RESUMO
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.
Assuntos
Síndrome Antifosfolipídica , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Humanos , Gravidez , Feminino , Aspirina/uso terapêutico , Complicações na Gravidez/terapia , Complicações na Gravidez/diagnóstico , Anticoagulantes/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Complicações Hematológicas na Gravidez/diagnóstico , Complicações Hematológicas na Gravidez/terapiaRESUMO
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.
Assuntos
Anticoagulantes , Neoplasias , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/tratamento farmacológico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Anticoagulantes/uso terapêutico , Anticoagulantes/efeitos adversos , Fatores de Risco , Heparina de Baixo Peso Molecular/uso terapêutico , Heparina de Baixo Peso Molecular/efeitos adversosRESUMO
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.
Assuntos
Heparina de Baixo Peso Molecular , Neoplasias , Pirazóis , Piridonas , Tromboembolia Venosa , Humanos , Piridonas/uso terapêutico , Piridonas/efeitos adversos , Piridonas/administração & dosagem , Pirazóis/uso terapêutico , Pirazóis/efeitos adversos , Pirazóis/administração & dosagem , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Heparina de Baixo Peso Molecular/efeitos adversos , Heparina de Baixo Peso Molecular/administração & dosagem , Masculino , Pessoa de Meia-Idade , Idoso , Anticoagulantes/uso terapêutico , Anticoagulantes/efeitos adversos , Anticoagulantes/administração & dosagem , Hemorragia/induzido quimicamente , Hemorragia/etiologia , Resultado do Tratamento , Adulto , Inibidores do Fator Xa/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/administração & dosagemRESUMO
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.
Assuntos
Anticoagulantes , Heparina de Baixo Peso Molecular , Cirrose Hepática , Veia Porta , Rivaroxabana , Trombose Venosa , Varfarina , Humanos , Projetos Piloto , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Masculino , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Rivaroxabana/uso terapêutico , Veia Porta/diagnóstico por imagem , Feminino , Trombose Venosa/tratamento farmacológico , Trombose Venosa/diagnóstico por imagem , Pessoa de Meia-Idade , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Varfarina/administração & dosagem , Varfarina/efeitos adversos , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/uso terapêutico , Heparina de Baixo Peso Molecular/efeitos adversos , Administração Oral , Resultado do Tratamento , Idoso , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/uso terapêutico , Adulto , Injeções Subcutâneas , Tomografia Computadorizada por Raios X , Quimioterapia CombinadaRESUMO
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.
Assuntos
Anticoagulantes , Hemorragia , Heparina de Baixo Peso Molecular , Neoplasias , Trombose Venosa , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Anticoagulantes/efeitos adversos , Trombose Venosa/tratamento farmacológico , Administração Oral , Hong Kong/epidemiologia , Hemorragia/induzido quimicamente , Resultado do Tratamento , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia , Estudos de Coortes , Hospitalização/estatística & dados numéricos , Substituição de Medicamentos , Idoso de 80 Anos ou maisRESUMO
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.
Assuntos
Biomarcadores Tumorais , Antígeno Ca-125 , Carcinoma Epitelial do Ovário , Terapia Neoadjuvante , Neoplasias Ovarianas , Tinzaparina , Humanos , Feminino , Tinzaparina/administração & dosagem , Terapia Neoadjuvante/métodos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/sangue , Biomarcadores Tumorais/sangue , Antígeno Ca-125/sangue , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/sangue , Adulto , Estadiamento de Neoplasias , Projetos Piloto , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/métodos , Heparina de Baixo Peso Molecular/uso terapêutico , Heparina de Baixo Peso Molecular/administração & dosagem , Prognóstico , IdosoRESUMO
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.
Assuntos
Nanopartículas , Nascimento Prematuro , Feminino , Gravidez , Animais , Nascimento Prematuro/prevenção & controle , Humanos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Resultado da Gravidez , Apoptose/efeitos dos fármacos , Heparina de Baixo Peso Molecular/farmacologia , Heparina de Baixo Peso Molecular/uso terapêutico , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Modelos Animais de Doenças , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismoRESUMO
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.
