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1.
Arch Soc Esp Oftalmol (Engl Ed) ; 96(11): 615-617, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34756286

RESUMO

We present the case of an 81-year-old woman who developed a bilateral spontaneous suprachoroidal hemorrhage while under treatment with sodium enoxaparin. Temporal suspension of anticoagulant therapy led to an improvement of the choroidal hemorrhage. After three months follow-up, there was a complete reabsorption of the choroidal detachments, but there was a persistent vitreous hemorrhage in the right eye, which had been more severely affected. Pars plana vitrectomy with air tamponade was successfully performed in the right eye. Vision improved to 20/50 in the right eye and 20/20 in the left eye. Suprachoroidal hemorrhage is a rare condition with a poor visual prognosis. Reports on the development of suprachoroidal hemorrhage in patients with no predisposing ocular conditions are scarce, and in none were both eyes affected. The case reported herein is, to the best of our knowledge, the first case of bilateral, simultaneous suprachoroidal hemorrhage without predisposing ocular factors due to treatment with anticoagulants, with a favourable visual outcome.


Assuntos
Hemorragia da Coroide , Idoso de 80 Anos ou mais , Hemorragia da Coroide/induzido quimicamente , Olho , Feminino , Heparina de Baixo Peso Molecular , Humanos , Acuidade Visual , Vitrectomia
2.
Cochrane Database Syst Rev ; 10: CD006466, 2021 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622445

RESUMO

BACKGROUND: Oral anticoagulants may improve the survival of people with cancer through an antithrombotic effect, yet increase the risk of bleeding. OBJECTIVES: To evaluate the efficacy and safety of oral anticoagulants in ambulatory people with cancer undergoing chemotherapy, targeted therapy, immunotherapy, or radiotherapy (either alone or in combination), with no standard therapeutic or prophylactic indication for anticoagulation. SEARCH METHODS: We conducted comprehensive searches on 14 June 2021, following the original electronic searches performed in February 2016 (last major search). We electronically searched the following databases: CENTRAL, MEDLINE, Embase. In addition, we handsearched conference proceedings, checked references of included studies, and searched for ongoing studies. As part of the living systematic review approach, we are running continual searches and will incorporate new evidence rapidly after it is identified. SELECTION CRITERIA: We included randomised controlled trials (RCTs) assessing the benefits and harms of vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) in ambulatory people with cancer (i.e., not hospital inpatients during the time of their participation in trials) These people are typically undergoing systemic anticancer therapy, possibly including chemotherapy, targeted therapy, immunotherapy, or radiotherapy, but otherwise have no standard therapeutic or prophylactic indication for anticoagulation. DATA COLLECTION AND ANALYSIS: Using a standardised form, two review authors independently extracted data on study design, participants, intervention outcomes of interest, and risk of bias. Outcomes of interest included all-cause mortality, pulmonary embolism, symptomatic deep vein thrombosis (DVT), major bleeding, minor bleeding and health-related quality of life. We assessed the certainty of evidence for each outcome using the GRADE approach. MAIN RESULTS: Of 12,620 identified citations, 10 RCTs fulfilled the inclusion criteria. The oral anticoagulant was a vitamin K antagonist (VKA) in six of these RCTs, and a direct oral anticoagulant (DOAC) in the remaining four RCTs (three studies used apixaban; one used rivaroxaban). The comparator was either placebo or no prophylaxis. Compared to no prophylaxis, vitamin K antagonists (VKAs) probably reduce mortality at six months slightly (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.77 to 1.13; risk difference (RD) 22 fewer per 1000, 95% CI 72 fewer to 41 more; moderate-certainty evidence), and probably reduce mortality at 12 months slightly (RR 0.95, 95% CI 0.87 to 1.03; RD 29 fewer per 1000, 95% CI 75 fewer to 17 more; moderate-certainty evidence). One study assessed the effect of a VKA compared to no prophylaxis on thrombosis; the evidence was very uncertain about the effect of VKA compared to no VKA on pulmonary embolism and symptomatic DVT (RR 1.05, 95% CI 0.07 to 16.58; RD 0 fewer per 1000, 95% CI 6 fewer to 98 more; very low-certainty evidence; RR 0.08, 95% CI 0.01 to 1.42; RD 35 fewer per 1000, 95% CI 37 fewer to 16 more; very low-certainty evidence, respectively). Also, VKAs probably increase major and minor bleeding at 12 months (RR 2.93, 95% CI 1.86 to 4.62; RD 107 more per 1000, 95% CI 48 more to 201 more; moderate-certainty evidence for major bleeding, and RR 3.14, 95% CI 1.85 to 5.32; RD 167 more per 1000, 95% CI 66 more to 337 more; moderate-certainty evidence for minor bleeding). Compared to no prophylaxis, at three to six months, direct oral anticoagulants (DOACs) probably reduce mortality slightly (RR 0.94, 95% CI 0.64 to 1.38, RD 11 fewer per 1000, 95% CI 67 fewer to 70 more; moderate-certainty evidence), probably reduce the risk of pulmonary embolism slightly compared to no prophylaxis (RR 0.48, 95% CI 0.24 to 0.98; RD 24 fewer per 1000, 95% CI 35 fewer to 1 fewer; moderate-certainty evidence), probably reduce symptomatic DVT slightly (RR 0.58, 95% CI 0.30 to 1.15; RD 21 fewer per 1000, 95% CI 35 fewer to 8 more; moderate-certainty evidence), probably do not increase major bleeding (RR 1.65, 95% CI 0.72 to 3.80; RD 9 more per 1000, 95% CI 4 fewer to 40 more; moderate-certainty evidence), and may increase minor bleeding (RR 3.58, 95% CI 0.55 to 23.44; RD 55 more per 1000, 95% CI 10 fewer to 482 more; low-certainty evidence). AUTHORS' CONCLUSIONS: In ambulatory people with cancer undergoing chemotherapy, targeted therapy, immunotherapy, or radiotherapy (either alone or in combination), the current evidence on VKA thromboprophylaxis suggests that the harm of major bleeding might outweigh the benefit of reduction in venous thromboembolism. With DOACs, the benefit of reduction in venous thromboembolic events outweighs the risk of major bleeding. Editorial note: this is a living systematic review. Living systematic reviews offer a new approach to review updating in which the review is continually updated, incorporating relevant new evidence, as it becomes available. Please refer to the 'What's new' section in the  Cochrane Database of Systematic Reviews for the current status of this review.


