Library, Scopus, and ClinicalTrials.gov using terms postpartum period AND thromboprophylaxis AND antithrombin medications including heparin and low molecular weight heparin., Methods of Study Selection: Studies that evaluated the outcome of VTE among postpartum patients exposed to pharmacologic VTE prophylaxis with or without a comparator group were eligible for inclusion. Studies of patients who received antepartum VTE prophylaxis, studies in which this prophylaxis could not be definitively ruled out, and studies of patients who received therapeutic dosing of anticoagulation for specific medical problems or treatment of VTE were excluded. Titles and abstracts were independently screened by two authors. Relevant full-text articles were retrieved and independently reviewed for inclusion or exclusion by two authors., Tabulation, Integration, and Results: A total of 944 studies were screened by title and abstract, and 54 full-text studies were retrieved for further evaluation after 890 studies were excluded. Fourteen studies including 11,944 patients were analyzed: eight randomized controlled trials (8,001 patients) and six observational studies (3,943 patients). Among the eight studies with a comparator group, there was no difference in the risk of VTE between patients who were exposed to postpartum pharmacologic VTE prophylaxis and those who were unexposed (pooled relative risk 1.02, 95% CI 0.29-3.51); however, six of eight studies had no events in either the exposed or unexposed group. Among the six studies without a comparator group, the pooled proportion of postpartum VTE events was 0.00, likely due to five of six studies having no events., Conclusion: The current literature provided an insufficient sample size to conclude whether postpartum VTE rates differ between those exposed to postpartum pharmacologic prophylaxis and those unexposed, given the rarity of VTE events., Systematic Review Registration: PROSPERO, CRD42022323841., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background:  In the past, pediatric patients with venous thromboembolic events (VTE) were treated with low-molecular-weight heparin (LMWH) which was successful in around 70% of the cases. However, anticoagulation alone might not restore patency in all patients, and advanced therapeutic options to prevent postthrombotic syndrome are needed. During recent years, endovascular interventions have become a treatment option for pediatric patients with persistent thrombotic occlusion, not only in life- or limb-threatening VTE., Methods:  We evaluated 12 consecutive patients (11-17 years) with newly diagnosed VTE being treated at our department during the last 4 years (2017-2020). In case follow-up examination showed persistent venoocclusion under anticoagulation, patients received secondary interventional therapy like recanalization, percutaneous transluminal angioplasty with or without catheter-directed thrombolysis, and stenting. Patients with no clinical signs of venoocclusion or regredient thrombosis in imaging examination received anticoagulation alone., Results:  Six of 12 (50%) patients underwent catheter intervention. Median time from diagnosis to intervention was 4 months (0-12 months). Reintervention was necessary in one (8%) case and complete recanalization failed in one (8%) case. There were no major bleeding events or other major postinterventional complications, no acute or late local recurrence, and all patients reported clinical improvement after the procedure., Conclusion:  If endovascular intervention is used in teenage patients with persistent symptomatic VTE, reduction of postthrombotic symptoms is possible, even if intervention is performed secondary to failure of anticoagulation. Multidisciplinary treatment decisions can be based on the clinical course and follow-up imaging., Competing Interests: B.Z. reports grants from Takeda, CSL Behring, Biotest to the University Medical Center Freiburg.B.S. reports grants from Studie CV185–362, Apixaban for Bristol-Myers Squibb GmbH & Co. KGaA Arnulfstraße 29, and D-80636 München.B.S. reports participation on a Data Safety Monitoring Board or Advisory Board from Studie CV185–362, Apixaban for Bristol-Myers Squibb GmbH & Co. KGaA Arnulfstraße 29, and D-80636 München., (Thieme. All rights reserved.)

