Heparin For Venous Thromboembolism Prophylaxis Research Articles

An observational study on the use of low-molecular-weight heparin for venous thromboembolism prophylaxis in acute stroke patients

Venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) are common complications post-stroke. The UK stroke guidelines recommend the early use of intermittent pneumatic compression devices (IPCDs). At our center, we noticed poor compliance with the use of these devices and sought to develop a pathway for early implementation of low-molecular-weight heparins (LMWH) instead. We retrospectively analyzed the data of 2351 patients in two separate groups and compared both groups to check the incidence of PEs and DVTs as stated on the discharge documentation. Group A consists of 1599 patients who used IPCDs as VTE prophylaxis, whereas Group B involved 752 patients who were placed on the new VTE prophylaxis protocol, which involved the early use of LMWH with enoxaparin delivered subcutaneously. It was observed that IPCDs were not well tolerated by patients, leading to poor compliance with VTE prophylaxis in Group A. VTE compliance was noted to be better in Group B in which the patients were given LMWH in the hospital. Furthermore, symptomatic DVT and PE were not found to be higher in Group B patients, but in fact, the incidence of these conditions was lower in this group. In conclusion, compared to IPCDs, LMWH appears to be well tolerated by patients during the admission period owing to acute stroke. It was observed that the incidence of VTE was reduced in patients who started on early LMWH in the post-stroke period. However, the long-term effects of LMWH prophylaxis, in terms of mortality and morbidity, need to be delineated. Therefore, an additional large trial on the early use of LMWH in comparison to IPCDs is warranted.

The efficacy of aspirin versus low-molecular-weight heparin for venous thromboembolism prophylaxis after knee and hip arthroplasty: A systematic review and meta-analysis of randomized controlled trials.

The purpose of this study was to assess the efficacy of aspirin versus low-molecular-weight heparin (LMWH) in preventing venous thromboembolism (VTE) following hip and knee arthroplasty. PubMed/Medline, Embase, Cochrane Library and Google Scholar databases were searched from inception till June 2024 for original trials investigating the outcomes of aspirin versus LMWH in hip and knee arthroplasty. The primary outcome was VTE. Secondary outcomes included minor and major bleeding events, and postoperative mortality within 90 days. This review was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 7 randomized controlled trials with 12,134 participants were included. The mean ages for the aspirin and LMWH cohorts were 66.6 (57.6-69.0) years and 66.8 (57.9-68.9) years, respectively. There was no statistically significant difference in the overall risk of VTE between the aspirin and the LMWH cohorts (odds ratio [OR]: 0.95; 95% confidence interval [CI]: 0.48-1.89; p: 0.877). A subanalysis based on the specific VTE entity (pulmonary embolism [PE] or deep venous thrombosis) showed a significantly higher PE risk for patients receiving aspirin than the LMWH cohort (OR: 1.79; 95% CI: 1.11-2.89; p: 0.017). There was no difference in minor (OR: 0.64; 95% CI: 0.40-1.04; p: 0.072) and major bleeding (OR: 0.77; 95% CI: 0.40-1.47; p: 0.424) episodes across both groups. Furthermore, subanalysis among the total knee arthroplasty group showed that the aspirin cohort was significantly more likely to suffer VTEs than their LMWH counterparts (OR: 1.55; 95% CI: 1.21-1.98; p < 0.001). This study demonstrated a significantly higher risk of PE among patients receiving aspirin compared to LMWH following hip or knee arthroplasty for osteoarthritis. Aspirin was associated with a significantly higher overall VTE risk among patients undergoing knee arthroplasty, in particular. This might suggest the inferiority of aspirin compared to LMWH in preventing VTE following such procedures. Level I.

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.

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. 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. 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 withthe 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. 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 III.

Comment on 'The role of aspirin versus low-molecular-weight heparin for venous thromboembolism prophylaxis after total knee arthroplasty: a meta-analysis of randomized controlled trials'.

Comment on 'The role of aspirin versus low-molecular-weight heparin for venous thromboembolism prophylaxis after total knee arthroplasty: a meta-analysis of randomized controlled trials'.