Assuntos
Neoplasias , Tromboembolia Venosa , Anticoagulantes/efeitos adversos , Heparina , Heparina de Baixo Peso Molecular , Humanos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Revisões Sistemáticas como Assunto , Tromboembolia Venosa/prevenção & controle
3.
Int J Mol Sci ; 22(19)2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34639073

RESUMO

Our objective is to reveal the molecular mechanism of the anti-inflammatory action of low-molecular-weight heparin (LMWH) based on its influence on the activity of two key cytokines, IFNγ and IL-6. The mechanism of heparin binding to IFNγ and IL-6 and the resulting inhibition of their activity were studied by means of extensive molecular-dynamics simulations. The effect of LMWH on IFNγ signalling inside stimulated WISH cells was investigated by measuring its antiproliferative activity and the translocation of phosphorylated STAT1 in the nucleus. We found that LMWH binds with high affinity to IFNγ and is able to fully inhibit the interaction with its cellular receptor. It also influences the biological activity of IL-6 by binding to either IL-6 or IL-6/IL-6Rα, thus preventing the formation of the IL-6/IL-6Rα/gp130 signalling complex. These findings shed light on the molecular mechanism of the anti-inflammatory action of LMWH and underpin its ability to influence favourably conditions characterised by overexpression of these two cytokines. Such conditions are not only associated with autoimmune diseases, but also with inflammatory processes, in particular with COVID-19. Our results put forward heparin as a promising means for the prevention and suppression of severe CRS and encourage further investigations on its applicability as an anti-inflammatory agent.


Assuntos
Anti-Inflamatórios/farmacologia , Anticoagulantes/farmacologia , Heparina de Baixo Peso Molecular/farmacologia , Interferon gama/imunologia , Interleucina-6/imunologia , COVID-19/tratamento farmacológico , COVID-19/imunologia , Linhagem Celular , Humanos , Modelos Moleculares , Receptores de Interleucina-6/imunologia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia
4.
J Pediatr Gastroenterol Nutr ; 73(5): 604-609, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34676833

RESUMO

OBJECTIVES: To evaluate for increased rectal bleeding following enoxaparin thromboprophylaxis in children hospitalized for ulcerative colitis (UC). METHODS: Retrospective cohort study (2007--2016) of 218 inpatients with active UC. Patients receiving enoxaparin were compared with a nonenoxaparin-treated patient group. Severity of UC was determined using the Pediatric Ulcerative Colitis Activity Index (PUCAI). Hemoglobin (Hb) values and packed red blood cell (pRBC) transfusions were reviewed for a 7-day period following hospital admission. A linear mixed effect model was used to compare change in Hb values between the groups. Risk of pRBC transfusion was compared using a log-rank test and Cox proportional hazard regression. A sub-analysis was also conducted restricting to patients with severe UC to provide more generalizable insight into safety profile of enoxaparin. RESULTS: Children hospitalized for UC and receiving enoxaparin were more likely to have severe disease, received infliximab therapy and be admitted after 2010. Use of enoxaparin showed there was not a difference (P = 0.60) in the fall of Hb detected among those with acute severe colitis (initial PUCAI ≥65) during the week following admission. Moreover, there was no difference in the risk of requiring a pRBC transfusion with enoxaparin use (log-rank test all patients: P = 0.80; severe UC: P = 0.88; Cox proportional hazard regression all patients: P = 0.72; severe UC: 0.85). CONCLUSIONS: There was no difference in Hb levels or need for blood transfusions in children hospitalized for severe UC (PUCAI ≥65) whether or not they received enoxaparin for thromboembolism prophylaxis.


Assuntos
Colite Ulcerativa , Tromboembolia Venosa , Anticoagulantes/efeitos adversos , Criança , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Heparina , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Estudos Retrospectivos
5.
Int J Mol Sci ; 22(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34638867

RESUMO

Heparin has been extensively studied as a safe medicine and biomolecule over the past few decades. Heparin derivatives, including low-molecular-weight heparins (LMWH) and heparin pentasaccharide, are effective anticoagulants currently used in clinical settings. They have also been studied as functional biomolecules or biomaterials for various therapeutic uses to treat diseases. Heparin, which has a similar molecular structure to heparan sulfate, can be used as a remarkable biomedicine due to its uniquely high safety and biocompatibility. In particular, it has recently drawn attention for use in drug-delivery systems, biomaterial-based tissue engineering, nanoformulations, and new drug-development systems through molecular formulas. A variety of new heparin-based biomolecules and conjugates have been developed in recent years and are currently being evaluated for use in clinical applications. This article reviews heparin derivatives recently studied in the field of drug development for the treatment of various diseases.


