Low Molecular Weight Heparin In Patients Research Articles

Unfractionated heparin or low molecular weight heparin in patients with acute pulmonary embolism: a meta-analysis of randomized controlled trials

Abstract Introduction There is limited data on the use of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) in patients admitted for acute pulmonary embolism (PE). Current ESC guidelines preferred LMWH over UFH based on extrapolated data. We aimed to compare UFH and LMWH in patients with acute PE using randomized controlled trials (RCTs). Methods A comprehensive literature search was performed from inception to 02/01/2024 of the PubMed database. Studies of adult patients comparing UFH to LMWH were evaluated for short-term (7-to-12 days) mortality, long-term mortality (90-days to 180-days), short-term (7-to-12 days) and long-term major bleeding (90-days to 180-days). Odds ratio (OR) with 95% confidence intervals (CI) were calculated using DerSimonian-Laird method. Results Of a total 2400 studies, nine RCTs with 1,996 subjects (1025 UFH and 971 LMWH) were included with mean age of 62.9 years and 48.5% males. There was no difference in short-term (OR= 0.89 [95% CI 0.44-1.82]; p=0.75; I2=0%; 6 trials) and long-term mortality (OR= 0.77 [95% CI 0.50-1.21]; p=0.26; I2=0%; 6 trials) with use of LMWH or UFH (Figure Panel A and B). Similarly, there was no difference in short-term (OR= 0.70 [95% CI 0.38-1.32]; p=0.27; I2=0%; 9 trials) and long-term major bleeding (OR= 0.92 [95% CI 0.53-1.60]; p=0.77; I2=0%; 6 trials) with use of LMWH or UFH (Figure Panel C and D). Overall, there was no evidence of publication bias using either funnel plot or eggers test (p > 0.05). Conclusions In this meta-analysis of 9 RCTs, there was similar efficacy and safety of UFH and LMWH in patients admitted for acute PE. However, future large-scale trials are needs to confirm these findings.

Bridging With Low-Molecular-Weight Heparin Versus Antiplatelet Therapy in Patients Undergoing Noncardiac Surgery After Percutaneous Coronary Intervention: A Comprehensive Review.

This review article discussed the use of bridging therapy with low-molecular-weight heparin (LMWH) in patients who undergo noncardiac surgery (NCS) after percutaneous coronary intervention (PCI). Patients who undergo PCI are at an increased risk of thrombotic events due to their underlying cardiovascular disease. However, many of these patients may require NCS at some point in their lives, which poses a significant challenge for clinicians as they balance the risk of thrombotic events against the risk of bleeding associated with antithrombotic therapy. This review evaluates the current evidence on the use of bridging therapy with LMWH in patients undergoing NCS after PCI, focusing on outcomes related to the efficacy and safety of antithrombotic therapy. The article also discusses the limitations of the current evidence and highlights areas where further research is needed to optimize the management of antithrombotic therapy in this patient population. The goal of this review was to provide clinicians with a comprehensive summary of the available evidence to guide clinical decision-making and improve patient outcomes.

Direct oral anticoagulants versus low-molecular-weight heparin in patients with cancer-associated venous thrombosis: a cost-effectiveness analysis.

Direct oral anticoagulants (DOACs) have demonstrated clinical benefits and better patient adherence over low-molecular-weight heparin (LMWH) in treating patients with cancer-associated venous thrombosis (CAT). We aimed to compare the cost-effectiveness of DOACs against LMWH in patients with CAT from the perspective of the Hong Kong healthcare system. A Markov state-transition model was performed to estimate the incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALYs) for DOACs and LMWH in a hypothetical cohort of 10,000 patients with CAT over a 5-year lifetime horizon. The model was primarily based on the health states of no event, recurrent venous thromboembolism, bleeding, and death. Transition probabilities, relative risks, and utilities were derived from the literature. Resource cost data were obtained from the Hong Kong Hospital Authority. Deterministic and probabilistic sensitivity analyses tested the robustness of the results. Relative to LMWH, DOACs were associated with increased QALYs (1.52 versus 1.50) at a lower medical cost of USD 2,232 versus 8,224 in five years. The cost of LMWH was the main contributor to the outcome. Out of 10,000 simulated cases, DOACs were dominant in 15.8% and cost-effective in 42.1%, at the willingness-to-pay threshold of USD 148,392 per additional QALY. DOACs were associated with greater QALY improvements and lower overall costs compared to LMWH. Accounting for uncertainty, DOACs were between cost-effective and dominant in 57.9% of cases. DOACs are a cost-effective alternative to LMWH in the management of CAT in Hong Kong.

