Molecular Weight Heparin In Patients Research Articles

Apixaban versus low molecular weight heparin in patients with cancer associated venous thromboembolism: A systematic review and meta analysis

Background: Optimal treatment regimen for patients with cancer-associated venous thromboembolism (CA-VTE) remain unclear. Therefore, we sought to compare the outcomes of (VKAs) versus direct apixaban and low molecular weight heparin (LMWH) in patients with CA-VTE. Methods: MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials (RCTs) and observational studies comparing efficacy and safety of apixaban and LMWH in patients with CA-VTE. Major bleeding, clinically relevant non major bleeding (CRNMB), recurrence of pulmonary embolism (PE), deep venous thrombosis (DVT) and bleeding related mortality were among outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate relative risks (RRs) with 95 percent confidence intervals (CIs). Results: The analysis included 12011 patients from 3 RCTs and 2 observational studies. Compared to LMWH, apixaban significantly decreased the risk of major bleeding (RR 0.67 [95% CI 0.54, 0.83]; P=0.0003, I2=0%) without significantly changing the risk of clinically relevant non major bleeding (RR 0.96 [95% CI 0.64, 0.1.45]; P=0.85, I2=57%). Patients on apixaban had a noticeably reduced the risk of recurrence of PE than those taking LMWH, according to a meta-analysis (RR 0.56 [95% CI 0.32, 0.99]; P=0.05, I2=0%). There was no discernible difference between apixaban and LMWH in bleeding related mortality events (RR 0.20 [95% CI 0.01, 4.18]; P=0.30, I2=NA%), and recurrence of DVT (RR 0.60 [95% CI 0.22, 1.59]; P=0.23, I2=32%), Conclusion: Due to its lower risk of severe bleeding and reduced PE recurrence, apixaban may be a preferable treatment option for CA-VTE, but additional research is required to validate these conclusions and evaluate its long-term efficacy and safety.

Tolerability of Direct Oral Anticoagulants and Low Molecular Weight Heparin in Patients with Brain Tumors or CNS Metastases

Background: Despite the increase in the use of direct oral anticoagulants (DOACs) for cancer-associated thrombosis, limited data exists regarding the safety of DOACs in patients with brain metastases or primary brain tumors. The purpose of this retrospective cohort study is to describe overall tolerability of DOACs compared to low-molecular weight heparin (LMWH) for the treatment of venous thromboembolism (VTE) or for stroke prevention in atrial fibrillation (AF), in patients with brain tumors or CNS metastases. Methods: This is a single center, institutional review board approved retrospective cohort study at New York University Langone Health of patients with primary brain tumors or CNS metastasis that received therapeutic dosed anticoagulation with either a DOAC or LMWH (enoxaparin) between December 1, 2018 and August 19, 2022. Electronic medical records were reviewed for pertinent data. The primary outcome was tolerability of anticoagulation, which included continuation of initial anticoagulation therapy and absence of any switches in anticoagulation, dose adjustments or temporary interruptions. Reasons for discontinuations included bleeding events, intolerance/patient preference (such as the need for subcutaneous administration or cost of therapy), provider preference, or a change in clinical status such as transition to hospice or unable to determine based on chart review. Secondary outcomes included the incidence of anticoagulation discontinuations secondary to an intracerebral hemorrhage (ICH). Results: A total of 153 patients were included (DOAC n = 105, 69%; enoxaparin n = 48, 31%). The study population was predominantly White (74%), male (59%), with a median BMI≥30 kg/m2 in 40% of the cohort and age of 65 (IQR 56-73) years; however, the enoxaparin group was younger than the DOAC group at 59.5 years vs. 67 years (p <0.001), respectively at the time of anticoagulation initiation. Primary brain tumors were the most prevalent in the total cohort at 89%, with enoxaparin most commonly prescribed at 71% versus a DOAC at 47%, p = 0.005. Other primary malignancies included anaplastic astrocytoma, glioma, anaplastic oligodendroglioma, and tanycytic ependymoma. Non-small cell lung cancer was the most common malignancy that resulted in CNS metastasis (7.2%). The most common indication for anticoagulation was for the treatment of VTE at 70%, followed by stroke prevention in AF at 28%, with the remainder 2% as off-label. The primary outcome of remaining on initial anticoagulant chosen without any anticoagulant therapy changes occurred in only 52% of the cohort. There were more changes in therapy in the enoxaparin cohort at 29, 60% vs. 44, 42% for the DOAC cohort, p = 0.033, driven by provider preference in 48% of the cohort and patient intolerance in 29% of the cohort. More patients in the enoxaparin cohort were switched to a DOAC (n = 17) and more patients in the DOAC cohort had their initial anticoagulation discontinued for non- ICH reasons (n = 14). The median time to any anticoagulation switch was 2.12 months (IQR 0.35-4.27 months). Discontinuations in patients who were still alive was primarily driven by completion of therapy, deemed by the treatment team, intolerance or patient preference, and provider preference (Table 1). Though the reason for provider preference was not always clearly elucidated upon chart review, this trend supports the movement towards increasing DOAC use. The secondary outcome of the incidence of ICH was also lower in the DOAC cohort compared to enoxaparin at 3.8 vs 14.6% (p = 0.037). (Figure 1) Conclusions: Our study demonstrates real world prescribing practice of anticoagulants for the treatment of VTE or stroke prevention in AF in patients with primary brain tumors or metastases. Although initial anticoagulants chosen were either discontinued or switched to an alternative agent, we observed a shift towards a preference for DOACs, similar to the shift towards DOACs for cancer associated thrombosis. We also observed a lower incidence of ICH with DOACs compared to LMWH. However, these results should be confirmed in a randomized controlled trial to account for the inherent selection biases we could not account for, which may have favored the initial anticoagulant chosen, the reason for switch, and overall tolerability.

