Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis after a Fracture.

BACKGROUND: Clinical guidelines recommend low-molecular-weight heparin for thromboprophylaxis in patients with fractures, but trials of its effectiveness as compared with aspirin are lacking. METHODS: In this pragmatic, multicenter, randomized, noninferiority trial, we enrolled patients 18 years of age or older who had a fracture of an extremity (anywhere from hip to midfoot or shoulder to wrist) that had been treated operatively or who had any pelvic or acetabular fracture. Patients were randomly assigned to receive low-molecular-weight heparin (enoxaparin) at a dose of 30 mg twice daily or aspirin at a dose of 81 mg twice daily while they were in the hospital. After hospital discharge, the patients continued to receive thromboprophylaxis according to the clinical protocols of each hospital. The primary outcome was death from any cause at 90 days. Secondary outcomes were nonfatal pulmonary embolism, deep-vein thrombosis, and bleeding complications. RESULTS: A total of 12,211 patients were randomly assigned to receive aspirin (6101 patients) or low-molecular-weight heparin (6110 patients). Patients had a mean (±SD) age of 44.6±17.8 years, 0.7% had a history of venous thromboembolism, and 2.5% had a history of cancer. Patients received a mean of 8.8±10.6 in-hospital thromboprophylaxis doses and were prescribed a median 21-day supply of thromboprophylaxis at discharge. Death occurred in 47 patients (0.78%) in the aspirin group and in 45 patients (0.73%) in the low-molecular-weight-heparin group (difference, 0.05 percentage points; 96.2% confidence interval, -0.27 to 0.38; P<0.001 for a noninferiority margin of 0.75 percentage points). Deep-vein thrombosis occurred in 2.51% of patients in the aspirin group and 1.71% in the low-molecular-weight-heparin group (difference, 0.80 percentage points; 95% CI, 0.28 to 1.31). The incidence of pulmonary embolism (1.49% in each group), bleeding complications, and other serious adverse events were similar in the two groups. CONCLUSIONS: In patients with extremity fractures that had been treated operatively or with any pelvic or acetabular fracture, thromboprophylaxis with aspirin was noninferior to low-molecular-weight heparin in preventing death and was associated with low incidences of deep-vein thrombosis and pulmonary embolism and low 90-day mortality. (Funded by the Patient-Centered Outcomes Research Institute; PREVENT CLOT ClinicalTrials.gov number, NCT02984384.).

Pharmacology of Heparin and Related Drugs: An Update.

Heparin has been used extensively as an antithrombotic and anticoagulant for close to 100 years. This anticoagulant activity is attributed mainly to the pentasaccharide sequence, which potentiates the inhibitory action of antithrombin, a major inhibitor of the coagulation cascade. More recently it has been elucidated that heparin exhibits anti-inflammatory effect via interference of the formation of neutrophil extracellular traps and this may also contribute to heparin's antithrombotic activity. This illustrates that heparin interacts with a broad range of biomolecules, exerting both anticoagulant and nonanticoagulant actions. Since our previous review, there has been an increased interest in these nonanticoagulant effects of heparin, with the beneficial role in patients infected with SARS2-coronavirus a highly topical example. This article provides an update on our previous review with more recent developments and observations made for these novel uses of heparin and an overview of the development status of heparin-based drugs. SIGNIFICANCE STATEMENT: This state-of-the-art review covers recent developments in the use of heparin and heparin-like materials as anticoagulant, now including immunothrombosis observations, and as nonanticoagulant including a role in the treatment of SARS-coronavirus and inflammatory conditions.

Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19.

BACKGROUND: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. METHODS: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level. RESULTS: The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis. CONCLUSIONS: In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.).

Impact of perioperative low-molecular-weight heparin therapy on clinical events of elderly patients with prior coronary stents implanted > 12 months undergoing non-cardiac surgery: a randomized, placebo-controlled trial.

