Subcutaneous Enoxaparin Research Articles

Enoxaparin Dosing for Venous Thromboembolism Prophylaxis in Low Body Weight Patients.

Background:The appropriate dose of enoxaparin for venous thromboembolism (VTE) prophylaxis in low body weight patients is unknown.Objective:The aim of this study is to evaluate the impact of enoxaparin dosing on major and minor bleeding events in low body weight patients.Methods:This was a retrospective cohort study of patients weighing less than 45 kg receiving subcutaneous (SC) enoxaparin for VTE prevention. The primary objective was to determine whether enoxaparin dose was associated with major and minor bleeding. The secondary objective was to determine the incidence of VTE by enoxaparin dose.Results:There were 173 patients included in the study, of which 37 patients received 2 different courses of enoxaparin during hospitalization, resulting in 210 enoxaparin courses. Among all enoxaparin courses, 16.2% were associated with major bleeding and 5.2% with minor bleeding. There was no difference in the incidence of major bleeding by dose (enoxaparin 30 mg SC daily, 30 mg SC twice daily, or 40 mg SC daily; P = .409). Patients who experienced major bleeding were older (54.9 ± 16.1 years) than patients who did not (48.4 ± 18.4 years) (P = .043). There was no difference in the incidence of minor bleeding by dosing schedule (P = .14). No patients experienced a VTE.Conclusion and Relevance:The risk of bleeding was similar by enoxaparin dose but increased with age in low body weight patients. Given the low incidence of VTE in this study, it is reasonable to consider decreasing the prophylactic enoxaparin dose in low body weight patients, especially in the elderly population.

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.

Resolution of Intractable Leg Ulcers Associated with Antiphospholipid Syndrome (APS) with Prophylactic Dose of Aspirin (ASA) and Enoxaparin: A Case Report

Background: Lower extremity ulcers are one of the most common skin manifestation in patients (pts) with APS, observed in 20-30% of pts. These skin ulcers typically respond poorly to conventional treatment. Although incompletely understood, the pathogenesis of the skin ulcers (and most of the clinical manifestations of APS) appears to be the result of vascular endothelial damage at the microcirculation level, leading to intracapillary thrombosis and focal inflammation. Systemic treatments with immunomodulatory agents such as glucocorticoids, intravenous immunoglobulin (IVIG) and immunosuppressants have been reported to improve outcomes, but typically carry substantial side-effects, and may not be available outside specialized referralcenters. The use of anticoagulation, with or without immunosuppression, in pts with APS and skin ulcers has been reported with variable results. Our group and others have documented an excellent safety profile with the combination of ASA 81 mg orally and enoxaparin 40 mg subcutaneously given to pregnant patients with APS and recurrent pregnancy loss. Patient with APS appear to share similar microcirculatory changes in the organs involved.Methods: Case report.Results: A 72 year-old gentleman was diagnosed with APS in 2000, when he was evaluated for recurrent deep venous thrombosis in the lower extremities, and was found to have a positive lupus anticouagulant serum test. He received anticoagulation with warfarin, with a target International Normalized Ratio (INR) of 2.5-3.5. In 2011, the patient was evaluated for full-thickness ulceration of the bilateral medial distal legs. He had been treated years earlier with venous ablation, and screening for lower extremity arterial insufficiency showed adequate peripheral circulation. The ulcers were treated with moist antimicrobial wound dressings, serial wound debridement, ongoing compression therapy, and a course of skin substitute therapy. After over one year of treatment the ulcers healed. Over the next several years the patient experienced several episodes of re-ulceration of the lower extremity ulcers despite continued use of compression stockings. He was treated in the same fashion, and each episode of re-ulceration required months of therapy to achieve healing. In mid-2017 he developed another episode of re-ulceration. Similar treatment was again initiated, with little improvement over the first several months of therapy. Physical findings and the recalcitrant nature of the ulcers suggested a direct casual relation with his underlying APS. Since our pt was not a candidate for any form of immunosuppression, he was started on daily subcutaneous enoxaparin 1 mg/kg and daily oral ASA 81 mg. A complete healing of the skin ulcers was noted three months after initiation of the above therapy. He continues on this treatment without any side-effects.Conclusion: A multidisciplinary approach allows for a more detailed evaluation of these challenging cases and helps to improve clinical outcomes. DisclosuresNo relevant conflicts of interest to declare.

