Intestinal obstruction as a result of intra-abdominal hematoma: a complication of low molecular weight heparin in pediatric patients. / Obstrucción intestinal por hematoma intraabdominal: una complicación de la heparina de bajo peso molecular en el paciente pediátrico.

INTRODUCTION: Hematomas are a rare cause of intestinal obstruction. Subcutaneous heparin can bring about direct punctures on small bowel loops, potentially leading to traumatic hematoma and intestinal obstruction. CASE REPORTS: We present three cases of pediatric patients with clinical signs of intestinal obstruction treated with subcutaneous heparin. Two cases had increased acute-phase reactants and radiological signs of intestinal suffering, so surgical treatment was decided upon, with intramural hematoma emerging as an intraoperative finding. The third case was conservatively managed with anticoagulant discontinuation and gut rest, since the patient had an adequate general condition and no findings compatible with ischemia or necrosis were noted in the complementary tests. DISCUSSION: The administration of subcutaneous heparin may cause intestinal wall hematomas due to its anticoagulating effect and to the risk of inadvertent punctures on small bowel loops.

INTRODUCCION: Los hematomas son una causa poco frecuente de obstrucción intestinal. La heparina subcutánea tiene riesgo de producir la punción directa de un asa intestinal, provocando un hematoma traumático que genere una obstrucción intestinal. CASOS CLINICOS: Se describen tres casos de pacientes pediátricos con clínica de obstrucción intestinal en tratamiento con heparina subcutánea. Dos casos presentaron elevación de reactantes de fase aguda y signos radiológicos de sufrimiento intestinal por lo que se optó por tratamiento quirúrgico, con el hallazgo intraoperatorio de hematoma intramural. El tercer caso fue manejado de manera conservadora con supresión de la anticoagulación y reposo intestinal, dado el adecuado estado general y ausencia de hallazgos compatibles con isquemia o necrosis en las pruebas complementarias. COMENTARIOS: La administración de heparina subcutánea puede provocar la aparición de hematomas de pared intestinal, tanto por su efecto anticoagulante, como por el riesgo de punción inadvertida de un asa intestinal.

Low albumin combined with low-molecular-weight heparin as risk factors for liver injury using azvudine: Evidence from an analysis of COVID-19 patients in a national prospective pharmacovigilance database.

OBJECTIVE: Azvudine is an effective treatment for patients infected with common COVID-19. However, physicians have reported a series of adverse reactions, including multiple cases of liver injury, caused by azvudine in clinical practice. This study assessed the incidence, clinical features, and associated risk factors of liver injury induced by azvudine in real-world settings, offering guidance for safe clinical use. MATERIALS AND METHODS: This study utilized the Chinese Hospital Pharmacovigilance System (CHPS) to retrospectively analyze the treatment of COVID-19 patients with azvudine at Changsha Central Hospital from December 19, 2022, to June 6, 2023. A case-control study was conducted to analyze the occurrence of azvudine-induced liver injury in COVID-19 patients who triggered a CHPS alert compared to normal COVID-19 patients. RESULTS: Among the total of 2,141 COVID-19 patients, 31 (1.45%) developed azvudine-induced liver injury, which is classified as an occasional adverse reaction. Liver injury was observed in 93.55% of patients between days 4 and 12 of the azvudine treatment, with elevated transaminases as the primary clinical manifestation. Univariate and binary logistic regression analyses indicated that low albumin levels and co-administration of low-molecular-weight heparin were statistically significant risk factors (p < 0.05). CONCLUSION: This study represents the first investigation of azvudine-induced liver injury and high-risk patients using the CHPS. The findings provide valuable insights to promote the safety of anti-COVID-19 drugs, serving as an important reference for future drug safety measures.

Trends in Anticoagulant Utilization and Clinical Outcomes for Cancer-Associated Thrombosis: A Multicenter Cohort Study in Thailand's Upper-Middle-Income Country Setting.

