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1.
Medicine (Baltimore) ; 100(10): e25099, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725904

RESUMO

INTRODUCTION: The occurrence of massive hemorrhages in various emergency situations increases the need for blood transfusions and the risk of mortality. Use of fibrinogen concentrate (FC) may increase plasma fibrinogen levels more rapidly than the use of fresh-frozen product or cryoprecipitate. However, thus far, the efficacy of FC in significantly improving the risk of mortality and significantly reducing transfusion requirements has not been effectively demonstrated in several systematic reviews and meta-analyses. METHODS AND ANALYSIS: We will conduct a systematic review and meta-analysis of FC for hemorrhages in emergency situations. We will include controlled trials, but will exclude randomized controlled trials in elective surgeries. We will include patients with hemorrhages in emergency situations. Intervention will be emergency supplementation of FC. The control group will be administered with ordinal transfusion or placebo. The primary outcome of the study is in-hospital mortality.We will search in electronic databases such as MEDLINE (PubMed), Web of Science, and the Cochrane Central Register of Controlled Trials. Two reviewers will independently screen the title and abstract, retrieve the full text of the selected articles, and extract the essential data. We will apply uniform criteria for evaluating the risk of bias associated with individual randomized controlled trial based on the Cochrane risk of bias tool. Values of the risk ratio will be expressed as a point estimate with 95% confidence intervals (CIs). Data of continuous variables will be expressed as the mean difference along with their 95% CIs and P values. We will assess the strength of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: This systematic review will provide physicians with updated information on the efficacy and safety of using FC for hemorrhage in emergency settings. Approval from the ethics board and patient consent were not required in our study.This study protocol has been funded through a protocol registry. The registry number is UMIN000041598.


Assuntos
Transfusão de Sangue , Tratamento de Emergência/métodos , Fibrinogênio/administração & dosagem , Hemorragia/terapia , Hemostáticos/administração & dosagem , Ensaios Clínicos Controlados como Assunto , Fibrinogênio/efeitos adversos , Hemorragia/mortalidade , Hemostáticos/efeitos adversos , Mortalidade Hospitalar , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto , Resultado do Tratamento
2.
Medicine (Baltimore) ; 100(12): e25087, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761670

RESUMO

BACKGROUND: Topical hemostatic agents are commonly used for reducing perioperative blood loss and transfusion requirement in primary total knee arthroplasty (TKA), although the optimal option has yet to be defined. This study aimed to evaluate the efficacy and safety of topical hemostatic agents and rank the best intervention using the network meta-analysis (NMA) method. METHODS: We searched Web of science, PubMed, and Cochrane Library database up to April 2020, for randomized controlled trials (RCTs) on topical hemostatic agents in primary TKA. The quality of included studies was assessed using the Cochrane "risk of bias" tool. Direct and indirect comparisons were performed for the result of network meta-analysis followed by consistency test. RESULTS: Thirty seven RCTs with 3792 patients were included in this NMA and the pooled results indicated that tranexamic acid plus diluted epinephrine (TXA+DEP) displayed the highest efficacy in reducing total blood loss, hemoglobin drop and transfusion requirement. None of the included treatments was found to increase risk of thromboembolic events compared to placebo. According to the results of ranking probabilities, TXA+DEP had the highest possibility to be the best topical hemostatic agent with regard to the greatest comparative efficacy and a relatively high safety level. CONCLUSION: Current evidence supports that administration of TXA+DEP may be the optimal topical hemostatic agent to decrease blood loss and transfusion requirement in primary TKA. More direct studies that focused on the topical application of TXA+DEP versus other treatments are needed in the future.


Assuntos
Artroplastia do Joelho/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Epinefrina/administração & dosagem , Hemostasia Cirúrgica/métodos , Hemostáticos/administração & dosagem , Ácido Tranexâmico/administração & dosagem , Administração Tópica , Adulto , Transfusão de Sangue/estatística & dados numéricos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto Jovem
3.
Carbohydr Polym ; 253: 117256, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33279006

RESUMO

Timely hemostatic treatment is important to reduce blood loss and improve survival. To increase the speed of blood coagulation, hemostatic microspheres with varying degrees of surface roughness were prepared by emulsion cross-linking of sodium alginate (SA) and silk fibroin (SF). Surface morphology and hemostatic properties were analyzed with scanning electron microscope (SEM), infrared spectroscopy, and blood coagulation experiments. The results showed that microsphere have the roughest surface when the volume ratio of SA to SF is 2:1 (SF/SA2). These microspheres have the largest number of aggregated red blood cells, the fastest coagulation rates, and the strongest coagulation strength. Not only microspheres are they non-cytotoxic but they also promote cell growth. In vitro and in vivo coagulation experiments demonstrated that SF/SA2 microspheres can reduce bleeding time and volume and improve hemostatic efficiency, which suggests that SF/SA2 microspheres are potential hemostatic agents equipped with excellentbiosecurity.