Betrixaban: A Novel Factor Xa Inhibitor for the Prevention of Venous Thromboembolism in Acutely Ill Medical Patients.

Venous thromboembolism (VTE) is a common and preventable cause of morbidity and mortality in hospitalized patients. Low-molecular-weight heparin, low-dose unfractionated heparin, fondaparinux, and warfarin have been the mainstay options for the prevention and treatment of VTE before the emergence of nonvitamin K antagonist oral anticoagulants (NOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban. Despite the advantages of NOACs in improving patient adherence, none of them are approved for the prevention of VTE in acutely ill medical patients at high risk of thromboembolism. Betrixaban is a new NOAC and a factor Xa inhibitor that was approved for extended-duration thromboprophylaxis in these high-risk patients. The approval was based on the results of the APEX (Acute Medically Ill VTE Prevention with Extended Duration Betrixaban) study. In this Phase III randomized controlled trial, once-daily oral betrixaban (35 to 42 days extended duration) was associated with a reduction of composite VTE with no difference in major bleeding when compared to once-daily subcutaneous enoxaparin (6 to 14 days standard duration). Betrixaban differs from other NOACs by having a longer half-life, minimal CYP450 interactions, and minimal renal clearance. This article provides an overview of betrixaban's pharmacological profile, clinical trial results, and potential roles in therapy.

Erratum: Effectiveness and Safety of Apixaban versus Warfarin as Outpatient Treatment of Venous Thromboembolism in U.S. Clinical Practice.

In the AMPLIFY clinical trial, apixaban was non-inferior to warfarin plus subcutaneous enoxaparin bridge therapy in the treatment of acute venous thromboembolism (VTE) and was associated with significantly less bleeding. This study evaluated their comparative effectiveness and safety in routine clinical practice. A matched-cohort design and data from four U.S. private health care claims databases were employed. Study population comprised patients who initiated outpatient treatment with apixaban versus warfarin (plus parenteral anticoagulant bridge therapy) within 30 days of their initial VTE episode; apixaban and warfarin patients were matched on age, characteristics of VTE episode, study database and propensity score. Major bleeding, clinically relevant non-major (CRNM) bleeding and recurrent VTE during the 180-day (maximum) follow-up period were compared using shared frailty models. During mean follow-up of 143 days among apixaban patients (n = 17,878) and 152 days among warfarin patients (n = 17,878), incidence proportions for apixaban versus warfarin, respectively, were 1.7% versus 2.3% for major bleeding, 7.0% versus 9.4% for CRNM bleeding and 2.3% versus 2.9% for recurrent VTE. In shared frailty models, risks of major bleeding (hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.64–0.87), CRNM bleeding (HR = 0.77, 95% CI = 0.71–0.83) and recurrent VTE (HR = 0.80, 95% CI = 0.70–0.91) were lower for apixaban versus warfarin. In this large-scale evaluation of VTE patients receiving outpatient treatment with apixaban or warfarin in U.S. clinical practice, risks of major bleeding, CRNM bleeding and recurrent VTE were significantly lower among patients who received apixaban.