Efficacy and safety of long-term use of low molecular weight heparins in patients with systemic lupus erythematosus and antiphospholipid syndrome

To date, the management of patients with antiphospholipid syndrome (APS) with ineffectiveness and/or intolerance to vitamin K antagonists and direct oral anticoagulants remains controversial. One of the treatment strategies is the administration of low molecular weight heparins (LMWH) over a long period of time. Objective: to evaluate the efefficacy and safety of long-term treatment with LMWH in patients with APS. Material and methods. The study included 15 patients (13 women and 2 men) with APS. In 2 of them APS was isolated, in 12 it was combined with systemic lupus erythematosus (SLE), and in 1 – with SLE and psoriatic arthritis. The mean age of patients was 44 ± 12 years, and the mean duration of disease was 12 [6; 18] years. All patients were repeatedly examined in the V. A. Nasonova Research Institute of Rheumatology during hospitalizations and continued outpatient care in the clinical diagnostic center of the Institute. Results and discussion. Ten (67 %) patients received nadroparin, 5 (33 %) patients received enoxaparin. The median duration of therapy was 4 [1; 10] years. Indications for the use of LMWH were inefficacy and intolerance of oral anticoagulants (n = 12, 100 %) and vascular involvement such as thromboangiitis obliterans with the development of chronic arterial insufficiency, ulcers and necrosis of the toes (n = 6, 40 %). During therapy, 13 (86 %) of 15 patients showed clinical improvement: healing of ulcers and necrosis, reduction in the stage of arterial insufficiency, recanalization of venous blood clots. During the entire treatment period with LMWH, one patient experienced a relapse of thrombosis due to an insufficient dose of the drug. No hemorrhagic complications occurred in any case. Other adverse events, including elevated liver aminotransferases, osteoporosis, and thrombocytopenia, were also not observed. Conclusion. The results obtained suggest that long-term therapy with LMWH may be safe and effective in patients with APS.

PB0938 Direct Oral Anticoagulants versus Low Molecular Weight Heparins in Patients with Brain Tumor Receiving Therapeutic Anticoagulation: A Systematic Review and Meta-Analysis

PB0938 Direct Oral Anticoagulants versus Low Molecular Weight Heparins in Patients with Brain Tumor Receiving Therapeutic Anticoagulation: A Systematic Review and Meta-Analysis

Management of bleeding in patients on direct oral anticoagulants in emergency department: where we are and where we are going.