Assuntos
Alginatos/química , Reagentes para Ligações Cruzadas/química , Fibroínas/química , Hemorragia/tratamento farmacológico , Hemostasia/efeitos dos fármacos , Hemostáticos/administração & dosagem , Hemostáticos/química , Microesferas , Animais , Tempo de Sangramento , Coagulação Sanguínea/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Emulsões/química , Camundongos , Pós/química , Ratos , Ratos Sprague-Dawley , Propriedades de Superfície
4.
J Am Acad Orthop Surg Glob Res Rev ; 4(12): e20.00100, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33332853

RESUMO

INTRODUCTION: Wide-awake local anesthesia no tourniquet (WALANT) presents a nonstandard anesthetic approach initially described for use in hand surgery that has gained interest and utilization across a variety of orthopaedic procedures. In response to operating room resource constraints imposed by the COVID-19 pandemic, our orthopaedic service rapidly adopted and expanded its use of WALANT. METHODS: A retrospective review of 16 consecutive cases performed by 7 surgeons was conducted. Patient demographics, surgical details, and perioperative outcomes were assessed. The primary end point was WALANT failure, defined as intraoperative conversion to general anesthesia. RESULTS: No instances of WALANT failure requiring conversion to general anesthesia occurred. In recovery, one patient (6%) required narcotics for pain control, and the average postoperative pain numeric rating scale was 0.6. The maximum pain score experienced was 4 in the patient requiring postoperative narcotics. The average time in recovery was 42 minutes and ranged from 8 to 118 minutes. CONCLUSION: The WALANT technique was safely and effectively used in 16 cases across multiple orthopaedic subspecialties, including three procedures not previously described in the literature. WALANT techniques hold promise for use in future disaster scenarios and should be evaluated for potential incorporation into routine orthopaedic surgical care.


Assuntos
Anestesia Local/métodos , Salas Cirúrgicas/organização & administração , Procedimentos Ortopédicos , Adulto , Idoso , Anestésicos Locais/administração & dosagem , Epinefrina/administração & dosagem , Feminino , Hemostáticos/administração & dosagem , Humanos , Lidocaína/administração & dosagem , Masculino , Pessoa de Meia-Idade , Entorpecentes/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Pandemias , Estudos Retrospectivos , Vasoconstritores/administração & dosagem , Adulto Jovem
5.
Medicine (Baltimore) ; 99(43): e22876, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120829

RESUMO

BACKGROUND: Spontaneous intracerebral hemorrhage (sICH) is a serious stroke subtype. The effective therapies for patients with sICH are still unclear, and the role of hemostatic agents in sICH is still unclear. Although some studies have shown that hemostatic agents could benefit patients with sICH, different hemostatic drugs have different effects on patients with sICH, and which hemostatic drug has the best effect on the prevention of hematoma expansion and neurological deterioration in sICH patients remains unclear. To better understand the effects of hemostatic agents in patients with sICH, it is necessary to carry out a network meta-analysis to comprehensively compare the effects of different hemostatic agents. METHODS: This protocol has been designed following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols statement. Related studies in the following databases will be searched until September 2020: PubMed, Embase, Scopus, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, VIP and Wanfang. Randomized controlled trials and nonrandomized controlled studies comparing at least 2 different hemostatic agents in sICH patients will be included. A quality assessment will be conducted with the Cochrane Collaboration tool or the Newcastle-Ottawa Scale based on the study design. The primary outcome will be the incidence of hematoma expansion, and the secondary outcome will be the functional outcome. Pairwise and network meta-analyses will be conducted using STATA V.14 (StataCorp, College Station, Texas, USA). Mean ranks and the surface under the cumulative ranking curve will be used to evaluate every agent. Statistical inconsistency assessment, subgroup analysis, sensitivity analysis and publication bias assessment will be performed. RESULTS: According to disseminate through academic conferences, the results of this network meta-analysis are expected to publish in a peer-reviewed journal. CONCLUSION: This study will provide high quality evidence about effects of different hemostatic agents in patients with sICH. REGISTRATION NUMBER: CRD42020196039.


