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1.
JAMA ; 323(2): 130-139, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31935028

RESUMO

Importance: The efficacy of factor XIa inhibition for thromboprophylaxis is unknown. Osocimab is a long-acting, fully human monoclonal antibody that inhibits factor XIa. Objective: To compare different doses of osocimab with enoxaparin and apixaban for thromboprophylaxis in patients who have undergone knee arthroplasty. Design, Setting, and Participants: Randomized, open-label, adjudicator-blinded, phase 2 noninferiority trial with observer blinding for osocimab doses, conducted at 54 hospitals in 13 countries. Adult patients undergoing unilateral knee arthroplasty were randomized from October 2017 through August 2018 and followed up until January 2019. Interventions: Single intravenous osocimab postoperative doses of 0.3 mg/kg (n = 107), 0.6 mg/kg (n = 65), 1.2 mg/kg (n = 108), or 1.8 mg/kg (n = 106); preoperative doses of 0.3 mg/kg (n = 109) or 1.8 mg/kg (n = 108); or 40 mg of subcutaneous enoxaparin once daily (n = 105) or 2.5 mg of oral apixaban twice daily (n = 105) for at least 10 days or until venography. Main Outcomes and Measures: The primary outcome was venous thromboembolism incidence between 10 and 13 days postoperatively (assessed by mandatory bilateral venography performed 10 to 13 days after surgery or confirmed symptomatic deep vein thrombosis or pulmonary embolism). A 5% noninferiority margin compared with enoxaparin was chosen. The primary safety outcome of major or clinically relevant nonmajor bleeding was assessed until 10 to 13 days postoperatively. Results: Of 813 randomized participants (mean [SD] age, 66.5 years [8.2 years]; body mass index, 32.7 [5.7]; and 74.2% women), 600 were included in the per-protocol population used for the primary analysis. The primary outcome occurred in 18 patients (23.7%) receiving 0.3 mg/kg, 8 (15.7%) receiving 0.6 mg/kg, 13 (16.5%) receiving 1.2 mg/kg, and 14 (17.9%) receiving 1.8 mg/kg of osocimab postoperatively; 23 (29.9%) receiving 0.3 mg/kg and 9 (11.3%) receiving 1.8 mg/kg of osocimab preoperatively; 20 (26.3%) receiving enoxaparin; and 12 (14.5%) receiving apixaban. Osocimab given postoperatively met criteria for noninferiority compared with enoxaparin with risk differences (1-sided 95% CIs) of 10.6% (95% CI, -1.2% to ∞) at the 0.6-mg/kg dose; 9.9% (95% CI, -0.9% to ∞) at the 1.2-mg/kg dose, and 8.4% (95% CI, -2.6 to ∞) at the 1.8-mg/kg dose. The preoperative dose of 1.8 mg/kg of osocimab met criteria for superiority compared with enoxaparin with a risk difference of 15.1%; 2-sided 90% CI, 4.9% to 25.2%). Postoperative and preoperative doses of 0.3 mg/kg of osocimab did not meet the prespecified criteria for noninferiority, with risk differences (1-sided 95% CIs) of 2.6% (95% CI, -8.9% to ∞) and -3.6% (95% CI, -15.5% to ∞), respectively. Major or clinically relevant nonmajor bleeding was observed in up to 4.7% of those receiving osocimab, 5.9% receiving enoxaparin, and 2% receiving apixaban. Conclusions and Relevance: Among patients undergoing knee arthroplasty, postoperative osocimab 0.6 mg/kg, 1.2 mg/kg, and 1.8 mg/kg met criteria for noninferiority compared with enoxaparin, and the preoperative 1.8-mg/kg dose of osocimab met criteria for superiority compared with enoxaparin for the primary outcome of incidence of venous thromboembolism at 10 to 13 days postoperatively. Further studies are needed to establish efficacy and safety of osocimab relative to standard thromboprophylaxis. Trial Registration: ClinicalTrials.gov Identifier: NCT03276143.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Anticoagulantes/administração & dosagem , Artroplastia do Joelho , Inibidores do Fator Xa/administração & dosagem , Hemorragia/induzido quimicamente , Complicações Pós-Operatórias/prevenção & controle , Tromboembolia Venosa/prevenção & controle , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticoagulantes/efeitos adversos , Relação Dose-Resposta a Droga , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Embolia Pulmonar/prevenção & controle , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Método Simples-Cego , Trombose Venosa/prevenção & controle
2.
Am J Health Syst Pharm ; 76(11): 815-819, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31361813