Assuntos
Anticoagulantes , Materiais Biocompatíveis , Sistemas de Liberação de Medicamentos , Heparina de Baixo Peso Molecular , Engenharia Tecidual , Anticoagulantes/química , Anticoagulantes/uso terapêutico , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Heparina de Baixo Peso Molecular/química , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos
6.
Mymensingh Med J ; 30(4): 1177-1182, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34605494

RESUMO

Cross linked fibrin as D-Dimer fragments formed by fibrinolysis and mainly detected in the blood sample. High D-Dimer level is associated with liver disease, malignancy, chronic kidney disease, cardio vascular disease, lung disease, pregnancy, inflammation and vacuities. The normal serum D-Dimer level considered upto 0.50mg/L in serological immunochromatography which is indicated to exclude the risk of thrombus formation related to life threatening deep vein thrombosis (DVT), disseminated intravascular coagulation (DIC), pulmonary embolism (PE), and critical cardiovascular events. Anticoagulant therapy by Low molecular weight heparin (LMWH) is the choice of treatment. These case report represent increased D-Dimer might be considered as a strong biomarker to distinguish the moribund of COVID-19 positive patients in hospital.


Assuntos
COVID-19 , Heparina de Baixo Peso Molecular , Produtos de Degradação da Fibrina e do Fibrinogênio , Humanos , Prognóstico , Estudos Retrospectivos , SARS-CoV-2
7.
Glob Heart ; 16(1): 68, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692393

RESUMO

Objective: To compare cardiac complications and pregnancy outcomes in women with mechanical heart valves (MHVs) on two different anticoagulation regimens in a middle-income country. Methods: We conducted a retrospective cohort study comparing outcomes in pregnant women with MHVs that received vitamin K antagonists (VKAs) throughout pregnancy versus sequential anticoagulation (heparins in the first trimester and peripartum period and VKAs for the remainder of pregnancy), at a tertiary centre in South India, from January 2011 to August 2020. Results: We identified 138 pregnancies in 121 women, of whom 32 received VKAs while 106 were on sequential anticoagulation. There were no differences between groups with regard to maternal deaths [0 vs. 6 (5.7%), p = 0.34], thromboembolic events [2 (6.3%) vs. 15 (14.2%), p = 0.36], haemorrhagic complications [4 (12.5%) vs. 12 (11.3%), p = 0.85], cardiac events [1 (3.1% vs. 17 (16%), p = 0.07], spontaneous miscarriages [5 (15.6%) vs. 13 (12.3%), p = 0.62], stillbirths [0 vs. 5 (5.4%), p = 0.581] or neonatal deaths [2 (8.7%) vs. 1 (1.1%), p = 0.11]. Both cases of warfarin embryopathy received >5 mg warfarin in the first trimester. Thromboembolic events were associated with subtherapeutic doses of heparin in the first and third trimesters and the early postpartum period. Fetal growth restriction and preterm birth complicated 34 (29.3%) and 26 (22.4%) pregnancies respectively. Conclusion: Pregnancy complications associated with MHVs in middle-income countries may be reduced by multidisciplinary surveillance, avoiding first-trimester warfarin if daily doses >5 mg and ensuring therapeutic levels of heparin during bridging in the first and third trimesters and peripartum period. Administration of low-dose aspirin should be considered as this may prevent placentally-mediated complications of pregnancy. Highlights: Pregnancy complications associated with MHVs in LMICs may be reduced by multidisciplinary surveillance, avoiding first-trimester warfarin if the daily dose is >5 mg, ensuring therapeutic levels of heparin in the first trimester and peripartum period.Placentally-mediated complications of pregnancy can be prevented by administering low-dose aspirin.Vitamin K antagonists or sequential regimen can be used as suitable alternatives to LMWH for anticoagulation in pregnant women with MHVs.


Assuntos
Complicações Cardiovasculares na Gravidez , Nascimento Prematuro , Anticoagulantes/efeitos adversos , Estudos de Coortes , Países em Desenvolvimento , Feminino , Valvas Cardíacas , Heparina de Baixo Peso Molecular , Humanos , Recém-Nascido , Gravidez , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Complicações Cardiovasculares na Gravidez/epidemiologia , Complicações Cardiovasculares na Gravidez/prevenção & controle , Resultado da Gravidez/epidemiologia , Gestantes , Estudos Retrospectivos
8.
Clin Appl Thromb Hemost ; 27: 10760296211039288, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595937