Many patients who access in the emergency department for acute bleeding are on anticoagulants; before specific reversal agents were developed, bleeding on anticoagulants was burdened with a substantial increase in morbidity and mortality. Clinical trials demonstrated favourable risk-benefit profiles of direct-acting oral anticoagulants compared with vitamin K antagonists in patients with atrial fibrillation and compared with low molecular weight heparin in patients treated and prevented from venous thromboembolism. Even if they drastically reduced some types of bleeding, particularly intracranial haemorrhage, they have not completely eliminated this risk. The arrival of a patient with active bleeding in the emergency department is always a critical scenario that involves resources and costs. In critical setting, the diagnosis and treatment of bleeding should occurred simultaneously. Understanding the pathophysiological mechanisms that occur during bleeding is essential for establish the most appropriate therapies and improve the standard of care of the haemorrhagic patients.

Co-administration of tacrolimus and low molecular weight heparin in patients with a history of implantation failure and elevated peripheral blood natural killer cell proportion.

To investigate the therapeutic effect of co-administration of tacrolimus (TAC) and low-molecular-weight heparin (LMWH) or LMWH only on pregnancy outcomes in the female with a history of implantation failure and elevated peripheral blood natural killer (pNK) cell proportion in frozen-thawed embryo transfer cycles. To evaluate the pregnancy parameters for 249 patients with ≥2 implantation failures and pNK cell proportion ≥12% by analyzing a retrospective observational cohort study. Sixty patients had received the co-administration TAC and LMWH (TAC & LMWH group), 85 others had only taken LMWH (LWMH group), and the rest did not take any particular drugs (control group). The experimental finding indicated that the TAC & LMWH group and the LMWH group showed higher clinical pregnancy rates than the control group (p < 0.05), and TAC & LMWH group had a much higher live birth rate. According to the binary logistic regression analysis, the combination of TAC and LMWH was conducive to clinical pregnancy and live birth rate and reduced the possibility of miscarriage. It would not affect the result of spontaneous abortion and live birth, although the LMWH was only beneficial to clinical pregnancy. In addition, these findings were similar for these three groups' obstetrical and neonatal outcomes. The combination of TAC and LMWH can improve clinical pregnancy and live birth rates and reduce the risk of spontaneous miscarriage in patients with a history of implantation failure and elevated pNK ratio. LMWH is also beneficial to clinical pregnancy.

Clinical and Experimental Study of Low Molecular Weight Heparin in Patients with Chronic Anemia

Objective: To preliminary study the significance of low molecular weight heparin (LMWH) in the treatment patients of with anemia of chronic diseases (ACD), and the changes in the serum levels of BMP6, hepcidin and IL-6. To preliminary study the significance of low molecular weight heparin (LMWH) in the treatment the patients with anemia of chronic diseases (ACD), and the changes in the serum levels of BMP6, hepcidin and IL-6. Methods: Used LMWH (4000 u/day, 7 - 15 days) to therapy 61 patients with ACD, and ELISA method was used to determine Hepcidin and BMP6 before and after treatment, and the determination of IL-6 by Electro-chemi-luminescence, and to analyze its clinical significance. Results: 1) In all 61 cases, the levels of Hepcidin in post-therapy were 0.82 ± 0.24 mg/L, which were lower than 1.05 ± 3.83 mg/L in pre-therapy (t = 2.5726, P P P > 0.05). However, The levels of Hb in post-therapy were higher than in pre-therapy (t = 1.9832, P P P P P > 0.05). 5) Although Hb level increased slightly in the non-tumor anemia group, there was no statistical significance (P > 0.05), and there was no statistical difference in other indexes (all P > 0.05). 6) After treatment, the level of Hb was negatively correlated with Hepcidin and IL-6 (respectively r = -0.2809, t = 2.2490, P P P < 0.05). There was no correlation between BMP6 and Hb, Hepcidin and IL-6 levels. Conclusion: LMWH could up-regulate the levels of Hb, and better for the degree of anemia in patients with ACD. The possible mechanism is to reduce the level of Hepcidin and IL-6.