RESUMO

PURPOSE: The study analyzes the effectiveness and safety of a higher than standard enoxaparin dosing protocol implemented for pediatric patients requiring initiation of therapeutic anticoagulation. METHODS: A retrospective review of 2 enoxaparin dosing and monitoring protocols was performed. The standard protocol used 1.5 mg/kg/dose (in patients <3 months of age) and 1 mg/kg/dose (in patients ≥3 months of age) with anti-Xa monitoring following the first dose. The high-dose protocol was implemented at 1.7 mg/kg/dose (in patients <3 months of age), 1.5 mg/kg/dose (in patients 3 through 11 months of age), 1.2 mg/kg/dose (in patients 1 through 4 years of age), and 1.1 mg/kg/dose (in patients 5 through 17 years of age), with anti-Xa monitoring after the second dose. Primary outcomes were number of dosing changes prior to and time to first target anti-Xa level. Secondary outcomes included percentage of patients with anti-Xa levels above target level. RESULTS: The median number of dose changes required to achieve a target anti-Xa level was 1 (interquartile range [IQR], 0-1.5) and 0 (IQR, 0-1) for the standard-dose (n = 87) and high-dose groups (n = 132) (p = 0.17), respectively. The median number of dose adjustments to achieve target anti-Xa levels in the 3 through 11 months of age subgroup declined from 2 (IQR, 1-3.25) to 0 (IQR, 0-1) in the standard- versus high-dose groups, respectively (p < 0.01). No difference was seen in other age subgroups. Patients with above-target levels did not differ statistically between groups. CONCLUSION: Initiating enoxaparin at higher doses in pediatric patients may result in fewer dosing changes than standard dosing. Benefit was demonstrated for the 3-11 months of age high-dose subgroup. Across all groups, the high-dose strategy was safe and did not result in a statistically significant increase in above-target levels.


Assuntos
Monitoramento de Medicamentos/métodos , Enoxaparina/administração & dosagem , Inibidores do Fator Xa/administração & dosagem , Adolescente , Coagulação Sanguínea/efeitos dos fármacos , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Enoxaparina/efeitos adversos , Enoxaparina/sangue , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/sangue , Feminino , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Lactente , Masculino , Estudos Retrospectivos
3.
Dis Colon Rectum ; 62(11): 1381-1389, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31318768