Dengue shock syndrome complicated with acute liver failure and kidney injury, infective endocarditis, and deep vein thrombosis: a case report

BackgroundDengue fever is a mosquito-borne viral disease with a very high incidence in Southeast Asia. Most patients with dengue fever recover following a self-limiting febrile illness, while a small proportion may progress to develop severe disease with complications such as acute liver failure, acute kidney injury, and multiorgan failure. Secondary bacterial infections and thrombotic events are very rare.Case presentationA 38-year-old previously healthy Sri Lankan woman from Colombo, Sri Lanka, presented with dengue shock syndrome leading to acute liver failure and kidney injury. She was managed with intravenously administered fluid resuscitation with close monitoring of her hemodynamic status, and hemodialysis. Her renal and liver functions and platelet count improved gradually, but the fever persisted and there was a neutrophil leukocytosis. A clinical examination and investigations to identify a focus of secondary infection revealed staphylococcal infective endocarditis. She was started on intravenously administered vancomycin, but as the response was poor the antibiotic was changed to intravenously administered linezolid, to which the response was good. She also developed right proximal femoral deep vein thrombosis, and was commenced on subcutaneous enoxaparin and warfarin. Enoxaparin was stopped after her international normalized ratio reached the desirable range, and warfarin was continued for 3 months.ConclusionsDengue virus is known to cause endothelial dysfunction that allows bacteria to invade tissues, defective functioning and reduction in the number of cells of the immune system, and alteration of cytokines leading to immune dysregulation, predisposing patients to develop secondary bacterial infections. Evidently, patients with dengue fever who have prolonged fever (more than 5 days) and acute kidney injury are at high risk for concurrent bacteremia. Dengue virus interferes with the components of the anti-clotting pathway, such as thrombomodulin-thrombin-protein C complex. It also activates endothelial cells and increases the expression of procoagulant factors. These factors may predispose patients with dengue viral infections to develop thrombotic complications. Therefore it is important to be aware of the possibility of serious secondary bacterial infections occurring following dengue viral infections, especially in patients with prolonged fever and acute kidney injury, and to keep in mind that thrombotic events may occur as complications of dengue viral infections.

Superior mesenteric venous thrombophlebitis: A rare complication of a common disease

We would like to report a case of acute appendicitis complicated with superior mesenteric venous (SMV) thrombophlebitis. A 61‐year‐old gentleman presented with abdominal pain and high fever with elevated white cell count and slightly deranged liver function and clotting profile. Besides features of acute appendicitis, a thrombus in superior mesenteric vein was demonstrated on computed tomography (CT). Patient was treated with emergency laparoscopic appendectomy, a course of antibiotics and subcutaneous enoxaparin. CT 2 months after operation showed features of resolving SMV thrombophlebitis. Mesenteric venous thrombophlebitis is difficult to diagnose as the clinical presentation is often nonspecific and it depends on the site and timing of thrombus formation. Such rare complication has to be suspected if the patient presents late or when there were high fever and deranged liver function. Prompt appendectomy and antibiotics therapy remain the essential components of treatment for acute appendicitis. The need of additional anticoagulation therapy and its optimal duration for SMV thrombophlebitis remains unclear. Nevertheless, the use of anticoagulation therapy should be weighed against the risk of bleeding complication.

Enoxaparin 20 mg for thromboprophylaxis in severe renal impairment.

ObjectiveThis study was performed to evaluate the efficacy of daily subcutaneous enoxaparin 20 mg in patients with renal failure.MethodsThis retrospective cohort study included nonsurgical patients aged ≥18 years with a creatinine clearance rate of <30 mL/minute who were prescribed enoxaparin 20 mg subcutaneously (SC) daily for ≥3 days. The main outcome measures were the occurrence of a venous thromboembolic event (VTE) and bleeding events.ResultsOne hundred sixty patients were identified. VTE occurred in 9 patients (5.6%), and bleeding events occurred in 37 (23.1%). Multivariable analysis showed that an age of >75 years was significantly associated with an increased risk of bleeding, while a creatinine clearance rate of 15 to 29 mL/minute was significantly associated with a lower risk of bleeding.ConclusionIn patients with renal failure, enoxaparin 20 mg SC daily resulted in a 5.6% incidence of VTE, which is similar to the previously published acceptable incidence of VTE in patients with normal renal function receiving enoxaparin 40 mg SC daily. The incidence of major bleeding events was 10%, which is lower than that previously published in the literature.

