RESUMEN
BACKGROUND: The purpose of the study is to examine if prolonged thromboprophylaxis decreases the risk of thrombosis after intended curative surgery for oesophageal cancer. Study results are expected to inform a guideline for thromboprophylaxis after oesophageal cancer surgery. The perspective is to reduce morbidity and mortality in this critically ill patient group. Thrombosis is the second-most common cause of cancer death after the cancer itself. The risk of thrombosis depends on the cancer type, and upper gastrointestinal cancers are considered high risk. This risk is further increased when patients undergo surgery. However, only few studies have investigated the peri- and postoperative coagulation profile in oesophageal cancer patients. Due to this lack of knowledge, prophylaxis is currently restricted to 5000 IU (international units) low-molecular weight heparin daily from surgery until discharge from hospital (approximately 10 days), whereas patients with gastric cancer receive 30 days of treatment. The present study examines whether a 30-day treatment is superior and safe, compared with the current standard treatment. METHODS: The study is a randomised controlled trial. Inclusion is ongoing, and we aim to include 100 patients. Blood samples are drawn before and after surgery, and the coagulation is extensively examined. The primary endpoint is the difference in plasma levels of prothrombin fragment 1 + 2 (F1 + 2) 30 days after surgery between the intervention and the standard group. Furthermore, patients are examined with ultrasound to screen for asymptomatic venous thrombotic events (VTE). Secondary endpoints are incidence of bleeding, symptomatic and asymptomatic VTE and mortality 30 days 1 one year after surgery. DISCUSSION: The study will provide valuable information on the perioperative coagulation profile and VTE risk of oesophageal cancer patients. The study seeks to aid in optimising the postoperative thromboprophylaxis, and the perspective is to reduce morbidity and mortality in this at-risk patient population. TRIALS REGISTRATION: The trial was prospectively registered at the EU Clinical Trials Register with ID 2021-001335-24 on 30 June 2021 and at ClinicalTrials.gov with study identifier NCT05067153.
Asunto(s)
Anticoagulantes , Neoplasias Esofágicas , Protrombina , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/mortalidad , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Esofagectomía/efectos adversos , Factores de Tiempo , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina de Bajo-Peso-Molecular/administración & dosificación , Fragmentos de Péptidos/sangre , Resultado del Tratamiento , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/etiología , Coagulación Sanguínea/efectos de los fármacos , Factores de Riesgo , Esquema de MedicaciónRESUMEN
BACKGROUND: 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). HYPOTHESES: 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. RESULTS: 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. CONCLUSION: 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.
Asunto(s)
Heparina de Bajo-Peso-Molecular , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Humanos , Intervención Coronaria Percutánea/métodos , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Heparina de Bajo-Peso-Molecular/uso terapéutico , Anticoagulantes/uso terapéutico , Hemorragia/inducido químicamente , Factores de Riesgo , Resultado del Tratamiento , Procedimientos Quirúrgicos Operativos/efectos adversos , Trombosis/prevención & control , Trombosis/etiología , Medición de RiesgoRESUMEN
BACKGROUND: Recent studies suggest that low-molecular-weight heparin (LMWH) may play a role in mitigating the severity of acute pancreatitis (AP). This systematic review and meta-analysis aims to synthesise existing evidence on the effectiveness and safety of LMWH in the treatment of moderately-severe and severe AP. METHODS: This systematic review and meta-analysis was conducted in accordance with the 2020 update of the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The systematic search was conducted in MEDLINE, the Cochrane Central Register of Controlled Trials, Scopus, and EMBASE, covering studies published up to February 2024. Randomised controlled trials (RCTs) and observational studies (n-RCTs) that reported the differences in the outcomes of AP for patients receiving LMWH in addition to the standard treatment (Intervention), compared to patients managed by standard treatment without LMWH (Control) were eligible. A random-effects model was used to calculate the pooled relative risk (RR) and mean differences (MD) with the corresponding 95% CI. RESULTS: Thirteen studies were included in the meta-analysis, all published between 2004 and 2022. Eight studies were RCTs, and five were n-RCTs. Data from 13,709 patients (6.971 Interventions and 6.738 Controls) were analysed. The comparison of Intervention and Control groups showed the superiority of LMWH to standard treatments in terms of overall mortality (RR = 0.44, 95% CI = 0.31; 0.64, P < 0.0001, I2 = 51%), acute necrotic collections (RR = 0.24, 95% CI = 0.09; 0.62, P = 0.003, I2 = 0%), and organ failure (RR = 0.67, 95% CI = 0.48; 0.93, P = 0.02, I2 = 78%). The Intervention group showed superior outcomes compared with the Control group for gastrointestinal bleeding (RR = 0.64, 95% CI = 0.44; 0.94, P = 0.02, I2 = 0%), length of hospital stay (MD= - 6.08, 95% CI = - 10.08; - 2.07, P = 0.003, I2 = 98%), need for operative interventions (RR = 0.50, 95% CI = 0.29; 0.87, P = 0.01, I2 = 61%), and vascular thrombosis (RR = 0.43, 95% CI = 0.31; 0.61, P < 0.00001, I2 = 0%). CONCLUSIONS: Moderate to high-quality evidence suggests that early intervention with LMWH could improve the prognosis of non-mild AP in terms of mortality, organ failure, and decreased incidence of vascular thrombosis. In light of our findings, integrating LMWH into the treatment regimen for moderate-severe to severe AP is advocated.
