Term Low Molecular Weight Heparin Research Articles

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.

Regional citrate anticoagulation versus low molecular weight heparin for CRRT in hyperlactatemia patients: A retrospective case-control study

There were controversial opinions on the use of regional citrate anticoagulation (RCA) versus low molecular weight heparin (LMWH) for continuous renal replacement therapy (CRRT) in hyperlactatemia patients, which was considered as one of the contraindications of citrate. The aim of our present study is to evaluate the efficacy and safety of RCA versus LMWH for CRRT in hyperlactatemia patients. Adult patients with hyperlactatemia who underwent RCA or LMWH CRRT in our center between January 2014 and March 2018 were retrospectively recruited. Filter lifespan, ultrafiltration, purification, bleeding, citrate accumulation, filter clot, and the infusion of blood production were evaluated as endpoints. Of the 127 patients included in the original cohort, 81 and 46 accepted RCA and LMWH CRRT, respectively. The filter lifespan was significantly prolonged in the RCA group compared to the LMWH group (44.25 h [2 -83] vs. 24 h [4 -67], p < 0.001). The accumulated filter survival proportions were significantly improved in the RCA group compared to the LMWH group in the original cohort (p < 0.001) as well as the matched group (p < 0.001). The filters clotted more frequently in the LMWH group than in the RCA group in both of the original (52.2% vs 26.8%, p = 0.001) and matched cohort (58.6% vs 19.4%, p = 0.001). The bleeding complication was significantly reduced in the RCA group than in the LMWH group in the matched cohort (28.6% vs 4.5%, p = 0.04). In critically ill patients with hyperlactatemia requiring CRRT, RCA is superior to LMWH in terms of filter lifespan and bleeding risk without significantly increased risk of citrate accumulation and citrate related metabolic complications. RCA most likely is a safe and effective anticoagulation method for CRRT in patients with hyperlactatemia.

Programmable One-Pot Synthesis of Heparin Pentasaccharide Fondaparinux.

The clinically approved Fondaparinux (Arixtra) has been used for the treatment of deep vein thrombosis and acute pulmonary embolism since 2002 and is considered to be better than the low-molecular weight heparin in terms of anticoagulation response, duration of action, and biosafety. However, the synthetic methods previously developed for its manufacture are relatively complicated, thus restricting its extensive use. We report here a potentially scalable and programmable one-pot synthesis of Fondaparinux using the [1,2,2] strategy and designed thioglycosides with well-defined reactivity as building blocks.

Direct oral anticoagulants more effective than low-molecular-weight heparin for venous thrombo-embolism in cancer: an updated meta-analysis of randomized trials.

In the recent past, low-molecular-weight heparin (LMWH) was the first choice in the treatment of cancer related venous thrombo-embolism (VTE). Evidence supporting the preferential use of direct anticoagulants (DOACs) in patients with cancer, instead, is less robust so far. We therefore aimed to assess in an updated meta-analysis of randomized controlled trials whether the use of DOACs may be associated with a more favorable profile when compared to LMWH. We performed a meta-analysis of RCTs enrolling patients with VTE and cancer. We assessed Mantel-Haenszel pooled estimates of risk ratios (RRs) and 95% CIs for recurrence of VTE, major bleeding, and mortality comparing subjects treated with DOACs with those with LMWH. After study selection, three RCTs (HOKUSAI-Cancer, SELECT-D and ADAM-VTE) were included for the analysis with an overall population of 1739 patients. DOACs patients had a lower incidence of 6-month recurrent VTE when compared to LMWHs (RR 0.56, 95% CI 0.40-0.79; p < 0.001). Incidence of major bleeding was not significantly different between DOACs and LMWH treated patients (RR 1.56, 95% CI 0.95-2.47, p = n.s.), and mortality rates were comparable (RR 1.03, 95% CI 0.91-2.47, p = n.s.). In a meta-analysis of RCTs therapy with DOACs was superior to LMWH in terms of efficacy and lower recurrence of VTE with a comparable safety profile in terms of bleeding events and complications.