Anticoagulant therapy is the cornerstone of treatment and prevention of arterial and venous thromboembolism. Taking a historical perspective, starting in the 1960s, and progressing through to 2022, we discuss key clinical trials of anticoagulants that have changed clinical practice, and examine obstacles encountered in bringing these anticoagulants to the clinic. The design of some of the early studies that shaped clinical practice was poor by current standards, but their results were influential because nothing better was available. Both heparin and vitamin K antagonists had been in clinical use for several decades before well-designed trials in the 1980s optimized their dosing and enhanced their safety and efficacy. Low-molecular-weight heparin then replaced unfractionated heparin because it had a more predictable dose-response and a longer half-life, thereby allowing it to be used conveniently in out-of-hospital settings. More recently, direct oral anticoagulants became the oral anticoagulants of choice for most indications because they were shown to be at least as safe and effective as vitamin K antagonists when used in fixed doses without the need for laboratory monitoring. The design of the trials that led to the approval of the direct oral anticoagulants was excellent, but further studies are required to optimize their dosing in selected patients who were underrepresented in these trials., Competing Interests: T.A.C.d.V. reports nonfinancial support from Daiichi Sankyo, and personal fees from Bristol-Myers-Squibb, both outside the submitted work. He is also being considered for the adjudication committee of the LIMIT & DANCE trials, which are sponsored by the Population Health Research Institute (PHRI). V.B. reports personal fees from Bayer and Pfizer, outside the submitted work. N.C.C. reports personal fees from Stago and Boehringer Ingelheim, outside the submitted work. J.W.E. reports grants and personal fees from Anthos, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Ionis, Janssen, Merck, and Pfizer, personal fees from USV, during the conduct of the study; grants and personal fees from Anthos, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Ionis, Janssen, Merck, and Pfizer, personal fees from USV, outside the submitted work., (Thieme. All rights reserved.)

Abstract: Introduction: Cell-free DNA (CFDNA) has emerged as a prognostic biomarker in patients with sepsis. Circulating CFDNA is hypothesized to be associated with histones in the form of nucleosomes. In vitro, DNA activates coagulation and inhibits fibrinolysis, whereas histones activate platelets and are cytotoxic to endothelial cells. Previous studies have targeted CFDNA or histones in animal models of sepsis using DNase I or heparins, respectively, which has reduced inflammatory and thrombosis markers, thereby improving survival. In this study, we explored the possibility that the combination of DNase I and a low-molecular weight heparin (LMWH) may be a better therapeutic approach than monotherapy in a murine model of abdominal sepsis. Methods: C57Bl/6 mice (8-12 weeks old, both sexes) were subjected to either cecal ligation and puncture or sham surgery. Mice were given antibiotics, fluids, and either saline, DNase I (intraperitoneally, 20 mg/kg/8 h), LMWH (dalteparin, subcutaneously 500 IU/kg/12 h), or a combination of both (n = 12-31). Mice were monitored over 72 h for survival. Organs and blood were harvested for analysis. Levels of LMWH, CFDNA, IL-6, citrullinated histone-H3, thrombin-antithrombin complexes, and protein C were measured in plasma. Results: Administration of either DNase I (81.8%) or LMWH (83.3%, prophylactic range of 0.12 ± 0.07 IU/mL achieved) improved the survival of septic mice compared with saline- (38.7%) and combination-treated mice (48.8%, P < 0.05). Combination-treated mice also showed a small but insignificant improvement in survival compared with saline-treated cecal ligation and puncture mice. Monotherapies may be improving survival by reducing blood bacterial loads, citrullinated histone-H3, and thrombin-antithrombin complexes, and improving protein C levels. Conclusions: Compared with saline- and combination-treated mice, administration of monotherapies to septic mice improved survival. These findings suggest that there may be a negative drug-drug interaction between DNase I and LMWH when DNase I is administered intraperitoneally in a murine model of polymicrobial abdominal sepsis., Competing Interests: The authors report no conflict of interests., (Copyright © 2023 by the Shock Society.)