The role of aspirin versus low-molecular-weight heparin for venous thromboembolism prophylaxis after total knee arthroplasty: a meta-analysis of randomized controlled trials.

There is a debate over the use of aspirin after total knee arthroplasty (TKA) for venous thromboembolism (VTE) prophylaxis. To evaluate the clinical effectiveness and safety of aspirin after TKA, the authors performed a meta-analysis of randomized controlled trials that compared aspirin with low-molecular-weight heparin (LMWH). PubMed, Cochrane Library, Embase, and Web of Science were last searched on 31 January 2023 for studies comparing the effect of VTE prophylaxis between aspirin and LMWH. The results of eligible studies were analyzed in terms of VTE, deep venous thrombosis, pulmonary embolism, and bleeding complications rates. Six randomized controlled trials including 6772 patients met the inclusion criteria. LMWH showed a statistically significant reduction in the overall VTE rate (RR 1.46, 95% CI: 1.16-1.84). No significant differences in deep venous thrombosis, pulmonary embolism, and bleeding complications rates were found between aspirin and LMWH. Compared with LMWH, aspirin presents a higher risk of VTE after TKA. In terms of safety, aspirin and LMWH show comparable outcomes. The results do not support the role of aspirin role as an anticoagulant for preventing VTE after TKA.

Unfractionated heparin or low-molecular-weight heparin for venous thromboembolism prophylaxis after hepatic resection: A meta-analysis.

Two systematic reviews summarized the efficacy and safety of pharmacological prophylaxis for venous thromboembolism (VTE) after hepatic resection, but both lacked a discussion of the differences in the pharmacological prophylaxis of VTE in different ethnicities. Therefore, we aimed to evaluate the efficacy and safety of low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) for VTE prophylaxis in Asian and Caucasian patients who have undergone hepatic resection. We searched PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Data, and VIP databases for studies reporting the primary outcomes of VTE incidence, bleeding events, and all-cause mortality from January 2000 to July 2022. Ten studies involving 4318 participants who had undergone hepatic resection were included: 6 in Asians and 4 in Caucasians. A significant difference in VTE incidence was observed between the experimental and control groups (odds ratio [OR] = 0.39, 95% confidence interval [CI]: 0.20, 0.74, P = .004). No significant difference in bleeding events and all-cause mortality was observed (OR = 1.29, 95% CI: 0.80, 2.09, P = .30; OR = 0.71, 95% CI: 0.36, 1.42, P = .33, respectively). Subgroup analyses stratified by ethnicity showed a significant difference in the incidence of VTE in Asians (OR = 0.16, 95% CI: 0.06, 0.39, P < .0001), but not in Caucasians (OR = 0.69, 95% CI: 0.39, 1.23, P = .21). No significant differences in bleeding events were found between Asians (OR = 1.60, 95% CI: 0.48, 5.37, P = .45) and Caucasians (OR = 1.11, 95% CI: 0.58, 2.12, P = .75). The sensitivity analysis showed that Ejaz's study was the main source of heterogeneity, and when Ejaz's study was excluded, a significant difference in VTE incidence was found in Caucasians (OR = 0.58, 95% CI: 0.36, 0.93, P = .02). This study's findings indicate that the application of UFH or LMWH for VTE prophylaxis after hepatic resection is efficacious and safe in Asians and Caucasians. It is necessary for Asians to receive drug prophylaxis for VTE after hepatic resection. This study can provide a reference for the development of guidelines in the future, especially regarding the pharmacological prevention of VTE in different ethnicities.

Low molecular weight heparin for venous thromboembolism prophylaxis in general Intensive Care Unit patients: an anti-factor Xa level-based approach.

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. 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. 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. 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.

