Propensity weighted analysis of chemical venous thromboembolism prophylaxis agents in isolated severe traumatic brain injury: An EAST sponsored multicenter study.

In patients with severe traumatic brain injury (TBI), clinicians must balance preventing venous thromboembolism (VTE) with the risk of intracranial hemorrhagic expansion (ICHE). We hypothesized that low molecular weight heparin (LMWH) would not increase risk of ICHE or VTE as compared to unfractionated heparin (UH) in patients with severe TBI. Patients ≥ 18 years of age with isolated severe TBI (AIS ≥ 3), admitted to 24 level I and II trauma centers between January 1, 2014 to December 31, 2020 and who received subcutaneous UH and LMWH injections for chemical venous thromboembolism prophylaxis (VTEP) were included. Primary outcomes were VTE and ICHE after VTEP initiation. Secondary outcomes were mortality and neurosurgical interventions. Entropy balancing (EBAL) weighted competing risk or logistic regression models were estimated for all outcomes with chemical VTEP agent as the predictor of interest. 984 patients received chemical VTEP, 482 UH and 502 LMWH. Patients on LMWH more often had pre-existing conditions such as liver disease (UH vs LMWH 1.7 % vs. 4.4 %, p = 0.01), and coagulopathy (UH vs LMWH 0.4 % vs. 4.2 %, p < 0.001). There were no differences in VTE or ICHE after VTEP initiation. There were no differences in neurosurgical interventions performed. There were a total of 29 VTE events (3 %) in the cohort who received VTEP. A Cox proportional hazards model with a random effect for facility demonstrated no statistically significant differences in time to VTE across the two agents (p = 0.44). The LMWH group had a 43 % lower risk of overall ICHE compared to the UH group (HR = 0.57: 95 % CI = 0.32-1.03, p = 0.062), however was not statistically significant. In this multi-center analysis, patients who received LMWH had a decreased risk of ICHE, with no differences in VTE, ICHE after VTEP initiation and neurosurgical interventions compared to those who received UH. There were no safety concerns when using LMWH compared to UH. Level III, Therapeutic Care Management.

Ratnasekera AM ，Seng SS ，Kim D ，Ji W ，Jacovides CL ，Kaufman EJ ，Sadek HM ，Perea LL ，Poloni CM ，Shnaydman I ，Lee AJ ，Sharp V ，Miciura A ，Trevizo E ，Rosenthal MG ，Lottenberg L ，Zhao W ，Keininger A ，Hunt M ，Cull J ，Balentine C ，Egodage T ，Mohamed AT ，Kincaid M ，Doris S ，Cotterman R ，Seegert S ，Jacobson LE ，Williams J ，Moncrief M ，Palmer B ，Mentzer C ，Tackett N ，Hranjec T ，Dougherty T ，Morrissey S ，Donatelli-Seyler L ，Rushing A ，Tatebe LC ，Nevill TJ ，Aboutanos MB ，Hamilton D ，Redmond D ，Cullinane DC ，Falank C ，McMellen M ，Duran C ，Daniels J ，Ballow S ，Schuster KM ，Ferrada P ... -  《-》

Direct factor Xa inhibitors versus low molecular weight heparins or vitamin K antagonists for prevention of venous thromboembolism in elective primary hip or knee replacement or hip fracture repair.