Enoxaparin: A cause of postoperative fever?

Enoxaparin (clexane) is a low-molecular-weight heparin commonly prescribed for the chemoprophylaxis of venous thromboembolism in postoperative hip or knee replacement or abdominal surgery patients. We herein report a case of persistent postoperative fever in a patient, likely due to enoxaparin use. Prompt resolution of the patient’s fever was observed after discontinuation of subcutaneous enoxaparin for chemical thromboprophylaxis. Reliable incidence data are lacking. A comprehensive search of PubMed, MEDLINE and EMBASE databases, as well as grey literature, found only two prior single case reports on enoxaparin-related fever. The mechanism responsible for the febrile reaction is likely an idiosyncratic response. Enoxaparin is typically derived from bovine or porcine intestines and lungs, hence its potential to cause hypersensitivity reactions is perhaps unsurprising. Clinicians should be alert to this possibility.

Development and evaluation of thermo-sensitive hydrogel system with nanocomplexes for prolonged subcutaneous delivery of enoxaparin

Here we report the combination of thermo-sensitive hydrogel systems and nanocomplexes for prolonged subcutaneous delivery of enoxaparin (EX). Thermo-sensitive hydrogels were prepared with enoxaparin solution and dispersion of enoxaparin nanocomplexes. Nanocomplexes (NC) were formed by self-assembly of enoxaparin with cationic polymers. Three polymers namely ε-polylysine (Plys), chitosan (CS), polyethylenimine (PEI), were tested. Three nanocomplexes were optimized in terms of different EX/polymer mass ratio, and their size, zeta-potential and morphology were evaluated. Thermo-sensitive hydrogels were examined by gelation temperature, gel dissolution. In vitro EX release study demonstrated that nanocomplexes incorporation into thermo-sensitive hydrogels could prolong the EX release. Overall, nanocomplexes in thermo-sensitive hydrogels is promising delivery systems for prolonged subcutaneous EX delivery.

Overview of betrixaban and its role in clinical practice.

The role of betrixaban in the prevention of venous thromboembolism (VTE) in acutely medically ill patients and its efficacy and safety profiles are reviewed. Acutely medically ill patients have a high risk of developing VTE during hospitalization, and this risk continues into the postdischarge phase. Extended-duration betrixaban therapy has been evaluated in a large clinical trial (the APEX trial) and in a meta-analysis of pooled data on acutely medically ill patients. These studies have shown positive outcomes when betrixaban was compared with conventional-duration subcutaneous enoxaparin therapy for prevention of VTE in acutely medically ill patients. In parallel with these results, oral betrixaban therapy was found to be associated with a rate of major bleeding comparable to that associated with subcutaneous enoxaparin therapy; however, betrixaban use was associated with a higher cumulative rate of major and clinically relevant nonmajor bleeding. In the APEX trial, the primary endpoint was not met in 1 of the prespecified cohorts, but betrixaban appeared to confer benefit in another cohort and in the overall study population. Certain populations of patients, including the elderly, are at high risk for bleeding (mainly attributable to altered pharmacokinetics and polypharmacy); such patients are not appropriate candidates for extended-duration betrixaban therapy. Betrixaban can be a potential option for VTE prevention in medical patients; however, drug interaction potential and third-party coverage should be evaluated prior to prescribing. Betrixaban is an oral option for VTE prevention in medical patients.

Sodium pentosan polysulfate efficacy as thromboprophylaxis agent in high-risk women following gynecological surgery.