RESUMO

Coronavirus disease 2019 (COVID-19) is a systemic disease that can be life-threatening involving immune and inflammatory responses, and that can result in potentially lethal complications, including venous thrombo-embolism (VTE). Forming an integrative approach to thrombo-prophylaxis and coagulation treatment for COVID-19 patients ensues. We aim at reviewing the literature for anticoagulation in the setting of COVID-19 infection to provide a summary on anticoagulation for this patient population. COVID-19 infection is associated with a state of continuous inflammation, which results in macrophage activation syndrome and an increased rate of thrombosis. Risk assessment models to predict the risk of thrombosis in critically ill patients have not yet been validated. Currently published guidelines suggest the use of prophylactic intensity over intermediate intensity or therapeutic intensity anticoagulant for patients with critical illness or acute illness related to COVID-19 infection. Critically ill COVID-19 patients who are diagnosed with acute VTE are considered to have a provoking factor, and, therefore, treatment duration should be at least 3 months. Patients with proximal deep venous thrombosis or pulmonary embolism should receive parenteral over oral anticoagulants with low-molecular-weight heparin or fondaparinux preferred over unfractionated heparin. In patients with impending hemodynamic compromise due to PE, and who are not at increased risk for bleeding, reperfusion may be necessary. Internists should remain updated on new emerging evidence regarding anticoagulation for COVID-19 patients. Awaiting these findings, we invite internists to perform individualized decisions that are unique for every patient and to base them on clinical judgment for risk assessment.


Assuntos
Anticoagulantes/uso terapêutico , COVID-19/complicações , SARS-CoV-2 , Trombofilia/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Consenso , Estado Terminal , Gerenciamento Clínico , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fondaparinux/efeitos adversos , Fondaparinux/uso terapêutico , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Pacientes Internados , Masculino , Guias de Prática Clínica como Assunto , Gravidez , Complicações Hematológicas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/sangue , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/etiologia , Embolia Pulmonar/prevenção & controle , Risco , Trombofilia/etiologia , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Trombose Venosa/tratamento farmacológico , Trombose Venosa/etiologia , Trombose Venosa/prevenção & controle
9.
Ann Palliat Med ; 10(10): 11141-11147, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34498484

RESUMO

BACKGROUND: Venous thromboembolism (VTE) is one of the most common causes of preventable harm for patients in hospitals. Nearly half of all VTE events was estimated to occur after surgical procedure. The Caprini risk score is the most extensively used risk assessment tool in predicting postoperative VTE, which is too complicate for surgeons to use properly in their clinical practice. METHODS: The CHAT-3 trial will be a prospective, multicenter, randomized, parallel-group trial, which is designed to identify patients at moderate or high risk of VTE after inguinal hernia surgery using the previously established three-factor model, and to use low molecular weight heparin (LMWH) for VTE prevention, in comparison to the current routine assessment and practice used in those patients. Totally, 1,008 patients planned to undergo inguinal hernia surgery will be enrolled, with cluster randomization at 1:1 ratio into intervention arm and control arm. The primary outcomes are the accordance of perioperative VTE prophylaxis based on current guidelines and the rate of pharmacological prophylaxis for VTE. The secondary outcomes are the occurrences of perioperative VTE, major bleeding, mortality of patients after inguinal hernia surgery, and trend of D-dimer during the follow-up period. DISCUSSION: This study will create evidence that whether the administration based on a simple model is of efficacy and safety for VTE prophylaxis among Chinese patients underwent inguinal hernia surgery. TRIAL REGISTRATION: The CHAT-3 trial (Trial registration number: ChiCTR2000033769).


Assuntos
Hérnia Inguinal , Tromboembolia Venosa , Adulto , China , Heparina de Baixo Peso Molecular , Hérnia Inguinal/cirurgia , Humanos , Estudos Prospectivos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
10.
Cochrane Database Syst Rev ; 9: CD014739, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34582035