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

The optimal treatment regimen for patients with cancer-associated venous thromboembolism (CA-VTE) remains unclear. Therefore, the authors sought to compare the outcomes of (VKAs) versus direct apixaban and low molecular weight heparin (LMWH) in patients with CA-VTE. MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials (RCTs) and observational studies comparing the 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% CIs. 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%]. 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.

Factor XI inhibitors: a new option for the prevention and treatment of cancer-associated thrombosis

Venous thromboembolism (VTE) is a relatively common complication in cancer patients with potentially dire consequences. Anticoagulants are the mainstay of treatment of cancer-associated VTE. The anticoagulants most often used are low-molecular-weight heparin (LMWH) and direct oral factor (F) Xa inhibitors, which include apixaban, edoxaban, and rivaroxaban. Most guidelines recommend primary VTE prophylaxis with LMWH, apixaban, or rivaroxaban after abdominal or pelvic cancer surgery, or in high-risk ambulatory cancer patients. Both oral FXa inhibitors and LMWH have limitations. LMWH requires daily subcutaneous injections, and because of its renal clearance, its use may be problematic in patients with severe kidney disease. The risk of bleeding with oral FXa inhibitors may be higher than with LMWH in patients with intraluminal gastrointestinal or genitourinary cancers. Other problems with oral FXa inhibitors include potential drug-drug interactions and dosing issues in patients with thrombocytopenia or severe kidney or liver disease. Therefore, there remains a need for convenient and safer anticoagulants for VTE treatment in cancer patients. FXI has emerged as a potentially safer target for anticoagulants than FXa because FXI is essential for thrombosis, but mostly dispensable for hemostasis. This review summarizes the currently available therapeutic options for cancer-associated VTE, highlights knowledge gaps, and discusses the potential of FXI inhibitors to address key unmet clinical needs in this vulnerable patient population.

Effectiveness of Taohong Siwu decoction in the prevention of deep vein thrombosis in hip surgery patients: A systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis aimed to evaluate the effects of Taohong Siwu Decoction (THSWD) combined with low molecular weight heparin (LMWH), as well as THSWD alone, on the incidence of Deep vein thrombosis (DVT), D-dimer levels, prothrombin time (PT), activated partial thromboplastin time (APTT), visual analogue scale (VAS) pain score, and calf swelling in patients undergoing hip fracture or replacement surgery, compared to LMWH. According to the predefined inclusion criteria, we conducted a comprehensive search for randomized controlled trials (RCTs) examining the efficacy of THSWD combined with LMWH or THSWD compared to LMWH in patients with hip fractures or undergoing replacement surgery. The search was performed across multiple databases including China National Knowledge Internet, WanFang, Sinomed, Duxiu, PubMed, Embase, Google Scholar, Cochrane, and Web of Science from their inception until December 2023. Additionally, relevant literature references were retrieved and hand searching of pertinent journals was conducted. The methodological quality assessment of the included trials was carried out following the guidelines outlined in the Cochrane Handbook. Review Manager 5.4 was applied in analyzing and synthesizing. A total of 18 RCTs with 1353 patients were included. The results of meta-analysis showed that compared with the control group, the combined group had a better effect on the incidence of DVT [RR = 0.32, 95% CI(0.17, 0.58; P = .0002], D-dimer [SMD = -5.88, 95% CI(-7.66, -4.11); P < .00001], VAS [MD = -1.16, 95% CI(-1.81, -0.50); P = .0005], Calf circumference difference [MD = -0.56, 95% CI(-1.05, -0.08); P = .02]. There was no significant difference in PT and APTT between the combined group and the control group. Meta-analysis results show that the D-dimer, incidence of DVT, PT, and APTT did not significantly differ between the THSWD and the LMWH groups. This meta-analysis shows that compared with LMWH, THSWD combined with LMWH has a better efficacy in the treatment of DVT after hip surgery, without a significant increase in the incidence of adverse events. Additionally, the combined therapy can also reduce D-dimer, VAS, and swelling. However, due to the limitations of the included studies (such as small sample size and low-quality evidence), the results need to be further verified in more rigorous multicenter clinical trials with a large sample size.

Efficacy and safety of direct oral anticoagulants for preventing venous thromboembolism in hospitalized cancer patients: a national multicenter retrospective cohort study.