PURPOSE: To evaluate anticoagulant trends and clinical outcomes in the management of cancer-associated thrombosis (CAT) within Thailand, an upper-middle-income country (UMIC). METHODS: This multicenter retrospective cohort study included adult patients with cancer diagnosed with venous thromboembolism (VTE) hospitalized in Thailand from 2017 to 2021. Anticoagulants were classified as low-molecular-weight heparin (LMWH), direct oral anticoagulants (DOACs), and warfarin. Prescription trends were assessed, and patients were followed for 1 year, or until 2022 to evaluate outcomes. The primary effectiveness outcome was recurrent VTE, whereas the primary safety outcome was major bleeding. Secondary outcomes included net clinical benefit and all-cause mortality. Treatment effects were examined using inverse probability of treatment weighting (IPTW) Cox proportional hazards models. RESULTS: Among 1,611 patients (61.3% female; mean age, 58.8 years; standard deviation, 13.1 years), 86% received LMWH, 10% warfarin, and 4% DOACs. In the study cohort, LMWH prescriptions remained consistent, warfarin use declined, and DOAC prescriptions notably increased. In IPTW analysis, DOACs showed comparable rates of VTE recurrence (weighted hazard ratio [HR], 0.77 [95% CI, 0.22 to 2.70]; P = .679) and major bleeding (weighted HR, 0.62 [95% CI, 0.15 to 2.55]; P = .506) with LMWH. Warfarin had a higher risk of major bleeding (weighted HR, 2.74 [95% CI, 1.12 to 6.72]; P = .028) but a similar rate of VTE recurrence (weighted HR, 1.46 [95% CI, 0.75 to 2.84]; P = .271) compared with LMWH. Secondary outcomes were consistent across groups. CONCLUSION: LMWH remains the primary treatment for CAT, in line with current guidelines. The study highlights the challenges faced in these settings with the continuous use of warfarin. The comparable efficacy and safety of DOACs with LMWH suggest a potential shift in CAT management within UMICs.

Aspirin is as effective as low molecular weight heparins in preventing symptomatic venous thromboembolism following arthroscopic anterior cruciate ligament reconstruction.

OBJECTIVE: The optimal agent for thromboprophylaxis following arthroscopic anterior cruciate ligament reconstruction (ACLR) remains unclear, particularly in patients with a low baseline risk for venous thromboembolism (VTE). This retrospective cohort study aims to compare the effectiveness and safety of aspirin versus low molecular weight heparins (LMWHs) in this specific patient population. METHODS: We analyzed data from patients who underwent ACLR between March 2016 and March 2021, focusing on those with a low risk for VTE. High-risk individuals, identified by factors such as cardiac disease, pulmonary disease, diabetes mellitus, previous VTE, inflammatory bowel disease, active cancer, and a BMI > 40, were excluded (n = 33). Our approach included a thorough review of medical charts, surgical reports, and pre-operative assessments, complemented by telephone follow-up conducted over a 3-month period by a single investigator. We assessed the incidence of symptomatic VTE, including deep vein thrombosis and pulmonary thromboembolism, as the primary outcome. The secondary outcomes included to complications related to the surgery and thromboprophylaxis. Statistical analysis included descriptive statistics, univariate logistic regression models, and calculations of incidence rates. RESULT: In our study, 761 patients (761 knees) were included, with 458 (60.18%) receiving aspirin and 303 (39.82%) receiving LMWH. The two groups showed no significant differences in demographic factors except for age. The incidence of VTE was reported at 1.31% (10 individuals). Specifically, five patients in the aspirin group (1.09%) and five patients in the LMWH group (1.65%) developed a symptomatic VTE event (p = 0.53). Additionally, the two groups did not significantly differ in terms of other complications, such as hemarthrosis or surgical site infection (p > 0.05). Logistic regression analysis revealed no statistically significant difference in VTE risk between the two groups. CONCLUSION: This study, focusing on isolated ACLR in patients with a low baseline risk for venous thromboembolism, demonstrated that aspirin is equally effective as low molecular weight heparins for VTE prophylaxis following this surgery. LEVEL OF EVIDENCE: III.