BACKGROUND: Little is known about the safety and efficacy of discontinuing antiplatelet therapy via LMWH bridging therapy in elderly patients with coronary stents implanted for > 12 months undergoing non-cardiac surgery. This randomized trial was designed to compare the clinical benefits and risks of antiplatelet drug discontinuation via LMWH bridging therapy. METHODS: Patients were randomized 1:1 to receive subcutaneous injections of either dalteparin sodium or placebo. The primary efficacy endpoint was cardiac or cerebrovascular events. The primary safety endpoint was major bleeding. RESULTS: Among 2476 randomized patients, the variables (sex, age, body mass index, comorbidities, medications, and procedural characteristics) and percutaneous coronary intervention information were not significantly different between the bridging and non-bridging groups. During the follow-up period, the rate of the combined endpoint in the bridging group was significantly lower than in the non-bridging group (5.79% vs. 8.42%, p = 0.012). The incidence of myocardial injury in the bridging group was significantly lower than in the non-bridging group (3.14% vs. 5.19%, p = 0.011). Deep vein thrombosis occurred more frequently in the non-bridging group (1.21% vs. 0.4%, p = 0.024), and there was a trend toward a higher rate of pulmonary embolism (0.32% vs. 0.08%, p = 0.177). There was no significant difference between the groups in the rates of acute myocardial infarction (0.81% vs. 1.38%), cardiac death (0.24% vs. 0.41%), stroke (0.16% vs. 0.24%), or major bleeding (1.22% vs. 1.45%). Multivariable analysis showed that LMWH bridging, creatinine clearance < 30 mL/min, preoperative hemoglobin < 10 g/dL, and diabetes mellitus were independent predictors of ischemic events. LMWH bridging and a preoperative platelet count of < 70 × 109/L were independent predictors of minor bleeding events. CONCLUSIONS: This study showed the safety and efficacy of perioperative LMWH bridging therapy in elderly patients with coronary stents implanted > 12 months undergoing non-cardiac surgery. An alternative approach might be the use of bridging therapy with half-dose LMWH. TRIAL REGISTRATION: ISRCTN65203415.

Combination anticoagulation strategy in pregnancy with mechanical valves: The KYBELE study.

BACKGROUND: Optimal first-trimester anticoagulation is still challenging in pregnant women with mechanical heart valves (MHVs) requiring high-dose warfarin. This multicenter prospective study aims to determine the optimal anticoagulation regimens for pregnant patients with MHVs. METHODS: All women were allocated to one of three treatment options during first trimester including lone low-molecular-weight heparin (LMWH), combination of LMWH + 2.5 mg warfarin, and LMWH+4 mg warfarin. Primary maternal outcome included a combination of death, thromboembolism, severe bleeding, and need for treatment of mechanical valve thrombosis (MVT). Any fetal loss was determined as primary fetal outcome. RESULTS: The study included 78 pregnancies in 65 women with MHVs. Primary maternal outcome rate was 44%, 12.5%, 3.5%, respectively. The rates of primary maternal outcome (44 vs 3.5%, P < .001), obstructive MVT (16 vs 0%, P = .04), MVT requiring treatment (28 vs 0%, P = .003), and cerebral embolism (24 vs 3.4%, P = .041) were found to be significantly higher in lone LMWH group compared to LMWH + 4 mg warfarin group. Moreover, the rates of primary maternal outcome (12.5 vs 44%, P = .015) and treatment for MHV thrombus (4.2 vs 28%, P = .049) were significantly lower in LMWH + 2.5 mg warfarin group compared to lone LMWH group. The incidences of fetal loss were 8 (32%) in the lone LMWH group, 8 (33.3%) in LMWH + 2.5 mg warfarin group, and 11 (37.9%) in LMWH + 4 mg warfarin group (P = .890 for 3-group).Warfarin related-embryopathy was not observed in any case. CONCLUSIONS: The combined anticoagulation strategy of LMWH plus low-dose warfarin during the first trimester of pregnancy may result in less maternal complications with comparable fetal outcomes in patients with MHVs. CONDENSED ABSTRACT: Low-molecular-weight heparin (LMWH) is thought to be safer for the fetus, however it is suspected to be less protective for the mother. To solve this dilemma, the authors suggested a novel anticoagulation strategy in pregnant women with prosthetic valves. Seventy-eight pregnancies of 65 women (median age 32 [27-35] years) were included in the study. A combination of LMWH and a reduced dose warfarin were associated with low rates of thrombus-related complications in pregnant patients with mechanical heart valves.

How I treat and prevent venous thrombotic complications in patients with lymphoma.