Assuntos
Hemorragia Cerebral/tratamento farmacológico , Hematoma/prevenção & controle , Hemostáticos/uso terapêutico , Doenças do Sistema Nervoso/prevenção & controle , China/epidemiologia , Gerenciamento de Dados , Feminino , Hematoma/epidemiologia , Hemostáticos/administração & dosagem , Humanos , Incidência , Masculino , Metanálise em Rede , Ensaios Clínicos Controlados não Aleatórios como Assunto , Avaliação de Resultados da Assistência ao Paciente , Garantia da Qualidade dos Cuidados de Saúde/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Khirurgiia (Mosk) ; (8): 61-68, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32869617

RESUMO

OBJECTIVE: To analyze an opinion of surgeons on advisability, efficacy and choice of topical hemostatic agents. MATERIAL AND METHODS: The research was based on anonymous questioning of surgeons. The questionnaires were developed by using of interactive Google Forms tool (https://www.google.ru/forms). Distribution of questionnaires and invitation of respondents to participation in research were carried out through the Internet. RESULTS: The study enrolled 135 surgeons. Colleagues with considerable experience and length of surgical practice prevailed: 10-15 years - 16 people; 15-20 years - 22 people; over 20 years - 38 people. Opinion of less experienced surgeons was also considered: less than 5 years - 40 people; 5-10 years - 19 people. General surgeons prevailed (49%). Hemostatic sutures (30%) and application of topical hemostatic agents (27%) were the most common methods to stop parenchymal bleeding. Efficacy of local hemostatics is confirmed by small number of cases of recurrent intraoperative bleeding (n=24). Thirty-four respondents reported recurrent bleeding after hemostasis by conventional methods. Postoperative suppuration of hemostatic implant was noted by 9.5% of respondents. Most respondents (77%) prefer combination of hemostatic implants and other traditional methods of hemostasis. CONCLUSION: According to surgeons' opinion, local hemostatic agents are effective for parenchymal bleeding. This method may be used as basic (injury grade I by E. Moore classification) or additional method of hemostasis (grade I-III). Many respondents consider that application of topical hemostatic agent after imposing hemostatic sutures ensures the greatest efficiency of hemostasis. Moreover, placement of the agent over or under sutures seems to be the most advisable.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Hemostasia Cirúrgica/métodos , Hemostáticos/administração & dosagem , Técnicas de Sutura , Administração Tópica , Pesquisas sobre Serviços de Saúde , Humanos , Internet , Recidiva
7.
Med Hypotheses ; 143: 110150, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32763660

RESUMO

COVID-19 due to the SARS-CoV-2 infection is a multi-systemic immune syndrome affecting mainly the lungs, oropharyngeal region, and other vascular endothelial beds. There are tremendous ongoing efforts for the aim of developing drugs against the COVID-19 syndrome-associated inflammation. However, currently no specific medicine is present for the absolute pharmacological cure of COVID-19 mucositis. The re-purposing/re-positioning of already existing drugs is a very important strategy for the management of ongoing pandemy since the development of a new drug needs decades. Apart from altering angiotensin signaling pathways, novel drug candidates for re-purposing comprise medications shall target COVID-19 pathobiology, including pharmaceutical formulations that antagonize proteinase-activated receptors (PARs), mainly PAR-1. Activation of the PAR-1, mediators and hormones impact on the hemostasis, endothelial activation, alveolar epithelial cells and mucosal inflammatory responses which are the essentials of the COVID-19 pathophysiology. In this context, Ankaferd hemostat (Ankaferd Blood Stopper, ABS) which is an already approved hemostatic agent affecting via vital erythroid aggregation and fibrinogen gamma could be a potential topical remedy for the mucosal management of COVID-19. ABS is a clinically safe and effective topical hemostatic agent of plant origin capable of exerting pleiotropic effects on the endothelial cells, angiogenesis, cell proliferation and vascular dynamics. ABS had been approved as a topically applied hemostatic agent for the management of post-surgical/dental bleedings and healing of infected inflammatory mucosal wounds. The anti-inflammatory and proteinase-activated receptor axis properties of ABS with a considerable amount of oestrogenic hormone presence highlight this unique topical hemostatic drug regarding the clinical re-positioning for COVID-19-associated mucositis. Topical ABS as a biological response modifier may lessen SARS-CoV-2 associated microthrombosis, endothelial dysfunction, oropharyngeal inflammation and mucosal lung damage. Moreover, PAR-1 inhibition ability of ABS might be helpful for reducing the initial virus propagation and mocasal spread of COVID-19.