Long Term Low Molecular Weight Heparin Anticoagulant Therapy Modulates Thrombin Generation and D-dimer in Patients with Cancer and Venous Thromboembolism

ABSTRACTWe enrolled 62 consecutive patients with advanced stage cancers and venous thromboembolism (VTE), prospectively followed until 1 year. All patients received 6 month low-molecular-weight heparin (LMWH) therapy. We evaluated thrombin generation (TG) and D-dimer levels at different time points, to determine whether they were sensitive to LMWH and explore a possible association with VTE recurrence, bleeding, and overall survival. During LMWH, levels of TG and D-dimer significantly dropped. No VTE recurrences occurred, one patient had cancer-related intestinal hemorrhage. LMWH treatment was effective in controlling patient hypercoagulation. No VTE recurrences were detected. High D-dimer concentration was an independent predictor of poor survival.

Use of Rivaroxaban for Prophylaxis of Superficial Venous Thrombosis in Klippel-Trenaunay- Weber Syndrome - Case Report and Systematic Review

INTRODUCTIONWe present a case of a young man with Klippel Trenaunay Weber Syndrome (KTWS) characterized by recurrent superficial vein thrombosis (SVT) complicated by an episode of disseminated intravascular coagulation (DIC) who ultimately was maintained on prophylactic rivaroxaban to prevent recurrent thrombotic events. We performed a literature search to identify similar cases and to summarize common presenting features and attempted treatment modalities. CASE DESCRIPTIONAn 18 year old man with KTWS presented with a large vascular malformation over his left chest and arm developed acute worsening SVT post sodium tetradecyl injection. Further investigation revealed a severe DIC was also present. On exam, the venous malformation and left arm were extremely tender with significant bruising. Presenting labs: Hg 24, platelet 98, bilirubin 588 (unconjugated 212), LDH 1597, PTT 32, INR 1.9, fibrinogen 1.1, Ddimer >20. He was treated with aggressive supportive care for DIC and routine deep vein thrombosis (DVT) prophylaxis with low-molecular-weight heparin (LMWH). Symptoms improved after anticoagulation was started. Ultrasound of his left arm revealed old SVT with recanulization within the venous malformation. He subsequently developed recurrent painful crises in his arm secondary to recurrent SVT. These were usually treated with short term LMWH. Imaging studies ruled out any deep vein thrombotic events. We eventually elected to commence indefinite duration anticoagulation with rivaroxaban 10mg daily with significant decrease in further acute flares. METHODSTo review how thrombotic manifestations of KTWS are managed, we performed a comprehensive literature search on PubMed using MESH terms: Klippel Trenaunay Weber Syndrome, Thrombosis, DIC and Kasabach-Merritt coagulopathy. RESULTSWe found 99 abstracts. 87 were excluded for non thrombotic complications of KTWS. 13 case reports focusing on treatment of thrombotic manifestations of KTWS were analyzed further. These included 12 case reports reviewing management of DVT in KTWS and 1 case report reviewing management of SVT in KTWS however with no DIC. 3 of these abstracts also reviewed management of coagulopathy (DIC or local intravascular coagulopathy). Of the 12 case reports, 5 described patients with deep vein thrombosis in KTWS treated with therapeutic warfarin; 4 patients improved however 1 died of cor pulmonale. An additional 5 cases of DVT in KTWS were successfully managed with therapeutic LMWH. 2 of these cases were also complicated by DIC. One case report described use of therapeutic rivaroxaban (20mg daily) to manage DVT in KTWS. This case was also complicated by DIC. There were no case reports describing the prevention of SVT in KTWS. CONCLUSIONTo our knowledge this is the first case report to describe successful off-label use of prophylactic rivaroxaban to prevent further thrombotic events in a patient with KTWS. DisclosuresOff Label Use: RIVAROXABAN -- PROPHYLACTIC ANTI-THROMBOSIS FOR SUPERFICIAL VEIN THROMBOSIS. Wu:Leo Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Long-Term Anticoagulant Therapy of Patients with Venous Thromboembolism. What Are the Practices?