Assuntos
Anti-Inflamatórios , Aterosclerose , Curcumina , Nanopartículas , Placa Aterosclerótica , Espécies Reativas de Oxigênio , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Curcumina/farmacologia , Curcumina/química , Aterosclerose/tratamento farmacológico , Nanopartículas/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Humanos , Placa Aterosclerótica/tratamento farmacológico , Ácido Tióctico/química , Ácido Tióctico/farmacologia , Heparina de Baixo Peso Molecular/farmacologia , Heparina de Baixo Peso Molecular/química , Heparina de Baixo Peso Molecular/uso terapêutico , Camundongos Endogâmicos C57BL , Inflamação/tratamento farmacológico , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Masculino , Selectina-P/metabolismo , Portadores de Fármacos/química , Antioxidantes/farmacologia , Antioxidantes/químicaRESUMO
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.
Assuntos
Síndrome Antifosfolipídica , Complicações na Gravidez , Humanos , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/terapia , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/complicações , Gravidez , Feminino , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/terapia , Aborto Habitual/etiologia , Aborto Habitual/imunologia , Aborto Habitual/diagnóstico , Anticorpos Antifosfolipídeos/sangue , Anticorpos Antifosfolipídeos/imunologia , Heparina de Baixo Peso Molecular/uso terapêutico , Aspirina/uso terapêutico , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/terapia , Pré-Eclâmpsia/etiologiaRESUMO
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.
Assuntos
Anticoagulantes , Trombose dos Seios Intracranianos , Deficiência de Vitamina B 12 , Vitamina B 12 , Humanos , Deficiência de Vitamina B 12/complicações , Deficiência de Vitamina B 12/tratamento farmacológico , Trombose dos Seios Intracranianos/etiologia , Trombose dos Seios Intracranianos/tratamento farmacológico , Masculino , Feminino , Adulto , Vitamina B 12/uso terapêutico , Vitamina B 12/administração & dosagem , Anticoagulantes/uso terapêutico , Resultado do Tratamento , Alimentos Fortificados , Hiper-Homocisteinemia/complicações , Cefaleia/etiologia , Heparina de Baixo Peso Molecular/uso terapêutico , Pessoa de Meia-Idade , Dieta Vegetariana/efeitos adversosRESUMO
BACKGROUND: Patients with suspected deep vein thrombosis (DVT) are typically referred to the emergency department for immediate evaluation. To enhance efficiency, our hospital implemented a regional, general practitioner (GP)-driven DVT care pathway, deferring diagnostic evaluation to a scheduled outpatient DVT clinic appointment the following day. Patients receive a single dose anticoagulant from their GP to prevent thrombosis progression while awaiting diagnostic workup. This prospective study aimed to evaluate the safety and patient preferences regarding the DVT care pathway and the type of single dose anticoagulant (low-molecular-weight heparin (LMWH) vs. direct oral anticoagulant (DOAC)). METHODS: Patients enrolled in the DVT care pathway between June 2021 and July 2023 were eligible. Until July 2022, LMWH was administered, and thereafter, the protocol recommended DOAC as the single dose anticoagulant. Patients completed questionnaires, incorporating patient-reported outcome and experience measures (PROMs/PREMs), during their DVT clinic visit and after five days. The primary endpoint was bleeding events within 72 h of receiving the single dose anticoagulant. RESULTS: Of 460 included patients, 229 received LMWH and 231 received DOAC as the single dose anticoagulant. DVT was confirmed in 24.8 % of patients. No major or clinically relevant non-major bleeding were reported. LMWH was associated with more minor bleedings (22.3 % vs. DOAC 13.4 %), primarily attributed to injection site hematomas. Patients reported high satisfaction with the DVT care pathway (96.5 %) and generally preferred DOAC over LMWH. CONCLUSION: Deferring diagnostic evaluation for DVT using a single dose of either LMWH or DOAC in a real-world population is deemed safe. Considering practical advantages, patient preferences, and fewer skin hematomas, we favor DOACs as the single dose anticoagulant in this care pathway.