Clinical Efficacy Analysis of Nifedipine Combined with Low Molecular Weight Heparin in the Treatment of Pregnancy Hypertension

This research aims to investigate nifedipine and low molecular weight heparin clinical efficacy in cure patients with hypertension during pregnancy. A retrospective analysis of 180 patients with hypertension during pregnancy admitted to the obstetric ward of our hospital from December 2017 to December 2020 was selected. Among them, 90 patients with hypertension during pregnancy were treated with nifedipine combined with low molecular weight heparin (observation group). Nifedipine was used to treat 90 patients with pregnancy-induced hypertension (control group). Contrast the blood pressure, D-dimer, pregnancy-related complications and adverse events incidence in both groups before and after treatment were compared. The observation group clinical effective rate was 90 % while the control group was 70 % (p<0.05). The blood pressure and D-dimer of both groups decreased obviously after treatment, but the observation group decreased more significantly than it (p<0.01). The observation group incidence of pregnancy-related complications (uterine weakness, postpartum hemorrhage) was significantly lower than the other (p<0.05). There was no diversity in these two groups in incidence of fetal distress, placental abruption and neonatal asphyxia (p<0.05), both groups incidence of adverse reactions were almost the same and there was no statistical difference (p>0.05). Nifedipine and low molecular weight heparin in patients cure with hypertension during pregnancy can lower blood pressure and reduce the incidence of uterine asthenia, postpartum hemorrhage and other related complications without increasing patient’s incidence of adverse reactions. The medication is meaningful for clinical promotion.

Cost-effectiveness analysis and budget impact of rivaroxaban compared with dalteparin in patients with cancer at risk of recurrent venous thromboembolism

ObjectivesIn the ‘Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism’ (SELECT-D) trial, rivaroxaban showed relatively low venous thromboembolism (VTE)...

A retrospective single-center evaluation of the safety and efficacy of direct oral anticoagulants versus low molecular weight heparin in patients with cancer-associated thrombosis.

e24102 Background: Over the past decade, there has been an increase in the use of direct oral anticoagulants (DOACs) in the cancer population despite limited data comparing its use against low molecular weight heparin (LMWH), the standard of care in cancer patients. Increasing data supporting DOACs in cancer-associated thrombosis has emerged over the past few years. Nonetheless, this study will evaluate the relative safety and efficacy of DOACs versus LMWH in cancer-associated thrombosis within an urban setting associated with low socioeconomic status. Methods: This is a retrospective chart review of medical records from patients treated at an urban academic medical center from October 2010 through October 2018. Patients met study inclusion if they had a diagnosis of venous thromboembolism occurring after the date of diagnosis of active cancer and were prescribed a direct oral anticoagulant (rivaroxaban, apixaban, dabigatran, edoxaban) or a low molecular weight heparin (dalteparin, enoxaparin, or fondaparinux) as monotherapy for the treatment of venous thromboembolic disease. Patients were excluded if they had less than 6 months of follow up data for reasons other than death. The primary outcomes were recurrent venous thromboembolism, major bleeding and death. Results: Of the 914 patients who met inclusion criteria, 286 were excluded due to lack of follow up data. The remaining patients included 472 in the LMWH arm and 156 in the DOAC arm. At 6 months, recurrent thromboembolism occurred in 5 of the 472 patients (1.1%) in the LMWH group as compared with 4 of the 156 patients (2.6%) in the DOAC group (p = 0.170). Major bleeding occurred in 36 patients (7.6%) in the LMWH group and 11 patients (7.0%) in the DOAC group (p = 0.813). Death within 6 months of starting anticoagulation occurred in 76 patients (16.1%) in the LMWH group and 16 patients (9.6%) in the DOAC group (p = 0.046). Discontinuation before 6 months of treatment occurred in 241 patients (51.2%) in the LMWH group and 46 patients (29.5%) in the DOAC group. Conclusions: The LMWH and DOAC groups had similar rates of recurrent thromboembolism and major bleeding. The mortality rate within 6 months of starting anticoagulation was significantly higher in the LMWH group and this difference requires further evaluation. These results help support the continued use of DOACs for the treatment of cancer-associated thrombosis and demonstrate that DOACs are as safe and effective as LMWH in this patient population.

Chromogenic anti-FXa assay calibrated with low molecular weight heparin in patients treated with rivaroxaban and apixaban: possibilities and limitations.