RESUMO

BACKGROUND: There is increasing evidence to support extended thromboprophylaxis after colorectal surgery to minimize the incidence of postdischarge venous thromboembolic events. However, the absolute number of events is small, and extended thromboprophylaxis requires significant resources from the health care system. OBJECTIVE: This study aimed to determine the cost-effectiveness of extended thromboprophylaxis in patients undergoing colorectal surgery for malignancy or IBD. DESIGN: An individualized patient microsimulation model (1,000,000 patients; 1-month cycle length) comparing extended thromboprophylaxis (28-day course of enoxaparin) to standard management (inpatient administration only) after colorectal surgery was constructed. SETTINGS: The sources for this study were The American College of Surgeons National Surgical Quality Improvement Project Participant User File and literature searches. OUTCOMES: Costs (Canadian dollars), quality-adjusted life-years, and venous thromboembolism-related deaths prevented over a 1-year time horizon starting with hospital discharge were determined. The results were stratified by malignancy or IBD. RESULTS: In patients with malignancy, extended prophylaxis was associated with higher costs (+113$; 95% CI, 102-123), but increased quality-adjusted life-years (+0.05; 95% CI, 0.04-0.06), resulting in an incremental cost-effectiveness ratio of 2473$/quality-adjusted life-year. For IBD, extended prophylaxis also had higher costs (+116$; 95% CI, 109-123), more quality-adjusted life-years (+0.05; 95% CI, 0.04-0.06), and an incremental cost-effectiveness ratio of 2475$/quality-adjusted life-year. Extended prophylaxis prevented 16 (95% CI, 4-27) venous thromboembolism-related deaths per 100,000 patients and 22 (95% CI, 6-38) for malignancy and IBD. There was a 99.7% probability of cost-effectiveness at a willingness-to-pay threshold of 50,000$/quality-adjusted life-year. To account for statistical uncertainty around variables, sensitivity analysis was performed and found that extended prophylaxis is associated with lower overall costs when the incidence of postdischarge venous thromboembolic events reaches 1.8%. LIMITATIONS: Significant differences in health care systems may affect the generalizability of our results. CONCLUSIONS: Despite the rarity of venous thromboembolic events, extended thromboprophylaxis is a cost-effective strategy. See Video Abstract at http://links.lww.com/DCR/A976. COSTO-EFECTIVIDAD DE LA TROMBOPROFILAXIS EXTENDIDA EN PACIENTES SOMETIDOS A CIRUGÍA COLORRECTAL DESDE UNA PERSPECTIVA DEL SISTEMA DE SALUD CANADIENSE:: Cada vez hay más pruebas que apoyen la tromboprofilaxis extendida después de la cirugía colorrectal para minimizar la incidencia de eventos tromboembólicos venosos después del alta hospitalaria. Sin embargo, el número absoluto de eventos es pequeño y la tromboprofilaxis extendida requiere recursos significativos del sistema médico.Determinar la rentabilidad (relación costo-efectividad) de la tromboprofilaxis extendida en pacientes sometidos a cirugía colorrectal por neoplasia maligna o enfermedad inflamatoria intestinal.Un modelo de microsimulación de paciente individualizado (1,000,000 de pacientes; ciclo de 1 mes) que compara la tromboprofilaxis extendida (curso de enoxaparina de 28 días) con el tratamiento estándar (solo para pacientes hospitalizados) después de la cirugía colorrectal.Archivo de usuario participante del Proyecto de Mejoramiento de la Calidad Quirúrgica del Colegio Nacional de Cirujanos Americanos (ACS-NSQIP) y búsquedas bibliográficas.Costos (en dólares Canadienses), años de vida ajustados por la calidad y muertes relacionadas con el tromboembolismo venoso prevenidas en un horizonte temporal de 1 año a partir del alta hospitalaria. Los resultados fueron estratificados por malignidad o enfermedad inflamatoria intestinal.En pacientes con neoplasias malignas, la profilaxis extendida se asoció con costos más altos (+113 $; IC del 95%, 102-123), pero con un aumento de la calidad de vida ajustada por años de vida (+0.05; IC del 95%, 0.04-0.06), lo que resultó en un incremento de relación costo-efectividad de 2473 $/año de vida ajustado por calidad. Para la enfermedad inflamatoria intestinal, la profilaxis extendida también tuvo costos más altos (+116 $; 95% IC, 109-123), más años de vida ajustados por calidad (+0.05; 95% IC, 0.04-0.06) y una relación costo-efectividad incremental de 2475 $/año de vida ajustado por calidad. La profilaxis prolongada evitó 16 (95% IC, 4-27) muertes relacionadas con tromboembolismo venoso por cada 100,000 pacientes y 22 (95% IC, 6-38) por malignidad y enfermedad inflamatoria intestinal, respectivamente. Hubo un 99.7% de probabilidad de costo-efectividad en un límite de disposición a pagar de 50,000 $/año de vida ajustado por calidad. Para tener en cuenta la incertidumbre estadística en torno a los variables, se realizó un análisis de sensibilidad y se encontró que la profilaxis extendida se asocia con menores costos generales cuando la incidencia de eventos tromboembólicos venosos después del alta hospitalaria alcanza 1.8%.Las diferencias significativas en los sistemas de salud pueden afectar la generalización de nuestros resultados.A pesar de la escasez de eventos tromboembólicos venosos, la tromboprofilaxis extendida es una estrategia rentable. Vea el video del resumen en http://links.lww.com/DCR/A976.