Background: At present, there is no comprehensive evaluation of the efficacy and safety of low molecular weight heparin (LMWH) for the treatment of thrombophilia during pregnancy in clinical practice. This study aimed to systematically evaluate the efficacy of LMWH in the treatment of patients and its effects on coagulation function, thereby providing a reference for the clinical treatment and prognosis evaluation of thrombophilia during pregnancy., Methods: Database PubMed, Web of Science and Embase as well as China National Knowledge Infrastructure and Wanfang Database were applied for the search of data. A comparative study on the efficacy of LMWH in the treatment of gestational thrombophilia was enrolled. Stata 16.0 software (Stata, College Station, TX, USA) was utilized to conduct the meta-analysis., Results: A total of 487 relevant articles were retrieved and 14 studies were finally included. Patients in the LMWH combined with the low-dose aspirin group had a significantly higher live birth rate than those in the aspirin or LMWH treat group (OR (odds ratio) = 4.54, 95% CI (confidence interval): 2.76, 7.45). The adverse effects rate was lower in the LMWH combined with the low-dose aspirin group than in the aspirin or LMWH treatment group (OR = 0.40, 95% CI: 0.29, 0.56). After treatment, patients in the LMWH combined with the low-dose aspirin group had significantly lower D-dimer (SMD (standardized mean differences) = -1.50, 95% CI: -2.19, 0.80) and platelet count (PLT; SMD = -0.13, 95% CI: -0.35, 0.09) than those in the aspirin or LMWH treatment group. However, activated partial thromboplastin time (APTT; SMD = 0.16, 95% CI: -0.10, 0.42), thrombin time (TT; SMD = 0.60, 95% CI: -0.14, 1.34), plasma prothrombin time (PT; SMD = 0.42, 95% CI: -0.71, 1.56), and fibrin values (FIB; SMD = -0.92, 95% CI: -2.12, 0.28) were significantly higher in the LMWH combined with low-dose aspirin group than those in the aspirin or LMWH treatment group., Conclusions: LMWH heparin combined with low-dose aspirin can effectively correct coagulation function in pregnant women, improve prothrombotic state and increase the live birth rate, which has high clinical value.

Objectives: To describe the management of superficial vein thrombosis (SVT) of the lower limbs in patients treated in Spanish hospital emergency departments (EDs). To evaluate the impact of ED management of venous thromboembolic complications on outcomes and to determine the characteristics of patients who develop complications., Material and Methods: The retrospective multicenter ALTAMIRA study (Spanish acronym for risk factors, complications, and assessment of Spanish ED management of SVT) used recorded data for consecutive patients with a diagnosis of isolated SVT treated in 18 EDs. We gathered data on symptomatic venous thromboembolic disease (deep vein thrombosis, pulmonary embolism, or the extension or recurrence of SVT), clinically significant bleeding, and 180-day mortality. Cox regression analysis was used to explore variables associated with complications., Results: A total of 703 patients were included. Anticoagulation was prescribed for 84.1% of the patients for a median of 30 days (interquartile range, 15-42 days); 81.3% were treated with low molecular weight heparin. A prophylactic dose was prescribed for 48% and an intermediate therapeutic dose for 52%. Sixty-four patients (9.2%) developed symptomatic thromboembolic disease within 180 days, 12 (1.7%) experienced clinically significant bleeding, and 4 (0.6%) died. Complications developed later in patients receiving anticoagulant therapy than in those not taking an anticoagulant (66 vs 11 days , P=.009), and 76.6% of those developing complications were not on anticoagulant when symptoms appeared. A history of thromboembolic disease was associated with developing complications (adjusted hazard ratio, 2.20; 95% confidence interval, 1.34-3.62)., Conclusion: ED treatment of SVT varies and is often suboptimal. The incidence of thromboembolic complications after SVT is high. Starting anticoagulation in the ED delays the development of complications. Patients with a history of thromboembolic disease are more at risk of complications.

Background: International COVID-19 guidelines recommend thromboprophylaxis for non-critically ill inpatients to prevent thrombotic complications. It is still debated whether full-dose thromboprophylaxis reduces all-cause mortality. The main aim of this updated systematic review and meta-analysis is to evaluate the effect of full-dose heparin-based thromboprophylaxis on survival in hospitalized non-critically ill COVID-19 patients., Methods: A systematic review was performed across Pubmed/Medline, EMBASE, Cochrane Central Register of clinical trials, Clinicaltrials.gov, and medRxiv.org from inception to November 2022. We conducted a meta-analysis of randomized clinical trials (RCTs) comparing full-dose heparin-based anticoagulation to prophylactic or intermediate dose anticoagulation or standard treatment in hospitalized non-critically ill COVID-19 patients. The risk of bias was assessed using the Cochrane risk-of-bias tool for randomized trials and Grading of Recommendations Assessment, Development and Evaluation was applied. The primary outcome was all-cause mortality at the longest follow-up available., Results: We identified 6 multicenter RCTs involving 3297 patients from 13 countries across 4 continents. The