IntroductionClinical application of rivaroxaban and apixaban does not require therapeutic monitoring. Commercial anti-activated factor X (anti-FXa) inhibition methods for all anti-FXa drugs are based on the same principle, so there are attempts to evaluate potential clinical application of heparin-calibrated anti-FXa assay as an alternative method for direct FXa inhibitors. We aimed to evaluate relationship between anti-FXa methods calibrated with low molecular weight heparin (LMWH) and with drug specific calibrators, and to determine whether commercial LMWH anti-FXa assay can be used to exclude the presence of clinically relevant concentrations of rivaroxaban and apixaban.Materials and methodsLow molecular weight heparin calibrated reagent (Siemens Healthineers, Marburg, Germany) was used for anti-FXa activity measurement. Innovance heparin (Siemens Healthineers, Marburg, Germany) calibrated with rivaroxaban and apixaban calibrators (Hyphen BioMed, Neuville-sur-Oise, France) was used for quantitative determination of FXa inhibitors.ResultsAnalysis showed good agreement between LMWH calibrated and rivaroxaban calibrated activity (κ = 0.76) and very good agreement with apixaban calibrated anti-Xa activity (κ = 0.82), respectively. Low molecular weight heparin anti-FXa activity cut-off values of 0.05 IU/mL and 0.1 IU/mL are suitable for excluding the presence of clinically relevant concentrations (< 30 ng/mL) of rivaroxaban and apixaban, respectively. Concentrations above 300 ng/mL exceeded upper measurement range for LMWH anti-FXa assay and cannot be determined by this method.ConclusionLow molecular weight heparin anti-FXa assay can be used in emergency clinical conditions for ruling out the presence of clinically relevant concentrations of rivaroxaban and apixaban. However, use of LMWH anti-FXa assay is not appropriate for their quantitative determination as an interchangeable method.

Bleeding Risk of Therapeutic Unfractionated Heparin and Low Molecular Weight Heparin in Patients with Cirrhosis.

Patients with cirrhosis are simultaneously at an increased risk of bleeding and thrombosis. Studies comparing the safety of parenteral anticoagulants in this population are lacking. This study evaluated the safety of therapeutic unfractionated heparin versus low molecular weight heparin in patients with cirrhosis. This system-wide, retrospective cohort study included adults with cirrhosis receiving unfractionated heparin or low molecular weight heparin for the treatment of acute venous thromboembolism. The primary endpoint was the incidence of major bleeding. Eighty-two patients were included in this study, with 52 receiving unfractionated heparin and 30 receiving low molecular weight heparin. More major bleeding occurred in the unfractionated heparin arm compared to the low molecular weight heparin arm (19.2% vs 0%, p = 0.010). Low molecular weight heparin may be a safer option in patients with cirrhosis treated for acute venous thromboembolism, but future studies should confirm these findings.

Decreased Bleeding Incidence with Direct Oral Anticoagulants Compared to Vitamin K Antagonist and Low Molecular Weight Heparin in Patients with Sickle Cell Disease and Venous Thromboembolism

Decreased Bleeding Incidence with Direct Oral Anticoagulants Compared to Vitamin K Antagonist and Low Molecular Weight Heparin in Patients with Sickle Cell Disease and Venous Thromboembolism

In-hospital Outcome of Use of Low Molecular Weight Heparin in Patients Undergoing Percutaneous Coronary Intervention

This prospective observational study was carried out in the Department of Cardiology of national institute of cardiovascular diseases (NICVD), Dhaka to assess the safety of low molecular weight heparin (LMWH) in patients undergoing percutaneous coronary intervention (PCI). Safety of low molecular weight heparin in comparison to unfractionated heparin (UFH) was observed in this study. In total data from 100 patients undergoing elective PCI was evaluated. Among them 50 patients in group I received I mg/kg intra-arterial LMWH and rest in group II received UFH. Demographic profile of individuals in both groups was almost similar. There was no significant difference in major coronary risk factors between the two groups. Patients were monitored during their stay in hospital for any complications like bleeding, haematoma, myocardial infraction and death. No death was observed in any group. Minor bleeding in group I and II (6% vs 105), Major bleeding (2% vs4%) and haematoma (6% vs 10%). Myocardial infraction no incidence in group I and 4% in group II. So complications was more prevalent in group II who were treated with UFH, but those were not statistically significant. The intra-arterial administration of LMWH in patients undergoing PCI is safe. The risk of acute and sub-acute coronary events and bleeding complications are similar in both groups and in hospital outcome there is less complication with LMWH used during PCI.Bangladesh Heart Journal 2018; 33(1) : 22-27

Clinical News.