Fondaparinux sodium and low molecular weight heparin for venous thromboembolism prophylaxis in Chinese patients with major orthopedic surgery or trauma: a real-world study

BackgroundThe present real-world study aimed to compare the efficacy and safety between fondaparinux sodium (FPX) and low molecular weight heparin (LMWH) for venous thromboembolism (VTE) prophylaxis in Chinese patients with major orthopedic surgery or trauma.MethodsA total of 2429 patients, with major orthopedic surgery or trauma, underwent FPX (n = 1177) or LMWH (n = 1252) for VTE prophylaxis and were retrospectively reviewed. Primary outcomes, including in-hospital VTE and in-hospital major bleeding incidences, as well as the secondary outcomes, including in-hospital minor bleeding, in-hospital death, and VTE/bleeding/death within 2 months after discharge, were analyzed. Inverse probability of treatment weighting (IPTW) was conducted.ResultsFPX group exhibited lower in-hospital VTE (0.1% vs. 0.8%; P = 0.032, crude OR = 0.11 before IPTW; P = 0.046, weighted OR = 0.12 after IPTW) and in-hospital minor bleeding (17.8% vs. 26.8%; P < 0.001, crude OR = 0.59 before IPTW; P < 0.001, weighted OR = 0.67 after IPTW) compared to LMWH group. Furthermore, no difference of in-hospital major bleeding, in-hospital death, and VTE/bleeding/death within 2 months after discharge was observed between FPX group and LMWH group (all P > 0.05). Further subgroup analyses identified, in specific cluster of patients such as older age, renal function impairment, hypertension and so on, in-hospital VTE was declined in FPX group compared to LMWH group (all P < 0.001).ConclusionsFPX is probable to exhibit a superior thromboprophylaxis efficacy compared with LMWH in in-hospital patients with major orthopedic surgery or trauma, especially in some special patients such as older age, renal function impairment, hypertension, etc.

Effectiveness and Safety of Twice- Versus Thrice-Daily Subcutaneous Heparin for Venous Thromboembolism Prophylaxis at a Large Academic Medical Center.

Dosing variation of subcutaneous unfractionated heparin (UFH) exist for venous thromboembolism prophylaxis (VTEP). The purpose of this study was to compare the safety and effectiveness of thrice-daily (TID) versus twice-daily (BID) administration of UFH during a heparin shortage for VTEP. A single-center retrospective analysis was conducted in patients with orders for BID subcutaneous UFH during a heparin shortage from September 1, 2019, to February 4, 2020. These patients were matched to patients with TID subcutaneous UFH orders from January 1, 2019, to May 31, 2019. The primary outcome was the incidence of deep-vein thrombosis or pulmonary embolism confirmed by imaging during hospitalization. The secondary outcome was the incidence of major or clinically relevant nonmajor bleeding events as defined by International Society on Thrombosis and Haemostasis (ISTH) definitions. A total of 277 patients with orders for BID UFH and meeting inclusion criteria were evaluated and matched to patients who received TID UFH. After the exclusion criteria were implemented, 510 patients remained in the TID group. The primary outcome occurred in 4% of patients in the BID group and 3% in the TID group (P = 0.645). Major bleeding or clinically relevant nonmajor bleeding events occurred in 10% of patients in the BID group and 8% in the TID group (P = 0.310). There was no difference in effectiveness or safety of TID versus BID subcutaneous UFH for VTEP. During a heparin shortage, transitioning patients to BID UFH for VTEP to conserve supply may be considered.

CRISTAL (a cluster-randomised, crossover, non-inferiority trial of aspirin compared to low molecular weight heparin for venous thromboembolism prophylaxis in hip or knee arthroplasty, a registry nested study): statistical analysis plan