Venous thromboembolism (VTE) is a common complication occurring in 5% to 10% of patients with lymphoma. As the complexity of lymphoma management has increased with novel therapies, so too has the treatment of VTE. Therapeutic options for the treatment of cancer-associated VTE have expanded from only warfarin and low-molecular-weight heparins (LMWHs) to include the direct oral anticoagulants (DOACs) apixaban, edoxaban and rivaroxaban. There have been no head-to-head trials comparing different DOACs in this setting, and randomized trials comparing a DOAC with LMWH dalteparin differ in trial design and results. Drug-drug interactions, drug-specific side effects, and patient selection are important considerations when prescribing anticoagulant therapy. In all patients, the relative risks of thrombosis and bleeding, the availability of the anticoagulant, and the life expectancy of the patient are vital elements in selecting the most appropriate anticoagulant (which can vary over time) for the individual patient. We describe the intricacies and challenges of treating thrombotic complications in patients with lymphoma with an emphasis on evidence and guideline-based care.

Low molecular weight heparin decreases pro-coagulant activity in clinical MSC products.

BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) are multipotent adult cells that can be isolated from tissues including bone marrow [MSC(BM)], adipose [MSC(AT)] and umbilical cord [MSC(CT)]. Previous studies have linked expression of tissue factor (TF) on MSC surfaces to a procoagulant effect. Venous thromboembolism (VTE), immediate blood-mediated inflammatory reaction (IBMIR) and microvascular thrombosis remain a risk with intravascular MSC therapy. We examined the effect of low molecular weight heparin (LMWH) on clinical-grade MSCs using calibrated automated thrombography (CAT). METHODS: Clinical grade MSC(BM)s, MSC(AT)s and MSC(CT)s harvested at passage 4 were added to normal pooled plasma (NPP) to a final concentration of either 400 000 or 50 000 cells/mL. LMWH was added to plasma in increments of 0.1 U/mL. Thrombin generation (TG) was measured using CAT. Flow cytometry was conducted on the cells to measure MSC phenotype and TF load. RESULTS: Presence of MSCs decreased lag time and increased peak TG. All cell lines demonstrated a dose response to LMWH, with MSC(AT) demonstrating the least thrombogenicity and most sensitivity to LMWH. TG was significantly reduced in all cell lines at doses of 0.2 U/mL LMWH and higher. DISCUSSION: All MSC types and concentrations had a decrease in peak thrombin and TG with increasing amounts of LMWH. While this in vitro study cannot determine optimal dosing, it suggests that LMWH can be effectively used to lower the risk of VTE associated with intravascular administration of MSCs. Future in vivo work can be done to determine optimal dosing and effect on IBMIR and VTE.

The effect of serum triglyceride levels and different lipid-lowering methods on the prognosis of hypertriglyceridemic acute pancreatitis: a single-center 12-year retrospective study by propensity score matching.

AIM: To investigate the impact of triglyceride on hypertriglyceridemic acute pancreatitis (HTG-AP) and different lipid-lowering methods on triglyceride-lowering efficiency and HTG-AP. METHODS: The patients with HTG-AP from January 2012 to December 2023 in Civil Aviation General Hospital were analyzed, retrospectively. Patients were divided and compared according to whether their triglycerides were below 5.56 mmol/L at 48 and 72 h of admission. The patients were divided into control group, insulin group, and low molecular weight heparin (LMWH)+bezafibrate group based on the different methods of lipid-lowering. Propensity score matching (PSM) was employed to balance the baseline characteristics. RESULTS: There was no correlation between the severity of HTG-AP and the triglyceride at admission. The incidence of severity, local complications, and persistent organ failure (POF) were significantly decreased in patients with 48-h and 72-h triglyceride attainment. Following PSM, the incidence of infectious pancreatic necrosis (IPN) (3.3% vs. 13.3%) was significantly reduced in insulin group compared with control group (p < .05). Compared with control group, LMWH + bezafibrate group had higher lipid reduction efficiency, and the incidence of IPN (0.9% vs. 10.1%) and POF (8.3% vs. 19.3%) was significantly decreased (p < .05). There was no significant difference in the efficiency of lipid-lowering, complications, and POF between LMWH + bezafibrate group and insulin group (p > .05). CONCLUSION: The severity of HTG-AP is not associated with the triglyceride levels at admission. However, rapid reduction of triglyceride levels can lower the incidence of local complications and respiratory failure. Compared with conservative treatment, insulin and LMWH + bezafibrate can both reduce the incidence of IPN in patients with HTG-AP.