Sodium pentosan polysulfate (Na-PPS) is a plant-based agent that has similar action with low-molecular-weight heparin. It inhibits factor Xa, preventing blood clot formation. To date, its use in clinical practice as thromboprophylaxis agent is still limited. In addition, the efficacy and safety profile of this agent was not robustly reported globally, especially for countries with major Muslim population. We hypothesized that Na-PPS was equally effective as the standard thromboprophylaxis. We aim to compare the efficacy and safety of Na-PPS against standard agent (fondaparinux or enoxaparin). This was a randomized control, open-label trial. Women underwent major gynecological surgery were randomized to receive either subcutaneous 50 mg of Na-PPS twice daily or subcutaneous enoxaparin 40 mg once daily. Fondaparinux 2.5 mg once daily was given to Muslim women as an alternative to enoxaparin. The treatment was started 6 h postoperatively, for at least 3 days. All the patients received thromboembolic deterrent stockings. The primary efficacy outcome was venous thromboembolism up to 3 days postsurgery. The main safety outcomes were minor and major bleeding. Among 109 participants, there was no incidence of venous thromboembolism. None of the women developed major bleeding. Minor bleeding was observed in 28.3% (15/53) and 5.4% (3/56) of Na-PPS and standard thromboprophylaxis group, respectively (P = 0.001). Na-PPS was associated with increased risk of minor bleeding. There was insufficient data to conclude its efficacy as thromboprophylaxis. Further research is needed to evaluate Na-PPS safety as a standard thromboprophylactic agent.

Incidence of symptomatic venous thromboembolism in 2372 knee and hip replacement patients after discharge: data from a thromboprophylaxis registry in Montreal, Canada.

BackgroundLow-molecular-weight heparin (LMWH) is a recommended anticoagulant for thromboprophylaxis after major orthopedic surgery. Dabigatran etexilate is an oral anticoagulant recognized as noninferior to LMWH. We aimed to assess the incidence of symptomatic venous thromboembolic events (VTEs) after discharge in patients who underwent joint replacement, using a hospital registry.Patients and methodsPatients who underwent total knee and hip arthroplasty between September 2011 and March 2015 were selected. Subcutaneous enoxaparin (30 mg twice daily) was given during hospitalization. At discharge, patients received either enoxaparin 30 mg twice daily/40 mg once daily or dabigatran 220 mg/150 mg once daily. Patients were seen or called at 2, 6, and 12 weeks after surgery. Outcomes were the number of VTEs, including deep venous thrombosis, pulmonary embolism, and the number of major/minor bleeding events after discharge.ResultsAfter discharge, 1468 patients were prescribed enoxaparin and 904 dabigatran (1396 total knee arthroplasty and 976 total hip arthroplasty patients). Mean age was 66±10 years, and 60% were female. The cumulative incidence of VTEs during the 12-week follow-up was 0.7%. One patient sustained a VTE during the switch window. Seven patients sustained a pulmonary embolism (0.3%). There was no statistical difference between the total knee arthroplasty and total hip arthroplasty groups. The incidence of major and minor bleeding events during follow-up was 0.3% and 30.3%, respectively. These events had a higher incidence in the dabigatran group compared to the enoxaparin group after discharge (p<0.05), but not between knee and hip replacement groups for major bleeding events.ConclusionA pharmaceutical prophylaxis protocol using LMWH and dabigatran during the post-discharge period resulted in low incidences of VTE and equivalence between treatments. However, the increased number of major and minor bleeding events in patients taking dabigatran is of concern regarding the safety and needs to be evaluated using analyses adjusted for risk factors.

Betrixaban for prevention of venous thromboembolism in acute medically ill patients.