Studies on the use of direct oral anticoagulants (DOACs) for preventing venous thromboembolism (VTE) in hospitalized cancer patients are lacking. Therefore, we conducted a multicenter retrospective cohort study to evaluate the efficacy and safety of DOACs versus low-molecular-weight heparin (LMWH) for the primary prevention of VTE in hospitalized cancer patients. Clinical outcomes included thrombosis, VTE, other thrombosis, all bleeding, major bleeding, nonmajor bleeding, and all-cause death. A 1:1 cohort of rivaroxaban and LMWH patients was created by propensity score matching. A total of 2,385 cancer patients were included in this study. During the 3-month follow-up period, 129 (5.4%) thrombosis events occurred, 63 (2.7%) of which were VTEs and 66 (2.8%) of which were other thrombosis events. All bleeding occurred in 163 (6.8%) patients, 68 (2.9%) had major bleeding, and 95 (4.0%) had nonmajor bleeding. All-cause deaths occurred in 113 (4.7%) patients. After adjusting for various confounders, the incidence of thrombosis and other thromboses was significantly lower in the rivaroxaban group than in the LMWH group [OR 0.543, 95% CI (0.343-0.859), p = 0.009; OR 0.461, 95% CI (0.241-0.883), p = 0.020]. There were no significant differences in incidence of VTE, total bleeding, major bleeding, nonmajor bleeding, or all-cause death. In oncology patients receiving thromboprophylaxis, rivaroxaban has a lower incidence of thrombosis and other thrombosis and a similar incidence of VTE as LMWH and does not increase the risk of bleeding. Rivaroxaban may be an attractive alternative to LMWH for preventing VTE in hospitalized cancer patients.

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.

P-506 Administration of low molecular weight heparin alleviate immune physiology in recurrent implantation failure modulating CCL2-CCR2 axis during frozen embryo transfer: effort from clinic to bench

Abstract Study question Does low molecular-weight heparin (LMWH) administration modulate CCL2-CCR2 axis in recurrent implantation failure (RIF) patients undergoing frozen embryo transfer (FET) to improve pregnancy salvage? Summary answer LMWH treatment attests beneficial immunological tolerance in vivo and in vitro through modulation of CCL2-CCR2 axis suggesting possible restoration of weak pro-inflammatory response in RIF. What is known already Immune imbalance in proportion of activated macrophages (M1) and alternatively activated macrophages (M2) impede endometrial receptivity and contribute to RIF. CCL2 (M2-asscociated) - CCR2 (t-helper-2 associated) axis orders macrophage polarization by influencing expression of functionally relevant and polarization associated genes and down-modulate pro-inflammatory cytokine production. Immunological effects of LMWH regulate pregnancy-promoting processes at foetal-maternal interface to provide an appropriate implantation process; outcomes being controversial. We aim to investigate the potential immunoregulatory properties of LMWH in patients with RIF undergoing FET, with particular regard to effects on macrophages and T-helper (Th) cells; two key players in promoting immune tolerance during pregnancy. Study design, size, duration This prospective cohort study constituted 121 women with RIF (≥3 failed embryo transfer) undergoing FET at Institute of Reproductive Medicine between January to October 2022. An incremental dose (4-12mg/day) of estradiol with (Group A; n = 62) or without (Group B; n = 59) LMWH (40 mg/day) from d2 to d12 with sequential ultrasound following intra-muscular progesterone (100mg/day) for 4 days was administered in all participants. Blood samples were collected to isolate plasma and peripheral-blood-mononuclear-cells (PBMCs). Participants/materials, setting, methods Monocytes were purified from PBMCs and cultured with GM-CSF or M-CSF to analyze factor/s which control CCL2-CCR2 expression along macrophage polarization by flow cytometry. Influence of CCL2 on GM-CSF-cultured macrophages (GM-MØ) and M-CSF-cultured macrophages (M-MØ) specific gene markers was analysed using quantitative RT-PCR (qRT-PCR). To assess immunological effects of LMWH in-vivo, Th-specific cytokine profile/s and respective chemokines were measured from plasma by Luminex xMAP technology. Statistical significance was set at p &amp;lt; 0.05. Main results and the role of chance The clinical pregnancy rate was higher in group A. (A vs B: 37.09% vs. 27.11%, p = 0.24). LMWH exposure significantly decreased the secretion of CCL2 (p &amp;lt; 0.01) and CCL22 (p &amp;lt; 0.001) in GM-CSF-cultured macrophages, while it increased CCL2, CCL20 production (p &amp;lt; 0.001) in both GM-MØ and M-MØ. However, expression of CCL7 was significantly lower (p &amp;lt; 0.01) in M-MØ and GM-MØ generated from CD14+ CD16+ monocytes and CD14 ++ CD16- monocytes respectively under LMWH exposure. qPCR analysis revealed a significant increase (p &amp;lt; 0.01) in the expression of various GM-MØ–specific genes including EGLN3, and SERPINE1 in macrophage supernatant post LMWH treatment. Expression of various M-MØ-specific marker/s such as IGF1, FOLR2, and HTR2B, is significantly up-regulated (p &amp;lt; 0.01) in Group B. Group A, although documented a decreased concentration/s (pg/ml) of Th17-type cytokine/s (IL-6 (1.88 ± 0.65 vs. 0.91 ± 0.43; p &amp;lt; 0.04 and IL-23 (17.94 ± 9.76 vs. 7.78 ± 3.43; p &amp;lt; 0.01)), at end of treatment, concentration of TGF-β was significantly higher (3909.05 ± 1248.35 vs. 2469.83 ± 1058.71; p &amp;lt; 0.01) which cue to probable maintenance in balance of inflammatory response at the time of implantation. No differences were observed in Th1-type cytokine level/s (IFN-γ and TNF-α). CXCL10, CXCL11, CXCL1, CXCL8, CCL17, CCL22 do not differ in vivo. Limitations, reasons for caution Beneficial effects of LMWH administration with a good sample size are clearly needed to confirm this hypothesis; hence result/s should be dealt with caution. Further to this, inclusion of other arm/s (corticosteroids, intralipid and/or intravenous immunoglobulin) will make the study much robust and conclusive. Wider implications of the findings The identification of atypical Th1-associated pro-inflammatory effects of LMWH drives to evaluate modulation of CCL2 expression to limit or potentiate macrophage activation in RIF; especially where anticoagulant effect is not the primary goal. Further, modification of cytokine expression/s might potentiate novel strategy derived from deregulated macrophage polarization. Trial registration number Not Applicable