Current guidelines of antithrombotic therapy suggest early initiation of vitamin K antagonists (VKA) in non-cancer patients with venous thromboembolism (VTE), and long-term therapy with low-molecular weight heparin (LMWH) for those with cancer. We used data from RIETE (international registry of patients with VTE) to report the use of long-term anticoagulant therapy over time and to identify predictors of anticoagulant choice (regarding international guidelines) in patients with- and without cancer. Among 35,280 patients without cancer, 82% received long-term VKA (but 17% started after the first week). Among 4,378 patients with cancer, 66% received long term LMWH as monotherapy. In patients without cancer, recent bleeding (odds ratio [OR] 2.70, 95% CI 2.26–3.23), age >70 years (OR 1.15, 95% CI 1.06–1.24), immobility (OR 2.06, 95% CI 1.93–2.19), renal insufficiency (OR 2.42, 95% CI 2.15–2.71) and anemia (OR 1.75, 95% CI 1.65–1.87) predicted poor adherence to guidelines. In those with cancer, anemia (OR 1.83, 95% CI 1.64–2.06), immobility (OR 1.51, 95% CI 1.30–1.76) and metastases (OR 3.22, 95% CI 2.87–3.61) predicted long-term LMWH therapy. In conclusion, we report practices of VTE therapy in real life and found that a significant proportion of patients did not receive the recommended treatment. The perceived increased risk for bleeding has an impact on anticoagulant treatment decision.

Controversial imaging diagnosis of cardiac cause of recurrent pulmonary embolism

A 44 years old lady with a past medical history of asthma and pulmonary emboli receiving adjuvant cytotoxic chemotherapy via a pICC line for a triple negative grade 3 invasive ductal carcinoma of right breast, presented to emergency with acute shortness of breath. she was managed initially as asthma, but 2 days latter was hospitalised due to worsening symptoms. An urgent V/Q scan confirmed further multiple pulmonary emboli despite therapy dose low molecular weight heparin. A trans-thoracic echocardiography revealed a large 2.6 x 2.5cm mass attached to the tricuspid valve. Inflammatory markers were elevated and a blood culture and sensitivity confirmed coagulase-negative staphylococcus which, in the presence of pICC line (Fig 2) raised the suspicion of endocarditis. A trans-oesophageal echocardiogram (Fig 1,2,3,4) and Ct chest were both in favour of possible intra cardiac neoplasm or metastases. Further investigation with cardiac MRI and pet were not in favour of metastasis or primary neoplasm. the patient was treated for pICC line infection with i.v. antibiotics and i.v. heparin resulting initially in reduced mass size but subsequent progression. despite adequate anticoagulation the patient had further pulmonary embolism and subsequently proceeded to surgical removal of the mass. the histopathology analysis at the tertiary care centre confirmed fibrin core and large amount of neutrophils consistent with thrombus with no features of neoplasm or malignancy. the patient made good post-operative recovery and was commenced on long term low molecular weight heparin as per protocol. the four cardiac imaging modalities agreed on the presence of the mass as the most likely cause for the recurrent pulmonary embolism but disagreed on the exact diagnosis regarding the nature of the mass. the differential diagnosis was intracardiac metastases from the breast cancer, pICC line associated endocarditis particularly with a positive blood culture or intracardiac thrombus. the latter was confirmed following surgical excision. Justifiably, imaging experts consider the shape and position of masses as well as patient’s other related conditions and past history to obtain a diagnosis but histopathological confirmation remains the ultimate diagnostic tool. ! !

Anticoagulation for the long-term treatment of venous thromboembolism in patients with cancer.