Structured benefit-risk assessment for enoxaparin, in the context of its label extension, for the extended treatment of deep vein thrombosis and pulmonary embolism, and prevention of its recurrence in patients with active cancer.

PURPOSE: Guidelines recommend low-molecular-weight heparins (LMWHs) for patients with cancer-associated thrombosis. However, until recently, only dalteparin and tinzaparin were approved in the European Economic Area (EEA) for these patients. This study compares the benefit-risk profile of enoxaparin with dalteparin and tinzaparin for the extended treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrence in adult patients with active cancer. METHODS: A semi-quantitative structured benefit-risk assessment was conducted for the label-extension application of enoxaparin based on the benefit-risk action team descriptive framework: define decision context; determine key benefit and risk outcomes; identify data sources; extract data; interpret results. RESULTS: The key benefits were defined as reduced all-cause mortality and venous thromboembolism (VTE) recurrence (including symptomatic DVT, fatal PE or non-fatal PE); the key risks were major and non-major bleeding of clinical significance, and heparin-induced thrombocytopenia (HIT). Enoxaparin demonstrated comparable effects for the reduction of VTE recurrence and all-cause mortality versus other EEA-approved LMWHs (dalteparin, tinzaparin). There was no evidence of a significant difference between enoxaparin and the comparator groups with regard to incidence of major and non-major bleeding. The data on HIT were too limited to assess the difference between the two groups. CONCLUSIONS: The assessment demonstrated a favourable benefit-risk profile for enoxaparin similar to that of other EEA-approved LMWHs for the treatment of DVT and PE and the prevention of recurrence in patients with active cancer and thus supported the label-extension approval.

Direct oral anticoagulants (DOACs) versus low-molecular-weight heparin (LMWH) for extended thromboprophylaxis following major abdominal/pelvic cancer-related surgery: a systematic review and meta-analysis.

BACKGROUND: The use of direct oral anticoagulants (DOACs) as an alternative to low-molecular-weight heparin (LMWH) for extended thromboprophylaxis of abdominal/pelvic cancer-related postoperative thromboembolism (VTE) is unclear. We aim to investigate the efficacy and safety of DOACs vs. LMWH in these patients. METHODS: A systematic review was conducted using EMBASE, MEDLINE, CENTRAL, and Web of science through May 19th, 2023 for all randomized controlled trials (RCTs) and observational studies that compared the outcomes with DOACs vs. LMWH for extended thromboprophylaxis among patients undergoing abdominal/pelvic cancer surgery. Primary efficacy outcome was clinical VTE, and safety outcome was clinically relevant bleeding complications reported within the 30-day postoperative period. This study was registered in PROSPERO (CRD42023413175). RESULTS: We identified 5078 articles and selected 29 full-text articles for eligibility. A total of 9 studies (2 RCTs and 7 observational studies) encompassing 2651 patients were included for systematic review and 7 for meta-analysis. When compared with LMWH extended thromboprophylaxis, DOACs had a similar incidence of VTE (RR: 0.65 [95% CI: 0.32-1.33], I2 = 0%), major bleeding (RR: 1.68 [95% CI: 0.36-7.9], I2 = 26%), and clinically relevant non-major bleeding (RR: 0.68 [95% CI: 0.39-1.19], I2 = 0%). Subgroup analysis suggested no difference according to the study type (RCTs versus observational studies) regarding clinical VTE or major bleeding (Pinteraction = 0.43 and Pinteraction = 0.71, respectively). CONCLUSION: Our results suggest that DOACs for extended thromboprophylaxis were an effective and safe alternative to LMWH after major abdominal/pelvic cancer-related surgery.

A systematic review of therapeutic enoxaparin dosing in obesity.