Assuntos
Anti-Inflamatórios/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/complicações , Estrogênios/fisiologia , Hemostáticos/uso terapêutico , Mucosite/tratamento farmacológico , Pandemias , Fitoestrógenos/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Pneumonia Viral/complicações , Receptor PAR-1/antagonistas & inibidores , Administração Tópica , Distribuição por Idade , Anti-Inflamatórios/administração & dosagem , Infecções por Coronavirus/sangue , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/fisiopatologia , Reposicionamento de Medicamentos , Endotélio Vascular/efeitos dos fármacos , Estrogênios/agonistas , Hemostáticos/administração & dosagem , Humanos , Mucosite/etiologia , Fitoestrógenos/administração & dosagem , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Pneumonia Viral/sangue , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Receptor PAR-1/fisiologia , Estomatite/tratamento farmacológico , Estomatite/etiologia , Trombofilia/sangue , Trombofilia/etiologia
8.
Eur J Vasc Endovasc Surg ; 60(3): 469-478, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32620348

RESUMO

OBJECTIVE: In vascular and cardiac surgery, the ability to maintain haemostasis and seal haemorrhagic tissues is key. Fibrin and thrombin based sealants were introduced as a means to prevent or halt bleeding during surgery. Whether fibrin and thrombin sealants affect surgical outcomes is poorly established. A systematic review and meta-analysis was performed to examine the impact of fibrin or thrombin sealants on patient outcomes in vascular and cardiac surgery. DATA SOURCES: Cochrane CENTRAL, Embase, and MEDLINE, as well as trial registries, conference abstracts, and reference lists of included articles were searched from inception to December 2019. REVIEW METHODS: Studies comparing the use of fibrin or thrombin sealant with either an active (other haemostatic methods) or standard surgical haemostatic control in vascular and cardiac surgery were searched for. The Cochrane risk of bias tool and the ROBINS-I tool (Risk Of Bias In Non-randomised Studies - of Interventions) were used to assess the risk of bias of the included randomised and non-randomised studies; quality of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Two reviewers screened studies, assessed risk of bias, and extracted data independently and in duplicate. Data from included trials were pooled using a random effects model. RESULTS: Twenty-one studies (n = 7 622 patients) were included: 13 randomised controlled trials (RCTs), five retrospective, and three prospective cohort studies. Meta-analysis of the RCTs showed a statistically significant decrease in the volume of blood lost (mean difference 120.7 mL, in favour of sealant use [95% confidence interval {CI} -150.6 - -90.7; p < .001], moderate quality). Time to haemostasis was also shown to be reduced in patients receiving sealant (mean difference -2.5 minutes [95% CI -4.0 - -1.1; p < .001], low quality). Post-operative blood transfusions, re-operation due to bleeding, and 30 day mortality were not significantly different for either RCTs or observational data. CONCLUSION: The use of fibrin and thrombin sealants confers a statistically significant but clinically small reduction in blood loss and time to haemostasis; it does not reduce blood transfusion. These Results may support selective rather than routine use of fibrin and thrombin sealants in vascular and cardiac surgery.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Procedimentos Cirúrgicos Cardíacos , Adesivo Tecidual de Fibrina/administração & dosagem , Hemostasia , Hemostáticos/administração & dosagem , Hemorragia Pós-Operatória/prevenção & controle , Trombina/administração & dosagem , Adesivos Teciduais/administração & dosagem , Procedimentos Cirúrgicos Vasculares , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Adesivo Tecidual de Fibrina/efeitos adversos , Hemostáticos/efeitos adversos , Humanos , Hemorragia Pós-Operatória/etiologia , Fatores de Risco , Trombina/efeitos adversos , Fatores de Tempo , Adesivos Teciduais/efeitos adversos , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos
10.
Ther Adv Cardiovasc Dis ; 14: 1753944720924255, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32449469

RESUMO

BACKGROUND: Recombinant factor VIIa (rFVIIa) (Novoseven®) is utilized for the reversal of anticoagulation-associated bleeding and refractory bleeding in cardiac surgery. In August 2015, rFVIIa was transferred from the blood bank to the pharmacy at New York University (NYU) Langone Health. Concordantly, an off-label dosing guideline was developed. The objective of this study was to describe utilization and cost of rFVIIa and assess compliance to our dosing guideline. METHODS: We performed a retrospective, observational review of rFVIIa administrations post-implementation of an off-label dosing guideline. All patients who received rFVIIa between September 2015 and June 2017 were evaluated. For each rFVIIa administration, anticoagulation and laboratory values, indications for use, dosing, ordering and administration times, concomitant blood products, and adverse events were collected. Adverse events included venous thromboembolism, stroke, myocardial infarction, and death due to systemic embolism and mortality. The primary endpoint was the utilization of rFVIIa in accordance with the off-label dosing guideline. Secondary endpoints included hemostatic efficacy of rFVIIa, adverse events, blood products administered, and cost-effectiveness of rFVIIa transition to pharmacy. RESULTS: A total of 63 patients [pediatric (n = 6), adult (n = 57)] received rFVIIa, with the majority of use for refractory bleeding after cardiac surgery. The utilization of rVIIa decreased after development of the off-label dosing guideline and transition from blood bank to pharmacy. The total incidence of thromboembolic events within 30 days was 19.6%; 17.6% arterial and 2% venous; 70% of patients with an adverse event were over 70 years of age. Use of rFVIIa reduced the median number of units of blood products administered. CONCLUSION: Administration of rFVIIa for cardiac surgery appears to be effective for hemostasis. Transitioning rFVIIa from the blood bank to pharmacy and implementation of a dosing guideline appears to have reduced utilization. Patients receiving rFVIIa should be monitored for thromboembolic events. Elderly patients may be at higher risk for thromboembolic events.