British Journal of Hospital MedicineVol. 79, No. 6 Clinical NewsClinical NewsOlof Dahlqvist, Johann Motsch, Sue Lyon, Jan van der MeulenOlof DahlqvistSearch for more papers by this author, Johann MotschSearch for more papers by this author, Sue LyonSearch for more papers by this author, Jan van der MeulenSearch for more papers by this authorOlof Dahlqvist; Johann Motsch; Sue Lyon; Jan van der MeulenPublished Online:12 Jun 2018https://doi.org/10.12968/hmed.2018.79.6.308AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Linge J, Borga M, West J et al.. Body composition profiling in the UK Biobank Imaging Study. Obesity 2018; https://doi.org/https://doi.org/10.1002/oby.22210 Crossref, Medline, Google ScholarSchuster C, Mayer FJ, Wohlfahrt C et al.. Acute HIV infection results in subclinical inflammatory cardiomyopathy. J Infect Dis. 2018. https://doi.org/https://doi.org/10.1093/infdis/jiy183 Crossref, Medline, Google ScholarFiranescu CE, de Vries J, Lodder P et al.. Vertebroplasty versus sham procedure for painful acute osteoporotic vertebral compression fractures (VERTOS IV): randomised sham controlled clinical trial. BMJ. 2018 May 9;361:k1551. https://doi.org/https://doi.org/10.1136/bmj.k1551 Medline, Google ScholarChapman JL, Cayanan EA, Hoyos CM et al.. Does armodafinil improve driving task performance and weight loss in sleep apnea? A randomized trial. Am J Respir Crit Care Med. 2018 May 18. https://doi.org/https://doi.org/10.1164/rccm.201712-2439OC Crossref, Google ScholarMaria Mavroul M, Vrioni G, Tsakris A et al.. 2018. Reemergence of West Nile Virus infections in humans in Southern Greece, July to September 2017. Abstract P0550 Google ScholarMotsch J, de Oliveira C, Stus V et al.. 2018. RESTORE-IMI 1: a multicentre, randomised, double-blind, comparator-controlled trial comparing the efficacy and safety of imipenem/relebactam versus colistin plus imipenem in patients with imipenem-non-susceptible bacterial infections. Abstract O0427 Google ScholarRobesyn E, Nakitanda OA, Sdona E et al.. 2018. How does the outcome of measles cases under one year of age differ from that of older cases, EU/EEA 2013-2017. Abstract O0060 Google ScholarVallance AE, Fearnhead NS, Kuryba A et al.. Effect of public reporting of surgeons' outcomes on patient selection, “gaming,” and mortality in colorectal cancer surgery in England: population based cohort study. BMJ. 2018;361:k1581. https://doi.org/https://doi.org/10.1136/bmj.k1581 Medline, Google ScholarGilbert T, Neuburger J, Kraindler J et al.. Development and validation of a Hospital Frailty Risk Score focusing on older people in acute care settings using electronic hospital records: an observational study. Lancet. 2018;391(10132):1775–1782. https://doi.org/https://doi.org/10.1016/S0140-6736(18)30668-8 Crossref, Medline, Google ScholarYoung AM, Marshall A, Thirlwall J et al.. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol. 2018 May 10:JCO2018788034. https://doi.org/https://doi.org/10.1200/JCO.2018.78.8034 Medline, Google Scholar FiguresReferencesRelatedDetails 2 June 2018Volume 79Issue 6ISSN (print): 1750-8460ISSN (online): 1759-7390 Metrics History Published online 12 June 2018 Published in print 2 June 2018 Information© MA Healthcare LimitedPDF download

Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D).