Enoxaparin is a hydrophilic drug with obesity having little effect on its apparent volume of distribution, therefore patients with obesity receiving standard 1 mg/kg dosing may be at a higher risk of supratherapeutic dosing. Conversely, dose reducing patients with obesity could place already at risk patients at higher risk of a thrombotic event. Data and recommendations are variable for the most appropriate weight-based dose of therapeutic enoxaparin in obese patients, particularly those a weight > 100 kg or a body mass index (BMI) ≥ 40 kg/m2. The purpose of this systematic review was to globally evaluate these data to surmise optimal dosing recommendations for patients with obesity. A systematic review of English language studies was conducted and identified articles via Pubmed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) searches. Studies were included if they reported therapeutic enoxaparin use in adult patients with a BMI ≥ 40 kg/m2 or body weight > 100 kg and the percentage of patients achieving a therapeutic anti-Xa based on a weight-based dose or the weight-based dose required to produce a therapeutic anti-Xa level. Therapeutic attainment of anti-Xa levels were assessed across enoxaparin weight-based dosing categories including a very low dose group: < 0.75 mg/kg, low dose group: 0.75-0.85 mg/kg, and standard dose group: ≥ 0.95 mg/kg. Rates of bleeding and thrombosis were also evaluated. A total of eight studies were included. For anti-Xa level assessment, 682 patients were included. A total of 62% of anti-Xa levels were therapeutic in the very low dose group, 66% in the low dose group, and 42% in the standard dose group. Overall rates of total bleeding and thrombosis were assessed in 798 patients. A total of 29 bleedings (3.6%) occurred, and 27 reported a relationship to dose. Most bleedings, 85.2% (n = 23/27), occurred with doses in the standard dose group (≥ 0.95 mg/kg). Thrombosis occurred in 5 patients (0.6%). Utilization of a reduced weight-based dosing strategy for therapeutic enoxaparin in obese patients may increase the percentage of patients with a therapeutic anti-Xa level.

Anticoagulant prescribing patterns in patients with primary central nervous system malignancies and secondary metastases.

To evaluate the safety of direct oral anticoagulants (DOACs) versus low-molecular weight heparin (LMWH) in patients with central nervous system (CNS) malignancies and secondary metastases. All adult patients with CNS malignancies and secondary metastases who were treated with a DOAC or LMWH for any indication from 2018 to 2022 were included. The primary outcome was the incidence of any intracranial hemorrhage (ICH) after anticoagulation initiation. Secondary outcomes included non-ICH bleeding events and thromboembolic events. Tolerability was assessed by any changes in anticoagulant therapy during study period. 153 patients were included; 48 patients received enoxaparin and 105 received DOACs, of which apixaban was used most commonly. The population was predominantly White (74%) and male (59%) with a median age of 65. Data was censored for immortal time bias for outcomes evaluated beyond 3 months. ICH occurred in 7.7% of the population, more frequently in the enoxaparin group (DOACs 4, 4% vs. enoxaparin 7, 16%, p = 0.037). Non-ICH bleeds were predominantly minor and more common in the DOAC group (DOACs 13, 13% vs. enoxaparin 1, 2%, p = 0.037). Thromboembolic events were not different between groups (DOACs 9. 9% vs, enoxaparin 2, 4%, p = 0.503). Anticoagulant switches occurred more in the enoxaparin group (DOACs 12, 12.4% vs. enoxaparin, 37.8%, p < 0.001), primarily due to patient or provider preference. Our data supports DOACs to be preferred over LMWH for the treatment of VTE or for stroke prevention with AF to prevent ICH in patients with brain tumors or metastases.

Is early bilateral compression ultrasonography and D-dimer monitoring appropriately for prophylaxis and diagnosis of deep venous thrombosis after cesarean section women: a single-center observation study of Chinese Han population.