BackgroundThis a priori statistical analysis plan describes the analysis for CRISTAL.MethodsCRISTAL (cluster-randomised, crossover, non-inferiority trial of aspirin compared to low molecular weight heparin for venous thromboembolism prophylaxis in hip or knee arthroplasty, a registry nested study) aims to determine whether aspirin is non-inferior to low molecular weight heparin (LMWH) in preventing symptomatic venous thromboembolism (VTE) following hip arthroplasty (HA) or knee arthroplasty (KA). The study is nested within the Australian Orthopaedic Association National Joint Replacement Registry. The trial was commenced in April 2019 and after an unplanned interim analysis, recruitment was stopped (December 2020), as the stopping rule was met for the primary outcome.The clusters comprised hospitals performing > 250 HA and/or KA procedures per annum, whereby all adults (> 18 years) undergoing HA or KA were recruited. Each hospital was randomised to commence with aspirin, orally, 85–150 mg daily or LMWH (enoxaparin), 40 mg, subcutaneously, daily within 24 h postoperatively, for 35 days after HA and 14 days after KA. Crossover was planned once the registration target was met for the first arm.The primary end point is symptomatic VTE within 90 days. Secondary outcomes include readmission, reoperation, major bleeding and death within 90 days, and reoperation and patient-reported pain, function and health status at 6 months.The main analyses will focus on the primary and secondary outcomes for patients undergoing elective primary total HA and KA for osteoarthritis. The analysis will use an intention-to-treat approach with cluster summary methods to compare treatment arms. As the trial stopped early, analyses will account for incomplete cluster crossover and unequal cluster sizes.ConclusionsThis paper provides a detailed statistical analysis plan for CRISTAL.Trial registrationAustralian and New Zealand Clinical Trials Registry ACTRN12618001879257. Registered on 19/11/2018.

HIT Diagnosis: A Proposed New Definition for Clinical Research

Introduction: Heparin-induced thrombocytopenia (HIT) is a rarely diagnosed but often suspected complication of heparin therapy. Initial diagnosis is generally made based upon a combination of pretest probability (such as the 4Ts score) and the results of readily available immunoassays. However, confirmation requires the result of a functional assay such as the serotonin release assay (SRA), which is currently considered to be the gold standard. Because the SRA is technically challenging, it is offered only in a few reference laboratories, resulting in a turnaround time of several days to a week. In addition, recent data suggest that the accuracy of the SRA may not be as high as previously thought. Thus, new laboratory assays that are both highly sensitive and specific for HIT antibodies are urgently needed. Here we propose a new set of criteria, independent of the SRA, that may be used to define HIT in the evaluation of novel assays.Methods: We conducted a retrospective cohort study of adult inpatients undergoing laboratory testing for suspicion of acute HIT at the University of Washington Medical center and/or Harborview Medical Center between May 2016 and July 2017. All patients underwent enzyme-linked immunosorbent assay (ELISA) testing for antiPF4/heparin antibodies (IgG-specific Zymutest EIA, Hyphen Biomed). According to institutional policy, those samples with optical density (OD) ≥ 0.300 were reflexively sent to a reference laboratory for SRA testing. Charts were examined by trained reviewers for calculation of the 4Ts score, results of ELISA and SRA testing (when available) and outcomes at 30 days including clinical diagnosis/management of HIT and mortality.Results: We identified 155 patients undergoing evaluation for HIT. Each patient was placed into one of three categories: ‘negative’, ‘indeterminate’, or ‘positive’, based upon a combination of 4Ts score and the optical density (OD) resulting from ELISA testing. Any patient with an OD ≤0.300 was considered to be ‘negative’ regardless of the 4Ts score. Patients with ODs ranging from 0.301-0.999 were defined as ‘negative’ unless the 4Ts score was high (6-8), in which case they were defined as ‘indeterminate’. Patients with an OD of 1.000-1.999 were defined as ‘positive’ if the 4Ts was high (6-8), indeterminate if the 4Ts was intermediate (4-5) and negative if the 4Ts was low (0-3). Patients with an OD ≥2.000 were defined as ‘positive’ unless the 4Ts score was low (0-3) in which case they were defined as ‘indeterminate’. The number of patients that fell into each category as well as the number of subjects with a clinically confirmed diagnosis of HIT are shown in Table 1.The median age of all subjects was 60 and was this was roughly similar across ‘negative’, ‘indeterminate’, and ‘positive’ categories (60, 62, and 66, respectively). Males represented 62% of all subjects and 71% of patients categorized as HIT positive. Seventy percent of all subjects received heparin for venous thromboembolism prophylaxis. Eighty-nine percent of ‘negative’ and 100% of ‘indeterminate’ subjects were exposed to unfractionated heparin (UFH). Six of 7 ‘positive’ patients were exposed to UFH and 1 to low molecular weight heparin (LMWH). All ‘positive’ patients were clinically managed for HIT by stopping all heparin products and/or beginning patients on direct thrombin inhibitor therapy, with 57% mortality within 30 days of ELISA testing. One (0.8%) ‘negative’ and 7 (32%) ‘indeterminate’ patients were clinically managed for HIT. Thirty-day mortality was 25% and 4.5% in ‘negative’ and ‘indeterminate’ groups respectively.Discussion: Our study proposes a framework for the use of clinical pretest probability scores and rapidly available HIT ELISA testing to define HIT in research studies. Such a strategy allows for assessment of accuracy of newly developed assays. The inclusion of an ‘indeterminate’ category adds statistical complexity but is necessary to avoid misclassification of patients who may or may not have true HIT. Mortality in HIT positive patients defined in this manner was high, although small numbers limit definitive conclusions and unfractionated heparin was implicated in most cases of HIT, as has been observed previously. [Display omitted] DisclosuresPadmanabhan:BloodCenter of Wisconsin: Patents & Royalties: A patent application has been filed related to the PF4-dependent P-selectin expression assay (Method of Detecting Platelet- Activating Antibodies That Cause Heparin-Induced Thrombocytopenia/Thrombosis; PCT/US14/62591).; Retham Technologies LLC: Equity Ownership.

