Quality control, safety assessment and preparation approaches of low molecular weight heparin.

Low Molecular Weight Heparins (LMWHs) are well-established for use in the prevention and treatment of thrombotic diseases, and as a substitute for unfractionated heparin (UFH) due to their predictable pharmacokinetics and subcutaneous bioavailability. LMWHs are produced by various depolymerization methods from UFH, resulting in heterogeneous compounds with similar biochemical and pharmacological properties. However, the delicate supply chain of UFH and potential contamination from animal sources require new manufacturing approaches for LMWHs. Various LMWH preparation methods are emerging, such as chemical synthesis, enzymatic or chemical depolymerization and chemoenzymatic synthesis. To establish the sameness of active ingredients in both innovator and generic LMWH products, the Food and Drug Administration has implemented a stringent scientific method of equivalence based on physicochemical properties, heparin source material and depolymerization techniques, disaccharide composition and oligosaccharide mapping, biological and biochemical properties, and in vivo pharmacodynamic profiles. In this review, we discuss currently available LMWHs, potential manufacturing methods, and recent progress for manufacturing quality control of these LMWHs.

A Comparison Between Fondaparinux Sodium and Low-Molecular-Weight Heparin in Preventing Patients Undergoing Hip Replacement from Deep Vein Thrombosis.

OBJECTIVES: Total hip arthroplasty (THA) is a highly successful and effective surgery for improving hip functions and relieving pain. However, the lower extremities are prone to deep vein thrombosis (DVT) and swelling after surgery, thereby delaying recovery. In this study, we investigated the preventive effects of fondaparinux sodium (FS) and low-molecular-weight heparin (LMWH) on DVT of the lower extremity after THA. METHODS: Firstly, 60 patients who underwent THA at the First Affiliated Hospital of Wannan Medical College from March 2020 to December 2020 were included. Next, the patients were randomly divided into an LMWH group (n = 30) and an FS group (n = 30). Then, the indexes related to DVT were compared between both groups. RESULTS: Specifically, the differences in baseline data, such as age, gender and body mass index (BMI), between the two groups were not statistically significant. The postoperative weight bearing time of patients in the FS group was much shorter than that in the LMWH group. CONCLUSION: Subcutaneous injection of FS not only exhibits superior effects to LMWH in preventing DVT after THA but also has a correlation with reducing the risk of thrombosis and improving patient symptoms.

[Is monitoring of anti-factor Xa levels required for low molecular weight heparin prophylaxis of venous thromboembolism in critically ill patients?]

The incidence and mortality of venous thromboembolism (VTE) are high in critically ill patients, and there is still a risk of VTE and bleeding after the use of fixed-dose low molecular weight heparin (LMWH) for prophylaxis. The level of anti-factor Xa is not up to standard after LMWH prophylaxis in patients with surgery or trauma. The condition of critically ill patients is complicated, and the proportion of patients with low antithrombin III is high, which can affect the prophylactic efficacy of LMWH and contribute to VTE occurrence. There is currently no consensus on whether adjusting LMWH dose according to anti-factor Xa levels can reduce VTE occurrence in critically ill patients. High-quality multicenter randomized controlled studies are needed in the future to establish new approaches for precise prevention of VTE in critically ill patients.

Increased risk of adverse gestational outcomes in pregnant women with primary Sjögren's syndrome.

OBJECTIVES: This study aimed to identify risk factors contributing to diverse pregnancy outcomes in primary Sjögren's syndrome (pSS) cases. METHODS: A retrospective analysis was conducted on pregnant individuals with pSS, who received outpatient or inpatient care across multiple hospitals in Anhui Province, China, from January 2015 to December 2022. RESULTS: This study included 164 pregnant women with pSS and 328 control subjects, with no statistically significant difference in average age between the two groups. Analysis of pregnancy outcomes revealed that, compared with the control group, pregnant women in the pSS group were more likely to experience miscarriages, both spontaneous (12.80% vs 1.52%, p<0.001) and therapeutic (6.10% vs 0.91%, p<0.05). The proportion of placental abnormalities detected during prenatal ultrasound in women from the pSS group was higher (14.63% vs 6.40%, p<0.05). In the analysis of pregnancy outcomes for live-born neonates, a higher incidence of congenital heart abnormalities was observed in the pSS group (27.34% vs 12.03%, p<0.05). While there were no significant differences between the pSS pregnancies in terms of both normal and adverse pregnancy outcomes, a comparison of fetal survival and fetal loss in pSS pregnancies revealed a greater use of prophylactic anticoagulant therapy in the fetal survival group. Notably, the application of low molecular weight heparin (LMWH) emerged as an independent protective factor for fetal survival. CONCLUSIONS: Compared with non-autoimmune controls, pregnancy in women with pSS presents more challenges. Importantly, we observed that the use of LMWH as anticoagulant therapy is an independent protective measure for fetal survival.