People undergoing major orthopaedic surgery are at increased risk of postoperative thromboembolic events. Low molecular weight heparins (LMWHs) are recommended for thromboprophylaxis in this population. New oral anticoagulants, including direct factor Xa inhibitors, are recommended as alternatives. They may have more advantages than disadvantages compared to LMWHs and vitamin K antagonists (VKAs, another type of anticoagulant). To assess the benefits and harms of prophylactic anticoagulation with direct factor Xa inhibitors compared with low molecular weight heparins and vitamin K antagonists in people undergoing major orthopaedic surgery for elective total hip or knee replacement or hip fracture surgery. We searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, two other databases, and two trial registers to 11 November 2023. We conducted reference checks to identify additional studies. We included randomised controlled trials (RCTs) comparing the effects of direct factor Xa inhibitors to LMWHs or VKAs in people undergoing major orthopaedic surgery. We used standard Cochrane methods. Our primary outcomes were all-cause mortality, major venous thromboembolism (VTE), symptomatic VTE, major bleeding, and serious hepatic and non-hepatic adverse events. We evaluated the risk of bias in the included studies using Cochrane's risk of bias 1 tool. We calculated estimates of treatment effects using risk ratios (RR) with 95% confidence intervals (CIs), and used GRADE criteria to assess the certainty of the evidence. We included 53 RCTs (44,371 participants). Participants' average age was 64 years (range: 18 to 93 years). Only one RCT compared a VKA with direct factor Xa inhibitors. All 53 RCTs compared direct factor Xa inhibitors with LMWHs. Twenty-three studies included participants undergoing total hip replacement; 21 studies, total knee replacement; and three studies included people having hip fracture surgery. The studies' average duration was approximately 42 days (range: two to 720 days). Compared to LMWHs, direct factor Xa inhibitors may have little to no effect on all-cause mortality, but the evidence is very uncertain (RR 0.83, 95% CI 0.52 to 1.31; I2 = 0%; 28 studies, 29,698 participants; very low-certainty evidence). Direct factor Xa inhibitors may make little to no difference to major venous thromboembolic events compared to LMWHs, but the evidence is very uncertain (RR 0.51, 95% CI 0.37 to 0.71; absolute risk difference: 12 fewer major VTE events per 1000 participants, 95% CI 16 fewer to 7 fewer; I2 = 48%; 28 studies, 24,574 participants; very low-certainty evidence). Compared to LMWHs, direct factor Xa inhibitors may reduce symptomatic VTE (RR 0.64, 95% CI 0.50 to 0.83; I2 = 0%; 33 studies, 31,670 participants; low-certainty evidence). The absolute benefit of substituting factor Xa inhibitors for LMWHs may be between two and five fewer symptomatic VTE episodes per 1000 patients. In the meta-analysis with all studies pooled, direct factor Xa inhibitors appeared to make little or no difference to major bleeding compared to LMWHs, but the evidence was very uncertain (RR 1.05, 95% CI 0.86 to 1.30; I2 = 15%; 36 studies, 39,778 participants; very low certainty-evidence). • In a subgroup analysis limited to studies comparing rivaroxaban to LMWHs, people given rivaroxaban may have had more major bleeding events (RR 1.94, 95% CI 1.26 to 2.98; I2 = 0%; 17 studies, 17,630 participants; low-certainty evidence). The absolute risk of substituting rivaroxaban for LMWH may be between one and seven more major bleeding events per 1000 patients. • In a subgroup analysis limited to studies comparing direct factor Xa inhibitors other than rivaroxaban to LMWHs, people given these other direct factor Xa inhibitors may have had fewer major bleeding events, but the evidence was very uncertain (RR 0.80, 95% CI 0.63 to 1.02; absolute risk difference: 3 fewer major bleeding events per 1000 participants, 95% CI 5 fewer to 0 fewer; I2 = 0%; 19 studies, 22,148 participants; very low-certainty evidence). Direct factor Xa inhibitors may make little to no difference in serious hepatic adverse events compared to LMWHs, but the evidence is very uncertain (RR 3.01, 95% CI 0.12 to 73.93; 2 studies, 3169 participants; very low-certainty evidence). Only two studies reported this outcome, with one death in the intervention group due to hepatitis reported in one study, and no events reported in the other study. People given direct factor Xa inhibitors may have a lower risk of serious non-hepatic adverse events than those given LMWHs (RR 0.89, 95% CI 0.81 to 0.97; I2 = 18%; 15 studies, 26,246 participants; low-certainty evidence). The absolute benefit of substituting factor Xa inhibitors for LMWH may be between three and 14 fewer serious non-hepatic adverse events per 1000 patients. Only one study compared a direct factor Xa inhibitor with a VKA. It reported outcome data with imprecise results due to the small number of events. It showed no difference in the effects of the study drugs. Oral direct factor Xa inhibitors may have little to no effect on all-cause mortality, but the evidence is very uncertain. Oral direct factor Xa inhibitors may slightly reduce symptomatic VTE events when compared with LMWH. They may make little or no difference to major VTE events, but the evidence is very uncertain. In the evaluation of major bleeding, the evidence suggests rivaroxaban results in a slight increase in major bleeding events compared to LMWHs. The remaining oral direct factor Xa inhibitors may have little to no effect on major bleeding, but the evidence is very uncertain. Oral direct factor Xa inhibitors may reduce serious non-hepatic adverse events slightly compared to LMWHs. They may have little to no effect on serious hepatic adverse events, but the evidence is very uncertain. Due to the high rates of missing participants and selective outcome reporting, the effect estimates may be biased.

Salazar CA ，Basilio Flores JE ，Malaga G ，Malasquez GN ，Bernardo R ... -  《Cochrane Database of Systematic Reviews》

Unfractionated heparin versus low molecular weight heparin for avoiding heparin-induced thrombocytopenia in postoperative patients.

Junqueira DR ，Perini E ，Penholati RR ，Carvalho MG ... -  《Cochrane Database of Systematic Reviews》

Erratum: Eyestalk Ablation to Increase Ovarian Maturation in Mud Crabs.

《Jove-Journal of Visualized Experiments》

Unfractionated heparin versus low molecular weight heparins for avoiding heparin-induced thrombocytopenia in postoperative patients.

Junqueira DR ，Zorzela LM ，Perini E 《Cochrane Database of Systematic Reviews》