Purpose Venous thromboembolism (VTE) is common in patients with cancer. Long-term daily subcutaneous low molecular weight heparin has been standard treatment for such patients. The purpose of this study was to assess if an oral factor Xa inhibitor, rivaroxaban, would offer an alternative treatment for VTE in patients with cancer. Patient and Methods In this multicenter, randomized, open-label, pilot trial in the United Kingdom, patients with active cancer who had symptomatic pulmonary embolism (PE), incidental PE, or symptomatic lower-extremity proximal deep vein thrombosis (DVT) were recruited. Allocation was to dalteparin (200 IU/kg daily during month 1, then 150 IU/kg daily for months 2-6) or rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily for a total of 6 months). The primary outcome was VTE recurrence over 6 months. Safety was assessed by major bleeding and clinically relevant nonmajor bleeding (CRNMB). A sample size of 400 patients would provide estimates of VTE recurrence to within ± 4.5%, assuming a VTE recurrence rate at 6 months of 10%. Results A total of 203 patients were randomly assigned to each group, 58% of whom had metastases. Twenty-six patients experienced recurrent VTE (dalteparin, n = 18; rivaroxaban, n = 8). The 6-month cumulative VTE recurrence rate was 11% (95% CI, 7% to 16%) with dalteparin and 4% (95% CI, 2% to 9%) with rivaroxaban (hazard ratio [HR], 0.43; 95% CI, 0.19 to 0.99). The 6-month cumulative rate of major bleeding was 4% (95% CI, 2% to 8%) for dalteparin and 6% (95% CI, 3% to 11%) for rivaroxaban (HR, 1.83; 95% CI, 0.68 to 4.96). Corresponding rates of CRNMB were 4% (95% CI, 2% to 9%) and 13% (95% CI, 9% to 19%), respectively (HR, 3.76; 95% CI, 1.63 to 8.69). Conclusion Rivaroxaban was associated with relatively low VTE recurrence but higher CRNMB compared with dalteparin.

European guidelines on perioperative venous thromboembolism prophylaxis: Patients with preexisting coagulation disorders and after severe perioperative bleeding.

: In patients with inherited bleeding disorders undergoing surgery, we recommend assessment of individual risk for venous thromboembolism, taking into account the nature of the surgery and anaesthetic, type and severity of bleeding disorder, age, BMI, history of thrombosis, the presence of malignancy and other high-risk comorbidities. Venous thromboembolism risk should be balanced against the increased bleeding risk associated with anticoagulant use in patients with known bleeding disorders (Grade 1C). In these patients undergoing major surgery, we recommend against routine postoperative use of pharmacological thromboprophylaxis, especially for patients with haemophilia A and B (Grade 1B). Glomerular filtration rate should be assessed before initiation of each direct oral anticoagulant, and also at least once a year or more frequently as needed, such as postoperatively before the resumption of therapeutic direct oral anticoagulant administration, when it is suspected that renal function could decline or deteriorate (Grade 1C). Reduced dosages of low molecular weight heparins may be used relatively safely during transient severe (<50 × 10 l) thrombocytopaenia (Grade 2C). Monitoring of anti-Xa levels may be used to adjust the doses of low molecular weight heparin in patients with moderate or severe thrombocytopaenia (Grade 2C). The delay between major gastrointestinal bleeding and resuming warfarin should be at least 7 days (Grade 2C). For patients at a high risk of thromboembolism and with a high bleeding risk after surgery, we consider that administering a reduced dose of direct oral anticoagulant on the evening after surgery and on the following day (first postoperative day) after surgery is a good practice (Grade 2B).

Administration of prednisolone and low molecular weight heparin in patients with repeated implantation failures: a cohort study

Conflicting results exist for low molecular weight heparin (LMWH) and prednisolone when tested as separate adjuncts for the improvement of the clinical outcomes in patients with repeated implantation failures (RIF) undergoing IVF/ICSI treatment. Through a cohort study, we evaluated the combined effect of both drugs on pregnancy parameters in 115 women with RIF. Clinical pregnancy rate was the primary end point while the sample size was calculated through the results of a pilot study. Clinical and IVF cycle characteristics were also compared between the groups. Baseline and cycle characteristics were comparable between groups. Biochemical and clinical pregnancy rates were similar in both groups [23/57 (40.4%) vs. 14/58 (24.1%), and 17/57 (29.8%) vs. 11/58 (19%), p = .063, and .175, respectively]. Similarly, miscarriage rates were comparable between the groups (35.7% vs. 34.8%), as well as live birth rates [15/57 (26.3%) vs. 9/58 (15.5%), p = .154]. In conclusion, the administration of LMWH with prednizolone in subfertile women with RIF seems not to improve clinical pregnancy rates, but a full-scaled RCT would definitely be more accurate.