The Bifunctional Effects of Lactoferrin (LFcinB11) in Inhibiting Neural Cell Adhesive Molecule (NCAM) Polysialylation and the Release of Neutrophil Extracellular Traps (NETs).

The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM) is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and aggressive clinical status. Thus, it is important to select a proper drug to block tumor cell migration during clinical treatment. In this study, we proposed that lactoferrin (LFcinB11) may be a better candidate for inhibiting NCAM polysialylation when compared with CMP and low-molecular-weight heparin (LMWH), which were determined based on our NMR studies. Furthermore, neutrophil extracellular traps (NETs) represent the most dramatic stage in the cell death process, and the release of NETs is related to the pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis, and vascular disorders. In this study, the molecular mechanisms involved in the inhibition of NET release using LFcinB11 as an inhibitor were also determined. Based on these results, LFcinB11 is proposed as being a bifunctional inhibitor for inhibiting both NCAM polysialylation and the release of NETs.

Successful management of postpartum venous thrombosis following splenectomy for traumatic splenic rupture: a case report.

Traumatic splenic rupture is rare in pregnant women; and multiple venous thromboses of the portal vein system, inferior vena cava and ovarian vein after caesarean section and splenectomy for splenic rupture has not been previously reported. This case report describes a case of multiple venous thromboses after caesarean section and splenectomy for traumatic splenic rupture in late pregnancy. A 34-year-old G3P1 female presented with abdominal trauma at 33+1 weeks of gestation. After diagnosis of splenic rupture, she underwent an emergency caesarean section and splenectomy. Multiple venous thromboses developed during the recovery period. The patient eventually recovered after anticoagulation therapy with low-molecular-weight heparin and warfarin. These findings suggest that in patients that have had a caesarean section and a splenectomy, which together might further increase the risk of venous thrombosis, any abdominal pain should be thoroughly investigated and thrombosis should be ruled out, including the possibility of multiple venous thromboses. Anticoagulant therapy could be extended after the surgery.

Monitoring anti-Xa levels in elderly medical patients undergoing thromboprophylaxis: A prospective cohort study.

INTRODUCTION: Given the rising incidence of venous thromboembolism (VTE) and insufficient thromboprophylaxis dosing evidence in certain patients, the precise monitoring of anti-Xa (aFXa) levels is crucial. The aim of this study is to investigate the achievement of prophylactic aFXa levels in medical inpatients who were receiving parenteral anticoagulant and to evaluate the impact of various factors on aFXa levels. METHODS: This is a single-center observational cohort study conducted on patients admitted to the Department of Internal Medicine at the University Hospital of Heraklion, Greece, from March to August 2023. These individuals received low-molecular-weight heparins thromboprophylaxis owing to an increased risk of VTE. Data regarding demographics, past medical history, and somatometric and laboratory findings were recorded. The established range for peak prophylactic aFXa levels was defined as 0.2-0.5 IU/mL. RESULTS: In this study, we enrolled 150 individuals [91 (60.7%) women] with a mean age of 80.0 ± 14.1 years. Sixty-two (41.4%) patients exhibited non-prophylactic peak aFXa levels. Supratherapeutic levels were observed in all underweight patients and subtherapeutic levels in 12 of 13 obese patients in class II and III. A multivariate linear regression analysis revealed that body weight, cancer, and the Charlson Comorbidity Index (CCI) were independent factors influencing aFXa levels. CONCLUSIONS: Our study reveals a substantial portion of medical elderly inpatients on thromboprophylaxis with non-prophylactic aFXa levels, with a notable prevalence among underweight and severely obese patients. Body weight, cancer, and CCI were identified as independent factors influencing aFXa levels, advocating for tailored thromboprophylaxis strategies. Further research is warranted to validate personalized dosing approaches and to enhance clinical decision-making. Geriatr Gerontol Int 2024; 24: 587-594.