Assuntos
Centros Médicos Acadêmicos , Anticoagulantes/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Fator VIIa/administração & dosagem , Hemorragia/prevenção & controle , Hemostáticos/administração & dosagem , Padrões de Prática Médica , Centros Médicos Acadêmicos/economia , Idoso , Procedimentos Cirúrgicos Cardíacos/economia , Criança , Pré-Escolar , Custos de Medicamentos , Cálculos da Dosagem de Medicamento , Revisão de Uso de Medicamentos , Fator VIIa/efeitos adversos , Fator VIIa/economia , Feminino , Hemorragia/induzido quimicamente , Hemorragia/economia , Hemostáticos/efeitos adversos , Hemostáticos/economia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Uso Off-Label , Padrões de Prática Médica/economia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/economia , Estudos Retrospectivos , Fatores de Risco , Tromboembolia/induzido quimicamente , Resultado do Tratamento
11.
Medicine (Baltimore) ; 99(20): e20284, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443373

RESUMO

INTRODUCTION: Alveolar hemorrhage (AH) is characterized by the acute onset of alveolar bleeding and hypoxemia and can be fatal. Thrombin has been widely used to achieve coagulation and hemostasis. However, the efficacy of thrombin in patients with AH is unclear. Thus, this study aimed to evaluate the efficacy of thrombin administration in patients with hematological malignancy and AH. PATIENT CONCERNS AND DIAGNOSES: This retrospective study included 15 hematological malignancy patients (8 men and 7 women; mean age 47.7 ±â€Š17.3 years) with AH who were administered intrapulmonary thrombin between March 2013 and July 2018. INTERVENTIONS AND OUTCOMES: All patients received bovine-origin thrombin (1000 IU/ml, Reyon Pharmaceutical Co., Ltd., Seoul, Korea) via a fiberoptic bronchoscope. A maximum of 15 ml of thrombin was injected via the working channel to control bleeding. The ability of thrombin to control bleeding was assessed. Additionally, the change in the PaO2/FiO2 (PF) ratio after intrapulmonary thrombin administration was evaluated. Intrapulmonary thrombin was administered a minimum of 3 days after starting mechanical ventilation in all patients, and it immediately controlled the active bleeding in 13 of 15 patients (86.7%). However, AH relapse was noted in 3 of the 13 patients (23.1%). The PF ratio improved in 10 of 15 patients (66.6%), and the mean PF ratio was significantly higher after thrombin administration than before administration (P = .03). No adverse thromboembolic complications or systemic adverse events were observed. CONCLUSION: Thrombin administration was effective in controlling bleeding in hematological malignancy patients with AH. Intrapulmonary thrombin administration might be a good therapeutic option for treating AH.


Assuntos
Neoplasias Hematológicas/complicações , Hemorragia/tratamento farmacológico , Hemostáticos/uso terapêutico , Pneumopatias/tratamento farmacológico , Trombina/uso terapêutico , Adolescente , Adulto , Idoso , Feminino , Hemorragia/etiologia , Hemostáticos/administração & dosagem , Humanos , Pneumopatias/etiologia , Masculino , Pessoa de Meia-Idade , Alvéolos Pulmonares/patologia , Estudos Retrospectivos , Trombina/administração & dosagem , Adulto Jovem
12.
Thromb Haemost ; 120(5): 728-736, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32369844

RESUMO

BACKGROUND: Factor VIII (FVIII) trough levels > 1 IU/dL in patients with severe hemophilia A receiving regular prophylaxis may optimize bleed protection. OBJECTIVES: In this post hoc analysis of patients receiving tertiary prophylaxis for approximately 1 year, the relationship between estimated FVIII levels and reported bleeds was investigated to predict the potential for zero bleeds. METHODS: Sixty-three patients (median [range] age, 28 [7-59] years) with severe hemophilia A (229 bleeds) were included. FVIII levels at time of each bleed were estimated from single-dose individual pharmacokinetics. The highest estimated FVIII level at which patients experienced a bleed was considered the "potentially effective trough level" for that bleed type. Kaplan-Meier estimates of proportions of patients with no bleeds above certain estimated FVIII levels were determined. Those not experiencing a bleed in the trial were assumed to have a bleed at 0 IU/dL (pragmatic approach) or at their median trough level (conservative approach). RESULTS: Kaplan-Meier estimates based on pragmatic approach predicted zero all bleeds, joint bleeds, and spontaneous joint bleeds in 1 year in 40, 43, and 63% of patients, respectively, when the potentially effective trough FVIII level was set at 1 IU/dL. Between 1 and 10 IU/dL, every 1 IU/dL rise in estimated FVIII level was associated with an additional 2% of patients having zero all bleeds. CONCLUSION: This post hoc analysis confirms benefits with trough levels of approximately 1 to 3 IU/dL in most patients starting tertiary prophylaxis; prophylaxis with higher trough levels may help patients to achieve zero bleeds.