rate of all-cause mortality was 6.2% (103/1662) in the full-dose group vs 7.7% (126/1635) in the prophylactic or intermediate dose group (Risk Ratio [RR] = 0.76; 95% confidence interval [CI] = 0.59-0.98; P = 0.037). The probabilities of any mortality difference and of NNT ≤ 100 were estimated at 98.2% and 84.5%, respectively. The risk of bias was low for all included RCTs and the strength of the evidence was "moderate.", Conclusion: Our meta-analysis of high-quality multicenter RCTs suggests that full-dose anticoagulation with heparin or low molecular weight heparin reduces all-cause mortality in hospitalized non-critically ill COVID-19 patients., Study Registration: PROSPERO, review no. CRD42022348993., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are often administered to prevent venous thromboembolism (VTE) in critically ill patients. However, the preferred prophylactic agent (UFH or LMWH) is not known. We compared the all-cause mortality rate in patients receiving UFH to LMWH for VTE prophylaxis. We conducted a retrospective propensity score adjusted analysis of patients admitted to neuro-critical, surgical, or medical intensive care units. Patients were included if they were screened with venous duplex ultrasonography or computed tomography angiography for detection of VTE. The primary outcome was all-cause mortality. Secondary outcomes included the prevalence of VTE, deep vein thrombosis (DVT), pulmonary embolism (PE), and hospital length of stay (LOS). Initially 2228 patients in the cohort were included for analysis, 1836 (82%) patients received UFH, and 392 (18%) patients received enoxaparin. After propensity score matching, a well-balanced cohort of 618 patients remained in the study (309 patients receiving UFH; 309 patients receiving enoxaparin). The use of UFH for VTE prophylaxis in ICU patients was associated with similar rates of all-cause mortality compared with enoxaparin [RR 0.73; 95% CI 0.43-1.24, p = 0.310]. There were no differences in the prevalence of DVT, prevalence of PE or hospital LOS between the two groups, DVT [RR 0.93; 95% CI 0.56-1.53, p = 0.889], PE [RR 1.50; 95% CI 0.78-2.90, p = 0.296] and LOS [9 ± 9 days vs 9 ± 8; p = 0.857]. A trend toward mortality benefit was observed in NICU [RR 0.37; 95% CI 0.13-1.07, p = 0.062] and surgical patients [RR 0.43; 95% CI 0.17-1.02, p = 0.075] favoring the enoxaparin group. The use of UFH for VTE prophylaxis in ICU patients was associated with similar rates of VTE, all-cause mortality and LOS compared to enoxaparin. In subgroup analysis, neuro-critical and surgical patients who received UFH had a higher rate of mortality than those who received enoxaparin., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Low molecular weight heparin (LMWH) is a glycosaminoglycan long known for its anticoagulant properties. In recent times, recent evidence has associated this drug with extra pleiotropic anticoagulant effects that have also proven useful in the management of the treatment of COVID-19 infection indicating that heparin may play other roles in the management of the disease in addition to the prevention of thrombosis. Clinical observations and in vitro studies support that heparin has a potential multi-target effect. To date, the molecular mechanisms of these pleiotropic effects are not fully understood. This brief review presents some of the evidence from clinical and animal studies and describes the potential molecular mechanisms by which heparin may exert its anti-inflammatory/immunoregulatory and antiviral effects., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Direct oral anticoagulants (DOACs) could effectively prevent the occurrence of cancer-associated venous thromboembolism (CAVTE), which incidence rate was estimated to be 4-20%. But the efficacy and safety remain controversial between DOACs and low molecular weight heparin (LMWH)., Materials and Methods: PubMed, Cochrane Library, Embase, ClinicalTrials.gov databases for randomized controlled trials (RCTs) were systematically searched from inception to March 15, 2022. A random-effects model was used to report the odds ratio (OR) and 95% confidence interval (CI) for both direct and network meta-analyses., Results: Seven studies were included totaling 3242 patients. A lower rate of recurrence VTE was noted in the DOACs compared with LMWH (OR 0.62, 95% CI 0.47-0.82, I 2 =0.0%). The aspect of major bleeding (MB) was similar (OR 1.30, 95% CI 0.77-2.18, I 2 =34.9%). When assessing clinically relevant nonmajor bleeding (CRNMB) (OR 1.61, 95% CI 1.17-2.22, I 2 =20.7%) and clinically relevant bleeding (CRB) (OR 1.39, 95% CI 1.11-1.74, I 2 =0.0%), a higher risk of events was observed in DOACs. In subgroup analyses, the MB of gastrointestinal and genitourinary malignancies had a higher rate in the DOACs. For ranking, apixaban ranked the first in prevention of VTE and reducing MB events. Edoxaban had the highest risk drug in MB. In terms of CRNMB and CRB, LMWH showed the lowest risk., Conclusions: Compared with LMWH, DOACs seemed to have a decreased risk of recurrence VTE while increasing CRNMB and CRB. DOACs and LMWH were equivalent to the aspect of MB, but DOACs had a higher MB risk in patients with gastrointestinal and genitourinary malignancies. Apixaban may be the lowest risk compared to the other DOACs in precaution of VTE and reducing bleeding events., (Copyright © 2022 Elsevier España, S.L.U. All rights reserved.)