Asunto(s)
Heparina de Bajo-Peso-Molecular , Pancreatitis , Humanos , Heparina de Bajo-Peso-Molecular/uso terapéutico , Pancreatitis/tratamiento farmacológico , Anticoagulantes/uso terapéuticoRESUMEN
Antiphospholipid syndrome (APS) is the most frequent acquired thrombophilia of autoimmune basis. Pregnancy complications of APS may include recurrent miscarriage, and placental dysfunction presenting as fetal death, prematurity, intrauterine growth restriction and preeclampsia. For the management of obstetric APS, a coordinated medical-obstetric management is essential, and this should start for a preconceptional visit in order to estimate the individual risk for complications, adjust therapies and establish the indications for preconceptional and first-trimester therapy. The basis of APS therapy during pregnancy is low-dose aspirin, combined in certain clinical scenarios with low-molecular weight heparin. Induction of delivery should not be routinely indicated in the absence of maternal and/or fetal complications. Postpartum management should be warranted.
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Síndrome Antifosfolípido , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Humanos , Embarazo , Femenino , Aspirina/uso terapéutico , Complicaciones del Embarazo/terapia , Complicaciones del Embarazo/diagnóstico , Anticoagulantes/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Complicaciones Hematológicas del Embarazo/diagnóstico , Complicaciones Hematológicas del Embarazo/terapiaRESUMEN
Low-molecular-weight heparin (LMWH), derived from unfractionated heparin (UFH), has enhanced anticoagulant efficacy, long duration of action, and extended half-life. Patients receiving LMWH for preventive therapies would strongly benefit from its long-term effects, however, achieving this is challenging. Here, we design and evaluate a nanoengineered LMWH and octadecylamine conjugate (LMHO) that can act for a long time while maintaining close to 97 ± 3% of LMWH activity via end-specific conjugation of the reducing end of LMWH. LMHO can self-assemble into nanoparticles with an average size of 105 ± 1.7 nm in water without any nanocarrier and can be combined with serum albumin, resulting in a lipid-based albumin shuttling effect. Such molecules can circulate in the bloodstream for 4-5 days. We corroborate the self-assembly capability of LMHO and its interaction with albumin through molecular dynamics (MD) simulations and transmission electron microscopy (TEM) analysis. This innovative approach to carrier-free polysaccharide delivery, enhanced by nanoengineered albumin shuttling, represents a promising platform to address limitations in conventional therapies.
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Aminas , Anticoagulantes , Heparina de Bajo-Peso-Molecular , Simulación de Dinámica Molecular , Nanopartículas , Heparina de Bajo-Peso-Molecular/química , Aminas/química , Humanos , Nanopartículas/química , Anticoagulantes/química , Anticoagulantes/farmacología , Animales , Albúmina Sérica/química , Albúmina Sérica/metabolismo , Portadores de Fármacos/químicaRESUMEN
BACKGROUND: The risk of venous thromboembolism (VTE) is 15 to 35-fold higher in the postpartum period compared to non-pregnant individuals. Clinical practice guidelines recommend the use of postpartum thromboprophylaxis with low molecular weight heparin (LMWH) for 6 weeks in individuals at high risk of developing VTE. However, a marked reduction in the risk of VTE risk occurs beyond the third week of the postpartum period. OBJECTIVE: We sought to characterize practice patterns of clinicians who manage postpartum individuals at high risk of VTE. METHODS: We conducted a cross-sectional study using a self-administered electronic questionnaire. The survey explored the use of postpartum thromboprophylaxis in high-risk individuals. Descriptive statistics were used to summarize survey responses. RESULTS: Of the 113 participants that responded to the initial invitation, 78 completed the survey (Europe (53.9 %); North America (23.2 %); Australia and New Zealand (19.0 %)). For individuals with a prior unprovoked or provoked deep venous thrombosis or pulmonary embolism, cerebral vein thrombosis and splanchnic vein thrombosis, 97.4 %, 93.5 %, 91.0 % and 88.5 % of the respondents recommended six weeks of postpartum thromboprophylaxis using LMWH, respectively. The recommendation for 6 weeks of thromboprophylaxis in patients with sickle cell disease and obstetric APS was comparatively lower (70.5 and 78.2 % respectively). Respondents with higher practice volumes and more years of experience in clinical practice were more likely to recommend a shorter duration of thromboprophylaxis. CONCLUSION: Our study highlights the variability in clinician recommendations and the acceptability of treatment durations for postpartum thromboprophylaxis in high-risk conditions. Prospective studies are needed to determine optimal duration and establish evidence-based management.