Efficacy and safety of direct oral anticoagulants versus low-molecular-weight heparin for thromboprophylaxis after cancer surgery: a systematic review and meta-analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) used as an alternative to low-molecular-weight heparin (LMWH) for thromboprophylaxis after cancer surgery for venous thromboembolic events (VTE) remains unclear. This study aimed to investigate the efficacy and safety of DOACs versus LMWH in these patients. MATERIALS AND METHODS: A search of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science was carried out and included all randomized controlled trials (RCTs) and observational studies that directly compared DOACs with LMWH for thromboprophylaxis in patients after cancer surgery through July 25, 2023. The primary efficacy and safety outcomes were VTE, major bleeding, and clinically relevant non-major bleeding (CRNMB) within 30 days of surgery. The risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB2) tool for RCTs and ROBINS-I tool for non-randomized studies. This study was registered in PROSPERO (CRD42023445386). RESULTS: We retrieved 5149articles, selected 27 for eligibility, and included 10 studies (three RCTs and seven observational studies) encompassing 3054 patients who underwent postoperative thromboprophylaxis with DOACs (41%) or LMWH (59%). Compared to LMWH thromboprophylaxis, DOACs had a comparable risk of VTE (RR:0.69[95% CI:0.46-1.02], I2 = 0%), major bleeding (RR:1.55 [95% CI:0.82-2.93], I2 = 2%), and CRNMB (RR, 0.89 [95% CI, 0.4-1.98], I2 = 31%) during the 30-day postoperative period. Subgroup analysis of VTE and major bleeding suggested no differences according to study type, extended thromboprophylaxis, tumor types, or different types of DOAC. CONCLUSION: DOACs are potentially effective alternatives to LMWH for thromboprophylaxis in patients undergoing cancer surgery, without increasing the risk of major bleeding events.

Effectiveness and safety of anticoagulants among patients with venous thromboembolism and active cancer who also had prior bleed or prior renal disease.

OBJECTIVE: Patients with active cancer and venous thromboembolism (VTE) have elevated risk of recurrent VTE (rVTE) and major bleeding (MB). The risk is even higher within those with a prior bleeding event or renal disease. There is a need to understand the risk of rVTE and MB of commonly used anticoagulants among these high-risk patients. METHODS: VTE patients with active cancer and treated with apixaban, warfarin, or low molecular weight heparin (LMWH) within 30 days of VTE were identified from five claims databases in the United States. Inverse probability of treatment weighting (IPTW) was used to balance patient characteristics. The post-IPTW population was stratified by prior bleed or renal disease status. Cox proportional hazards models were used to evaluate interactions between treatment and prior bleed or renal disease on risk of rVTE and MB, with p value <.1 considered significant. RESULTS: Study criteria were met by 30,586 VTE cancer patients: 35.0% had prior bleed and 29.0% had renal disease. For apixaban, LMWH, and warfarin cohorts, the incidence (events per 100 person-years) of MB was higher in patients with prior bleed (17.48 vs 7.58, 25.61 vs 13.11, and 20.38 vs 8.97) or renal disease (15.79 vs 8.71, 22.11 vs 15.90, and 18.49 vs 10.39) vs those without the conditions. Generally, there were no significant interactions between anticoagulant use and prior bleed or renal disease on rVTE and MB (p for interaction >.1). CONCLUSION: The incidence of MB was higher among those with prior bleed or renal disease. Effects of apixaban, warfarin, or LMWH were generally consistent regardless of prior bleed or renal disease status.

Six-week low-molecular-weight heparin versus 12-week warfarin for calf deep vein thrombosis: A randomized, prospective, open-label study.

Current guidelines suggest a 3-month anticoagulant treatment course for isolated distal deep vein thrombosis (IDDVT), but shorter durations of treatment are frequently prescribed in clinical practice. We investigated whether a 6-week treatment with low-molecular-weight heparin (LMWH) at intermediate dosage can be an effective and safe alternative to vitamin K antagonists (VKA) in patients with IDDVT (non-inferiority trial). In a multicenter, open-label, randomized trial, 260 outpatients with symptomatic IDDVT were randomly assigned to receive either LMWH followed by VKA for 12 weeks or LMWH 1 mg/kg subcutaneously twice a day for 2 weeks followed by 1 mg/kg subcutaneously once a day for 4 weeks. The follow-up was 6 months and the primary endpoint was the composite measure of recurrent venous thromboembolism (VTE) defined as: recurrence or extension of IDDVT, proximal DVT, and pulmonary embolism (PE). The study was stopped prematurely due to slow recruiting rates. The primary efficacy outcome occurred in 14 patients receiving LMWH (10.8%) and in five patients receiving VKA (3.8%); risk difference was 0.069 (95% CI: 0.006-0.132), hazard ratio 2.8 (95% CI: 1.04-7.55). There was one PE in the VKA group and one proximal DVT in the LMWH group. IDDVT recurrence was 10.0% in the LMWH group versus 3.1% in the VKA group (p = .024). Two patients had clinically relevant bleedings (1.6%) in the LMWH group versus one (0.8%) in VKA group (p = .56). In conclusion, VKA for 12 weeks seems superior to LMWH for 6 weeks in reducing the risk of VTE recurrences in our cohort of outpatients with IDDVT.