Comparison of the Efficacy and Safety of Aspirin and Low-Molecular-Weight Heparin in Patients With a Fracture: A Meta-Analysis.

The aim of this study is to compare the efficacy and safety of aspirin and low-molecular-weight heparin (LMWH) in preventing thromboembolic events in patients with fractures.The present meta-analysis was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched EMBASE, PubMed, and EBSCO to find articles comparing aspirin and LMWH in patients with orthopedic trauma from inception to April 15, 2023. Limits were set to studies published in the English language only.Outcomes assessed in this meta-analysis included VTE and all-cause mortality. VTE can manifest as deep venous thrombosis (DVT) and pulmonary embolism. For safety analysis, rates of wound complication, infection, and bleeding complications were compared between the two study groups. A total of three studies were included in this meta-analysis enrolling 12884 patients. The study found no significant difference between the two groups in the risk of DVT and pulmonary embolism, and aspirin was non-inferior to LMWH for the prevention of all-cause mortality in patients. Additionally, no significant safety risk was associated with aspirin thromboprophylaxis. These findings suggest that inexpensive over-the-counter aspirin is as effective as LMWH in terms of safety and efficacy profile, making it a feasible option to consider in clinical practice.

Epidemiology, biology, and management of venous thromboembolism in gliomas: An interdisciplinary review.

Patients with diffuse glioma are at high risk of developing venous thromboembolism (VTE) over the course of the disease, with up to 30% incidence in patients with glioblastoma (GBM) and a lower but nonnegligible risk in lower-grade gliomas. Recent and ongoing efforts to identify clinical and laboratory biomarkers of patients at increased risk offer promise, but to date, there is no proven role for prophylaxis outside of the perioperative period. Emerging data suggest a higher risk of VTE in patients with isocitrate dehydrogenase (IDH) wild-type glioma and the potential mechanistic role of IDH mutation in the suppression of production of the procoagulants tissue factor and podoplanin. According to published guidelines, therapeutic anticoagulation with low molecular weight heparin (LMWH) or alternatively, direct oral anticoagulants (DOACs) in patients without increased risk of gastrointestinal or genitourinary bleeding is recommended for VTE treatment. Due to the elevated risk of intracranial hemorrhage (ICH) in GBM, anticoagulation treatment remains challenging and at times fraught. There are conflicting data on the risk of ICH with LMWH in patients with glioma; small retrospective studies suggest DOACs may convey lower ICH risk than LMWH. Investigational anticoagulants that prevent thrombosis without impairing hemostasis, such as factor XI inhibitors, may carry a better therapeutic index and are expected to enter clinical trials for cancer-associated thrombosis.