Incidence of venous thromboembolic events following major pelvic and abdominal surgery for cancer.

478 Background: The recommendation to administer extended-duration (28 days) venous thromboembolic events (VTE) prophylaxis with low molecular weight heparin in patients undergoing abdominal and pelvic surgery for cancer has not been widely implemented mainly because most studies focus on asymptomatic events with unknown clinical significance. The objective of this study was to determine the post-hospital discharge VTE incidence in these patients who do not receive post-hospital discharge prophylaxis. Methods: Prospective cohort study of patients undergoing abdominal and pelvic operations for cancer within the gastrointestinal tract, hepatobiliary (HPB) system or gynecological organs, with surgery lasting &gt; 1 hour, post-operative stay &lt; 28 days, and not undergoing anticoagulant therapy. Patients were evaluated at 1, 3 and 6 months from index operation for the presence of VTE by means of a screening ultrasound at 28 days and a questionnaire at each follow-up. The proportion with 95% confidence interval (CI) of VTE was calculated. Multivariable logistical regression was performed. Results: Of 284 patients, there were 79 (28%) colorectal, 97 (35%) HPB and 100 (35%) gynecology. All patients received pre- and post-operative in-patient prophylaxis. The proportion of VTE at 6 months was 7%, 95% CI 4.4-10.7 (20 events). Most events occurred between 3-6 months, 4.6%, 95% CI 2.46 – 7.7. Only one event occurred at one month after surgery (0.35%, 95% CI 0.06-1.97). 50% of the cohort had screening ultrasound, all of which were negative. Events were evenly distributed according to the type of surgery. The proportion of patients who died was 6.6%, 95% CI 3.5 – 9.4 (17 patients, 2 of which had a VTE-related death). In the multivariable analysis, post-operative chemotherapy was significantly associated with VTE, odds ratio (OR) 2.74, 95% CI 1.07-6.99. Caprini score was also associated with VTE but was not significant when included in the multivariable analysis, OR 1.19, 95% CI 0.99-1.42. Conclusions: Incidence of VTE following abdominal cancer surgery is low. Most events occur between 3-6 months from surgery. Post-operative chemotherapy is significantly associated with post-hospital discharge VTE.

Safety of fondaparinux for prevention of postoperative venous thromboembolism in urological malignancy: A prospective randomized clinical trial.

To prospectively evaluate the safety of postoperative fondaparinux in comparison with low molecular weight heparin in patients undergoing uro-oncological surgery. The present study was a prospective, single-blind, non-inferiority randomized trial. A total of 359 patients undergoing surgery for urological malignancy were enrolled from January 2011 to December 2012. A total of 298 of these patients (fondaparinux group, 152; low molecular weight heparin group, 146) were evaluable for the intention-to-treat-analysis. Patients were randomly assigned to low-dose unfractionated heparin, 5000 units twice daily until postoperative day 1 plus either fondaparinux 2.5 mg once daily or low molecular weight heparin 2000 units twice daily until postoperative day 5. The primary end-point was postoperative bleeding as by independent review, and the study was powered to show the non-inferiority of fondaparinux versus low molecular weight heparin. The other adverse events were evaluated. D-dimer and soluble fibrin monomer complex levels were measured perioperatively. Bleeding occurred in 21 patients (12 in the fondaparinux group and 9 in low molecular weight heparin group, respectively). No significant differences were detected in the incidence of postoperative bleeding and the other adverse events between the two groups. The D-dimer was elevated on postoperative day 1 in one patient (16.6 μg/mL). In another patient, the soluble fibrin monomer complex was elevated (109 μg/mL). Fondaparinux is non-inferior to low molecular weight heparin with respect to risk of bleeding. The favorable safety profile of fondparinux supports its prophylactic use as an alternative to low molecular weight heparin after surgery for urological malignancy.