Assuntos
Anticoagulantes , Heparina de Baixo Peso Molecular , Trombose Venosa , Humanos , Estudos Prospectivos , Trombose Venosa/tratamento farmacológico , Trombose Venosa/diagnóstico , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Heparina de Baixo Peso Molecular/administração & dosagem , Masculino , Pessoa de Meia-Idade , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Idoso , Administração Oral , Idoso de 80 Anos ou mais , AdultoRESUMO
While advanced liver disease was previously considered to be an acquired bleeding disorder, there is increasing recognition of an associated prothrombotic state with patients being at higher risk of atrial fibrillation (AF) and stroke and venous thromboembolism (VTE) including portal vein thrombosis (PVT). We review the available literature on epidemiology, pathophysiology, and risk factors and provide guidance on anticoagulant management of these conditions in adults with cirrhosis. In patients with Child-Pugh A or B cirrhosis and AF, we recommend anticoagulation with standard-dose direct oral anticoagulants (DOACs) in accordance with cardiology guideline recommendations for patients without liver disease. In those with Child-Pugh C cirrhosis, there is inadequate evidence with respect to the benefit and risk of anticoagulation for stroke prevention in AF. In patients with cirrhosis and acute deep vein thrombosis or pulmonary embolism, we recommend anticoagulation and suggest use of either a DOAC or low-molecular-weight heparin (LMWH)/vitamin K antagonist (VKA) in Child-Pugh A or B cirrhosis and LMWH alone (or as a bridge to VKA in patients with a normal baseline international normalized ratio) in Child-Pugh C cirrhosis. We recommend anticoagulation for patients with cirrhosis and symptomatic PVT. We suggest anticoagulation for those with asymptomatic, progressing PVT and recommend continuing extended anticoagulation for liver transplant candidates with PVT.
Assuntos
Anticoagulantes , Fibrilação Atrial , Cirrose Hepática , Veia Porta , Acidente Vascular Cerebral , Tromboembolia Venosa , Trombose Venosa , Humanos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Fatores de Risco , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/diagnóstico , Trombose Venosa/prevenção & controle , Trombose Venosa/tratamento farmacológico , Trombose Venosa/etiologia , Trombose Venosa/diagnóstico , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento , Hemorragia/induzido quimicamente , Coagulação Sanguínea/efeitos dos fármacos , Medição de Risco , Heparina de Baixo Peso Molecular/uso terapêutico , Heparina de Baixo Peso Molecular/administração & dosagemRESUMO
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.
Assuntos
Estado Terminal , Heparina de Baixo Peso Molecular , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/etiologia , Heparina de Baixo Peso Molecular/uso terapêutico , Heparina de Baixo Peso Molecular/administração & dosagem , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Inibidores do Fator Xa/uso terapêutico , Inibidores do Fator Xa/administração & dosagem , Fator XaRESUMO
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.
Assuntos
Anticoagulantes , Artroplastia de Quadril , Fondaparinux , Heparina de Baixo Peso Molecular , Trombose Venosa , Humanos , Artroplastia de Quadril/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Heparina de Baixo Peso Molecular/administração & dosagem , Fondaparinux/uso terapêutico , Masculino , Feminino , Trombose Venosa/prevenção & controle , Pessoa de Meia-Idade , Idoso , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Complicações Pós-Operatórias/prevenção & controleRESUMO
OBJECTIVES: Venous thromboembolism is one of the most serious complications of the postpartum period, and international societies have various thromboprophylaxis guidelines for its prevention. This study compares postpartum venous thromboprophylaxis recommendations from the American College of Obstetrics and Gynecology (ACOG) and the Royal College of Obstetricians and Gynecologists (RCOG) with real-life clinical practices. STUDY DESIGN: Data analysis of 1000 postpartum women at a tertiary care center focused on patient demographics, venous thromboembolism risk factors, and clinical thromboprophylaxis practices. Patient-specific risk factors were compared between ACOG and RCOG guidelines, assessing Low-Molecular-Weight-Heparin dosages and durations. Guideline compliance, undertreatment/overtreatment rates, and the required number of prefilled Low-Molecular-Weight-Heparin syringes were evaluated. RESULTS: Significant discrepancies were observed between ACOG and RCOG guidelines, particularly in Low Molecular Weight Heparin dosages and durations. Consensus rates with clinical approaches were around 53%, with inconsistencies leaning towards undertreatment (RCOG) and overtreatment (ACOG). The number of required prefilled Low-Molecular-Weight-Heparin syringes was notably higher according to RCOG compared to ACOG guidelines. CONCLUSION: Postpartum Venous thromboembolism prophylaxis guidelines from American College of Obstetrics and Gynecology and Royal College of Obstetricians and Gynecologists exhibit substantial differences, leading to variations in clinical practice. Further research on the significance of Venous thromboembolism risk factors is essential for improving risk assessment tools and refining guideline recommendations for pregnancy-related Venous thromboembolism prevention.