RESUMO

BACKGROUND: Multiple myeloma is a malignant plasma cell disorder characterised by clonal plasma cells that cause end-organ damage such as renal failure, lytic bone lesions, hypercalcaemia and/or anaemia. People with multiple myeloma are treated with immunomodulatory agents including lenalidomide, pomalidomide, and thalidomide. Multiple myeloma is associated with an increased risk of thromboembolism, which appears to be further increased in people receiving immunomodulatory agents. OBJECTIVES: (1) To systematically review the evidence for the relative efficacy and safety of aspirin, oral anticoagulants, or parenteral anticoagulants in ambulatory patients with multiple myeloma receiving immunomodulatory agents who otherwise have no standard therapeutic or prophylactic indication for anticoagulation. (2) To maintain this review as a living systematic review by continually running the searches and incorporating newly identified studies. SEARCH METHODS: We conducted a comprehensive literature search that included (1) a major electronic search (14 June 2021) of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE via Ovid, and Embase via Ovid; (2) hand-searching of conference proceedings; (3) checking of reference lists of included studies; and (4) a search for ongoing studies in trial registries. As part of the living systematic review approach, we are running continual searches, and we will incorporate new evidence rapidly after it is identified. SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing the benefits and harms of oral anticoagulants such as vitamin K antagonist (VKA) and direct oral anticoagulants (DOAC), anti-platelet agents such as aspirin (ASA), and parenteral anticoagulants such as low molecular weight heparin (LMWH)in ambulatory patients with multiple myeloma receiving immunomodulatory agents. DATA COLLECTION AND ANALYSIS: Using a standardised form, we extracted data in duplicate on study design, participants, interventions, outcomes of interest, and risk of bias. Outcomes of interest included all-cause mortality, symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE), major bleeding, and minor bleeding. For each outcome we calculated the risk ratio (RR) with its 95% confidence interval (CI) and the risk difference (RD) with its 95% CI. We then assessed the certainty of evidence at the outcome level following the GRADE approach (GRADE Handbook). MAIN RESULTS: We identified 1015 identified citations and included 11 articles reporting four RCTs that enrolled 1042 participants. The included studies made the following comparisons: ASA versus VKA (one study); ASA versus LMWH (two studies); VKA versus LMWH (one study); and ASA versus DOAC (two studies, one of which was an abstract). ASA versus VKA One RCT compared ASA to VKA at six months follow-up. The data did not confirm or exclude a beneficial or detrimental effect of ASA relative to VKA on all-cause mortality (RR 3.00, 95% CI 0.12 to 73.24; RD 2 more per 1000, 95% CI 1 fewer to 72 more; very low-certainty evidence); symptomatic DVT (RR 0.57, 95% CI 0.24 to 1.33; RD 27 fewer per 1000, 95% CI 48 fewer to 21 more; very low-certainty evidence); PE (RR 1.00, 95% CI 0.25 to 3.95; RD 0 fewer per 1000, 95% CI 14 fewer to 54 more; very low-certainty evidence); major bleeding (RR 7.00, 95% CI 0.36 to 134.72; RD 6 more per 1000, 95% CI 1 fewer to 134 more; very low-certainty evidence); and minor bleeding (RR 6.00, 95% CI 0.73 to 49.43; RD 23 more per 1000, 95% CI 1 fewer to 220 more; very low-certainty evidence). One RCT compared ASA to VKA at two years follow-up. The data did not confirm or exclude a beneficial or detrimental effect of ASA relative to VKA on all-cause mortality (RR 0.50, 95% CI 0.05 to 5.47; RD 5 fewer per 1000, 95% CI 9 fewer to 41 more; very low-certainty evidence); symptomatic DVT (RR 0.71, 95% CI 0.35 to 1.44; RD 22 fewer per 1000, 95% CI 50 fewer to 34 more; very low-certainty evidence); and PE (RR 1.00, 95% CI 0.25 to 3.95; RD 0 fewer per 1000, 95% CI 14 fewer to 54 more; very low-certainty evidence). ASA versus LMWH Two RCTs compared ASA to LMWH at six months follow-up. The pooled data did not confirm or exclude a beneficial or detrimental effect of ASA relative to LMWH on all-cause mortality (RR 1.00, 95% CI 0.06 to 15.81; RD 0 fewer per 1000, 95% CI 2 fewer to 38 more; very low-certainty evidence); symptomatic DVT (RR 1.23, 95% CI 0.49 to 3.08; RD 5 more per 1000, 95% CI 11 fewer to 43 more; very low-certainty evidence); PE (RR 7.71, 95% CI 0.97 to 61.44; RD 7 more per 1000, 95% CI 0 fewer to 60 more; very low-certainty evidence); major bleeding (RR 6.97, 95% CI 0.36 to 134.11; RD 6 more per 1000, 95% CI 1 fewer to 133 more; very low-certainty evidence); and minor bleeding (RR 1.42, 95% CI 0.35 to 5.78; RD 4 more per 1000, 95% CI 7 fewer to 50 more; very low-certainty evidence). One RCT compared ASA to LMWH at two years follow-up. The pooled data did not confirm or exclude a beneficial or detrimental effect of ASA relative to LMWH on all-cause mortality (RR 1.00, 95% CI 0.06 to 15.89; RD 0 fewer per 1000, 95% CI 4 fewer to 68 more; very low-certainty evidence); symptomatic DVT (RR 1.20, 95% CI 0.53 to 2.72; RD 9 more per 1000, 95% CI 21 fewer to 78 more; very low-certainty evidence); and PE (RR 9.00, 95% CI 0.49 to 166.17; RD 8 more per 1000, 95% CI 1 fewer to 165 more; very low-certainty evidence). VKA versus LMWH One RCT compared VKA to LMWH at six months follow-up. The data did not confirm or exclude a beneficial or detrimental effect of VKA relative to LMWH on all-cause mortality (RR 0.33, 95% CI 0.01 to 8.10; RD 3 fewer per 1000, 95% CI 5 fewer to 32 more; very low-certainty evidence); symptomatic DVT (RR 2.32, 95% CI 0.91 to 5.93; RD 36 more per 1000, 95% CI 2 fewer to 135 more; very low-certainty evidence); PE (RR 8.96, 95% CI 0.49 to 165.42; RD 8 more per 1000, 95% CI 1 fewer to 164 more; very low-certainty evidence); and minor bleeding (RR 0.33, 95% CI 0.03 to 3.17; RD 9 fewer per 1000, 95% CI 13 fewer to 30 more; very low-certainty evidence). The study reported that no major bleeding occurred in either arm. One RCT compared VKA to LMWH at two years follow-up. The data did not confirm or exclude a beneficial or detrimental effect of VKA relative to LMWH on all-cause mortality (RR 2.00, 95% CI 0.18 to 21.90; RD 5 more per 1000, 95% CI 4 fewer to 95 more; very low-certainty evidence); symptomatic DVT (RR 1.70, 95% CI 0.80 to 3.63; RD 32 more per 1000, 95% CI 9 fewer to 120 more; very low-certainty evidence); and PE (RR 9.00, 95% CI 0.49 to 166.17; RD 8 more per 1000, 95% CI 1 fewer to 165 more; very low-certainty evidence). ASA versus DOAC One RCT compared ASA to DOAC at six months follow-up. The data did not confirm or exclude a beneficial or detrimental effect of ASA relative to DOAC on DVT, PE, and major bleeding and minor bleeding (minor bleeding: RR 5.00, 95% CI 0.31 to 79.94; RD 4 more per 1000, 95% CI 1 fewer to 79 more; very low-certainty evidence). The study reported that no DVT, PE, or major bleeding events occurred in either arm. These results did not change in a meta-analysis including the study published as an abstract. AUTHORS' CONCLUSIONS: The certainty of the available evidence for the comparative effects of ASA, VKA, LMWH, and DOAC on all-cause mortality, DVT, PE, or bleeding was either low or very low. People with multiple myeloma considering antithrombotic agents should balance the possible benefits of reduced thromboembolic complications with the possible harms and burden of anticoagulants. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.