Assuntos
Fator VIII/farmacocinética , Hemartrose/prevenção & controle , Hemofilia A/tratamento farmacológico , Hemostasia/efeitos dos fármacos , Hemostáticos/farmacocinética , Modelos Biológicos , Prevenção Terciária , Adolescente , Adulto , Canadá , Criança , Europa (Continente) , Fator VIII/administração & dosagem , Hemartrose/sangue , Hemartrose/diagnóstico , Hemofilia A/sangue , Hemofilia A/diagnóstico , Hemostáticos/administração & dosagem , Hemostáticos/sangue , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença , Estados Unidos , Adulto Jovem
13.
Thromb Haemost ; 120(5): 737-746, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32369845

RESUMO

Long-term safety and efficacy data of extended half-life factor IX (FIX) prophylaxis in children with hemophilia B (HB) are sparse. paradigm 5 is a multinational, open-label, single-arm, phase III trial assessing once-weekly (40 IU/kg) prophylactic nonacog beta pegol (N9-GP) in previously treated patients (PTPs) aged ≤ 12 years with HB (FIX activity ≤ 2%). Primary endpoint: incidence of anti-FIX inhibitory antibodies (≥ 0.6 Bethesda Units). We present a 5-year analysis (N = 25, including remaining patients with ≥ 5 years' follow-up) and compare with a 1-year analysis (≥ 52 weeks' exposure). The main phase enrolled 25 children; 22 entered the extension phase; 17 remained in trial at data cutoff. Median treatment period: 5.6 years/patient; median total number of N9-GP exposure days: 290.0/patient. No patients developed anti-FIX inhibitory antibodies. No other safety concerns, including thromboembolic events, were reported. Neurological examinations have not revealed any new abnormal findings. Sixteen (64.0%) patients remained free from spontaneous bleeds; all bleeds were mild/moderate in severity; 93.0% were controlled with 1 to 2 N9-GP injections. No intracranial hemorrhages were reported. Annualized bleeding rates (ABRs) were very low at 5 years (median/Poisson-estimated mean overall ABR: 0.66/0.99), having decreased from the 1-year analysis (1.00/1.44). Median/Poisson-estimated mean spontaneous ABRs for the 1- and 5-year analyses: 0.00/0.45 and 0.00/0.33. Mean FIX trough activity at 5 years: 17.9%. Mean polyethylene glycol plasma concentration reached steady state at 6 months, increasing slightly over time, in line with increased FIX trough activity. N9-GP administered for ≥ 5 years shows favorable long-term safety and efficacy in PTPs with HB (FIX activity ≤ 2%).


Assuntos
Fator IX/administração & dosagem , Hemofilia B/tratamento farmacológico , Hemostáticos/administração & dosagem , Polietilenoglicóis/administração & dosagem , Adolescente , Fatores Etários , Ásia , Criança , Pré-Escolar , Esquema de Medicação , Europa (Continente) , Fator IX/efeitos adversos , Fator IX/farmacocinética , Hemofilia B/sangue , Hemofilia B/diagnóstico , Hemorragia/sangue , Hemorragia/diagnóstico , Hemorragia/prevenção & controle , Hemostáticos/efeitos adversos , Hemostáticos/sangue , Hemostáticos/farmacocinética , Humanos , Lactente , América do Norte , Segurança do Paciente , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/farmacocinética , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/sangue , Proteínas Recombinantes/farmacocinética , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
14.
Thromb Haemost ; 120(5): 747-757, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32369846