Assuntos
Anticoagulantes , Fidelidade a Diretrizes , Heparina de Baixo Peso Molecular , Período Pós-Parto , Guias de Prática Clínica como Assunto , Tromboembolia Venosa , Humanos , Feminino , Tromboembolia Venosa/prevenção & controle , Adulto , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Heparina de Baixo Peso Molecular/uso terapêutico , Heparina de Baixo Peso Molecular/administração & dosagem , Gravidez , Fatores de Risco , Obstetrícia , Transtornos Puerperais/prevenção & controleRESUMO
The etiology of recurrent pregnancy loss (RPL) is complex and multifactorial and in half of patients it remains unexplained (U-RPL). Recently, low-molecular-weight heparin (LMWH) has gained increasing relevance for its therapeutic potential. On this regard, the aim of this systematic review and meta-analysis is to analyze the efficacy of low molecular weight heparin (LMWH) from the beginning of pregnancy in terms of live birth rates (LBR) in U-RPL. Registered randomized controlled trials (RCTs) were included. We stratified findings based on relevant clinical factors including number of previous miscarriages, treatment type and control type. Intervention or exposure was defined as the administration of LMWH alone or in combination with low-dose aspirin (LDA). A total of 6 studies involving 1016 patients were included. The meta-analysis results showed that LMWH used in the treatment of U-RPL was not associated with an increase in LBR with a pooled OR of 1.01, a medium heterogeneity (26.42%) and no publication bias. Results of other sub-analyses according to country, treatment type, and control type showed no significant effect of LMWH on LBR in all subgroups, with a high heterogeneity. The results highlight a non-significant effect of LMWH in U-RPL on LBR based on moderate quality evidence.Registration number: PROSPERO: ( https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022326433 ).
Assuntos
Aborto Habitual , Heparina de Baixo Peso Molecular , Humanos , Aborto Habitual/prevenção & controle , Aborto Habitual/tratamento farmacológico , Heparina de Baixo Peso Molecular/uso terapêutico , Feminino , Gravidez , Aspirina/uso terapêutico , Anticoagulantes/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Nascido VivoRESUMO
OBJECTIVE: Free tissue transfer has an established place in oncologic head and neck surgery. However, the necessity and specific regimen of perioperative thromboprophylaxis remain controversial. Here, the risk of postoperative hemorrhage contrasts with vascular pedicle thrombosis and graft loss. This work compares three different heparin protocols (A-C) with regard to postoperative complications. PATIENTS AND METHODS: A retrospective analysis of our free flap transplants between 2004 and 2023 was conducted. Inclusion criteria were thromboprophylaxis with (A) 500 IU/h unfractionated heparin (UFH), (B) low-molecular-weight heparin (LMWH) once daily, and (C) LMWH once daily with additional immediate preoperative administration. Primary endpoints were the incidence of postoperative bleeding and hematoma and the appearance of flap thrombosis. RESULTS: We evaluated 355 cases, 87 in group A, 179 in group B, and in group C 89 patients. Overall, postoperative bleeding occurred in 8.7% of patients, and 83% underwent hemostasis under intubation anesthesia, with no significant difference between groups (p = 0.784). Hematoma formation requiring revision was found in 3.7% of patients (p = 0.660). We identified postoperative hematoma as a significant influencing factor for venous pedicle thrombosis (OR 3.602; p = 0.001). Venous and arterial flap thrombosis in the graft vessel showed no difference between the groups (p = 0.745 and p = 0.128). CONCLUSIONS: The three anticoagulation regimens appear to be equivalent therapy for the prevention of thrombosis without significant differences in postoperative bleeding. The use of LMWH with additional preoperative administration can, therefore, be administered in free flap reconstruction.