BACKGROUND: Venous thromboembolism (VTE) is most prevalent among parturients following a cesarean section (CS). The objective of this study was to assess the practical utility of bilateral compression ultrasonography (CUS) of the lower limbs, coupled with D-dimer monitoring, in the early diagnosis of VTE within the Han Chinese population. METHODS: Our prospective observational study included 742 women who underwent CUS and D-dimer testing on the first day post-CS. Subsequently, telephone or outpatient follow-ups were conducted until 42 days postpartum. States of hypercoagulation and thrombosis, as indicated by CUS, were classified as CUS abnormal. A D-dimer level ≥ 3 mg/l was considered the D-dimer warning value. Early ambulation and mechanical prophylaxis were universally recommended for all parturients post-CS. A sequential diagnostic strategy, based on the 2015 RCOG VTE risk-assessment tool, was employed. Therapeutic doses of low-molecular-weight heparin (LMWH) were administered for the treatment of thromboembolic disease. Prophylactic doses of LMWH were given for VTE prophylaxis in parturients with hypercoagulative status accompanied by D-dimer levels ≥ 3 mg/l. All high-risk women (RCOG score ≥ 4 points) were additionally treated with preventive LMWH. Statistical analyses were conducted using the R statistical software, with a two-sided P value < 0.05 considered statistically significant. RESULTS: Fifteen cases of VTE and 727 instances without VTE were observed. The overall VTE rate post-CS was 2.02% (15/742), with 66.7% (10/15) being asymptomatic. Eleven patients received a VTE diagnosis on the first postpartum day. Among the 41 parturients exhibiting hypercoagulation ultrasound findings and D-dimer levels ≥ 3 mg/l, despite receiving pharmacological VTE prophylaxis with LMWH, 4.88% (2/41) in the high-risk group were eventually diagnosed with VTE. A total of 30.86% (229/742) exhibited normal ultrasound findings and D-dimer levels < 3 mg/l on the first day post-CS, with no VTE occurrences in the postpartum follow-up. According to RCOG's recommendation, 78.03% (579/742) of cesarean delivery women should receive prophylactic anticoagulation, while only 20.62% (153/742) met our criterion for prophylactic anticoagulation. CONCLUSION: The strategy of timely routine bilateral CUS and D-dimer monitoring is conducive to the early diagnosis and treatment of VTE, significantly reducing the use of LMWH in the Chinese Han population.

Low-molecular-weight heparin for the prevention of preeclampsia in high-risk pregnancies without thrombophilia: a systematic review and meta-analysis.

OBJECTIVES: To systematically evaluate the efficacy of low molecular weight heparin (LMWH) to prevent preeclampsia in high risk pregnant women without thrombophilia. SEARCH STRATEGY: PubMed, Embase and the Cochrane library were searched for articles published before 1st August 2022 using the combination keywords "preeclampsia", "Low Molecular Weight Heparin", "LMWH", "Heparin, Low Molecular Weight", "Dalteparin", "Nadroparin", and "Tinzaparin". SELECTION CRITERIA: Randomized controlled trials evaluating the use of LMWH in pregnant women at high risk of preeclampsia without thrombophilia. DATA COLLECTION AND ANALYSIS: Ten studies were included in the meta-analysis (1758 patients in total). Outcomes were expressed as relative risk (RR) with 95% confidence intervals (CI). RESULTS: LMWH reduced the incidence of PE (RR = 0.67; 95% CI = 0.50-0.90; P = 0.009) in high risk pregnant women without thrombophilia. Subgroup analysis found that the prophylactic effect of LMWH was only significant in studies using low-dose aspirin (LDA) as the primary intervention. The combination of LMWH and LDA was also effective for the prevention of preterm birth and fetal growth restriction, but had no effect on the incidence of placenta abruption. CONCLUSION: For women at high risk of developing preeclampsia without thrombophilia, the combination of LMWH and low-dose aspirin is effective for the prevention of preeclampsia, preterm birth and fetal growth restriction and is superior to LDA alone.

A Comparison Between Fondaparinux Sodium and Low-Molecular-Weight Heparin in Preventing Patients Undergoing Hip Replacement from Deep Vein Thrombosis.

OBJECTIVES: Total hip arthroplasty (THA) is a highly successful and effective surgery for improving hip functions and relieving pain. However, the lower extremities are prone to deep vein thrombosis (DVT) and swelling after surgery, thereby delaying recovery. In this study, we investigated the preventive effects of fondaparinux sodium (FS) and low-molecular-weight heparin (LMWH) on DVT of the lower extremity after THA. METHODS: Firstly, 60 patients who underwent THA at the First Affiliated Hospital of Wannan Medical College from March 2020 to December 2020 were included. Next, the patients were randomly divided into an LMWH group (n = 30) and an FS group (n = 30). Then, the indexes related to DVT were compared between both groups. RESULTS: Specifically, the differences in baseline data, such as age, gender and body mass index (BMI), between the two groups were not statistically significant. The postoperative weight bearing time of patients in the FS group was much shorter than that in the LMWH group. CONCLUSION: Subcutaneous injection of FS not only exhibits superior effects to LMWH in preventing DVT after THA but also has a correlation with reducing the risk of thrombosis and improving patient symptoms.