Cancer increases the risk of thromboembolic events in patients including those receiving anticoagulation treatments. To compare the efficacy and safety of low molecular weight heparin (LMWH) and oral anticoagulants for the long-term treatment of venous thromboembolism (VTE) in patients with cancer. We conducted a comprehensive search for studies of anticoagulation in cancer patients including 1. a February 2013 electronic search of: the Cochrane Central Register of Controlled Trials (CENTRAL Issue 12, 2012), MEDLINE, and EMBASE; 2. a handsearch of conference proceedings; 3. checking of references of included studies; 4. use of the 'related citation' feature in PubMed; and 5. a search of clinicaltrials.gov for ongoing studies. We included randomized controlled trials (RCTs) comparing long-term treatment with LMWH versus oral anticoagulants (vitamin K antagonist (VKA) or ximelagatran) in patients with cancer and symptomatic objectively confirmed VTE. Using a standardized data form, we extracted data on methodological quality, participants, interventions and outcomes of interest: survival, recurrent VTE, major bleeding, minor bleeding, thrombocytopenia, and postphlebitic syndrome. We assessed the quality of evidence at the outcome level following the GRADE approach. Of 9559 identified citations, 10 RCTs (11 reports) were eligible and reported data for 1981 patients with cancer. We excluded 14 studies in which patients with cancer constituted study subgroups, but did not report outcome data for them. Meta-analysis of seven RCTs comparing LMWH with VKA found no statistically significant survival benefit (hazard ratio (HR) 0.96; 95% confidence interval (CI) 0.81 to 1.14) but a statistically significant reduction in VTE (HR 0.47; 95% CI 0.32 to 0.71). The remaining findings did not exclude a beneficial or harmful effect of LMWH compared with VKA for the outcomes of major bleeding (RR 1.07; 95% CI 0.52 to 2.19), minor bleeding (RR 0.89; 95% CI 0.51 to 1.55), or thrombocytopenia (RR 0.98; 95% CI 0.57 to 1.66). We judged the quality of evidence as low for mortality, major bleeding, and minor bleeding, and as moderate for recurrent VTE.One RCT comparing dabigatran with VKA did not exclude beneficial or harmful effects of one agent over the other. One RCT comparing six months' extension of anticoagulation with 18 months of ximelagatran 24 mg twice daily versus no extended ximelagatran did not exclude beneficial or harmful effects for the outcomes of reduction in VTE, mortality, and minor bleeding. One RCT comparing once-weekly subcutaneous injection of idraparinux for three or six months versus standard treatment (parenteral anticoagulation followed by warfarin or acenocoumarol) suggested a reduction in recurrent VTE (HR 0.39; 95% CI 0.14 to 1.11) at six months, but did not exclude beneficial or harmful effects for the outcomes of mortality (HR 0.99; 95% CI 0.66 to 1.48) and major bleeding (RR 1.04; 95% CI 0.39 to 2.83). For the long-term treatment of VTE in patients with cancer, LMWH compared with VKA reduces venous thromboembolic events but not mortality. The decision for a patient with cancer and VTE to start long-term LMWH versus oral anticoagulation should balance the benefits and harms and integrate the patient's values and preferences for the important outcomes and alternative management strategies.

Home Therapy With LMWH in Deep Vein Thrombosis: Randomized Study Comparing Single and Double Daily Administrations

The aim of this study was to assess the effectiveness of low-molecular-weight heparin (LMWH) treatment of deep vein thrombosis (DVT) in terms of the evolution of thrombosis, the incidence of adverse events, and compliance with heparin treatment using 2 types of LMWH available on the market administered in therapeutic doses throughout the period of treatment (Nadroparin) or at therapeutic doses only during the first month of treatment followed by a prophylactic phase at half dose (Parnaparin). A randomized prospective study was carried out on patients under observation with a recent diagnosis of DVT. The objectives of the study were to confirm the effectiveness of therapy with LMWH in terms of prevention of the risk of thromboembolism, of relapse of DVT, and of hemorrhagic complications, and to complete an evaluation of venous recanalization and residual valve competence in the 2 groups of patients. From December 2002 to June 2005, we randomized a total of 91 patients (51 in the Parnaparin group and 40 in the Nadroparin group). Overall, there was 1 case of nonfatal pulmonary embolism (1.1%) at 7 days into therapy with LMWH. There were 3 cases (3.3%) of progression of thrombosis despite therapy with LMWH, 2 cases (5%) in the Nadroparin group, and 1 case (2%) in the Parnaparin group (P = NS), and after suspension of the therapy, there was 1 case of relapse of thrombosis. Three of the 4 thrombotic events occurred in patients with active neoplasia. Moreover, only 1 major hemorrhagic event (1.1%) required blood transfusion. The Doppler ultrasound in the follow-up showed a complete resolution of 56% of the vein thromboses at an average of 6.1 +/- 4.6 (mean +/- SD) months. Valve competence recovered in 65.9% of cases with no significant difference between the 2 heparin groups. Home treatment of sural and femoral-popliteal DVT using LMWH represents a safe and effective method in the prevention of pulmonary embolism and encourages the process of recanalization of the thrombosed vessel, especially in cases of sural and/or popliteal DVT. Administration can be carried out with the same degree of safety at the therapeutic dose throughout the period of treatment or can be halved after the first month of treatment. In patients with active neoplasia, treatment with oral anticoagulant therapy must be considered.