Background: To provide guidance on data linkage in case of non-unique identifiers, we present a case study linking the Dutch Foundation for Pharmaceutical Statistics and Dutch Arthroplasty Register to investigate opioid prescriptions before/after arthroplasty., Methods: Deterministic data linkage was used. Records were linked on: sex, birthyear, postcode, surgery date, or thromboprophylaxis initiation as a proxy for the surgery date. Different postcodes were used, depending on availability: patient postcode (available from 2013 onwards), hospital postcode with codes for physicians/hospitals, and hospital postcode with catchment area. Linkage was assessed in several groups: linked arthroplasties, linked on patient postcode, linked on patient postcode, and low-molecular-weight heparin(LWMH). Linkage quality was assessed by checking prescriptions after death, antibiotics after revision for infection, and presence of multiple prostheses. Representativeness was assessed by comparing the patient-postcode-LMWH group with the remaining arthroplasties. External validation was performed by comparing our opioid prescription rates with those derived from datasets from Statistics Netherlands., Results: We linked 317,899 arthroplasties on patient postcode/hospital postcode(48%). Linkage on the hospital postcode appeared insufficient. Linkage uncertainty ranged from roughly 30% in all arthroplasties to 10-21% in the patient-postcode-LMWH-group. This subset resulted in 166.357(42%) linked arthroplasties after 2013 with somewhat younger age, fewer females, and more often osteoarthritis than other indications compared to the other arthroplasties. External validation showed similar increases in opioid prescription rates., Conclusions: After identifier selection, checking data availability and internal validity, assessing representativeness, and externally validating our results we found sufficient linkage quality in the patient-postcode-LMWH-group, which consisted of around 42% of the arthroplasties performed after 2013., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 van Brug et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Our study purposed to examine the complex relationship between low-molecular-weight heparin therapy, multiple pregnancy determinants, and adverse pregnancy outcomes during the third trimester in women with inherited thrombophilia., Methods: Patients were selected from a prospective cohort of 358 pregnant patients recruited between 2016 and 2018 at the Clinic for Obstetrics and Gynecology, University Clinical Centre of Serbia, Belgrade., Results: Gestational age at delivery (β=-0.081, p=0.014), resistance index of the umbilical artery (β=0.601, p=0.039), and D-dimer (β=0.245, p<0.001) between 36th and 38th weeks of gestation presented the direct predictors for adverse pregnancy outcomes. The model fit was examined using the root mean square error of approximation 0.00 (95%CI 0.00-0.18), the goodness-of-fit index was 0.998, and the adjusted goodness-of-fit index was 0.966., Conclusion: There is a need for the introduction of more precise protocols for the assessment of hereditary thrombophilias and the need for the introduction of low-molecular-weight heparin.