Venous thromboembolism (VTE) is a common, potentially preventable cause of morbidity and mortality among acute medically ill patients. More than half of VTE events in this population occur after hospital discharge. Thus, providing extended-duration VTE prophylaxis from in-hospital through the post-discharge continuum may improve the quality of care in patients at risk of VTE. Betrixaban is a new oral, once-daily factor Xa inhibitor approved by the United States (US) Food and Drug Administration (FDA) for extended-duration prophylaxis of VTE in acute medically ill patients. The clinical efficacy and safety of betrixaban in acute medically ill patients perceived to be at high risk for VTE were evaluated in a large, randomized, double-blind, active-controlled, multinational clinical trial [Acute Medically Ill VTE Prevention With Extended Duration Betrixaban (APEX)]. Patients were randomized to receive subcutaneous enoxaparin (10 ± 4 days) or oral betrixaban (35–42 days) plus matching placebos. The primary efficacy outcome was a composite of asymptomatic proximal deep vein thrombosis and symptomatic VTE; the primary safety measure was major bleeding. Extended-duration betrixaban reduced VTE events without an increase in major bleeding in the modified intent-to-treat analysis. Post hoc analyses of the APEX trial provided further evidence to support the efficacy and safety of betrixaban in reducing all-cause ischaemic stroke, fatal or irreversible ischaemic or bleeding events, as well as reducing VTE-related rehospitalization. In summary, analyses of the APEX study demonstrated a positive benefit–risk profile for extended prophylaxis of VTE with betrixaban in acute medically ill patients. This is likely to have important public health and health economic implications.

(16) Intravenous and Subcutaneous Enoxaparin Trends in a Pediatric ICU

(16) Intravenous and Subcutaneous Enoxaparin Trends in a Pediatric ICU

Targeting Coagulase Activity in Staphylococcus aureus Bacteraemia: A Randomized Controlled Single-Centre Trial of Staphylothrombin Inhibition.

Staphylococcus aureus (S. aureus) bacteraemia is frequent and carries a high morbidity and mortality. Coagulases secreted by S. aureus initiate blood coagulation by directly activating prothrombin. This pathogen-activated coagulation is insensitive to most antithrombotic drugs, with the exception of small molecule direct thrombin inhibitors (DTIs). DTIs inhibit the coagulase-prothrombin complex, or staphylothrombin, and improve outcome in preclinical models of S. aureus infection. A single-centre, randomized, controlled feasibility and safety trial of staphylothrombin inhibition with DTIs in patients with S. aureus bacteraemia. Consecutive eligible adult patients with S. aureus positive blood cultures in the University Hospitals Leuven (Belgium) were randomized 1:1 to DTI (oral dabigatran 110 mg twice daily or intravenous argatroban according to activated partial thromboplastin time [aPTT]) for 7 to 10 days, or subcutaneous enoxaparin 40 mg once daily. Primary outcomes were feasibility and safety of DTI in patients with S. aureus bacteraemia. Secondary outcomes include D-dimer evolution (day 0-4) as marker of coagulation activation; inflammatory and microbiological parameters; and clinical outcomes including metastatic infections. Thirty-one percent (94/303) of screened patients were enrolled. Dabigatran plasma levels inhibited staphylothrombin. Clinically relevant bleeding (5/47 vs. 5/47) and thrombotic (7/47 vs. 7/47) complications were similar in both groups. Coagulase inhibition with DTIs was associated with a trend towards faster D-dimer decrease at day 4 (-662 ± 249 ng/mL vs. -40 ± 213 ng/mL for DTI-treated patients vs. control; p = 0.06) and a numerically lower number of persistently positive blood cultures. No differences in inflammatory parameters or other clinical outcomes were observed. Targeting staphylothrombin with DTIs is feasible in a subset of S. aureus bacteraemic patients, with comparable safety to standard thromboprophylaxis. In future studies of staphylothrombin inhibition, feasibility can be further improved by rapid diagnostics and by strategies without concomitant anticoagulant effect.

Pilot study of gemcitabine, nab-paclitaxel, PEGPH20, and rivaroxaban for advanced pancreatic adenocarcinoma: An interim analysis.