Asunto(s)
Anticoagulantes , Personal de Salud , Periodo Posparto , Tromboembolia Venosa , Humanos , Femenino , Anticoagulantes/uso terapéutico , Estudios Transversales , Encuestas y Cuestionarios , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/tratamiento farmacológico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Adulto , Pautas de la Práctica en Medicina/estadística & datos numéricos , EmbarazoRESUMEN
Venous thromboembolism (VTE) is a common and potentially life-threatening complication in patients with cancer. Both cancer and its treatments increase the risk of developing VTE. Specific cancer types and individual patient comorbidities increase the risk of developing cancer-associated VTE, and the risk of bleeding is increased with anticoagulation therapies. The aims of this article are to summarize the latest evidence for treating cancer-associated VTE, discuss the practical considerations involved, and share best practices for VTE treatment in patients with cancer. The article pays particular attention to challenging contexts including patients with brain, lung, gastrointestinal, and genitourinary tumors and those with hematological malignancies. Furthermore, the article summarizes specific clinical scenarios that require additional treatment considerations, including extremes of body weight, nausea and gastrointestinal disturbances, compromised renal function, and anemia, and touches upon the relevance of drug-drug interactions. Historically, vitamin K antagonists and low-molecular-weight heparins (LMWHs) have been used as therapy for cancer-associated VTE. The development of direct oral anticoagulants has provided additional treatment options, which, in certain instances, offer advantages over LMWHs. There are numerous factors that need to be considered when treating cancer-associated VTE, and although various treatment guidelines are helpful, they do not reflect each unique scenario that may arise in clinical practice. This article provides a summary of the latest evidence and a practical approach for treating cancer-associated VTE.
Asunto(s)
Anticoagulantes , Neoplasias , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiología , Tromboembolia Venosa/tratamiento farmacológico , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Factores de Riesgo , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina de Bajo-Peso-Molecular/efectos adversosRESUMEN
BACKGROUND: Congenital portosystemic shunts (CPSS) are rare congenital abnormalities causing abnormal blood flow between the portal vein and systemic circulation. This study reports on the peri-operative anticoagulation management of CPSS patients post closure, focusing on the incidence of thrombotic and bleeding complications. METHODS: This is a single-center retrospective analysis of CPSS patients who underwent surgery or endovascular intervention between 2005 and 2021. The protocol included unfractionated heparin (UFH) during and immediately after surgery, followed by either warfarin or low molecular weight heparin (LMWH) postoperatively. Outcomes assessed included postoperative thrombotic and bleeding complications. RESULTS: A total of 44 patients were included. Postoperatively, 89% received treatment-dose UFH, transitioning to warfarin or LMWH at discharge. Thrombotic complications occurred in 16% of patients, predominantly in the superior mesenteric vein. Surgical interventions and continuous infusion of tissue plasminogen activator (tPA) were used for clot resolution. Bleeding complications were observed in 64% of patients, primarily managed with transfusions and temporary UFH interruption. No deaths related to thrombotic, or bleeding events were reported. CONCLUSIONS: Our findings underscore the delicate balance required in anticoagulation management for CPSS patients, revealing an occurrence of both thrombotic and bleeding complications postoperatively. LEVELS OF EVIDENCE: Level II, retrospective study.
Asunto(s)
Anticoagulantes , Heparina de Bajo-Peso-Molecular , Trombosis , Warfarina , Humanos , Estudios Retrospectivos , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Femenino , Masculino , Lactante , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina de Bajo-Peso-Molecular/administración & dosificación , Preescolar , Warfarina/uso terapéutico , Warfarina/efectos adversos , Warfarina/administración & dosificación , Trombosis/etiología , Trombosis/prevención & control , Trombosis/epidemiología , Niño , Vena Porta/anomalías , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Heparina/uso terapéutico , Heparina/administración & dosificación , Heparina/efectos adversos , Recién Nacido , Hemorragia Posoperatoria/etiología , Hemorragia Posoperatoria/epidemiología , Hemorragia Posoperatoria/prevención & control , Atención Perioperativa/métodos , Malformaciones Vasculares/complicaciones , Malformaciones Vasculares/cirugía , Sistema Porta/anomalías , AdolescenteRESUMEN
BACKGROUND: Limited real-world evidence is available comparing the safety and effectiveness of apixaban and low-molecular-weight heparins (LMWHs) for preventing recurrent venous thromboembolism (VTE) in patients with active cancer receiving anticoagulation in an extended treatment setting. This study evaluated the risk of bleeding and recurrent VTE in patients with cancer-associated VTE who were prescribed apixaban or LMWH for ≥3 months. METHODS: A US commercial claims database was used to identify adult patients with VTE and active cancer who initiated apixaban or LMWH 30 days following the first VTE diagnosis and had ≥3 months of continuous enrollment and 3 months of primary anticoagulation treatment. Patients were followed from the day after the end of primary anticoagulation treatment until the earliest of: date of disenrollment, discontinuation of index anticoagulant, switch to another anticoagulant, or end of the study period. Inverse-probability treatment weighting (IPTW) was used to balance treatment cohorts. Incidence rates (IRs) for the outcomes were calculated per 100 person-years (PY). Cox proportional hazard models were used to evaluate the adjusted risk of recurrent VTE, major bleeding (MB), and clinically relevant nonmajor bleeding (CRNMB). RESULTS: A total of 13,564 apixaban- and 2,808 LMWH-treated patients were analyzed. Post-IPTW, the treatment cohorts were balanced. Patients receiving apixaban had lower adjusted IRs for recurrent VTE (4.1 vs 9.6 per 100 PY), MB (6.3 vs 12.6), and CRNMB (26.1 vs 36.0) versus LMWH (P<.0001 for all comparisons) during the follow-up period. Patients on apixaban had a lower adjusted risk of recurrent VTE (hazard ratio [HR], 0.42; 95% CI, 0.34-0.53), MB (HR, 0.50; 95% CI, 0.41-0.61), and CRNMB (HR, 0.76; 95% CI, 0.68-0.85) versus LMWH. CONCLUSIONS: Extended anticoagulation treatment of ≥3 months with apixaban was associated with lower rates of recurrent VTE, MB, and CRNMB compared with LMWH in adults with cancer-associated VTE.