Abstract: Venous thromboembolism (VTE) is a major issue in trauma patients. Without prophylaxis, the rate of deep venous thrombosis approaches 60% and even with chemoprophylaxis may be nearly 30%. Advances in VTE reduction are imperative to reduce the burden of this issue in the trauma population. Novel approaches in VTE prevention may include new medications, dosing regimens, and extending prophylaxis to the postdischarge phase of care. Standard dosing regimens of low-molecular-weight heparin are insufficient in trauma, shifting our focus toward alternative dosing strategies to improve prophylaxis. Mixed data suggest that anti-Xa-guided dosage, weight-based dosing, and thromboelastography are among these potential strategies. The concern for VTE in trauma does not end upon discharge, however. The risk for VTE in this population extends well beyond hospitalization. Variable extended thromboprophylaxis regimens using aspirin, low-molecular-weight heparin, and direct oral anticoagulants have been suggested to mitigate this prolonged VTE risk, but the ideal approach for outpatient VTE prevention is still unclear. As part of the 2022 Consensus Conference to Implement Optimal Venous Thromboembolism Prophylaxis in Trauma, a multidisciplinary array of participants, including physicians from multiple specialties, pharmacists, nurses, advanced practice providers, and patients met to attack these issues. This paper aims to review the current literature on novel approaches for optimizing VTE prevention in injured patients and identify research gaps that should be investigated to improve VTE rates in trauma., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Systemic lupus erythematosus (SLE) is a chronic, multisystem, inflammatory autoimmune disease characterized by relapses (commonly called "flares") and remission. Many organs may be involved, and although the manifestations are highly variable, the kidneys, joints, and skin are commonly affected. Immunologic abnormalities, including the production of antinuclear antibodies, are also characteristic of the disease. Maternal morbidity and mortality are substantially increased in patients with systemic lupus erythematosus, and an initial diagnosis of systemic lupus erythematosus during pregnancy is associated with increased morbidity. Common complications of systemic lupus erythematosus include nephritis, hematologic complications such as thrombocytopenia, and a variety of neurologic abnormalities. The purpose of this document is to examine potential pregnancy complications and to provide recommendations on treatment and management of systemic lupus erythematosus during pregnancy. The following are the Society for Maternal-Fetal Medicine recommendations: (1) we recommend low-dose aspirin beginning at 12 weeks of gestation until delivery in patients with systemic lupus erythematosus to decrease the occurrence of preeclampsia (GRADE 1B); (2) we recommend that all patients with systemic lupus erythematosus, other than those with quiescent disease, either continue or initiate hydroxychloroquine (HCQ) in pregnancy (GRADE 1B); (3) we suggest that for all other patients with quiescent disease activity who are not taking HCQ or other medications, it is reasonable to engage in shared decision-making regarding whether to initiate new therapy with this medication in consultation with the patient's rheumatologist (GRADE 2B); (4) we recommend that prolonged use (>48 hours) of nonsteroidal antiinflammatory drugs (NSAIDs) generally be avoided during pregnancy (GRADE 1A); (5) we recommend that COX-2 inhibitors and full-dose aspirin be avoided during pregnancy (GRADE 1B); (6) we recommend discontinuing methotrexate 1-3 months and mycophenolate mofetil/mycophenolic acid at least 6 weeks before attempting pregnancy (GRADE 1A); (7) we suggest the decision to initiate, continue, or discontinue biologics in pregnancy be made in collaboration with a rheumatologist and be individualized to the patient (GRADE 2C); (8) we suggest treatment with a combination of prophylactic unfractionated or low-molecular-weight heparin and low-dose aspirin for patients without a previous thrombotic event who meet obstetrical criteria for antiphospholipid syndrome (APS) (GRADE 2B); (9) we recommend therapeutic unfractionated or low-molecular-weight heparin for patients with a history of thrombosis and antiphospholipid (aPL) antibodies (GRADE 1B); (10) we suggest treatment with low-dose aspirin alone in patients with systemic lupus erythematosus and antiphospholipid antibodies without clinical events meeting criteria for antiphospholipid syndrome (GRADE 2C); (11) we recommend that steroids not be routinely used for the treatment of fetal heart block due to anti-Sjögren's-syndrome-related antigen A or B (anti-SSA/SSB) antibodies given their unproven benefit and the known risks for both the pregnant patient and fetus (GRADE 1C); (12) we recommend that serial fetal echocardiograms for assessment of the PR interval not be routinely performed in patients with anti-SSA/SSB antibodies outside of a clinical trial setting (GRADE 1B); (13) we recommend that patients with systemic lupus erythematosus undergo prepregnancy counseling with both maternal-fetal medicine and rheumatology specialists that includes a discussion regarding maternal and fetal risks (GRADE 1C); (14) we recommend that pregnancy be generally discouraged in patients with severe maternal risk, including patients with active nephritis; severe pulmonary, cardiac, renal, or neurologic disease; recent stroke; or pulmonary hypertension (GRADE 1C); (15) we recommend antenatal testing and serial growth scans in pregnant patients with systemic lupus erythematosus because of the increased risk of fetal growth restriction (FGR) and stillbirth (GRADE 1B); and (16) we recommend adherence to the Centers for Disease Control and Prevention medical eligibility criteria for contraceptive use in patients with systemic lupus erythematosus (GRADE 1B)., (Copyright © 2022. Published by Elsevier Inc.)