405 Background: PEGPH20 (P) degrades hyaluronan (HA), a key component of pancreatic adenocarcinoma (PDAC) tumor microenvironment, leading to reduction of tumor interstitial pressure, decompression of tumor blood vessels and improvement in delivery of chemotherapeutics. A prior study of P with chemotherapy in PDAC (HALO-202) found an increased risk of thromboembolic (TE) events, 43%, effectively reduced with subcutaneous enoxaparin treatment. Rivaroxaban (R) is a safe and effective oral anticoagulant for treating cancer-related TE. Methods: 28 patients with advanced PDAC, KPS ≥ 70 and without prior TE were enrolled from January to June 2017. Patients received treatment with PAG (P; 3 µg/kg IV 2x/wk x 3 wks in C1, then 1x/wk x 3 wks in C2+, plus AG) every 28 days, with R (15 mg twice daily for 21 days, followed by 20 mg once daily). Primary endpoint is symptomatic TE event rate; secondary endpoints include PFS, OS, major bleeding rate and RR. Results: All 28 patients are evaluable for efficacy and safety. Key patient characteristics: age = 62 (range 45-76), M/F = 15/13, stage III/IV = 4/24, KPS 70/80/90 = 1/13/14. Median follow-up is 5.4 mo. No symptomatic and one grade 2, asymptomatic TE event (DVT) occurred (1/28 = 3.6%). Two grade 3 GI hemorrhages occurred. Best responses: partial response 11 (39%), stable disease 13 (46%), progressive disease 4 (14%), and overall disease control rate of 86%. Median PFS and OS have not been reached. Conclusions: Interim analysis shows R is safe and effectively prevents TE events in patients receiving PAG. Responses and disease control rate are encouraging in this tumor HA-level unselected patient population. Updated safety and efficacy data will be reported. Clinical trial information: NCT02921022.

Ecchymosis and/or haematoma formation after prophylactic administration of subcutaneous enoxaparin in the abdomen or arm of the critically ill patient

IntroductionEcchymosis and/or haematoma are the most common adverse events after subcutaneous administration of low molecular weight heparin. There is no strong recommendation as to the puncture site. ObjectiveTo evaluate the adverse events, ecchymosis and/or haematoma after the administration of prophylactic subcutaneous enoxaparin in the abdomen vs the arm in the critically ill patient. MethodologyA randomised, two-arm clinical trial (injection in the abdomen vs the arm), performed between July 2014 and January 2017, in an 18-bed, polyvalent intensive care unit. Patients receiving prophylactic enoxaparin, admitted >72h, with no liver or haematological disorders, a body mass index (BMI) >18.5, not pregnant, of legal age and with no skin lesions which would impede assessment were included. We excluded patients who died or who were transferred to another hospital before completing the evaluation. We gathered demographic and clinical variables, and the onset of ecchymosis and/or haematomas at the injection site after 12, 24, 48 and 72h. A descriptive analysis was undertaken, with group comparison and logistic regression. The study was approved by the ethics committee with the signed consent of patients/families. Results301 cases (11 excluded): 149 were injected in the abdomen vs 141 in the arm. There were no significant differences in demographic and clinical variables, BMI, enoxaparin dose or antiplatelet administration [ecchymosis, abdomen vs arm, n (%): 66 (44) vs 72 (51), P=0.25] [haematoma abdomen vs arm, n (%): 9 (6) vs 14 (10), P=0.2]. Statistical significance was found in the size of the haematomas after 72h: [area of haematoma (mm2) abdomen vs arm, median (IQR): 2 (1–5.25) vs 20(5.25–156), P=0.027]. ConclusionsIn our patient cohort, prophylactic subcutaneous enoxaparin administered in the abdomen causes fewer haematomas after 72h, than when administered in the arm. The incidence rate of ecchymosis and haematoma was lower than the published incidence in critically ill patients, although patients receiving anti-platelet agents present a higher risk of injury. No relationship was observed in relation to BMI.