Smaller nadroparin dose reductions required for patients with renal impairment: A multicenter cohort study.

BACKGROUND: Guidelines advise 50 % and 25 % dose reduction of the therapeutic nadroparin dose (86 IU/kg) in patients with eGFR 15-29 and 30-60 ml/min respectively. For monitoring, peak anti-Xa levels are suggested. Data lack whether this results in therapeutic anti-Xa levels or in anti-Xa levels that are comparable to those of patients without renal impairment. AIMS: To determine dose ranges in patients with renal impairment that result in therapeutic anti-Xa levels and to determine the percentage of the 86 IU/kg dose that results in anti-Xa levels normally occurring in patients without renal impairment. METHODS: A retrospective cohort study was conducted in five hospitals. Patients ≥18 years of age, with an eGFR ≥ 15 ml/min were included. The first correctly sampled peak (i.e. 3-5 h after ≥ third administration, regardless of dose per patient) was included. Simulated prediction models were developed using multiple linear regression. RESULTS: 770 patients were included. eGFR and hospital affected the association between dose and anti-Xa level. The doses for peak anti-Xa levels of 0.75 IU/ml differed substantially between hospitals and ranged from 55 to 91, 65-359 and 68-168 IU/kg in eGFR 15-29, 30-60 and > 60 ml/min/1.73m2, respectively. In eGFR 15-29 and 30-60 ml/min/1.73m2, doses of 75 % and 91 % of 86 IU/kg respectively, were needed for anti-Xa levels normally occurring in patients with eGFR > 60 ml/min. CONCLUSION: We advise against anti-Xa based dose-adjustments as long as anti-Xa assays between laboratories are not harmonized and an anti-Xa target range is not validated. A better approach might be to target levels similar to eGFR > 60 ml/min/1.73m2, which are achieved by smaller dose reductions.

Anticoagulation for people receiving long-term haemodialysis.