[Translation into French and republication of: "Management of venous thromboembolic disease in patients with malignant brain tumours"]. / Traduction et republication de : « Prise en charge de la maladie thromboembolique veineuse chez les patients atteints de tumeurs cérébrales malignes ¼.

This article addresses the management of venous thromboembolism in patients with malignant brain tumours, including both primary and secondary (metastatic) tumours. The available data on patients on venous thromboembolism recurrence and bleeding risks in patients with brain tumours is limited, since these patients have been excluded from most randomised, interventional, head-to-head, clinical trials comparing low molecular weight heparins to vitamin K antagonists or to direct oral factor Xa inhibitors. More information is available from retrospective observational studies, which however were generally small, and carried a high risk of confounding. Their findings suggest that direct factor Xa inhibitor use is associated with lower rates of intracranial haemorrhage compared with low molecular weight heparins. Overall, the safety profile of direct oral factor Xa inhibitors when used to prevent venous thromboembolism recurrence in patients with either primary or secondary brain tumours appears to be favourable. The available data are in favour of using an anticoagulant at a full therapeutic dose in patients with primary and secondary brain tumours experiencing a venous thromboembolism, although they are not yet sufficiently robust to permit recommending a direct factor Xa inhibitor over low-molecular weight heparin.

Intra-abdominal hematomas and identifiable risk factors in patients receiving subcutaneous enoxaparin.

BACKGROUND: Low molecular weight heparin has proven to be safe and effective but is not without potential risks such as spontaneous bleeding in the abdominal cavity. There is limited evidence evaluating the true incidence of this potential risk and the available literature is primarily via case reports. CASE SUMMARY: The purpose of this study was to identify the incidence and risk factors associated with enoxaparin use (prophylaxis or treatment) abdominal hematomas in a 350-bed community hospital during an 8-month time period. A total of 44 patients were identified as clinically significant bleeds receiving enoxaparin treatment or prophylactic therapy. Ultimately, 25 patients were excluded from the analysis due to an external cause of the abdominal hematoma or a temporal mismatch in enoxaparin administration and hematoma formation. After exclusion, there were a total of 19 patients that were assessed for the risk factors such as age, gender, renal function, and weight. After evaluation of risks, over half of the patients developing a clinically significant bleed were considered elderly (>65 years of age) and impaired renal function with a creatinine clearance of 60ml/min or less. CONCLUSION: Patients at risk for an enoxaparin associated hematoma include female patients with a CrCl <60ml/min and/or BMI >30 kg/m2 receiving enoxaparin treatment dosing.

Intestinal obstruction as a result of intra-abdominal hematoma: a complication of low molecular weight heparin in pediatric patients. / Obstrucción intestinal por hematoma intraabdominal: una complicación de la heparina de bajo peso molecular en el paciente pediátrico.

INTRODUCTION: Hematomas are a rare cause of intestinal obstruction. Subcutaneous heparin can bring about direct punctures on small bowel loops, potentially leading to traumatic hematoma and intestinal obstruction. CASE REPORTS: We present three cases of pediatric patients with clinical signs of intestinal obstruction treated with subcutaneous heparin. Two cases had increased acute-phase reactants and radiological signs of intestinal suffering, so surgical treatment was decided upon, with intramural hematoma emerging as an intraoperative finding. The third case was conservatively managed with anticoagulant discontinuation and gut rest, since the patient had an adequate general condition and no findings compatible with ischemia or necrosis were noted in the complementary tests. DISCUSSION: The administration of subcutaneous heparin may cause intestinal wall hematomas due to its anticoagulating effect and to the risk of inadvertent punctures on small bowel loops.