Formación de equimosis y/o hematoma tras la administración profiláctica de enoxaparina subcutánea en abdomen o brazo en pacientes críticos

IntroductionEcchymosis and/or haematoma are the most common adverse events after subcutaneous administration of low molecular weight heparin. There is no strong recommendation as to the puncture site. ObjectiveTo evaluate the adverse events, ecchymosis and/or haematoma after the administration of prophylactic subcutaneous enoxaparin in the abdomen vs the arm in the critically ill patient. MethodologyA randomised, two-arm clinical trial (injection in the abdomen vs the arm), performed between July 2014 and January 2017, in an 18-bed, polyvalent intensive care unit. Patients receiving prophylactic enoxaparin, admitted >72h, with no liver or haematological disorders, a body mass index (BMI) >18.5, not pregnant, of legal age and with no skin lesions which would impede assessment were included. We excluded patients who died or who were transferred to another hospital before completing the evaluation. We gathered demographic and clinical variables, and the onset of ecchymosis and/or haematomas at the injection site after 12, 24, 48 and 72hours. A descriptive analysis was undertaken, with group comparison and logistic regression. The study was approved by the ethics committee with the signed consent of patients/families. Results301 cases (11 excluded): 149 were injected in the abdomen vs 141 in the arm. There were no significant differences in demographic and clinical variables, BMI, enoxaparin dose or antiplatelet administration [ecchymosis, abdomen vs arm, n(%): 66(44) vs 72(51), P=.25] [haematoma abdomen vs arm, n(%): 9(6) vs 14(10), P=.2]. Statistical significance was found in the size of the haematomas after 72h: [area of haematoma (mm2) abdomen vs arm, median (IQR): 2(1-5.25) vs 20(5.25-156), P=.027]. ConclusionsIn our patient cohort, prophylactic subcutaneous enoxaparin administered in the abdomen causes fewer haematomas after 72hours, than when administered in the arm. The incidence rate of ecchymosis and haematoma was lower than the published incidence in critically ill patients, although patients receiving anti-platelet agents present a higher risk of injury. No relationship was observed in relation to BMI.

Association of D-dimer Levels with Clinical Event Rates and the Efficacy of Betrixaban versus Enoxaparin in the APEX Trial.

Background Elevated D-dimer concentrations are associated with an increased risk of venous thromboembolism (VTE). However, they may also provide prognostic value. The present analysis sought to study the association of D-dimer levels with VTE event rates and the efficacy of betrixaban versus enoxaparin in the APEX trial. Methods Hospitalized acutely medically ill subjects ( n = 7,513) were randomized in a double-dummy double-blind fashion to either extended-duration oral betrixaban (80 mg once daily for 35–42 days) or standard dose subcutaneous enoxaparin (40 mg once daily for 10 ± 4 days) for venous thromboprophylaxis. D-dimer was assessed using a central core laboratory measurement. Results For every 0.25 µg/mL increase in D-dimer concentration, there was a 2% increase in the relative risk of experiencing the primary efficacy endpoint (asymptomatic deep vein thrombosis [DVT], symptomatic DVT, nonfatal pulmonary embolism, or VTE-related death) in both the betrixaban ( p < 0.001) and enoxaparin ( p < 0.001) treatment arms. Among D-dimer-positive (≥ 2 × upper limit of normal; corresponding to ≥ 1.00 µg/mL) subjects, extended-duration betrixaban reduced the risk of experiencing the primary efficacy outcome (5.4% [ n = 124] vs. 7.6% [ n = 170]; odds ratio = 0.69; 95% confidence interval: 0.55–0.88; absolute risk reduction = 2.2%, number needed to treat = 46, p = 0.003). There was no interaction between D-dimer and the treatment effect ( p int = 0.53). Conclusion Extended-duration betrixaban was superior to standard-duration enoxaparin, irrespective of D-dimer level at baseline. To prevent one VTE event, 46 D-dimer-positive patients would need to be treated with betrixaban.