Assuntos
Anticoagulantes , Retalhos de Tecido Biológico , Heparina de Baixo Peso Molecular , Procedimentos de Cirurgia Plástica , Humanos , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Estudos Retrospectivos , Pessoa de Meia-Idade , Feminino , Masculino , Procedimentos de Cirurgia Plástica/efeitos adversos , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/uso terapêutico , Idoso , Trombose/prevenção & controle , Hemorragia Pós-Operatória/prevenção & controle , Heparina/administração & dosagem , Heparina/uso terapêutico , Adulto , Neoplasias de Cabeça e Pescoço/cirurgia , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/prevenção & controleRESUMO
BACKGROUND This prospective study from a single center aimed to compare the perioperative blood loss (PBL) in 79 patients with intertrochanteric fractures (IF) treated with intramedullary nailing (IMN) using 3 regimens of combined tranexamic acid (TXA) and low molecular weight heparin (LMWH), proposing a novel therapy of 4-dose TXA. MATERIAL AND METHODS We recruited 79 patients and randomly divided them into 3 groups. The 4-dose TXA group (22 patients) received 1.0 g intravenous TXA 30 min before surgery and 1.0 g at intervals of 3, 6, and 9 h before surgery. The 1-dose TXA group (25 patients) received 1.0 g intravenous TXA 30 min before surgery, while the control group (32 patients) did not receive TXA. LMWH was applied 12 h after surgery in each group. The primary metrics evaluated included hidden blood loss (HBL), total blood loss (TBL), and the number and incidence rate of deep vein thrombosis (DVT). RESULTS Analysis of the HBL revealed that the 4-dose TXA group had the lowest average (583.13±318.08 ml), followed by the 1-dose TXA group (902.94±509.99 ml), and the control group showed the highest (1154.39±452.06 ml) (P<0.05). A similar result was observed for TBL (4-dose group: 640.86±337.22 ml, 1-dose group: 971.74±511.14 ml, control group: 1226.27±458.22 ml, P<0.05). Regarding DVT, the 4-dose TXA group had 5 cases (incidence rate 22.73%), the 1-dose TXA group had 6 cases (incidence rate 24.00%), and the control group had 8 cases (incidence rate 25.00%), with no significant difference among groups (P>0.05). CONCLUSIONS Treatment using 4-dose TXA and LMWH can effectively reduce PBL without increasing the DVT risk in IF patients with IMN.
Assuntos
Perda Sanguínea Cirúrgica , Heparina de Baixo Peso Molecular , Fraturas do Quadril , Ácido Tranexâmico , Trombose Venosa , Humanos , Ácido Tranexâmico/administração & dosagem , Ácido Tranexâmico/uso terapêutico , Feminino , Masculino , Fraturas do Quadril/cirurgia , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/uso terapêutico , Idoso , Perda Sanguínea Cirúrgica/prevenção & controle , Trombose Venosa/tratamento farmacológico , Trombose Venosa/prevenção & controle , Estudos Prospectivos , Pessoa de Meia-Idade , Assistência Perioperatória/métodos , Antifibrinolíticos/administração & dosagem , Antifibrinolíticos/uso terapêutico , Idoso de 80 Anos ou mais , Fixação Intramedular de Fraturas/métodos , Fixação Intramedular de Fraturas/efeitos adversosRESUMO
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.
Assuntos
Cesárea , Esplenectomia , Ruptura Esplênica , Trombose Venosa , Humanos , Feminino , Trombose Venosa/etiologia , Trombose Venosa/cirurgia , Trombose Venosa/tratamento farmacológico , Adulto , Ruptura Esplênica/etiologia , Ruptura Esplênica/cirurgia , Ruptura Esplênica/diagnóstico , Gravidez , Cesárea/efeitos adversos , Período Pós-Parto , Anticoagulantes/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Varfarina/uso terapêuticoRESUMO
Although all patients with cancer-associated thrombosis (CAT) have a high morbidity and mortality risk, certain groups of patients are particularly vulnerable. This may expose the patient to an increased risk of thrombotic recurrence or bleeding (or both), as the benefit-risk ratio of anticoagulant treatment may be modified. Treatment thus needs to be chosen with care. Such vulnerable groups include older patients, patients with renal impairment or thrombocytopenia, and underweight and obese patients. However, these patient groups are poorly represented in clinical trials, limiting the available data on which treatment decisions can be based. Meta-analysis of data from randomised clinical trials suggests that the relative treatment effect of direct oral factor Xa inhibitors (DXIs) and low molecular weight heparin (LMWH) with respect to major bleeding could be affected by advanced age. No evidence was obtained for a change in the relative risk-benefit profile of DXIs compared to LMWH in patients with renal impairment or of low body weight. The available, albeit limited, data do not support restricting the use of DXIs in patients with TAC on the basis of renal impairment or low body weight. In older patients, age is not itself a critical factor for choice of treatment, but frailty is such a factor. Patients over 70 years of age with CAT should undergo a systematic frailty evaluation before choosing treatment and modifiable bleeding risk factors should be addressed. In patients with renal impairment, creatine clearance should be assessed and monitored regularly thereafter. In patients with an eGFR less than 30mL/min/1.72m2, the anticoagulant treatment may need to be adapted. Similarly, platelet count should be assessed prior to treatment and monitored regularly. In patients with grade 3-4, thrombocytopenia (less than 50,000platelets/µL) treatment with a LMWH at a reduced dose should be considered. For patients with CAT and low body weight, standard anticoagulant treatment recommendations are appropriate, whereas in obese patients, apixaban may be preferred.