INTRODUCCION: Los hematomas son una causa poco frecuente de obstrucción intestinal. La heparina subcutánea tiene riesgo de producir la punción directa de un asa intestinal, provocando un hematoma traumático que genere una obstrucción intestinal. CASOS CLINICOS: Se describen tres casos de pacientes pediátricos con clínica de obstrucción intestinal en tratamiento con heparina subcutánea. Dos casos presentaron elevación de reactantes de fase aguda y signos radiológicos de sufrimiento intestinal por lo que se optó por tratamiento quirúrgico, con el hallazgo intraoperatorio de hematoma intramural. El tercer caso fue manejado de manera conservadora con supresión de la anticoagulación y reposo intestinal, dado el adecuado estado general y ausencia de hallazgos compatibles con isquemia o necrosis en las pruebas complementarias. COMENTARIOS: La administración de heparina subcutánea puede provocar la aparición de hematomas de pared intestinal, tanto por su efecto anticoagulante, como por el riesgo de punción inadvertida de un asa intestinal.

Structured benefit-risk assessment for enoxaparin, in the context of its label extension, for the extended treatment of deep vein thrombosis and pulmonary embolism, and prevention of its recurrence in patients with active cancer.

PURPOSE: Guidelines recommend low-molecular-weight heparins (LMWHs) for patients with cancer-associated thrombosis. However, until recently, only dalteparin and tinzaparin were approved in the European Economic Area (EEA) for these patients. This study compares the benefit-risk profile of enoxaparin with dalteparin and tinzaparin for the extended treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrence in adult patients with active cancer. METHODS: A semi-quantitative structured benefit-risk assessment was conducted for the label-extension application of enoxaparin based on the benefit-risk action team descriptive framework: define decision context; determine key benefit and risk outcomes; identify data sources; extract data; interpret results. RESULTS: The key benefits were defined as reduced all-cause mortality and venous thromboembolism (VTE) recurrence (including symptomatic DVT, fatal PE or non-fatal PE); the key risks were major and non-major bleeding of clinical significance, and heparin-induced thrombocytopenia (HIT). Enoxaparin demonstrated comparable effects for the reduction of VTE recurrence and all-cause mortality versus other EEA-approved LMWHs (dalteparin, tinzaparin). There was no evidence of a significant difference between enoxaparin and the comparator groups with regard to incidence of major and non-major bleeding. The data on HIT were too limited to assess the difference between the two groups. CONCLUSIONS: The assessment demonstrated a favourable benefit-risk profile for enoxaparin similar to that of other EEA-approved LMWHs for the treatment of DVT and PE and the prevention of recurrence in patients with active cancer and thus supported the label-extension approval.

Acute pulmonary embolism in cancer patients admitted to intensive care unit: Impact of anticoagulant treatment on 90-day mortality and risk factors, results of a multicentre retrospective study.

BACKGROUND: Acute pulmonary embolism (PE) is a life-threatening situation in cancer patients. In this situation, anticoagulant therapy is complex to administer due to the risk of bleeding. Only few studies have been conducted when these patients are admitted to the intensive care unit (ICU). The aim of this study was to assess the association between anticoagulation strategies as well as other factors with 90-day mortality in patients with cancer and PE admitted to ICU. Major bleeding was also evaluated according to the type of anticoagulation. METHODS: Retrospective study carried out in 4 ICUs in France over a 12-year period (2009-2021). All patients with cancer and PE were included. An overlap propensity score weighting analysis was performed in the subgroup of patients treated with either unfractionated heparins (UFH) alone or low-molecular-weight heparins (LMWH) alone on 90-day mortality and major bleeding. RESULTS: A total of 218 consecutive cancer patients admitted to ICU and presenting PE were included. The 90-day mortality rate was 42 % for the global cohort. After propensity score analysis in the subgroup of patients treated with either "UFH alone" (n = 80) or "LMWH alone" (n = 71), the 90-day mortality was similar in patients treated with UFH alone (42.6 %) vs LMWH alone (39.9 %): OR = 1.124, CI 95 % [0.571-2.214], p = 0.750. There was a significant increased toward major bleeding rates in the "UFH alone" group (25.5 %) as compared to "LMWH alone" group (11.5 %), p = 0.04. CONCLUSION: In 218 patients admitted to ICU and presenting PE, the 90-day mortality rate was 42 %. Treatment with UFH alone was associated with a mortality comparable to treatment with LMWH alone but it appeared to be more prone to major bleeding.