Background: The safety of presurgical thromboprophylaxis using low molecular weight heparin (LMWH) has not been well described in head and neck oncologic surgery with free tissue transfer (HNS-FTT)., Methods: Retrospective chart review of HNS-FTT patients receiving versus not receiving presurgical subcutaneous enoxaparin (Px-LMWH) was performed. Outcomes included estimated blood loss (EBL), hematoma, flap compromise, DVT or pulmonary embolus (PE). Fisher's exact test and Wilcoxon Rank Sum test were performed to compare groups. Odds ratios and associated 95 % confidence intervals were provided as appropriate., Results: 43 of 128 patients (34 %) received Px-LMWH. There was no significant difference in EBL, hematoma, or flap complications between groups. Patients without Px-LMWH had higher rates of DVT and PE, although the difference did not reach statistical significance (p = 1.00, 0.095, respectively)., Conclusion: Presurgical Px-LMWH can be used in major head and neck reconstructive surgery without increased intraoperative blood loss or postoperative complications. Larger studies will need to be done to determine the impact of Px-LMWH on DVT and PE in this patient population., Competing Interests: Conflicts of interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To analyze the uterine artery blood flow parameters of patients with recurrent spontaneous abortion (RSA) at different gestational ages and to investigate the effects of aspirin and low molecular weight heparin (LMWH) on uterine artery blood flow parameters and pregnancy outcomes., Methods: This was a retrospective cohort study involving analysis of clinical data for 140 patients: 47 in an aspirin group, 49 in a combination group, and 44 in a control group. The uterine artery blood flow parameters of the three groups in the middle luteal period and 10th, 12th, 16th, and 20th gestational weeks were compared. Trends in uterine artery flow parameters were predicted by function fitting, and the uterine artery flow parameters and pregnancy outcomes between different drug administration regimens were compared., Results: With increasing gestational age, the uterine artery blood flow parameters of the three groups gradually decreased. In the middle luteal phase, the uterine artery blood flow parameters (mRI, mPI, mS/D) of the recurrent spontaneous abortion group, that is, the aspirin and combination groups, were significantly higher than those of the control group. Uterine artery blood flow parameters from 10 to 20 weeks of gestation were as follows: combined group < aspirin group < normal pregnancy group. The mean resistance index (mRI) in the combination group decreased most rapidly compared with the aspirin group between 10 and 20 weeks of gestation. The live birth rate was higher in the combination group than in the aspirin group., Conclusions: Both aspirin and aspirin combined with LMWH can reduce uterine artery blood flow parameters, and combination therapy is superior to aspirin alone. In the RSA group, the rate of mRI decline may predict pregnancy outcome to some extent. Combination therapy can improve the live birth rate and reduce the miscarriage rate., (© 2022 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

According to this study: In women who have a history of venous thromboembolism, weight-adjusted intermediate-dose low-molecular-weight heparin during the combined antepartum and postpartum periods didn't reduce the risk of recurrence compared with fixed low-dose low-molecular-weight heparin.Further study is needed to determine whether intermediate-dose low-molecular-weight heparin may be more effective than low-dose low-molecular-weight heparin during the postpartum period., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with increased venous thromboembolism (VTE). We sought to compare rates of bleeding complications and VTE in patients receiving extended postoperative thromboprophylaxis (EPT) to those who did not, and identify risk factors for VTE after pancreatectomy for PDAC., Methods: This is a retrospective review of pancreatectomies for PDAC. EPT was defined as 28 days of low molecular weight heparin. Multivariable analysis (MVA) was performed to identify independent risk factors of VTE., Results: Of 269 patients included, 142 (52.8%) received EPT. Of those who received EPT, 7 (4.9%) suffered bleeding complications, compared to 6 (4.7%) of those who did not (p = 0.938). There was no significant difference in VTE rate at 90 days (2.8% vs. 2.4%, p = 0.728) or at 1 year (6.3% vs. 7.9%, p = 0.624). On MVA, risk factors for VTE included worse performance status, lower preoperative hematocrit, R1/R2 resection, and minimally invasive (MIS) approach. Among those who received EPT, there was no difference in VTE rate between MIS and open approach., Conclusions: EPT was not associated with a difference in VTE risk or bleeding complications. MIS approach was associated with a higher risk of VTE; however, this was significantly lower among those who received EPT., (© 2022 Wiley Periodicals LLC.)