BACKGROUND: Haemodialysis (HD) requires safe and effective anticoagulation to prevent clot formation within the extracorporeal circuit during dialysis treatments to enable adequate dialysis and minimise adverse events, including major bleeding. Low molecular weight heparin (LMWH) may provide a more predictable dose, reliable anticoagulant effects and be simpler to administer than unfractionated heparin (UFH) for HD anticoagulation, but may accumulate in the kidneys and lead to bleeding. OBJECTIVES: To assess the efficacy and safety of anticoagulation strategies (including both heparin and non-heparin drugs) for long-term HD in people with kidney failure. Any intervention preventing clotting within the extracorporeal circuit without establishing anticoagulation within the patient, such as regional citrate, citrate enriched dialysate, heparin-coated dialysers, pre-dilution haemodiafiltration (HDF), and saline flushes were also included. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to November 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-randomised controlled studies (quasi-RCTs) evaluating anticoagulant agents administered during HD treatment in adults and children with kidney failure. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risk of bias using the Cochrane tool and extracted data. Treatment effects were estimated using random effects meta-analysis and expressed as relative risk (RR) or mean difference (MD) with 95% confidence intervals (CI). Evidence certainty was assessed using the Grading of Recommendation, Assessment, Development and Evaluation approach (GRADE). MAIN RESULTS: We included 113 studies randomising 4535 participants. The risk of bias in each study was adjudicated as high or unclear for most risk domains. Compared to UFH, LMWH had uncertain effects on extracorporeal circuit thrombosis (3 studies, 91 participants: RR 1.58, 95% CI 0.46 to 5.42; I2 = 8%; low certainty evidence), while major bleeding and minor bleeding were not adequately reported. Regional citrate anticoagulation may lower the risk of minor bleeding compared to UFH (2 studies, 82 participants: RR 0.34, 95% CI 0.14 to 0.85; I2 = 0%; low certainty evidence). No studies reported data comparing regional citrate to UFH on risks of extracorporeal circuit thrombosis and major bleeding. The effects of very LMWH, danaparoid, prostacyclin, direct thrombin inhibitors, factor XI inhibitors or heparin-grafted membranes were uncertain due to insufficient data. The effects of different LMWH, different doses of LMWH, and the administration of LMWH anticoagulants using inlet versus outlet bloodline or bolus versus infusion were uncertain. Evidence to compare citrate to another citrate or control was scant. The effects of UFH compared to no anticoagulant therapy or different doses of UFH were uncertain. Death, dialysis vascular access outcomes, blood transfusions, measures of anticoagulation effect, and costs of interventions were rarely reported. No studies evaluated the effects of treatment on non-fatal myocardial infarction, non-fatal stroke and hospital admissions. Adverse events were inconsistently and rarely reported. AUTHORS' CONCLUSIONS: Anticoagulant strategies, including UFH and LMWH, have uncertain comparative risks on extracorporeal circuit thrombosis, while major bleeding and minor bleeding were not adequately reported. Regional citrate may decrease minor bleeding, but the effects on major bleeding and extracorporeal circuit thrombosis were not reported. Evidence supporting clinical decision-making for different forms of anticoagulant strategies for HD is of low and very low certainty, as available studies have not been designed to measure treatment effects on important clinical outcomes.

A randomized, controlled clinical study of low-molecular-weight heparin improving pregnancy outcomes in PCOS women undergoing IVF: study protocol.

BACKGROUND: Polycystic ovary syndrome (PCOS), an incidence of 10-15% in women of reproductive age, shows sex hormone disorders, luteal insufficiency, and the tendency of placental villus space thrombus. The incidence of early pregnancy loss in women with PCOS is three to eight times higher than that in non-PCOS women. PCOS women were reported in a pre-thrombotic state, which was manifested by accelerated thrombin production, increased PAI-1 activity, and fibrinogen. Other research also found an over-activated state of women with PCOS in immune system. Therefore, changing the prethrombotic state of PCOS through anticoagulation may be a new way to improve the adverse pregnancy outcome of PCOS. Low-molecular-weight heparin (LMWH) is the most common used anticoagulant drug in pregnancy, and it also was proposed for the prevention of recurrent abortion, although the application of LMWH in PCOS population during early pregnancy has not been reported. The objective of this study is to investigate the effect of LMWH on pregnancy outcomes after invitro fertilization-frozen embryo transfer (IVF-FET) in patients with polycystic ovary syndrome. METHODS: A total of 356 PCOS women aged between 20 and 38 years which prepared for IVF followed with FET will be enrolled in the study. The patients, from four different hospitals stratified by age and body mass index (BMI), will be randomly divided into the study group who will be treated with LMWH started on the day of progesterone transformation (hormone therapy) during FET cycle and the control group without additional medicine. Serum or urine hCG test will be given 14 days after embryo transfer to confirm biochemical pregnancy. If pregnancy is positive, LMWH+ hormone therapy/hormone therapy will be continued for another 2 weeks. Transvaginal ultrasonography will be performed 14 days later to confirm intrauterine pregnancy. The primary outcome is the ongoing pregnancy, which is defined as intrauterine live fetus with ultrasound after 12 weeks of gestation. DISCUSSION: This is the first study protocol to investigate the efficacy of LMWH as an adjuvant drug for IVF-FET outcomes in PCOS women, by comparing differences in ongoing pregnancy rate, clinical pregnancy rate, live birth rate, and early pregnancy loss rate between LMWH group and the control group. TRIAL REGISTRATION: ClinicalTrials.gov ChiCTR2000036527. Registered on August 24, 2020.

Comparison of the Efficacy and Safety of Rivaroxaban and Low Molecular Heparin in Preventing Venous Thromboembolism in Inpatient Cancer Patients.