Effectiveness and Safety of Rivaroxaban and Low Molecular Weight Heparin in Cancer-Associated Venous Thromboembolism

Direct-acting oral anticoagulants (DOACs) are alternatives to low molecular weight heparin (LMWH) in most cancer-associated thrombosis (CAT) patients. This study sought to compare the effectiveness and safety of rivaroxaban and LMWH for venous thromboembolism (VTE) treatment in patients with an active cancer type not associated with a high risk of DOAC bleeding. An analysis of electronic health records from January 2012 to December 2020 was performed. Patients were adults, had active cancer, experienced an index CAT event, and were treated with rivaroxaban or LMWH. Patients with cancers with an established high risk of bleeding on DOACs were excluded. Baseline covariates were balanced using propensity score-overlap weighting. HRs with 95% CIs were calculated. We identified 3,708 CAT patients treated with rivaroxaban (29.5%) or LMWH (70.5%). The median (25th-75th percentiles) time on anticoagulation was 180 (69-365) and 96 (40-336) days for rivaroxaban and LMWH patients. At 3months, rivaroxaban was associated with a 31% reduced risk of recurrent VTE vs LMWH (4.2% vs 6.1%; HR: 0.69; 95% CI: 0.51-0.92). No difference in bleeding-related hospitalizations or all-cause mortality was observed (HR: 0.79; 95% CI: 0.55-1.13 and HR: 1.07; 95% CI: 0.85-1.35, respectively). Rivaroxaban reduced the recurrent VTE risk (HR: 0.74; 95% CI: 0.57-0.97) but not bleeding-related hospitalizations or all-cause mortality at 6months. At 12months, no difference was observed between cohorts for any of the previously mentioned outcomes. Among active cancer patients experiencing VTE and not at high risk of bleeding on DOACs, rivaroxaban was associated with a reduced risk of recurrent VTE versus LMWHs at 3 and 6months but not 12months. (Observational Study in Cancer-Associated Thrombosis for Rivaroxaban-United States Cohort [OSCAR-US]; NCT04979780).

Bleeding and venous thromboembolism events in cancer patients taking direct oral anticoagulants vs. low molecular weight heparin

IntroductionPatients with cancer have an increased risk of developing venous thromboembolism (VTE), and subsequently a higher risk of bleeding secondary to anticoagulants. Low-molecular weight heparin (LMWH) has been the standard of care for these patients, with emerging data on the use of direct oral anticoagulants (DOACs). The primary objective of the study was to determine the prevalence of major bleeding events in cancer patients taking DOACs or LMWH for VTE. Secondary objectives included the rate of first VTE recurrence and the effect of concomitant antiplatelet agents and/or significant drug interactions on major bleeding or recurrent VTE. Materials and methodsUsing the electronic medical record at the University of Rochester Medical Center, we retrospectively identified adult patients with active malignancy who had a diagnosis of VTE requiring therapeutic anticoagulation within the study period of July 1st, 2015 to June 1st, 2019. Patients were excluded if they were receiving prophylactic doses of LMWH per the institution VTE guidelines. Data on anticoagulant medications were collected as well as information on major bleeding and recurrent VTE events. Results and conclusionsThere is insufficient evidence of difference in risk of major bleeding among patients who received a DOAC vs LMWH (cause-specific hazard ratio (HR) = 0.77, 95% CI 0.29–2.04, P = 0.60). There was also no evidence of a difference in risk of recurrent VTE between patients who received DOAC vs. LMWH (cause-specific HR = 0.98, 95% CI 0.15–6.26, P = 0.98). These results suggest that DOACs are not significantly less safe than LMWH for patients with cancer.

Risk of Intracranial Hemorrhage with Direct Oral Anticoagulants (DOACs) Versus Low Molecular Weight Heparin (LMWH) in Primary and Secondary Brain Cancers: An up-to-Date Meta-Analysis of Comparative Studies

Introduction Patients with brain tumors, primary or metastatic, are at high risk for thromboembolic events and anticoagulant-associated bleeding. LMWH has been the standard treatment for many years. Recently, DOACs are more frequently used in cancer patients. However, such patient populations have been under-represented in anticoagulation trials. As such, there continues to be concerns regarding their safety in patients with primary and metastatic brain cancers especially with respect to intracranial hemorrhages (ICH). There are no trials in brain cancers comparing the safety of DOACs to LMWH in a head-to-head manner. This meta-analysis was conducted to compare the relative risk (RR) of ICH of DOACs to that of LMWH in patients with brain cancers. Methods A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of primary brain cancers (PBC) or metastatic brain cancers (MBC), comparative studies using anticoagulation with LMWH versus DOACs, and studies that reported the incidence of ICH. A meta-analysis using the fixed effects and random effects models was conducted. Results Four retrospective comparative studies with a total of 488 patients were included. Three studies reported on ICH incidence of DOACs versus LMWH in PBC and MBC separately and one reported on ICH incidence in MBC only. DOACs were found to have significantly lower RR of all types of ICH in patients with PBC (RR=0.18, 95%CI 0.05-0.62) and a borderline significant lower RR in MBC (RR=0.66, 95%CI 0.41-1.08) than LMWH. However, there was no significant difference between DOACs and LMWH with respect to major ICH in patients with MBC. Conclusions This is the first meta-analysis to show that DOACs is associated with lower relative risk of all ICH compared to LMWH in patients with primary and metastatic brain cancers. In the absence of randomized clinical trials, it represents the most compelling data supporting the use of DOACs to treat thromboembolic events in these patient populations.