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Heparina de Bajo-Peso-Molecular , Neoplasias , Pirazoles , Piridonas , Tromboembolia Venosa , Humanos , Piridonas/uso terapéutico , Piridonas/efectos adversos , Piridonas/administración & dosificación , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Pirazoles/administración & dosificación , Tromboembolia Venosa/etiología , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/prevención & control , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Femenino , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina de Bajo-Peso-Molecular/efectos adversos , Heparina de Bajo-Peso-Molecular/administración & dosificación , Masculino , Persona de Mediana Edad , Anciano , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Hemorragia/inducido químicamente , Hemorragia/etiología , Resultado del Tratamiento , Adulto , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/administración & dosificaciónAsunto(s)
Anticoagulantes , Neoplasias Colorrectales , Heparina de Bajo-Peso-Molecular , Heparina , Humanos , Neoplasias Colorrectales/cirugía , Heparina de Bajo-Peso-Molecular/uso terapéutico , Anticoagulantes/uso terapéutico , Heparina/uso terapéutico , Heparina/efectos adversos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: The objective of this study is to compare and assess the efficacy and safety of low-molecular-weight heparin calcium (LMWH-Ca), followed by either warfarin or rivaroxaban, as treatment options for portal vein thrombosis (PVT) in patients with cirrhosis. METHODS: In this pilot study, cirrhotic (with liver function score of Child-Pugh A) patients diagnosed with PVT who were not on anticoagulant therapy received 2 weeks of subcutaneous injections of LMWH-Ca. They were then randomized to either warfarin (a full course of oral warfarin for 6 months) or rivaroxaban (a full course of oral rivaroxaban for 2 months), with 30 cases in each group. After a treatment period of up to 6 months, a comparative analysis was performed to assess the efficacy and safety of both groups. Volumetric changes in PVT were monitored dynamically using enhanced computed tomography scans before treatment at week 2 and month 6. RESULTS: There were no statistically significant differences in the clinical characteristics of the patients between the two groups. Rivaroxaban treatment reduced PVT median volume from 1.83 cm3 at week 2 to 0.0 cm3 at month 6 and prevented the worsening of PVT after 6 months of treatment with LMWH-Ca (Pâ <â 0.001). On the other hand, warfarin treatment increased PVT median volume from 1.95 cm3 at week 2 to 3.78 cm3 at month 6 (Pâ =â 0.002). None of the 30 patients in the rivaroxaban group had clinically significant gastrointestinal bleeding, while 2 of the 30 patients (7%) in the warfarin group had gastrointestinal bleeding (Pâ =â 0.317). CONCLUSION: Rivaroxaban followed by LMWH-Ca is an effective anticoagulant treatment strategy for PVT in cirrhosis.
Asunto(s)
Anticoagulantes , Heparina de Bajo-Peso-Molecular , Cirrosis Hepática , Vena Porta , Rivaroxabán , Trombosis de la Vena , Warfarina , Humanos , Proyectos Piloto , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Masculino , Rivaroxabán/administración & dosificación , Rivaroxabán/efectos adversos , Rivaroxabán/uso terapéutico , Vena Porta/diagnóstico por imagen , Femenino , Trombosis de la Vena/tratamiento farmacológico , Trombosis de la Vena/diagnóstico por imagen , Persona de Mediana Edad , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Warfarina/administración & dosificación , Warfarina/efectos adversos , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina de Bajo-Peso-Molecular/efectos adversos , Administración Oral , Resultado del Tratamiento , Anciano , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/uso terapéutico , Adulto , Inyecciones Subcutáneas , Tomografía Computarizada por Rayos X , Quimioterapia CombinadaRESUMEN
Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality worldwide, yet the cellular and molecular mechanisms driving this condition remain undeciphered, thus limiting discovery of new therapies. In-depth analyses of human and mouse tissues associated with PTB, in combination with cellular studies, indicated that aberrantly high-expressed neutrophil cytoplasmic factor (NCF) 1 leads to oxidative distress, recruitment, and pro-inflammatory activation of neutrophils and macrophages, while sequentially overexpressed pro-inflammatory mediators induce contractions of uterine smooth muscle cells (USMCs) as well as apoptosis of USMCs and amniotic epithelial cells, thereby causing PTB. According to these new findings, we rationally engineered an amphiphilic macromolecular conjugate LPA by covalently integrating low-molecular-weight heparin, a reactive oxygen species-responsive/scavenging component, and an anti-inflammatory peptide. This bioengineered macromolecular conjugate can self-assemble into multi-bioactive nanoparticles (LPA NP). In a mouse model of PTB, LPA NP effectively delayed PTB and inhibited adverse pregnancy outcomes, by regulating NCF1-mediated oxidative-inflammatory cascades, i.e., attenuating oxidative stress, inhibiting inflammatory cell activation, reducing local inflammation, and decreasing contraction/apoptosis of myometrial cells. Packaging LPA NP into temperature-responsive, self-healing, and bioadhesive hydrogel further potentiated its in vivo efficacies after intravaginal delivery, by prolonging retention time, sustaining nanotherapy release, and increasing bioavailability in the placenta/uterus. Importantly, both the conjugate/nanotherapy and hydrogel formulations exhibited excellent safety profiles in pregnant mice, with negligible side effects on the mother and offspring.