Assuntos
Fibrinolíticos , Mieloma Múltiplo , Anticoagulantes/efeitos adversos , Heparina , Heparina de Baixo Peso Molecular , Humanos , Mieloma Múltiplo/tratamento farmacológico , Revisões Sistemáticas como Assunto
11.
Korean J Gastroenterol ; 78(3): 177-182, 2021 Sep 25.
Artigo em Coreano | MEDLINE | ID: mdl-34565787

RESUMO

The treatment of portal vein thrombosis (PVT) in patients with liver cirrhosis (LC) has been controversial, and it is generally case- and institution-dependent. The occurrence of acute or extensive PVT is critical and requires urgent treatment because it is usually accompanied by symptoms, particularly when total occlusion occurs, causing acute decompensation of liver disease. Even in severe cases, drug selection and treatment duration are determined based on each institution's experience. Therefore, consistent guidelines for the treatment of patients with LC with PVT are required. Recently, a patient with acute occlusive PVT with LC who showed signs of acute decompensation was treated by administering low molecular weight heparin as anticoagulant therapy. After anticoagulant treatment, the portal vein was almost completely recanalized, and the deteriorated liver function improved. In addition, the patient recovered well and showed no recurrence of PVT for more than a year. Thus, the most recent knowledge regarding the treatment of nonmalignant PVT in LC was reviewed along with a case report.


Assuntos
Anticoagulantes , Trombose Venosa , Anticoagulantes/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Veia Porta , Trombose Venosa/complicações , Trombose Venosa/tratamento farmacológico , Trombose Venosa/patologia
12.
J Control Release ; 338: 662-679, 2021 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-34478751

RESUMO

Inflammatory feed-forward loops including the steps of "inflammatory cell recruitment", "inflammatory signaling pathway activation" and "inflammatory factor production" are essential in the development of breast cancer and its metastasis. Herein, a doxorubicin-loaded micellar low-molecular-weight-heparin-astaxanthin nanoparticle (LMWH-AST/DOX, LA/DOX NP) was developed. The hydrophilic LMWH could decrease the recruitment of neutrophils in liver and myeloid-derived suppressor cells (MDSCs) in lung and tumor through P-selectin blockage. The hydrophobic AST could inhibit nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) signaling pathways. Therefore, LA/DOX NPs could block these loops and suppress the liver metastasis by inhibiting the formation of neutrophil extracellular traps (NETs), inhibit the lung metastasis and alleviate the inflammatory and immunosuppressive microenvironment in tumor. This is the first functional nanoparticle reported to shut down inflammatory feed-forward loops and the formation of NETs, which provides a promising therapeutic strategy for breast cancer and its liver and lung metastasis.


Assuntos
Neoplasias da Mama , Neoplasias Pulmonares , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Doxorrubicina , Feminino , Heparina de Baixo Peso Molecular , Humanos , Fígado , Neoplasias Pulmonares/tratamento farmacológico , Metástase Neoplásica , Microambiente Tumoral
13.
Semin Reprod Med ; 39(5-06): 186-193, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34560808

RESUMO

Thrombosis in pregnancy is a major cause of maternal and fetal morbidity and mortality. Risk stratification of venous thromboembolism (VTE) during pregnancy is complex. The hypercoagulability observed in pregnant women can reduce bleeding during childbirth, but may cause thrombosis especially in the presence of additional prothrombotic risk factors such as antiphospholipid antibodies or genetic thrombophilic defects. The availability of large datasets allows for the identification of additional independent risk factors, including assisted reproductive technologies (ARTs), endometriosis, and recurrent pregnancy loss. Data on the risk of VTE linked to COVID-19 in pregnant women are very limited, but suggest that infected pregnant women have an increased risk of VTE. Current guidelines on the prevention and treatment of VTE in pregnancy are based on available, albeit limited, data and mainly present expert opinion. Low-molecular-weight heparins (LMWHs) are the mainstay of anticoagulation to be employed during pregnancy. Administration of LMWH for VTE treatment in pregnancy should be based on the personalized approach, taking into account a weight-based adjusted scheme. During gestation, due to physiological changes, in women at high risk of VTE, monitoring of anti-Xa activity is performed to ensure adequate LMWH dosing. As for the treatment duration for pregnant women with acute VTE, guidelines suggest that anticoagulation should be continued for at least 6 weeks postpartum for a minimum total duration of therapy of 3 months.