BACKGROUND: There are few studies on using rivaroxaban and low molecular heparin (LMWH) to prevent venous thromboembolism (VTE) in hospitalized cancer patients. OBJECTIVE: We conducted a retrospective study to evaluate the efficacy and safety of rivaroxaban versus LMWH for the primary prevention of VTE in inpatient cancer patients. METHODS: Information on patients was collected through 6-month follow-up and medical record inquiries. Clinical outcomes included VTE, total bleeding, thrombosis, major bleeding, minor bleeding, all-cause death, and a composite endpoint of bleeding, thrombosis, and death. RESULTS: A total of 602 hospitalized cancer patients were included in this study. During 6 months of follow-up, there were 26 VTE events (8.6%), 42 total bleeding events (7.0%), 62 all-cause deaths (10.3%), and 140 composite endpoints (23.3%). After adjusting for various confounding factors, there were no significant differences between the rivaroxaban and LMWH for VTE events (OR = 0.851, 95% CI [0.387-1.872], P=0.688), total bleeding (OR = 1.690, 95% CI [0.768-3.719], P = 0.192], thrombosis events (OR = 0.919, 95% CI [0.520-1.624], P = 0.772], major bleeding (OR = 0.276, 95% CI [0.037-2.059], P = 0.209), all-cause death (OR = 0.994, 95% CI [0.492-2.009], P = 0.987), and composite endpoints (OR = 0.994, 95% CI [0.492-2.009], P = 0.987), while minor bleeding (OR = 3.661 95% CI [1.000-7.083], P = 0.050) was significantly higher in the rivaroxaban than in the LMWH. CONCLUSIONS AND RELEVANCE: In thromboprophylaxis in inpatient cancer patients, rivaroxaban has a similar rate of VTE and bleeding events as LMWH. Our results may provide a reference for the clinical use of rivaroxaban to prevent VTE in hospitalized cancer patients.

Comparison of direct oral anticoagulants versus low-molecular-weight heparin in primary and metastatic brain cancers: a meta-analysis and systematic review.

BACKGROUND: The safety and efficacy of direct-acting oral anticoagulants (DOACs) for therapeutic anticoagulation in the setting of primary or metastatic brain cancer is not known. OBJECTIVES: To conduct a meta-analysis and systematic review of studies that compare the risk of intracranial hemorrhage (ICH) in patients with brain cancer treated with DOACs vs low-molecular-weight heparin (LMWH). METHODS: A literature search was conducted using PubMed, EMBASE, and Cochrane databases. Summary statistics were obtained by calculating the risk ratio (RR), and heterogeneity across studies was estimated using the I2 statistic. A total of 10 retrospective studies (n = 1638) met criteria for inclusion. The primary endpoint was the pooled RR for ICH in patients with brain tumors receiving anticoagulation with DOACs compared with those receiving LMWH. Secondary analyses included the risk of fatal ICH in each subgroup. RESULTS: The pooled RR for ICH in patients receiving DOACs vs those receiving LMWH was 0.65 (95% CI, 0.36-1.17; P = .15; I2 = 50%). In studies evaluating primary brain cancer, there was a reduction in risk of ICH with DOACs (RR, 0.35; 95% CI, 0.18-0.69; P = .003; I2 = 0%). In patients with metastatic brain cancer, there was no difference in the risk of ICH with the type of anticoagulation (RR, 1.05; 95% CI, 0.71-1.56; P = .80; I2 = 0%). The overall risk of fatal ICH was not different between anticoagulants. CONCLUSION: The risk of ICH in patients with brain cancer receiving therapeutic anticoagulation varies by anticoagulation agent and diagnosis of primary or metastatic disease.

Venous thromboembolism management in people with cystic fibrosis.