Asunto(s)
Nanopartículas , Nacimiento Prematuro , Femenino , Embarazo , Animales , Nacimiento Prematuro/prevención & control , Humanos , Ratones , Estrés Oxidativo/efectos de los fármacos , Resultado del Embarazo , Apoptosis/efectos de los fármacos , Heparina de Bajo-Peso-Molecular/farmacología , Heparina de Bajo-Peso-Molecular/uso terapéutico , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Modelos Animales de Enfermedad , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismoRESUMEN
BACKGROUND: Tinzaparin, a low-molecular weight heparin (LMWH), has shown anti-neoplastic properties in animal models and in in vitro studies of human cancer cell lines. The reduction of CA-125 levels during neoadjuvant chemotherapy (NACT) in patients with epithelial ovarian cancer (EOC) co-varies with the prognosis; the larger the decrease in CA-125, the better the prognosis. PURPOSE: This study aims to evaluate the potential anti-neoplastic effects of tinzaparin by investigating changes in serum CA-125 levels in advanced EOC patients who receive NACT. MATERIAL AND METHODS: This is an open randomized multicenter pilot trial. Forty patients with EOC selected to receive NACT will be randomized 1:1 to receive daily addition of tinzaparin or no tinzaparin. The processing and treatment of the patients will otherwise follow the recommendations in the Swedish National Guidelines for Ovarian Cancer. Before every cycle of chemotherapy, preoperatively, and 3 weeks after the last cycle of chemotherapy, a panel of biomarkers, including CA-125, will be measured. PATIENTS: Inclusion criteria are women aged 18 years or older, World Health Organization performance status 0-1, histologically confirmed high-grade serous, endometrioid or clear cell EOC, International Federation of Gynecology and Obstetrics (FIGO) stages III-IV. In addition, a CA-125 level of ≥ 250 kIE/L at diagnosis. Exclusion criteria are contraindications to LMWH, ongoing or recent treatment with unfractionated heparin, LMWH, warfarin or non-vitamin K antagonist oral anticoagulants. INTERPRETATION: This study will make an important contribution to the knowledge of the anti-neoplastic effects of tinzaparin in EOC patients and may thus guide the planning of a future study on the impact of tinzaparin on survival in EOC.
Asunto(s)
Biomarcadores de Tumor , Antígeno Ca-125 , Carcinoma Epitelial de Ovario , Terapia Neoadyuvante , Neoplasias Ováricas , Tinzaparina , Humanos , Femenino , Tinzaparina/administración & dosificación , Terapia Neoadyuvante/métodos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Ováricas/sangre , Biomarcadores de Tumor/sangre , Antígeno Ca-125/sangre , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/patología , Carcinoma Epitelial de Ovario/sangre , Adulto , Estadificación de Neoplasias , Proyectos Piloto , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante/métodos , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina de Bajo-Peso-Molecular/administración & dosificación , Pronóstico , AncianoRESUMEN
Recurrent pregnancy loss (RPL) affects 1-2â¯% of all couples trying to conceive and is a challenging heterogeneous condition. This study aimed to evaluate the prevalence and impact of various risk factors in patients suffering from RPL. We performed a prospective cohort study including patients at the tertiary RPL Unit in the Capital Region of Denmark between 1st January 2000 and 1st January 2023. The main outcome of the study was the first pregnancy after referral and whether the pregnancy was ongoing at least to the 22nd gestational week. A total of 2555 patients were included in the study, out of whom 1892 patients achieved a pregnancy after referral to the RPL Unit. This resulted in 1103 live births (58.3â¯%) and 718 pregnancy losses (37.9â¯%). Maternal age, BMI, smoking status and the number of prior pregnancy losses were negatively correlated with the likelihood of achieving pregnancy. Furthermore, maternal age, prior pregnancy losses, antiphospholipid syndrome (APS) and uterine malformations were associated with reduced birth rates. Patients with secondary RPL had a higher birth rate compared to those with primary RPL, and patients with APS treated with low-molecular-weight heparin (LMWH) demonstrated a significantly increased birth rate compared to untreated APS patients. These findings suggest that certain risk factors significantly impact the likelihood of achieving pregnancy and live birth following RPL, which can be used in patient guidance.