Statement of Retraction: Low-molecular weight heparin in patients with recurrent early miscarriages of unknown aetiology

Statement of Retraction: Low-molecular weight heparin in patients with recurrent early miscarriages of unknown aetiology

Treating unexplained recurrent pregnancy loss based on lessons learned from obstetric antiphospholipid syndrome and inherited thrombophilia: A propensity-score adjusted retrospective study

The efficacy of low molecular weight heparin (LMWH) is well-established in patients with obstetric antiphospholipid syndrome (O-APS). Their role in women with unexplained recurrent pregnancy loss (U-RPL) and late obstetrical complications (intrauterine growth restriction, IUGR and preeclampsia) is controversial. Here we compared rates of miscarriage and late obstetrical complications in RPL patients diagnosed with O-APS (n = 57) or hereditary thrombophilia (n = 25) (both assuming LMWH from the beginning of pregnancy) and in patients with a history of U-RPL (n = 118), assuming or not LMWH, followed at the ‘Pregnancy at risk’ and ‘Recurrent pregnancy loss’ outpatient clinics at the San Raffaele Hospital from April 2010 to April 2020. Patients with systemic autoimmune diseases other than primary O-APS were excluded. We tested for bivariate or multivariate associations among adverse pregnancy outcomes, the presence of thrombophilia and LMWH use by using chi-square test, Anova, propensity score adjusted univariate logistic regression and multivariate analysis as appropriate. U-RPL patients assuming LMWH from the beginning of pregnancy (group A) had a significantly lower rate of miscarriage compared to U-RPL patients who were not treated with LMWH (group B) (13 % vs. 41 % respectively, p 0.001) and similar pregnancy rates compared to both O-APS patients with a history of RPL taking LMWH (group C, 18 %) and RPL patients with thrombophilia and treated with LMWH (group D, 16 %). Our data highlight a protective effect of LMWH on miscarriage in patients with a history of U-RPL. In these patients, LMWH seems as effective as in O-APS and hereditary thrombophilia in reducing RPL

Risk of intracranial hemorrhage with direct oral anticoagulants versus low molecular weight heparin in glioblastoma: A retrospective cohort study.

2015 Background: Glioblastoma (GBM) is associated with a high rate of venous thromboembolism (VTE), but there is little data to guide anticoagulation in GBM patients, in whom the risks of VTE must be balanced against the risk of intracranial hemorrhage (ICH). Methods: We performed a single-institution retrospective cohort study of patients with GBM diagnosed with VTE from 2014-2021 who were treated with low molecular weight heparin (LMWH) or a direct oral anticoagulant (DOAC). The cumulative incidence of ICH was compared between the LMWH and DOAC groups. The primary outcome was clinically relevant ICH within the first 30 days of anticoagulation, defined as any ICH that was fatal, symptomatic, required surgical intervention, and/or led to cessation of anticoagulation. Key secondary outcomes included clinically relevant ICH within 6 months, fatal ICH within 30 days and 6 months, any bleeding within 30 days and 6 months, and recurrent VTE within 6 months. Fisher’s exact test was used for comparison of primary and secondary endpoints between the two groups. Cumulative incidence curves were generated using the Kaplan-Meier method, and the cumulative incidence of clinically relevant ICH at both the 30-day timepoint and 6-month timepoint was compared between the DOAC and LMWH groups using the Gray test to account for death as a competing risk. Results: A total of 121 patients were identified in the primary cohort for 30-day outcome analyses (DOAC, n = 33; LMWH, n = 88). For 6-month outcome analyses, the cohort included only patients who were maintained on their initial anticoagulant (DOAC or LMWH) and did not switch anticoagulants during the 6 months following diagnosis of VTE (DOAC, n = 32; LMWH, n = 75). The cumulative incidence of clinically relevant ICH at 30 days was 0% (0/33) in the DOAC group and 9% (8/88) in the LMWH group (p = 0.11). The cumulative incidence of clinically relevant ICH at 6 months was 0% (0/32) in the DOAC group and 24% (18/75) in the LMWH group (p = 0.001), with 4 fatal ICHs in the LMWH group. Other outcomes are displayed in the Table. Conclusions: Our study suggests that DOACs are associated with a lower incidence of clinically relevant ICH in patients with GBM-associated VTE compared to LMWH. These data support the use of DOACs as a safe alternative to LMWH in patients with GBM.[Table: see text]

Patients' Plasma Activity of Heparin, low-Molecular-Weight Heparin or no Anticoagulants on Urine Based DOAC Test Strips.