Assuntos
COVID-19 , Tromboembolia Venosa , Anticorpos Antifosfolipídeos , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Gravidez , Fatores de Risco , SARS-CoV-2 , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle
14.
Medicina (Kaunas) ; 57(9)2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34577883

RESUMO

Venous thromboembolism (VTE) is a common complication among patients suffering from malignancies, leading to an increased mortality rate. Novel randomized trials have added valuable information regarding cancer-associated thrombosis (CAT) management using direct oral anticoagulants (DOACs). The aim of this study is to present an overview of the current literature and recommendations in CAT treatment. A few randomized control trials (RCTs) have been integrated suggesting that DOACs may be effectively applied in CAT patients compared to low molecular weight heparins (LMWHs) with a decreased mortality and VTE recurrence rate. However, the risk of bleeding is higher, especially in patients with gastrointestinal malignancies. Real-world data are in accordance with these RCT findings, while in the currently available recommendations, DOACs are suggested as a reliable alternative to LMWH during the initial, long-term, and extended phase of treatment. Data retrieved from the current literature, including RCTs and "real-world" studies, aim to clarify the role of DOACs in CAT management, by highlighting their benefits and remarking upon the potential adverse outcomes. Current recommendations suggest the use of DOACs in well-selected patients with an increasing level of evidence through years.


Assuntos
Neoplasias , Trombose , Tromboembolia Venosa , Anticoagulantes/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia
15.
Rev Med Chil ; 149(2): 291-294, 2021 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-34479277

RESUMO

Low molecular weight heparin-induced hyperkalemia is not an uncommon side effect. The development of hyponatremia is well described although it is less common. We report a 72-year-old woman with lumbar metastases who developed hyponatremia and hyperkalemia on the tenth day of hospitalization. Hyponatremia, with limited criteria for syndrome of inappropriate secretion of antidiuretic hormone, did not resolve with vigorous volume restriction. Hyperkalemia without an acid-base disorder or baseline renal failure, did not resolve after losartan was stopped. Enoxaparin-induced hypoaldosteronism was proposed and the drug was discontinued. After four days' persistence of the electrolyte disturbance, dexamethasone was changed to Hydrocortisone, and parameters normalized in 24 hours. The patient remained well until discharge and during outpatient control.


Assuntos
Hiperpotassemia , Hiponatremia , Síndrome de Secreção Inadequada de HAD , Idoso , Feminino , Heparina de Baixo Peso Molecular , Hospitalização , Humanos , Hiperpotassemia/induzido quimicamente , Hiponatremia/induzido quimicamente
16.
Andes Pediatr ; 92(3): 395-405, 2021 Jun.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34479246

RESUMO

INTRODUCTION: In April 2020, the pediatric multisystem inflammatory syndrome temporarily associated with COVID-19 (MIS-C) was described for the first time. MIS-C could have a severe course and may require critical care support. OBJECTIVE: To describe the clinical, laboratory, and management characteristics of hospitalized children who meet MIS-C criteria with severe presentation in a pediatric critical pa tient unit. PATIENTS AND METHOD: Descriptive prospective study of children with severe MIS-C mana ged by treatment phases with immunoglobulin and methylprednisolone, according to their clinical response. Epidemiological, clinical, laboratory and imaging data were obtained. Phenotypes were classified into Kawasaki and not Kawasaki, comparing their findings. RESULTS: 20 patients were analy zed, the median age was 6 years, 60% were female, and 40% presented comorbidity. SARS-CoV-2 was detected in 90% of the patients. They presented fever as the first symptom, followed by brief and early gastrointestinal symptoms (70%). 75% presented the Kawasaki phenotype. They evolved with lymphopenia, hypoalbuminemia, coagulation alterations, and elevated systemic and cardiac in flammatory parameters. 80% of the cases presented echocardiographic alterations and 90% shock that required critical care support. All the patients had a short and favorable evolution. All patients responded to the established therapy, but 40% required a second phase of treatment. There were no differences when comparing phenotypes. No deaths were reported. CONCLUSION: MIS-C is a new childhood disease whose presentation could be life-threatening. It requires early suspicion, immuno modulatory management, critical care support, and a multidisciplinary approach to obtain the best results and optimize its prognosis.


Assuntos
COVID-19 , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica , Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/etiologia , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/terapia , Criança , Cuidados Críticos , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Hipoalbuminemia/etiologia , Imunoglobulinas Intravenosas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Unidades de Terapia Intensiva Pediátrica , Linfopenia/etiologia , Masculino , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Estudos Prospectivos , SARS-CoV-2/isolamento & purificação , Choque/etiologia , Choque/terapia , Avaliação de Sintomas , Síndrome de Resposta Inflamatória Sistêmica/complicações , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/terapia
17.
J Trauma Nurs ; 28(5): 323-331, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34491950