Asunto(s)
Aborto Habitual , Nacimiento Vivo , Humanos , Femenino , Embarazo , Aborto Habitual/epidemiología , Aborto Habitual/inmunología , Adulto , Estudios Prospectivos , Factores de Riesgo , Nacimiento Vivo/epidemiología , Síndrome Antifosfolípido/epidemiología , Síndrome Antifosfolípido/inmunología , Edad Materna , Dinamarca/epidemiología , Resultado del Embarazo/epidemiología , Heparina de Bajo-Peso-Molecular/uso terapéutico , Tasa de Natalidad , Estudios de CohortesRESUMEN
Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disorder associated with various pathological pregnancies, such as recurrent miscarriage, stillbirth, severe pre-eclampsia and severe placental insufficiency. The persistent presence of antiphospholipid antibodies (aPLs) is the most important laboratory characteristic of OAPS. OAPS severely affects the reproductive health of women of childbearing age in China. Reports indicate that approximately 9.6% stillbirths, 11.5% severe pre-eclampsia, and 54% recurrent miscarriages are associated with OAPS or aPLs. However, the pathogenesis of OAPS remains unclear. Previously, thrombosis at the maternal-fetal interface (MFI) was considered the main mechanism of OAPS-related pathological pregnancies. Consequently, the use of low molecular weight heparin and aspirin throughout pregnancy was recommended to improve outcomes in OAPS patient. In recent years, many studies have found that thrombosis in MFI is uncommon, but various inflammatory factors are significantly increased in the MFI of OAPS patients. Based on these findings, some clinicians have started using anti-inflammatory treatments for OAPS, which have preliminarily improved the pregnancy outcomes. Nevertheless, there is no consensus on these second-line treatments of OAPS. Another troubling issue is the clinical diagnosis of OAPS. Similar to other autoimmune diseases, there are only classification criteria for OAPS, and clinical diagnosis of OAPS depends on the clinicians' experience. The present classification criteria of OAPS were established for clinical and basic research purposes, not for patient clinical management. In clinical practice, many patients with both positive aPLs and pathological pregnancy histories do not meet the strict OAPS criteria. This has led to widespread issues of incorrect diagnosis and treatment. Timely and accurate diagnosis of OAPS is crucial for effective treatment. In this article, we reviewed the epidemiological research progress on OAPS and summarized its classification principles, including: 1) the persistent presence of aPLs in circulation; 2) manifestations of OAPS, excluding other possible causes. For the first point, accurate assessment of aPLs is crucial; for the latter, previous studies regarded only placenta-related pregnancy complications as characteristic manifestations of OAPS. However, recent studies have indicated that adverse pregnancy outcomes related to trophoblast damage, such as recurrent miscarriage and stillbirth, also need to be considered in OAPS. We also discussed several key issues in the diagnosis and treatment of OAPS. First, we addressed the definition of non-standard OAPS and offered our opinion on defining non-standard OAPS within the framework of the 2023 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) APS criteria. Then, we discussed the advantages and disadvantages of different aPL testing methods, emphasizing that harmonizing results across platforms and establishing specific reference values are keys to resolving controversies in aPL testing results. We also introduced the application of non-criteria aPLs, especially anti-phosphatidylserine/prothrombin antibody (aPS/PT) and anti-ß2 glycoprotein â domain â antibody (aß2GPâ Dâ ). Additionally, we discussed aPL-based OAPS risk classification strategies. Finally, we proposed potential treatment methods for refractory OAPS. The goal is to provide a reference for the clinical management of OAPS.
Asunto(s)
Síndrome Antifosfolípido , Complicaciones del Embarazo , Humanos , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/terapia , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/complicaciones , Embarazo , Femenino , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/terapia , Aborto Habitual/etiología , Aborto Habitual/inmunología , Aborto Habitual/diagnóstico , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Antifosfolípidos/inmunología , Heparina de Bajo-Peso-Molecular/uso terapéutico , Aspirina/uso terapéutico , Preeclampsia/diagnóstico , Preeclampsia/terapia , Preeclampsia/etiologíaRESUMEN
The etiology of cerebral venous sinus thrombosis (CVST) is multifactorial. Although many acquired and genetic factors have been recognized as risk factors, hyperhomocysteinemia (hHcy) is independently associated with CVST. We describe three cases of CVST in this case series. All of them presented with headache. Two patients had papilledema and visual disturbances. On evaluation, there was CVST, and prothrombotic workup showed hHcy. In addition, two of them reported very low Vitamin B12 levels. All of them were treated with low-molecular-weight heparin followed by oral anticoagulation and Vitamin B6, B9, and B12 supplements. All of them responded to treatment, and follow-up imaging studies in two of them showed resolution of thrombosis. hHcy should be considered in the evaluation of CVST, especially in the setting of a pure vegetarian diet. Fortification of the diet with Vitamin B12 may be considered the majority of Indians consume predominantly vegetarian food.