BACKGROUND: Rates of venous thromboembolism (VTE) are increasing in people with cystic fibrosis (PwCF). Providers treating VTE in PwCF have reported low confidence concerning anticoagulant drug selection, dose, duration, and drug-drug interactions. As there are currently no published reports regarding management of VTE in PwCF, our objective was to describe the management of VTE in PwCF. METHODS: PwCF and VTE at the University of Utah Health were identified through electronic medical record searches. Patients were categorized into one of three treatment groups: warfarin, direct oral anticoagulant (DOAC), and low molecular weight heparin (LMWH). The primary outcome was episodes of major bleeding. Secondary outcomes included clinically relevant nonmajor (CRNM) bleeding. RESULTS: Nine PwCF with a total of 12 unique VTE episodes were included in the study, with all but one episode associated with a peripherally inserted central catheter (PICC). Of the 12 VTE cases, 25% were treated with warfarin, 50% with a DOAC, and 25% with LMWH. There were no episodes of major bleeding and only one episode of CRNM bleeding (Hemoptysis) in the LMWH group. All anticoagulant doses and durations generally followed guidelines for persons without CF. DOACs were the most common VTE treatment, at doses and duration consistent with guidelines for persons without CF, with no major or CRNM bleeding. CONCLUSION: VTE treatment in PwCF is generally consistent with guidelines for persons without CF with low rates of bleeding. DOACs are a potential option for treatment of VTE in PwCF, but more research is needed.

The efficacy and safety of direct oral anticoagulants compared with low-molecular-weight heparin for venous thromboembolism prophylaxis after surgical resection of primary lower extremity bone or soft-tissue sarcoma.

INTRODUCTION: The incidence of postoperative venous thromboembolism (VTE) and wound complications is greater after sarcoma resection. We sought to identify differences in postoperative VTE and bleeding complications with direct oral anticoagulants (DOACs) versus low-molecular-weight heparin (LMWH) following resection of lower extremity primary bone or soft tissue sarcoma. METHODS: We retrospectively identified 2083 patients from the PearlDiver database who underwent resection of primary bone or soft tissue sarcoma of the lower extremity from January 2010 to October 2021 and prescribed LMWH or DOAC within 90-days postoperatively. The primary outcomes were comparison of postoperative incidence and odds of deep venous thrombosis (DVT), pulmonary embolism (PE), and bleeding complications within 90-days following resection. RESULTS: Patients prescribed DOACs had a greater odds of DVT (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.06-2.41; p = 0.024) and PE (OR: 3.38; 95% CI: 1.96-5.86; p < 0.001) within 90-days following resection of bone sarcoma when compared with the LMWH cohort. Patients undergoing resection of soft tissue sarcomas also had greater odds DVT (OR: 1.65; 95% CI: 1.09-2.49; p = 0.016) and PE (OR: 2.62; 95% CI: 1.52-4.54; p < 0.001) in the DOAC cohort. There was no difference in the odds of bleeding complications. CONCLUSION: This study demonstrated an increased incidence and odds of VTE, but not bleeding complications, when using DOACs versus LMWH after primary bone or soft tissue sarcoma resection. LEVEL OF EVIDENCE: Level III.

Low-molecular-weight heparin for the prevention of clinical worsening in severe non-critically ill COVID-19 patients: a joint analysis of two randomized controlled trials.

Coronavirus disease 2019 (COVID-19) carries a high risk of vascular thrombosis. However, whether a specific anticoagulation intensity strategy may prevent clinical worsening in severe COVID-19 patients is still debated. We conducted a joint analysis of two randomized controlled trials, COVID-19 HD (NCT044082359) and EMOS-COVID (NCT04646655), to assess the efficacy and safety of two anticoagulant regimens in hospitalized severe COVID-19 patients. Subjects with COVID-19-associated respiratory compromise and/or coagulopathy were randomly assigned to low (4000 IU qd) or high (70 IU Kg-1 every 12 h) enoxaparin dose. The primary efficacy endpoint was clinical worsening within 30 days, defined as the occurrence of at least one of the following events, whichever came first: in-hospital death, evidence of arterial or venous thromboembolism, acute myocardial infarction, need for either continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV) in patients receiving standard oxygen therapy or none at randomization, and need for mechanical ventilation in any patient. The safety endpoint was major bleeding. We estimated the relative risk (RR) and its 95% confidence interval (CI) for the outcomes. Among 283 patients included in the study (144 in the low-dose and 139 in the high-dose group), 118 (41.7%) were on NIV or CPAP at randomization. 23/139 (16.5%) patients in the high-dose group reached the primary endpoint compared to 33/144 (22.9%) in the low-dose group (RR 0.72, 95% CI 0.45-1.17). No major bleeding was observed. No significant differences were found in the clinical worsening of hospitalized COVID-19 patients treated with high versus low doses of enoxaparin.