Enoxaparin versus unfractionated heparin for venous thromboembolism prophylaxis in renally impaired ICU patients.

Intensive care unit (ICU) patients with renal insufficiency are more likely to develop venous thromboembolism and are at an increased risk for bleeding. There is conflicting data on whether enoxaparin or unfractionated heparin (UFH) is preferred for preventing thromboembolism in this population. Therefore, the purpose of this study was to evaluate the safety of prophylactic enoxaparin versus UFH in ICU patients with renal impairment. We conducted a single-center, retrospective cohort study of ICU patients with renal impairment who received venous thromboembolism prophylaxis with either enoxaparin or UFH. Patients were included if they were at least 18years of age, had renal impairment (acute kidney injury, severely decreased renal function, or end-stage renal disease), and an ICU length of stay ≥72h. The primary outcome was the proportion of patients experiencing a major bleeding event, including fatal bleed, symptomatic bleed in a critical area, or bleeding causing a ≥2g/dl decrease in hemoglobin leading to a transfusion of ≥2 units of packed red blood cells. A total of 460 patients were included in the study. Of these, 231 received enoxaparin and 229 received UFH. In the unadjusted analysis, there was no difference in major bleeding events observed with enoxaparin compared to UFH (29.4% vs. 22.3%; p=0.08) or rates of venous thromboembolism (4.3% vs. 3.5%; p=0.64), respectively. After adjusting for confounding factors, enoxaparin showed a significant increase in major bleeding (OR: 1.84; 95% CI: 1.11 - 3.04; p=0.02). Thromboprophylaxis with enoxaparin in critically ill patients with renal impairment was associated with an increased risk of major bleeding compared to UFH.

Effectiveness and Safety of Twice Daily Versus Thrice Daily Subcutaneous Unfractionated Heparin for Venous Thromboembolism Prophylaxis at a Tertiary Medical Center

Background: The direct comparison of twice daily (BID) and thrice daily (TID) dosing of subcutaneous low dose unfractionated heparin (LDUH) for venous thromboembolism (VTE) prophylaxis in a mixed inpatient population is not well-studied. Objective: This study evaluated the effectiveness and safety of BID compared to TID dosing of LDUH for prevention of VTE. Methods: Retrospective, single-center analysis of patients who received LDUH for VTE prophylaxis between July and September 2015. Outcomes were identified by ICD-9 codes. A matched cohort was created using propensity scores and multivariate analysis was conducted to identify independent risk factors for VTE. The primary outcome was incidence of symptomatic VTE. Results: In the full cohort, VTE occurred in 0.71% of patients who received LDUH BID compared to 0.77% of patients who received LDUH TID (p = 0.85). There was no difference in major (p = 0.85) and minor (p = 0.52) bleeding between the BID and TID groups. For the matched cohort, VTE occurred in 1.4% of BID patients and 2.1% of TID patients (p = 0.32). Major bleed occurred in 0.36% of BID patients and 0.52% of TID patients (p = 0.7), while a minor bleed was seen in 3.4% of BID patients and 2.1% of TID patients (p = 0.13). Personal history of VTE (p = 0.002) and weight (p = 0.035) were independently associated with increased risk of VTE. Conclusion: This study did not demonstrate a difference in effectiveness or safety between BID and TID dosing of LDUH for VTE prevention.