RésuméL'étiologie de la thrombose veineuse cérébrale (CVST) est multifactorielle. Bien que de nombreux facteurs acquis et génétiques aient été reconnus comme facteurs de risque, l'hyperhomocystéinémie (hHcy) est indépendamment associée à la CVST. Nous décrivons trois cas de CVST dans cette série de cas. Tous présentaient des maux de tête. Deux patients avaient un oedème papillaire et des troubles visuels. Lors de l'évaluation, il y avait une CVST et le bilan prothrombotique montrait une hHcy. De plus, deux d'entre eux ont rapporté des niveaux très bas de vitamine B12. Tous ont été traités avec de l'héparine de bas poids moléculaire suivie d'une anticoagulation orale et de suppléments de vitamines B6, B9 et B12. Tous ont répondu au traitement, et des études d'imagerie de suivi chez deux d'entre eux ont montré une résolution de la thrombose. L'hHcy doit être envisagée dans l'évaluation de la (CVST), en particulier dans le contexte d'un régime purement végétarien. La fortification de l'alimentation avec de la vitamine B12 peut être envisagée car la majorité des Indiens consomment principalement des aliments végétariens.
Asunto(s)
Anticoagulantes , Trombosis de los Senos Intracraneales , Deficiencia de Vitamina B 12 , Vitamina B 12 , Humanos , Deficiencia de Vitamina B 12/complicaciones , Deficiencia de Vitamina B 12/tratamiento farmacológico , Trombosis de los Senos Intracraneales/etiología , Trombosis de los Senos Intracraneales/tratamiento farmacológico , Masculino , Femenino , Adulto , Vitamina B 12/uso terapéutico , Vitamina B 12/administración & dosificación , Anticoagulantes/uso terapéutico , Resultado del Tratamiento , Alimentos Fortificados , Hiperhomocisteinemia/complicaciones , Cefalea/etiología , Heparina de Bajo-Peso-Molecular/uso terapéutico , Persona de Mediana Edad , Dieta Vegetariana/efectos adversosRESUMEN
Inflammatory factors and reactive oxygen species (ROS) are risk factors for atherosclerosis. Many existing therapies use ROS-sensitive delivery systems to alleviate atherosclerosis, which achieved certain efficacy, but cannot eliminate excessive ROS. Moreover, the potential biological safety concerns of carrier materials through chemical synthesis cannot be ignored. Herein, an amphiphilic low molecular weight heparin- lipoic acid conjugate (LMWH-LA) was used as a ROS-sensitive carrier material, which consisted of injectable drug molecules used clinically, avoiding unknown side effects. LMWH-LA and curcumin (Cur) self-assembled to form LLC nanoparticles (LLC NPs) with LMWH as shell and LA/Cur as core, in which LMWH could target P-selectin on plaque endothelial cells and competitively block the migration of monocytes to endothelial cells to inhibit the origin of ROS and inflammatory factors, and LA could be oxidized to trigger hydrophilic-hydrophobic transformation and accelerate the release of Cur. Cur released within plaques further exerted anti-inflammatory and antioxidant effects, thereby suppressing ROS and inflammatory factors. We used ultrasound imaging, pathology and serum analysis to evaluate the therapeutic effect of nanoparticles on atherosclerotic plaques in apoe-/- mice, and the results showed that LLC showed significant anti-atherosclerotic effects. Our finding provided a promising therapeutic nanomedicine for the treatment of atherosclerosis.
Asunto(s)
Antiinflamatorios , Aterosclerosis , Curcumina , Nanopartículas , Placa Aterosclerótica , Especies Reactivas de Oxígeno , Animales , Especies Reactivas de Oxígeno/metabolismo , Ratones , Curcumina/farmacología , Curcumina/química , Aterosclerosis/tratamiento farmacológico , Nanopartículas/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Humanos , Placa Aterosclerótica/tratamiento farmacológico , Ácido Tióctico/química , Ácido Tióctico/farmacología , Heparina de Bajo-Peso-Molecular/farmacología , Heparina de Bajo-Peso-Molecular/química , Heparina de Bajo-Peso-Molecular/uso terapéutico , Ratones Endogámicos C57BL , Inflamación/tratamiento farmacológico , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Masculino , Selectina-P/metabolismo , Portadores de Fármacos/química , Antioxidantes/farmacología , Antioxidantes/químicaRESUMEN
Given the existing uncertainty regarding the effectiveness and safety of switching from low-molecular-weight heparin (LMWH) to direct oral anticoagulants (DOACs) in patients with cancer-associated venous thrombosis (CAT), we conducted a comprehensive population-based cohort study utilizing electronic health database in Hong Kong. A total of 4356 patients with CAT between 2010 and 2022 were included, with 1700 (39.0%) patients switching to DOAC treatment. Compared to continuous LMWH treatment, switching to DOACs was associated with a significantly lower risk of hospitalization due to venous thromboembolism (HR: 0.49 [95% CI = 0.35-0.68]) and all-cause mortality (HR: 0.67 [95% CI = 0.61-0.74]), with no significant difference in major bleeding (HR: 1.04 [95% CI = 0.83-1.31]) within six months. These findings provide reassurance regarding the effectiveness and safety of switching from LMWH to DOACs among patients with CAT, including vulnerable patient groups.