RESUMO

BACKGROUND: The currently published population pharmacokinetic (PK) models used for PK-guided dosing in hemophilia patients are based on clinical trial data and usually not externally validated in clinical practice. The aim of this study was to validate a published model for recombinant factor VIII-Fc fusion protein (rFVIII-Fc) concentrate and to develop an enriched model using independently collected clinical data if required. METHODS: Clinical data from hemophilia A patients treated with rFVIII-Fc concentrate (Elocta) participating in the United Kingdom Extended Half-Life Outcomes Registry were collected. The predictive performance of the published model was assessed using mean percentage error (bias) and mean absolute percentage error (inaccuracy). An extended population PK model was developed using nonlinear mixed-effects modeling (NONMEM). RESULTS: A total of 43 hemophilia A patients (FVIII ≤ 2 IU/dL), aged 5 to 70 years, were included. The prior model was able to predict the collected 244 rFVIII-Fc levels without significant bias (-1.0%, 95% CI: -9.4 to 7.3%) and with acceptable accuracy (12.9%). However, clearance and central distribution volume were under predicted in patients <12 years, which was expected as this age group was not represented in the previous model population. An enriched population PK model was constructed, which was able to successfully characterize PK profiles of younger children. CONCLUSION: We concluded that the existing rFVIII-Fc population PK model is valid for patients ≥ 12 years. However, it is not reliable in younger patients. Our alternative model, constructed from real world patient data including children, allows for better description of patients ≥5 years.


Assuntos
Fator VIII/farmacocinética , Hemofilia A/tratamento farmacológico , Hemostáticos/farmacocinética , Modelos Biológicos , Proteínas Recombinantes de Fusão/farmacocinética , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Fator VIII/administração & dosagem , Fator VIII/efeitos adversos , Hemofilia A/sangue , Hemofilia A/diagnóstico , Hemostáticos/administração & dosagem , Hemostáticos/efeitos adversos , Humanos , Fragmentos Fc das Imunoglobulinas/administração & dosagem , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Países Baixos , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Sistema de Registros , Reprodutibilidade dos Testes , Reino Unido , Adulto Jovem
15.
Cerebrovasc Dis ; 49(2): 177-184, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32320990

RESUMO

BACKGROUND: Prevention of hematoma enlargement in oral anticoagulation-associated intracerebral hemorrhage (OAC-ICH) focuses on blood pressure (BP) reduction and OAC reversal. We investigated whether treatment efficiency and clinical outcomes differ between OAC-ICH patients admitted outside versus during regular working hours. METHODS: Based on pooled data of multicenter cohort studies, we grouped OAC-ICH patients (vitamin K antagonist [VKA], non-vitamin K oral anticoagulant [NOAC]) according to on- vs. off-hour admission. Primary outcome was the functional outcome using the modified Rankin scale (mRS) dichotomized into favorable (mRS 0-3) and unfavorable (mRS 4-6) and mortality at 3 months. Secondary outcome measures included the occurrence of hematoma enlargement, the proportions of patients with systolic BP <140 mm Hg and with anticoagulation treatment achieving international normalized ratio (INR) levels <1.3 at 4 h. Propensity score matching (PSM) was performed to account for imbalances in baseline characteristics. RESULTS: The study population consisted of 76/126 NOAC-ICH patients and 1,005/1,470 VKA patients presenting during off-hours. Functional outcome and mortality rates were not significantly different among PSM patients with VKA-ICH and NOAC-ICH during on- vs. off-hours (mRS 4-6 VKA-ICH: on-hour: 239/357 [66.9%] vs. 253/363 [69.7%] off-hour; p = 0.43; NOAC-ICH: on-hour 26/42 [61.9%] vs. off-hour: 37/57 [64.9%]; p = 0.76; mRS 6 VKA-ICH: on-hour: 127/357 [35.6%] vs. off-hour: 148/363 [40.8%]; p = 0.15; -NOAC-ICH: on-hour 17/42 [40.5%] vs. off-hour: 16/57 [28.1%]; p = 0.20). There were no differences detectable regarding the secondary outcome measures (i.e., hematoma enlargement, the proportion of patients who achieved systolic BP levels <140 mm Hg at 4 h as well as anticoagulation treatment achieving INR levels <1.3 at 4 h) in OAC patients. CONCLUSION: Our study implies that BP reduction and anticoagulation reversal management are well established and associated with similar rates of hematoma enlargement and clinical outcomes in on- vs. off-hour admitted OAC-ICH patients.


Assuntos
Plantão Médico , Anticoagulantes/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Hemorragia Cerebral/tratamento farmacológico , Hematoma/tratamento farmacológico , Hemostáticos/administração & dosagem , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/fisiopatologia , Avaliação da Deficiência , Progressão da Doença , Feminino , Alemanha , Hematoma/induzido quimicamente , Hematoma/mortalidade , Hematoma/fisiopatologia , Hemostáticos/efeitos adversos , Humanos , Coeficiente Internacional Normatizado , Masculino , Estudos Multicêntricos como Assunto , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
16.
Hosp Pract (1995) ; 48(3): 123-127, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32295428