DOAC Dipstick determines specifically the presence and absence of direct oral anticoagulants (DOACs) from patients’ urine samples and handmade test strips performed as well as the commercial version. To compare plasma activity (chromogenic substrate assays) from plasma samples with results from urine samples (DOAC test strips) of patients treated with heparin, low-molecular weight heparin (LMWH) and without anticoagulation. Plasma anti-factor Xa (aXa) activity was determined by Coamatic chromogenic substrate assay and compared to the presence of anticoagulants in urine by DOAC test strips. Patients were treated for least 5 days and samples were taken 4 hrs after administration in comparison to no treatment with an anticoagulant (n = 42). A total of 100 patients were included treated with heparin (n = 29), LMWH nadroparin (n = 29) or no anticoagulants (n = 42). Plasma aXa levels of patients treated with heparin (2 × 7.500 IU daily subcutaneously, 12 male, age 67.4 ± 11.5 years) were 0,18 IU/ml ± 0,15 IU/ml (mean, standard deviation), with LMWH (1 × 3000 IU daily subcutaneously, 15 male, age 64.2 ± 14.1 years) 0,17 IU/ml ± 0,16 IU/l, and with no anticoagulants (28 male, age 64.2 ± 15.6 years) 0,02 IU/ml ± 0.01 IU/ml. All factor Xa and thrombin inhibitor pad results of test strips were negative. We conclude that DOAC Dipstick has a high probability of not detecting heparin and LMWH in patients on treatment as well as in urine samples of patients not treated with an anticoagulant.

Routine use of LMWH prophylaxis is associated with a lower incidence of venous thromboembolic events following an ankle fracture

BackgroundVenous thromboembolic events (VTE) are well-known and serious complications following a trauma to the lower extremities. There is an ongoing debate on the benefit of low-molecular-weight heparin (LMWH) as prophylaxis following ankle fracture treatment. We examined the association between the incidence of VTE and the use of LMWH-prophylaxis following an ankle fracture, as well as factors affecting the risk of VTE. MethodsIn this retrospective cohort study, data on ankle fractures and fracture treatment from the Swedish Fracture Register was linked to data from the Swedish National Patient Register and the Swedish Prescribed Drug Register. Patients with VTE and patients who received LMWH prophylaxis were identified. The treating orthopedic departments were sent a questionnaire about their guidelines regarding the use of LMWH prophylaxis. Results222 cases of diagnosed VTE were identified among 14,954 ankle fractures. Orthopedic departments with higher-than-average use of LMWH prophylaxis among non-operatively treated ankle fractures had a lower incidence of VTE (OR 0.60, CI 0.39–0.92). Among operatively treated patients, departments with a guideline for the routine use of LMWH prophylaxis also had lower incidence of VTE (OR 0.56, CI 0.37–0.86). A later onset of VTE was seen among patients prescribed LMWH prophylaxis, with a mean of 56 days to onset (CI 44–67), compared to 39 days (CI 33–45) in patients without prescribed prophylaxis. During the first two weeks following injury, there was only one case of VTE in patients with prescribed LMWH, compared to 39 cases of VTE among patients without prescribed prophylaxis. ConclusionsRoutine use of LMWH in patients with operatively treated ankle fractures was associated with a lower incidence of VTE. A more frequent use of LMWH among patients with non-operatively treated ankle fractures were associated with a lower incidence of VTE. The onset occurred later among patients with LMWH-prophylaxis who still suffered a VTE.