Lower Mortality and Morbidity with Low-Molecular-Weight Heparin for Venous Thromboembolism Prophylaxis in Spine Trauma.

Retrospective review of prospectively collected data. The objective of this study was to evaluate outcomes between patients receiving LMWH versus UH in a retrospective cohort of patients with spine trauma. Although multiple clinical trials have been conducted, current guidelines do not have enough evidence to suggest low-molecular-weight heparin (LMWH) or unfractionated heparin (UH) for venous thromboembolism (VTE) prophylaxis in spine trauma. Patients with spine trauma in the Trauma Quality Improvement Program datasets were identified. Those who died, were transferred within 72 hours, were deemed to have a fatal injury, were discharged within 24 hours, suffered from polytrauma, or were missing data for VTE prophylaxis were excluded. A propensity score was created using age, sex, severity of injury, time to prophylaxis, presence of a cord injury, and altered mental status or hypotension upon arrival, and inverse probability weighted logistic regression modeling was used to evaluate mortality, venous thromboembolic, return to operating room, and total complication rates. E values were used to calculate the likelihood of unmeasured confounders. Those receiving UH (n = 7172) were more severely injured (P < 0.0001), with higher rates of spinal cord injury (32.26% vs. 25.32%, P < 0.0001) and surgical stabilization (29.52% vs. 22.94%, P < 0.0001) compared to those receiving LMWH (n = 20,341). Patients receiving LMWH had lower mortality (odds ratio [OR]: 0.47; 95% CI: 0.42-0.53; P < 0.001; E = 3.68), total complication (OR: 0.92; 95% CI: 0.88-0.95; P < 0.001; E = 1.39), and VTE event (OR: 0.80; 95% CI: 0.72-0.88; P < 0.001; E = 1.81) rates than patients receiving UH. There were no differences in rates of unplanned return to the operating room (OR: 1.01; 95% CI: 0.80-1.27; P = 0.93; E = 1.11). There is an association between lower mortality and receiving LMWH for VTE prophylaxis in patients with spine trauma. A large randomized clinical trial is necessary to confirm these findings. 3.

Aspirin versus low-molecular-weight heparin for venous thromboembolism prophylaxis in orthopaedic trauma patients: A patient-centered randomized controlled trial.

BackgroundEmerging evidence suggests aspirin may be an effective venous thromboembolism (VTE) prophylaxis for orthopaedic trauma patients, with fewer bleeding complications. We used a patient-centered weighted composite outcome to globally evaluate aspirin versus low-molecular-weight heparin (LMWH) for VTE prevention in fracture patients.MethodsWe conducted an open-label randomized clinical trial of adult patients admitted to an academic trauma center with an operative extremity fracture, or a pelvis or acetabular fracture. Patients were randomized to receive LMWH (enoxaparin 30-mg) twice daily (n = 164) or aspirin 81-mg twice daily (n = 165). The primary outcome was a composite endpoint of bleeding complications, deep surgical site infection, deep vein thrombosis, pulmonary embolism, and death within 90 days of injury. A Global Rank test and weighted time to event analysis were used to determine the probability of treatment superiority for LMWH, given a 9% patient preference margin for oral administration over skin injections.ResultsOverall, 18 different combinations of outcomes were experienced by patients in the study. Ninety-nine patients in the aspirin group (59.9%) and 98 patients in the LMWH group (59.4%) were event-free within 90 days of injury. Using a Global Rank test, the LMWH had a 50.4% (95% CI, 47.7–53.2%, p = 0.73) probability of treatment superiority over aspirin. In the time to event analysis, LMWH had a 60.5% probability of treatment superiority over aspirin with considerable uncertainty (95% CI, 24.3–88.0%, p = 0.59).ConclusionThe findings of the Global Rank test suggest no evidence of superiority between LMWH or aspirin for VTE prevention in fracture patients. LMWH demonstrated a 60.5% VTE prevention benefit in the weighted time to event analysis. However, this difference did not reach statistical significance and was similar to the elicited patient preferences for aspirin.