Perioperative Administration of Tranexamic Acid and Low Molecular Weight Heparin for Enhanced Blood Management in Intertrochanteric Fractures: A Randomized Controlled Study.

BACKGROUND This prospective study from a single center aimed to compare the perioperative blood loss (PBL) in 79 patients with intertrochanteric fractures (IF) treated with intramedullary nailing (IMN) using 3 regimens of combined tranexamic acid (TXA) and low molecular weight heparin (LMWH), proposing a novel therapy of 4-dose TXA. MATERIAL AND METHODS We recruited 79 patients and randomly divided them into 3 groups. The 4-dose TXA group (22 patients) received 1.0 g intravenous TXA 30 min before surgery and 1.0 g at intervals of 3, 6, and 9 h before surgery. The 1-dose TXA group (25 patients) received 1.0 g intravenous TXA 30 min before surgery, while the control group (32 patients) did not receive TXA. LMWH was applied 12 h after surgery in each group. The primary metrics evaluated included hidden blood loss (HBL), total blood loss (TBL), and the number and incidence rate of deep vein thrombosis (DVT). RESULTS Analysis of the HBL revealed that the 4-dose TXA group had the lowest average (583.13±318.08 ml), followed by the 1-dose TXA group (902.94±509.99 ml), and the control group showed the highest (1154.39±452.06 ml) (P<0.05). A similar result was observed for TBL (4-dose group: 640.86±337.22 ml, 1-dose group: 971.74±511.14 ml, control group: 1226.27±458.22 ml, P<0.05). Regarding DVT, the 4-dose TXA group had 5 cases (incidence rate 22.73%), the 1-dose TXA group had 6 cases (incidence rate 24.00%), and the control group had 8 cases (incidence rate 25.00%), with no significant difference among groups (P>0.05). CONCLUSIONS Treatment using 4-dose TXA and LMWH can effectively reduce PBL without increasing the DVT risk in IF patients with IMN.

Efficacy of 5-fluorouracil (5-FU) and low molecular weight heparin (LMWH) in high-risk pediatric retinal detachment; randomized clinical trial.

BACKGROUND: Pediatric rhegmatogenous retinal detachments (PRRDs) are complex, rare occurrences and are often related to trauma or congenital abnormalities. Children often do not recognize or report symptoms of retinal detachment. Thus at presentation, PRRD is typically advanced often with macular involvement, proliferative vitreoretinopathy (PVR), chronic duration, and poor visual acuity. Because 5-FU and LMWH are effective in different aspects in the PVR process, it was believed that a syngergistic approach to the prevention of PVR would be advantageous. METHODS: After informed consent, children under 14 years of age with high-risk PRRD underwent pars plana vitrectomy and silicone oil injection with scleral buckle divided into 2 groups in prospective randomized trial. Group A received intraoperative infusion of 5-FU (200 µg/ml) and LMWH (5 IU/ml), group B received infusion of normal saline. Primary outcome was occurrence of recurrent PRRD within 12 weeks, secondary outcomes were occurrence of PVR, best corrected visual acuity (BCVA), number and timing of secondary procedures within 12 weeks. RESULTS: The study included 42 eyes of 41 patients, 21 in group A and 21 in group B, the duration of PRRD ranged from 0.5 to 7 months in group A and 0.25-5 months in group B.The rate of recurrent PRRD was higher in group B 33% compared to 19% in group A (p = 0.292). The mean timing of occurrence of recurrent PRRD was 9.5 ± 5 weeks in group A compared to 2.86 ± 2.41 weeks in group B (p = 0.042), more patients in group B ended up with more advanced PVR (p = 0.038), BCVA was hand movement (HM) only in all cases preoperatively and improved to HM-0.3 Snellen in group A compared to light perception (PL)-0.1Snellen in group B (p = 0.035), there was no difference in any of secondary procedures but with later timing in group A 9.71 ± 3.73 weeks than in group B 4.0 ± 2.83 weeks (p = 0.042). CONCLUSION: This study concluded that the use of the 5-FU and LMWH combination in high risk PRRD resulted in lower rate of postoperative PVR, later recurrence of PRRD and better final BCVA. TRIAL REGISTRATION NUMBER: Registry: clinicaltrials.gov PRS NCT06166914 date of initial release 4/12/2023. Unique Protocol ID: 9,163,209 date 21/10/2021. Retrospectively registered.