Anticoagulant treatment of cancer-associated thromboembolism.

Venous thromboembolism (VTE) is a frequent and potentially fatal complication in patients with cancer. During the initial period after the thromboembolic event, a patient receiving anticoagulant treatment is exposed both to a risk of VTE recurrence and also to an elevated bleeding risk conferred by the treatment. For this reason, the choice of anticoagulant is critical. The choice should take into account patient-related factors (such as functional status, age, body mass index, platelet count and renal function), VTE-related factors (such as severity or site), cancer-related factors (such as activity and progression) and treatment-related factors (such as drug-drug interactions), which all potentially influence bleeding risk, and patient preference. These should be evaluated carefully for each patient during a multidisciplinary team meeting. For most patients, apixaban or a low molecular-weight heparin is the most appropriate initial choice for anticoagulant treatment. Such treatment should be offered to all patients with active cancer for at least six months. The patient and treatment should be re-evaluated regularly and anticoagulant treatment changed when necessary. Continued anticoagulant treatment beyond six months is justified if the cancer remains active or if the patient experienced recurrence of VTE in the first six months. In other cases, the interest of continued anticoagulant treatment may be considered on an individual patient basis in collaboration with oncologists.

Management of venous thromboembolic disease in patients with malignant brain tumours.

This article addresses the management of venous thromboembolism in patients with malignant brain tumours, including both primary and secondary (metastatic) tumours. The available data on patients on venous thromboembolism recurrence and bleeding risks in patients with brain tumours is limited, since these patients have been excluded from most randomised, interventional, head-to-head, clinical trials comparing low molecular weight heparins to vitamin K antagonists or to direct oral Factor Xa inhibitors. More information is available from retrospective observational studies, which however were generally small, and carried a high risk of confounding. Their findings suggest that direct Factor Xa inhibitor use is associated with lower rates of intracranial haemorrhage compared with low molecular weight heparins. Overall, the safety profile of direct oral Factor Xa inhibitors when used to prevent venous thromboembolism recurrence in patients with either primary or secondary brain tumours appears to be favourable. The available data are in favour of using an anticoagulant at a full therapeutic dose in patients with primary and secondary brain tumours experiencing a venous thromboembolism, although they are not yet sufficiently robust to permit recommending a direct Factor Xa inhibitor over low-molecular weight heparin.

Management of cancer-associated thromboembolism in vulnerable population.

Although all patients with cancer-associated thrombosis (CAT) have a high morbidity and mortality risk, certain groups of patients are particularly vulnerable. This may expose the patient to an increased risk of thrombotic recurrence or bleeding (or both), as the benefit-risk ratio of anticoagulant treatment may be modified. Treatment thus needs to be chosen with care. Such vulnerable groups include older patients, patients with renal impairment or thrombocytopenia, and underweight and obese patients. However, these patient groups are poorly represented in clinical trials, limiting the available data, on which treatment decisions can be based. Meta-analysis of data from randomised clinical trials suggests that the relative treatment effect of direct oral factor Xa inhibitors (DXIs) and low molecular weight heparin (LMWH) with respect to major bleeding could be affected by advanced age. No evidence was obtained for a change in the relative risk-benefit profile of DXIs compared to LMWH in patients with renal impairment or of low body weight. The available, albeit limited, data do not support restricting the use of DXIs in patients with CAT on the basis of renal impairment or low body weight. In older patients, age is not itself a critical factor for choice of treatment, but frailty is such a factor. Patients over 70 years of age with CAT should undergo a systematic frailty evaluation before choosing treatment and modifiable bleeding risk factors should be addressed. In patients with renal impairment, creatine clearance should be assessed and monitored regularly thereafter. In patients with an eGFR<30mL/min/1.72m2, the anticoagulant treatment may need to be adapted. Similarly, platelet count should be assessed prior to treatment and monitored regularly. In patients with grade 3-4, thrombocytopenia (<50,000 platelets/µL) treatment with a LMWH at a reduced dose should be considered. For patients with CAT and low body weight, standard anticoagulant treatment recommendations are appropriate, whereas in obese patients, apixaban may be preferred.