Asunto(s)
Anticoagulantes , Hemorragia , Heparina de Bajo-Peso-Molecular , Neoplasias , Trombosis de la Vena , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparina de Bajo-Peso-Molecular/efectos adversos , Heparina de Bajo-Peso-Molecular/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Trombosis de la Vena/tratamiento farmacológico , Administración Oral , Hong Kong/epidemiología , Hemorragia/inducido químicamente , Resultado del Tratamiento , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/etiología , Estudios de Cohortes , Hospitalización/estadística & datos numéricos , Sustitución de Medicamentos , Anciano de 80 o más AñosRESUMEN
INTRODUCTION: Patients with atrial fibrillation (AF) undergoing elective procedures are at risk for Major Adverse Cardiovascular Events (MACE) and symptomatic bleeding. We aimed to identify risk factors to guide perioperative risk stratification. METHODS: We conducted a post-hoc analysis of the "Bridging Anticoagulation in Patients who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery" randomized trial. The primary outcomes were MACE and symptomatic bleeding. Our statistical approach encompassed standard univariate analysis, logistic stepwise regression, and Cox regression models. Additional interaction analyses evaluated the interplay between low-molecular-weight heparin bridge therapy and other identified risk factors. RESULTS: Among a total of 1,813 participants (mean age 71.6 ± 8.8, 73.3 % male), MACE occurred in 25 (1.4 %) individuals, with pre-procedure clopidogrel use (adjusted hazard ratio [aHR] 7.73, 95 % CI 2.63-22.72, p < 0.001) and CHA2DS2-VASc score ≥ 5 (aHR 2.89, 95 % CI 1.26-6.63, p = 0.012) identified as risk factors. Symptomatic bleeding occurred in 57 (3.1 %) individuals, with bridge therapy (aHR 1.84, 95 % CI 1.07-3.19, p = 0.029), renal disease (aHR 2.50, 95 % CI 1.34-4.67, p = 0.004), post-procedure aspirin use (aHR 2.86, 95 % CI 1.66-4.91, p < 0.001), post-procedure nonsteroidal anti-inflammatory drug use excluding aspirin (aHR 3.40, 95 % CI 1.22-9.43, p = 0.019), and major surgery (aHR 3.94, 95 % CI 2.26-6.85, p < 0.001) identified as risk factors. The interactions between risk factors and bridging therapy on MACE and symptomatic bleeding outcomes were not significant (p > 0.05). CONCLUSION: We identified predictors for MACE and symptomatic bleeding in AF patients undergoing elective procedures. These insights may help guide perioperative decisions to reduce the risk of adverse outcomes.
Asunto(s)
Anticoagulantes , Fibrilación Atrial , Procedimientos Quirúrgicos Electivos , Hemorragia , Humanos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/cirugía , Fibrilación Atrial/epidemiología , Masculino , Femenino , Anciano , Factores de Riesgo , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Medición de Riesgo , Resultado del Tratamiento , Persona de Mediana Edad , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Procedimientos Quirúrgicos Electivos/efectos adversos , Anciano de 80 o más Años , Factores de Tiempo , Warfarina/efectos adversos , Warfarina/administración & dosificación , Esquema de Medicación , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Heparina de Bajo-Peso-Molecular/efectos adversos , Heparina de Bajo-Peso-Molecular/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: This large database study assessed whether extended pharmacologic prophylaxis for venous thromboembolism after colon cancer resection was associated with improved oncologic survival. BACKGROUND: Heparin derivatives may confer an antineoplastic effect via a variety of mechanisms (eg, inhibiting angiogenesis in the tumor microenvironment). Studies evaluating the oncologic benefit of heparin and its derivatives have been limited in postsurgical patients. Multiple society guidelines recommend consideration of 30-day treatment with low molecular weight heparin to reduce venous thromboembolism risk after abdominopelvic cancer surgery. However, utilization of extended prophylaxis remains low. METHODS: Surveillance, Epidemiology, and End Results-Medicare data were used to identify patients (age 65+) undergoing resection for nonmetastatic colon cancer from 2016 to 2017. The primary outcomes were overall and cancer-specific survival. Log-rank testing and multivariable Cox regression compared survival in patients who received extended prophylaxis versus those who did not in an inverse propensity treatment weighted cohort. RESULTS: A total of 20,102 patients were included in propensity-weighting and analyzed. Eight hundred (3.98%) received extended pharmacologic prophylaxis. Overall survival and cancer-specific survival were significantly higher in patients receiving prophylaxis on log-rank tests ( P =0.0017 overall, P =0.0200 cancer-specific). Multivariable Cox regression showed improved overall survival [adjusted hazard ratio 0.66 (0.56-0.78)] and cancer-specific survival [adjusted hazard ratio 0.56 (0.39-0.81)] with prophylaxis after controlling for patient, treatment, and hospital factors. CONCLUSIONS: Extended pharmacologic prophylaxis after colon cancer resection was independently associated with improved overall and cancer-specific survival. These results suggest a potential antineoplastic effect from heparin derivatives when used in the context of preventing postsurgical venous thromboembolism.