RESUMO

BACKGROUND: Appropriate venous thromboembolism (VTE) chemoprophylaxis in trauma and emergency general surgery (EGS) patients is crucial. OBJECTIVE: The purpose of this study is to review the recent literature and offer recommendations for VTE chemoprophylaxis in trauma and EGS patients. METHODS: We conducted a literature search from 2000 to 2021 for articles investigating VTE chemoprophylaxis in adult trauma and EGS patients. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. RESULTS: Our search resulted in 34 articles. Most studies showed low-molecular-weight heparin (LMWH) is similar to unfractionated heparin (UFH) for VTE prevention; however, LMWH was more commonly used. Adjusted chemoprophylaxis dosing did not change the VTE rate but the timing did. Direct oral anticoagulants (DOACs) have been shown to be safe and effective in trauma and traumatic brain injury (TBI)/spinal cord injury (SCI). Studies showed VTE prophylaxis in EGS can be inconsistent and improves with guidelines that lower VTE events. CONCLUSIONS: There may be no benefit to receiving LMWH over UFH in trauma patients. In addition, different drugs under the class of LMWH do not change the incidence of VTE. Adjusted dosing of enoxaparin does not seem to affect VTE incidence. The use of DOACs in the trauma TBI and SCI setting has been shown to be safe and effective in reducing VTE. One important consideration with VTE prophylaxis may be the timing of prophylaxis initiation, specifically as it relates to TBI, with a higher likelihood of developing VTE as time progresses. EGS patients are at a high risk of VTE. Improved compliance with clinical guidelines in this population is correlated with decreased thrombotic events.


Assuntos
Tromboembolia Venosa , Adulto , Anticoagulantes/efeitos adversos , Quimioprevenção , Heparina , Heparina de Baixo Peso Molecular , Humanos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
19.
Curr Hematol Malig Rep ; 16(5): 455-463, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34586561

RESUMO

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) is associated with a high rate of respiratory failure, thromboembolism, bleeding, and death. Patients with myeloproliferative neoplasms (MPNs) are prone to both thrombosis and bleeding, calling for special care during COVID-19. We reviewed the clinical features of MPN patients with COVID-19, suggesting guidance for treatment. RECENT FINDINGS: One study by the European LeukemiaNet collected 175 MPN patients with COVID-19 during the first wave of the pandemic, from February to May 2020. Patients with primary myelofibrosis (PMF) were at higher risk of mortality (48%) in comparison with essential thrombocythemia (ET) (25%) and polycythemia vera (19%); the risk of death was higher in those patients who abruptly discontinued ruxolitinib. In patients followed at home, in regular wards, or in ICU, the thrombosis rate was 1.0%, 2.8%, and 18.4%, respectively. Independent risk factors for thrombosis were ET phenotype, transfer to ICU, and neutrophil/lymphocyte ratio; major bleeding occurred in 4.3% of patients, particularly those with PMF. MPN patients with non-severe COVID-19 treated at home should continue their primary or secondary antithrombotic prophylaxis with aspirin or oral anticoagulants. In the case of hospitalization, patients assuming aspirin should add low molecular weight heparin (LMWH) at standard doses. In contrast, LMWH at intermediate/therapeutic doses should replace oral anticoagulants prescribed for atrial fibrillation or previous venous thromboembolism. Intermediate/high doses of LMWH can also be considered in ICU patients with ET, particularly in the case of a rapid decline in the number of platelets and progressive respiratory failure.


Assuntos
COVID-19 , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa , Anticoagulantes/uso terapêutico , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/terapia , Hemorragia/epidemiologia , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/complicações , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/diagnóstico , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/epidemiologia , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/terapia , Transtornos Mieloproliferativos/complicações , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/epidemiologia , Transtornos Mieloproliferativos/terapia , Pandemias , SARS-CoV-2/fisiologia , Trombose/epidemiologia
20.
EMBO J ; 40(20): e106765, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34510494

RESUMO

The current pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and outbreaks of new variants highlight the need for preventive treatments. Here, we identified heparan sulfate proteoglycans as attachment receptors for SARS-CoV-2. Notably, neutralizing antibodies against SARS-CoV-2 isolated from COVID-19 patients interfered with SARS-CoV-2 binding to heparan sulfate proteoglycans, which might be an additional mechanism of antibodies to neutralize infection. SARS-CoV-2 binding to and infection of epithelial cells was blocked by low molecular weight heparins (LMWH). Although dendritic cells (DCs) and mucosal Langerhans cells (LCs) were not infected by SARS-CoV-2, both DC subsets efficiently captured SARS-CoV-2 via heparan sulfate proteoglycans and transmitted the virus to ACE2-positive cells. Notably, human primary nasal cells were infected by SARS-CoV-2, and infection was blocked by pre-treatment with LMWH. These data strongly suggest that heparan sulfate proteoglycans are important attachment receptors facilitating infection and transmission, and support the use of LMWH as prophylaxis against SARS-CoV-2 infection.


Assuntos
COVID-19/transmissão , Proteoglicanas de Heparan Sulfato/metabolismo , Heparina de Baixo Peso Molecular/farmacologia , SARS-CoV-2/patogenicidade , Enzima de Conversão de Angiotensina 2/imunologia , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Anticorpos Neutralizantes/metabolismo , Anticorpos Neutralizantes/farmacologia , COVID-19/tratamento farmacológico , Chlorocebus aethiops , Células Dendríticas/metabolismo , Células Dendríticas/virologia , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Interações Hospedeiro-Patógeno , Humanos , Membrana Mucosa/citologia , Membrana Mucosa/virologia , SARS-CoV-2/metabolismo , Sindecana-1/metabolismo , Sindecana-4/metabolismo , Células Vero
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