A systematic review and meta-analysis of the effectiveness of primary thromboprophylaxis in acute lymphoblastic leukemia during early-phase therapy including asparaginase or its prolonged form.

Asparaginase is essential in the initial management of acute lymphoblastic leukemia (ALL) but frequently leads to venous thromboembolism (VTE). Using anticoagulants for primary VTE prevention has been studied with no consensus. We conducted a systematic literature search in PubMed, Scopus, and Web of science and performed random-effect meta-analysis using Mantel-Haenszel method in RevMan 5.4 to analyze primary pharmacological thromboprophylaxis during asparaginase treatment in early-phase (induction, consolidation, or intensification phase) therapy in patients with ALL with all ages and followed with subgroup analysis by age. Meta-analysis of 13 articles describing the effect of antithrombin supplementation in 1375 patients showed that antithrombin prophylaxis decreases the risk of VTE by 43% (RR, 0.57; 95% CI, 0.38 - 0.83; p=0.004), with mild heterogeneity (I2=35%, p=0.10) and moderate certainty by GRADE. 8 articles included for meta-analysis of low-molecular weight heparin (LMWH) treatment in 612 patients showed that it decreased the risk of VTE by nearly 40% (RR, 0.61; 95% CI, 0.45 - 0.81; p=0.00081), with minimal heterogeneity (I2=14%, p=0.31) but low certainty. Subgroup analysis showed that only prophylaxis with antithrombin supplementation significantly decreased the VTE rate in adult patients with moderate certainty. In pediatric patients, one nonrandomized prospective study showed that LMWH combined with antithrombin has a better thromboprophylaxis effect than antithrombin alone. In the PREVAPIX-ALL trial, prophylaxis with direct factor Xa inhibitor Apixaban did not benefit children younger than 18 years except for cases of obesity. We concluded that thromboprophylaxis with antithrombin is effective in ALL patients older than 18 years during the early phase of therapy, and LMWH combined with antithrombin supplementation might be effective for pediatric patients with ALL. Apixaban is effective in pediatric ALL patients with obesity and needs further study in other high-risk patients.

Clinical guidelines for prevention and treatment of CAT in Japan and other countries.

Cancer-associated thrombosis (CAT) is an important prognostic factor for an increasing number of cancer patients. Understanding of CAT among cancer care providers has grown in recent years, and guidelines for the prevention and treatment of CAT have been published in Japan and around the world. In this article, we introduce these major guidelines and discuss differences we identified between the Japanese guidelines and those of other countries, with a focus on problems and issues. Insurance coverage of low-molecular-weight heparin and indications for primary prevention with direct oral anticoagulants in particular require urgent consideration.

Obstrucción intestinal por hematoma intraabdominal: una complicación de la heparina de bajo peso molecular en el paciente pediátrico / Intestinal obstruction as a result of intra-abdominal hematoma: a complication of low molecular weight heparin in pediatric patients

Introducción: Los hematomas son una causa poco frecuente deobstrucción intestinal. La heparina subcutánea tiene riesgo de producirla punción directa de un asa intestinal, provocando un hematoma trau-mático que genere una obstrucción intestinal. Casos clínicos: Se describen tres casos de pacientes pediátricos conclínica de obstrucción intestinal en tratamiento con heparina subcutánea.Dos casos presentaron elevación de reactantes de fase aguda y signosradiológicos de sufrimiento intestinal por lo que se optó por tratamientoquirúrgico, con el hallazgo intraoperatorio de hematoma intramural. Eltercer caso fue manejado de manera conservadora con supresión de laanticoagulación y reposo intestinal, dado el adecuado estado generaly ausencia de hallazgos compatibles con isquemia o necrosis en laspruebas complementarias. Comentarios: La administración de heparina subcutánea puedeprovocar la aparición de hematomas de pared intestinal, tanto por suefecto anticoagulante, como por el riesgo de punción inadvertida deun asa intestinal.(AU)