Evaluation of the use of low-molecular-weight heparin for venous thromboembolism prophylaxis in medical patients.

Venous thromboembolism (VTE) complicates a significant proportion of medical admissions. As well as increasing patient morbidity, pulmonary embolism is one of the commonest preventable causes of in-hospital death. An increase in the use of pharmacological preventive measures has been advocated in recent years. South African (SA) and international guidelines have been published in an effort to promote the safe use of VTE prophylaxis. To describe adherence to both local and international recommendations for VTE prophylaxis in an SA hospital with regard to appropriateness of the decision to prescribe or withhold low-molecular-weight heparin (LMWH), and to observe the practice of dose adjustment in special population groups. This was a prospective, observational study, and data were collected from consenting adults admitted to the medical wards. We assessed the patients' VTE risk, bleeding risk and the presence of contraindications at the time of LMWH prescription as well as the dose prescribed, specifically taking into consideration adjustment for renal dysfunction and obesity. Three hundred and fifty-two patients were enrolled, of whom 51.4% were male and 58.5% received LMWH. Primary outcomes. The appropriate overall decision according to both SA and international guidelines was made in 254 cases (72.2%). The inappropriate decision according to both guidelines was made in 79 cases (22.4%) and the appropriate decision according to one guideline only was made in 18cases (5.1%), while 1 case (0.3%) was not categorised. Contraindications to VTE prophylaxis were present in 35 patients (9.9%), but 9 of these patients nevertheless received LMWH. An incorrect dose was prescribed in 36 cases (17.5%), the most common reason being an inappropriate reduction in the dose in mild renal dysfunction. Other medications that may have increased bleeding risk were prescribed in 46 patients who received LMWH (22.3%). Mechanical prophylaxis was indicated in 25 (7.1%) of the total sample; however, none received this. Overall adherence to published guidelines for VTE prophylaxis has improved compared with other published reviews on the topic, but documentation of patients' VTE risk in files is poor. Overuse in low-risk patients may be an unintended consequence of the widespread advocacy of LMWH use in hospital, highlighting the importance of adequate VTE risk stratification. Incorrect dosing in special population groups is an issue that needs to be addressed, as is non-utilisation of mechanical prophylaxis methods.

Safety and Efficacy of High-Dose Unfractionated Heparin Versus High-Dose Enoxaparin for Venous Thromboembolism Prevention in Morbidly Obese Hospitalized Patients

Venous thromboembolism is a cause of morbidity and mortality in hospitalized patients, and morbid obesity increases this risk. Various prophylaxis dosing strategies have been investigated. However, it is unclear if high-fixed dose enoxaparin or high-fixed dose unfractionated heparin thromboprophylaxis is optimal for minimizing the incidence of major bleeding and reducing hospital-acquired venous thromboembolism. A single-center retrospective observational study was conducted in hospitalized patients who were morbidly obese (body mass index ≥40 kg/m2) and who received either high-fixed dose enoxaparin (40 mg every 12 hours) or unfractionated heparin (7500 units every 8 hours) for venous thromboembolism prophylaxis. Co-primary outcomes included incidence of major bleeding and venous thromboembolism diagnosed during hospitalization. Predictors of major bleeding were evaluated by multivariable regression. In the 305 patients included (n=190 unfractionated heparin, n=115 enoxaparin), the incidence of major bleeding was significantly higher in the unfractionated heparin group (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.07-3.13; P=0.025), with no significant difference in the incidence of venous thromboembolism diagnosed during hospitalization. The only independent predictors of major bleeding were intensive care acuity (OR 3.32, 95% CI 1.91-5.78; P <0.001) and selection of unfractionated heparin rather than enoxaparin for venous thromboembolism prophylaxis (OR 2.16, 95% CI 1.22-3.82; P=0.008). High-fixed dose unfractionated heparin for venous thromboembolism prophylaxis may lead to a higher risk of major bleeding events compared with high-fixed dose enoxaparin in patients who are morbidly obese.