Anticoagulant Treatment Patterns and Outcomes in Patients with Venous Thromboembolism and Active Cancer - a Nationwide Cohort Study in France

BACKGROUND: Cancer is a major risk factor for venous thromboembolism (VTE) and for all-cause mortality following a VTE event. Higher risk can be attributed to certain cancer types and to metastatic disease. Until recently the gold standard for VTE and active cancer was low molecular weight heparin (LMWH), shown to be superior to warfarin in preventing thrombosis (Lee et al. 2003). Previously only minimal data from the direct oral anticoagulant (DOAC) pivotal RCTs were available in this population. However recent RCTs have been conducted that provide rationale for the use of DOACs as an alternative to LMWH in this patient group (Agnelli et al. 2020; Raskob et al. 2018; Young et al. 2018). This evidence is reflected in international guidelines (ASH 2021; ESC 2019; ITAC 2019, NCCN 2021) where DOACs are now proposed in VTE and active cancer patients without gastrointestinal cancer.PURPOSE: To describe patient characteristics, anticoagulant (AC) treatment patterns and outcomes among patients with VTE and active cancer in France. The analysis included all relevant ACs that were available for the treatment of VTE to understand how treatment recommendations were being reflected in clinical practice.METHODS: A nationwide retrospective cohort study of all adult patients (identified via the French national health data system: SNDS) with VTE and active cancer prescribed LMWH, a vitamin K antagonist (VKA), or a DOAC (apixaban or rivaroxaban) from 2013 to 2018. AC treatment-naïve (defined as patients without an AC prescription 24 months prior to index VTE) and AC treatment-experienced patients were included. Active cancer was defined by the presence of medical claims for cancer diagnosis or cancer-specific treatment in the 6 months prior or 30 days after index VTE event. A modified Khorana VTE risk scale (based on ICD codes and not blood tests) was used to evaluate the distribution of baseline VTE risk associated with different cancers. Rates of bleeding (defined as principal diagnoses of hospital stays), recurrent VTE, and all-cause mortality were assessed at 6 months for the standard of care (LMWH) cohort.RESULTS: 39,023 patients with VTE and active cancer were included. Most patients were prescribed LMWH 31,771 (81.42%), followed by rivaroxaban 2,259 (5.79%), VKAs 1,591 (4.08%), and apixaban 678 (1.74%). 2,724 (6.98%) were prescribed other parenteral anticoagulants (PAC) or PAC combinations. A slightly lower proportion of patients prescribed LMWH or VKAs were AC treatment naïve (44.4% and 45% respectively) compared to those prescribed rivaroxaban (51.2%) or apixaban (51.6%). Median duration of treatment (months; IQR) was shortest for LMWH patients (3.84; 1.35-8.48) and similar amongst the other ACs: VKAs (5.26; 1.05-14.16), rivaroxaban (5.85; 1.91-10.74), and apixaban (5.73; 1.74-9.07).Patients initiating VKAs and apixaban were older than those initiating rivaroxaban or LMWH (mean age in years: VKAs, 74; apixaban, 73; rivaroxaban, 67; LMWH, 66) however, LMWH patients had a higher comorbidity burden (mean CCI score: LMWH 6.4, VKAs, 4.95; rivaroxaban, 4.20; apixaban, 4.31). The proportion of patients with pulmonary embolism (PE), with or without DVT, was lower for LMWH and VKA cohorts (58.74% and 61.85% respectively) compared to rivaroxaban (71.76%) and apixaban (69.32%).Amongst patients with a medical claim for cancer diagnosis, the majority receiving LMWH (19,300 (61.8%)) had cancers with very high risk (brain, pancreatic, stomach) or high risk (gynaecological, lung, lymphoma, testicular, renal cell) for VTE. This proportion was lower in patients receiving VKAs, 484 (40.27%); rivaroxaban, 719 (43.52%); or apixaban, 194 (40%). Metastatic disease was present in most LMWH patients 21,994 (72.14%) but only in about a third of those receiving other ACs: VKAs, 406 (34.18%); rivaroxaban, 591 (36.37%); and apixaban, 152 (31.73%).Event rates for LMWH are reported in the table.CONCLUSIONS: AC therapy for a significant majority of patients with VTE and active cancer was LMWH. Most LMWH patients had metastatic disease. Median LMWH treatment was less than 4 months and VTE-related clinical event rates remained high in this population, suggesting a key unmet medical need. Future studies reflecting potential changes in clinical practice, because of guideline updates and the emergence of new RCT evidence, are required to understand clinical outcomes with different AC treatments. [Display omitted] DisclosuresBertoletti: Pfizer: Honoraria, Other: Personal fees; BMS: Honoraria, Other: Personal Fees; Aspen: Other: Personal Fees; Bayer: Other: Personal Fees; Leo Pharma: Other: Personal Fee. Gusto: Pfizer: Consultancy. Khachatryan: Pfizer: Consultancy. Quignot: Pfizer: Consultancy. Chaves: Pfizer: Current Employment. Moniot: Pfizer: Current Employment. Mokgokong: Pfizer: Current Employment.