RESUMO

OBJECTIVES: Despite the availability of FDA-labeled anticoagulant reversal agents, there is considerable variability in clinical practice as to the regimen and agent used for reversal. The objective of this study was to characterize the current practices of pharmacists surrounding the reversal of anticoagulant-associated life-threatening hemorrhage. Methods: A cross-sectional analysis of critical care and emergency medicine pharmacists. Current practice was compared for the type of hospital, country region, and type of ordering physician. In addition, pharmacists were asked to rank their involvement with activities involved with the reversal of anticoagulants. Respondents ranked their involvement with these activities as either never involved, rarely involved, occasionally involved, frequently involved, or always involved. Results:281 respondents were included. The majority used 4-factor PCC for warfarin reversal (92.9%) and factor Xa inhibitor reversal (79.7%). However, only 58.7% used the labeled dose of 4-PCC for warfarin reversal. Of the 30.6% that utilized a fixed-dose regimen, the most common regimen was 1500 units once. A higher proportion of respondents practicing in a teaching hospital reported that they used activated prothrombin complex concentrates for reversal of factor Xa inhibitor (22 [12.2%] vs. 5 [5%]; p < 0.05) or coagulation factor Xa (recombinant)-inactivated-zhzo (31 [17.2%] vs. 5 [5%]; p < 0.05). In addition, the majority of respondents utilized idarucizumab for dabigatran reversal. The only involvement activity in which <50% of respondents said they were frequently involved or always involved was 'administration of reversal agent.' Conclusions: There is considerable variability in which agents were utilized for anticoagulant-associated bleeding reversal.


Assuntos
Anticoagulantes/efeitos adversos , Cuidados Críticos/organização & administração , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Hemostáticos/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Fatores de Coagulação Sanguínea/administração & dosagem , Cuidados Críticos/normas , Estudos Transversais , Relação Dose-Resposta a Droga , Inibidores do Fator Xa/efeitos adversos , Humanos , Metilmetacrilatos , Padrões de Prática Médica , Características de Residência
18.
J Trauma Acute Care Surg ; 88(5): 661-670, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32068718

RESUMO

BACKGROUND: Fibrinogen concentrate is widely used in traumatic hemorrhagic shock despite weak evidence in the literature. The aim of the study was to evaluate the effect of fibrinogen concentrate administration within the first 6 hours on 24-hour all-cause mortality in traumatic hemorrhagic shock using a causal inference approach. METHODS: Observational study from a French multicenter prospective trauma registry was performed. Hemorrhagic shock was defined as transfusion of four or more red blood cell units within the first 6 hours after admission. The confounding variables for the outcome (24-hour all-cause mortality) and treatment allocation (fibrinogen concentrate administration within the first 6 hours) were chosen by a Delphi method. The propensity score was specified with a data-adaptive algorithm and a doubly-robust approach with inverse proportionality of treatment weighting allowed to compute the average treatment effect. Sensitivity analyses were performed. RESULTS: Of 14,336 patients in the registry during the study period, 1,027 in hemorrhagic shock were analyzed (758 receiving fibrinogen concentrate within 6 hours and 269 not receiving fibrinogen concentrate). The average treatment effect, expressed as a risk difference, was -0.031 (95% confidence interval, -0.084 to 0.021). All sensitivity analysis confirmed the results. CONCLUSIONS: Fibrinogen concentrate administration within the first 6 hours of a traumatic hemorrhagic shock did not decrease 24-hour all-cause mortality. LEVEL OF EVIDENCE: Prognostic, level III.


Assuntos
Transfusão de Eritrócitos/estatística & dados numéricos , Fibrinogênio/administração & dosagem , Hemostáticos/administração & dosagem , Choque Hemorrágico/terapia , Choque Traumático/terapia , Adulto , Técnica Delfos , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Prospectivos , Sistema de Registros/estatística & dados numéricos , Choque Hemorrágico/etiologia , Choque Hemorrágico/mortalidade , Choque Traumático/etiologia , Choque Traumático/mortalidade , Fatores de Tempo , Tempo para o Tratamento/estatística & dados numéricos , Resultado do Tratamento , Adulto Jovem
20.
J Clin Ultrasound ; 48(5): 294-297, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31981367

RESUMO

Although external jugular vein (EJV) aneurysms are infrequent, regardless of etiology, spontaneous pseudoaneurysms (PAs) are extremely rare and generally require surgery. We describe a case of spontaneous PA of the EJV, which was successfully treated by percutaneous thrombin injection.


Assuntos
Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/tratamento farmacológico , Hemostáticos/uso terapêutico , Veias Jugulares/diagnóstico por imagem , Trombina/uso terapêutico , Ultrassonografia Doppler em Cores/métodos , Feminino , Hemostáticos/administração & dosagem , Humanos , Pessoa de Meia-Idade , Terapêutica , Trombina/administração & dosagem
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