CRISTAL: protocol for a cluster randomised, crossover, non-inferiority trial of aspirin compared to low molecular weight heparin for venous thromboembolism prophylaxis in hip or knee arthroplasty, a registry nested study

IntroductionVenous thromboembolism (VTE) is a serious complication following hip arthroplasty (HA) and knee arthroplasty (KA). This study aims to determine whether aspirin is non-inferior to low molecular weight heparin (LMWH)...

Anti-Xa activity by weight in critically ill patients receiving unfractionated heparin for venous thromboembolism prophylaxis

PurposeThis study compared anti-Xa activity in critically ill patients receiving UFH for VTE prophylaxis between two weight groups (<100 kg vs ≥100 kg). MethodsThis prospective, observational study included critically ill patients on UFH 5000 or 7500 units every 8 h. A peak and trough anti-Xa activity assay was ordered for each patient at steady state. Goal peak anti-Xa activity was 0.1–0.3 units/mL. ResultsFrom March 2017 to June 2018, 75 patients were enrolled with 44 in the <100 kg group and 31 in the ≥100 kg group. There was no significant difference in the percentage of patients with peak anti-Xa activity within goal range between patients <100 kg and ≥ 100 kg (55.3% vs 35.7%, p = 0.12). The odds ratio for achieving peak anti-Xa activity within goal range as weight-based dose increased was 1.03 (95% CI 0.99–1.07). No differences were found in trough anti-Xa activity, VTE, bleeding, length of stay, or death. ConclusionsThough only one-third of patients ≥100 kg had peak anti-Xa activity within goal range, no significant difference was found between the weight groups. Additional prospective studies with adequate sample sizes are warranted to further investigate appropriate weight-based dosing of UFH in critically ill patients.

Anticoagulant activity of enoxaparin and unfractionated heparin for venous thromboembolism prophylaxis in obese patients undergoing sleeve gastrectomy

BackgroundOne risk of bariatric surgery is venous thromboembolism and the optimal strategy to reduce risk requires further clarification. ObjectivesThe objectives of this study were to identify antiXa goal attainment with the institutional standard chemoprophylaxis, analyze discordance between antiXa and thrombin generation assay (TGA) in terms of adequacy of anticoagulation, and to identify correlations between patient characteristics or covariates and markers of coagulation status. SettingLarge academic medical center in Northeastern United States. MethodsA total of 60 sleeve gastrectomy patients were enrolled in this institutional review board–approved, prospective cohort study. Patients received the institutional standard prophylactic therapy (subcutaneous enoxaparin 40 mg twice daily or unfractionated heparin [UFH]). The UFH dose was weight based, 5000 units (<120 kg) or 7500 units (≥120 kg) every 8 hours. Various measures of coagulation status were measured at or near steady state. ResultsPatients receiving enoxaparin achieved goal antiXa more frequently compared with the UFH group, and statistical significance was demonstrated (93.8 % versus 4.5%, respectively; P < .0001). Target endogenous thrombin potential reduction from baseline was more frequently obtained in the enoxaparin group versus UFH (50% versus 27.7%, respectively; P = .12). AntiXa was below the limit of detection for the majority of UFH patients; while TGA suggested patients did experience anticoagulation at some level of effectiveness. Endogenous thrombin potential change in the enoxaparin group was correlated to several measures of body composition. ConclusionsPatients receiving enoxaparin achieved goal antiXa more often versus UFH. There was discordance between antiXa and TGA-based assessment of coagulation status. TGA may provide a more robust assessment of the adequacy of chemoprophylaxis.