Introduction: Hematomas are a rare cause of intestinal obstruc-tion. Subcutaneous heparin can bring about direct punctures on smallbowel loops, potentially leading to traumatic hematoma and intestinalobstruction. Case reports: We present three cases of pediatric patients withclinical signs of intestinal obstruction treated with subcutaneous heparin. Two cases had increased acute-phase reactants and radiological signsof intestinal suffering, so surgical treatment was decided upon, withintramural hematoma emerging as an intraoperative finding. The thirdcase was conservatively managed with anticoagulant discontinuationand gut rest, since the patient had an adequate general condition andno findings compatible with ischemia or necrosis were noted in thecomplementary tests. Discussion: The administration of subcutaneous heparin may causeintestinal wall hematomas due to its anticoagulating effect and to therisk of inadvertent punctures on small bowel loops.(AU)

Effectiveness and safety of rivaroxaban for anticoagulation therapy in COVID-19: A meta-analysis of randomized controlled trials.

OBJECTIVES: To evaluate the effectiveness and safety of rivaroxaban anticoagulation in COVID-19 patients. METHODS: PubMed, Embase, Cochrane Library electronic databases, and ClinicalTrials.gov were searched to identify all relevant randomized controlled trial studies from December 2019 to July 2023. RESULTS: A total of 6 randomized controlled trials, which included a total of 3323 patients, were considered for evaluation. Overall, short-term all-cause mortality and hospitalization rates were not significantly different between the rivaroxaban and control groups. Thrombotic events were significantly reduced in the rivaroxaban prophylaxis group compared to the placebo control group. However, the reduction in thrombotic events was not significantly different between rivaroxaban therapy and heparin or low-molecular-weight heparin (LMWH). Rivaroxaban prophylaxis and the therapeutic dose may be associated with a higher rate of overall bleeding rate, but major bleeding rates did not differ substantially. CONCLUSION: Rivaroxaban may reduce thrombotic events in COVID-19 patients, but it does not appear to have an advantage over heparin or LMWH, and it may increase the risk of bleeding.INPLASY Reg. No.: INPLASY 202370097.

Clinical study of tirofiban compared to low molecular weight heparin in the antithrombotic treatment of progressive pontine infarction.

OBJECTIVE: To investigate the efficacy and safety of tirofiban and low molecular weight heparin (LMWH) in the treatment of patients undergoing acute progressive pontine infarction. PATIENTS AND METHODS: Patients with acute progressive pontine infarction who were hospitalized in the Neurology Department from June 2021 to June 2023 were included in the study and randomly divided into two groups, namely the experimental group (tirofiban group) and the control group (LMWH group). All patients in both groups were required to receive conventional comprehensive treatment and dual antiplatelet therapy with aspirin + clopidogrel at the beginning of admission. The National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index (BI) were used to evaluate the neurological deficits on the first day of admission, the next day with stroke progression, and at discharge after treatment with tirofiban and LMWH, respectively in the two groups. The modified Rankin Scale was employed to assess prognosis on the 90th day after treatment. Clinical adverse events were followed up for 90 days, comparing the clinical efficacy and safety of the two treatment methods. RESULTS: There was no statistical significance in NIHSS score and Barthel Index between the tirofiban group and the LMWH group on the first day of admission and the next day with stroke progression (p > 0.05). After stroke progression, tirofiban and LMWH were separately used for treatment in the two groups. We found that the NIHSS score of the tirofiban group was lower than that of the LMWH group, and the Barthel Index score was higher than that of the LMWH group at discharge (p < 0.05). After three months of follow-up, the mRS score of the tirofiban group was dramatically higher than that of the LMWH group (p < 0.05). No significant harmful or adverse reactions, such as bleeding events, were found in the two groups (p > 0.05). CONCLUSIONS: Tirofiban may be more effective and safer than LMWH in controlling the progression of acute pontine infarction, but further and large-sample studies are still needed to confirm this finding.