In adults with cancer and VTE, DOACs were noninferior to LMWH for recurrent, nonfatal VTE at 6 mo.

SOURCE CITATION: Schrag D, Uno H, Rosovsky R, et al; CANVAS Investigators. Direct oral anticoagulants vs low-molecular-weight heparin and recurrent VTE in patients with cancer: a randomized clinical trial. JAMA. 2023;329:1924-1933. 37266947.

Anticoagulant Therapy for Cancer-Associated Thrombosis : A Cost-Effectiveness Analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) offer an alternative to low-molecular-weight heparin (LMWH) and warfarin for treating cancer-associated thrombosis (CAT). OBJECTIVE: To determine the cost and effectiveness of DOACs versus LMWH. DESIGN: Cohort-state transition decision analytic model. DATA SOURCES: Network meta-analysis comparing DOACs versus LMWH. TARGET POPULATION: Adult patients with cancer at the time they develop thrombosis. TIME HORIZON: Lifetime. PERSPECTIVE: Health care sector. INTERVENTION: Strategies of 1) enoxaparin, 2) apixaban, 3) edoxaban, and 4) rivaroxaban for treatment of CAT. OUTCOME MEASURES: Incremental cost-effectiveness ratio (ICER) in 2022 U.S. dollars per quality-adjusted life-year (QALY) gained. RESULTS OF BASE-CASE ANALYSIS: In the base-case scenario, using drug prices from the U.S. Department of Veterans Affairs Federal Supply Schedule, apixaban dominated enoxaparin and edoxaban by being less costly and more effective. Rivaroxaban was slightly more effective than apixaban, with an ICER of $493 246. In a scenario analysis using "real-world" drug prices from GoodRx, rivaroxaban was cost-effective with an ICER of $50 053 per QALY. RESULTS OF SENSITIVITY ANALYSIS: Results were highly sensitive to monthly drug costs. Probabilistic sensitivity analyses showed that at a willingness-to-pay threshold of $50 000 per QALY, apixaban was preferred in 80% of simulations. However, sensitivity analyses also demonstrated that apixaban only remained cost-effective if monthly medication costs were below $530. Above this, rivaroxaban became cost-effective. LIMITATIONS: An assumption was made that patients would continue anticoagulation indefinitely unless they suffered a major bleed. Nonmedical costs such as patient and caregiver loss of productivity were not accounted for, and long-term thrombotic complications were not explicitly modeled. CONCLUSION: The 3 DOACs are more effective and more cost-effective than LMWH. The most cost-effective DOAC depends on the relative cost of each of these agents. These are important considerations for treating physicians and health policymakers. PRIMARY FUNDING SOURCE: None.

Perioperative anticoagulation in head and neck free flap reconstructions: Experience of an anticoagulative scheme and its modification.

OBJECTIVES: Microvascular anastomoses in microvascular reconstructions induce rheological changes in the anastomosed vessels and are usually counteracted by anticoagulative medication. There is no regimen commonly agreed on. This study provides an easy to use anticoagulative regimen. PATIENTS AND METHODS: Consecutive cases of either anticoagulative regimen between 2013 and 2018 that underwent microvascular reconstruction in the head and neck area were included in this retrospective study, resulting in 400 cases in total. Two different anticoagulative regimens were applied to 200 patients in each group: (a) intraoperatively administered unfractionated 5000 I.U. high molecular weight heparin (HMWH) and postoperatively low molecular weight heparin (LMWH, Enoxaparin) 1 mg/kg/body weight postoperatively and (b) intraoperatively LMWH 0.5 mg/kg/body weight as well as 12 h later and 1 mg/kg/body weight postoperatively. RESULTS: The LMWH cohort showed fewer overall thromboembolic (8.5% vs. 11%; p = .40) and peripheral thrombotic events (1% vs. 3.5%; p = .18) and lung embolisms (3% vs. 4%; p = .59). The number of thromboses at the site of the anastomosis was equally distributed. In regard to flap-specific complications, LMWH was associated with a positive effect, in particular with respect to total flap losses (5% vs. 7%; p = .40) and wound-healing disorders (14.5% vs. 20%; p = .145). CONCLUSION: Findings indicate that intra- and postoperatively administered LMWH as the only anticoagulative medication seems reliable in our clinical routine of head and neck free flap reconstructions.