Impact of perioperative low-molecular-weight heparin therapy on clinical events of elderly patients with prior coronary stents implanted > 12 months undergoing non-cardiac surgery: a randomized, placebo-controlled trial.

BACKGROUND: Little is known about the safety and efficacy of discontinuing antiplatelet therapy via LMWH bridging therapy in elderly patients with coronary stents implanted for > 12 months undergoing non-cardiac surgery. This randomized trial was designed to compare the clinical benefits and risks of antiplatelet drug discontinuation via LMWH bridging therapy. METHODS: Patients were randomized 1:1 to receive subcutaneous injections of either dalteparin sodium or placebo. The primary efficacy endpoint was cardiac or cerebrovascular events. The primary safety endpoint was major bleeding. RESULTS: Among 2476 randomized patients, the variables (sex, age, body mass index, comorbidities, medications, and procedural characteristics) and percutaneous coronary intervention information were not significantly different between the bridging and non-bridging groups. During the follow-up period, the rate of the combined endpoint in the bridging group was significantly lower than in the non-bridging group (5.79% vs. 8.42%, p = 0.012). The incidence of myocardial injury in the bridging group was significantly lower than in the non-bridging group (3.14% vs. 5.19%, p = 0.011). Deep vein thrombosis occurred more frequently in the non-bridging group (1.21% vs. 0.4%, p = 0.024), and there was a trend toward a higher rate of pulmonary embolism (0.32% vs. 0.08%, p = 0.177). There was no significant difference between the groups in the rates of acute myocardial infarction (0.81% vs. 1.38%), cardiac death (0.24% vs. 0.41%), stroke (0.16% vs. 0.24%), or major bleeding (1.22% vs. 1.45%). Multivariable analysis showed that LMWH bridging, creatinine clearance < 30 mL/min, preoperative hemoglobin < 10 g/dL, and diabetes mellitus were independent predictors of ischemic events. LMWH bridging and a preoperative platelet count of < 70 × 109/L were independent predictors of minor bleeding events. CONCLUSIONS: This study showed the safety and efficacy of perioperative LMWH bridging therapy in elderly patients with coronary stents implanted > 12 months undergoing non-cardiac surgery. An alternative approach might be the use of bridging therapy with half-dose LMWH. TRIAL REGISTRATION: ISRCTN65203415.

Aspirin versus low-molecular-weight heparin for thromboprophylaxis after orthopaedic surgery: a systematic review and meta-analysis.

The article aimed to compare the efficiency and safety of aspirin with low-molecular-weight heparin (LMWH) for thromboprophylaxis in orthopaedic surgery patients. According to the inclusion and exclusion criteria, PubMed, Embase and Cochrane Library database were searched for studies comparing aspirin and LMWH in venous thromboembolism (VTE) prophylaxis until 25 April 2023. The outcome measures included deep venous thrombosis(DVT)/Pulmonary embolism(PE) events, major bleeding events, wound complications, wound infection and death. Six studies met the requirements of our meta-analysis, including 12 470 patients in the aspirin group and 10 857 patients in the LMWH group. The meta-analysis showed that results showed that LMWH was superior to aspirin in preventing VTE events (odds ratio (OR) 1.44, 95% CI 1.24-1.68, P  < 0.00001), whereas there was no significant difference between them in bleeding events (OR 0.95, 95% CI 0.86-1.05, P  = 0.33), wound complication (OR 0.58, 95% CI 0.28-1.17, P  = 0.13), wound infection (OR 1.12, 95% CI 0.86-1.47, P  = 0.39) and mortality (OR 1.04, 95% CI 0.70-1.55, P  = 0.83). In addition, subgroup analysis showed that compared with aspirin, LMWH was more likely to reduce the incidence of DVT events in orthopaedic surgery patients (OR 1.59, 95% CI 1.33-1.91, P  < 0.00001), whereas there was no advantage in reducing the incidence of PE events (OR 1.22, 95% CI 0.62-2.40, P  = 0.56). Despite the similar safety profiles, this meta-analysis showed that LMWH was significantly superior to aspirin in thromboprophylaxis after orthopaedic surgery. LMWH was still the first-line drug for thrombosis prevention in patients who underwent major orthopaedic surgeries.