Assuntos
Quimioprevenção , Colectomia/efeitos adversos , Enoxaparina , Complicações Pós-Operatórias , Tromboembolia Venosa , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/economia , Quimioprevenção/economia , Quimioprevenção/métodos , Colectomia/métodos , Neoplasias do Colo/cirurgia , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Enoxaparina/economia , Feminino , Humanos , Síndrome do Intestino Irritável/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/prevenção & controle , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/mortalidade , Tromboembolia Venosa/prevenção & controle
4.
J Thromb Thrombolysis ; 48(3): 422-429, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31222563

RESUMO

The extended use of thromboprophylaxis with direct oral anticoagulants (DOACs) for more than 30 days has been evaluated as an alternative for the standard duration thromboprophylaxis (7-10 days) with low molecular weight heparin in medically ill patients to reduce the risk of venous thromboembolism (VTE) after hospital discharge. EMBASE and MEDLINE were searched for studies evaluating extended duration thromboprophylaxis with DOACs versus standard thromboprophylaxis with enoxaparin in medically ill patients through October 2018. Search was limited to randomized-controlled trials. Symptomatic VTE, VTE-related death, and death from any cause, and major and clinically relevant non-major bleeding were used to assess the efficacy and safety, respectively. The Mantel-Haenszel random-effects model risk ratio (RR) and corresponding 95% CIs were calculated using the metan routine in Stata (version 14.2) to estimate the pooled treatment effects. Heterogeneity was assessed by the I2 statistics. Four studies met the inclusion criteria. DOACs were superior to enoxaparin in preventing symptomatic VTE (RR = 0.59, 95% CI 0.44-0.79). There were no significant differences in thromboprophylactic efficacy between extended and standard thromboprophylaxis as to VTE-related death (RR = 0.81, 95% CI 0.60-1.10) and death from any cause (RR = 0.98, 95% CI 0.87-1.09). Compared to the standard duration, extended thromboprophylaxis was associated with approximately two-fold greater risk of major (RR = 1.95, 95% CI 1.25-3.04), and clinically relevant non-major (RR = 1.81, 95% CI 1.29-2.53) bleeding. The superior efficacy was diminished by the unfortunate safety profile. Therefore, we continue to support both the American Society of Hematology (ASH) and the American College of Chest Physicians (ACCP) guidelines recommendation against the extended use of thromboprophylaxis beyond the hospital stay.


Assuntos
Inibidores do Fator Xa/uso terapêutico , Pré-Medicação/métodos , Tromboembolia Venosa/prevenção & controle , Enoxaparina/efeitos adversos , Enoxaparina/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Humanos , Tempo de Internação , Pré-Medicação/mortalidade , Fatores de Risco , Fatores de Tempo
5.
World J Surg Oncol ; 17(1): 110, 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31248419

RESUMO

BACKGROUND: Pharmacological thromboprophylaxis after colorectal cancer (CRC) surgery is internationally recommended for venous thromboembolism (VTE) prevention. The aim of this retrospective study was to evaluate the risk factors of postoperative bleeding after elective surgery for patients with primary CRC receiving pharmacological thromboprophylaxis of fondaparinux or enoxaparin. METHODS: We experienced consecutive 266 patients who underwent elective surgery for CRC during the study period. Finally, the medical records of 218 patients with CRC administrated fondaparinux or enoxaparin following surgery were retrospectively reviewed to evaluate symptomatic VTE until 28 days and postoperative bleeding comparing perioperative D-dimer levels. RESULTS: The significant differences in TNM classification staging and type of thromboprophylaxis were observed between postoperative bleeding-negative and bleeding-positive group. There was no statistical significance among other backgrounds of patients between the two groups. One case (0.46%) of symptomatic VTE and total 11 cases (5%) of postoperative bleeding were observed. In the univariate analysis, fondaparinux thromboprophylaxis and early disease-stage CRC (stages 0 and I) were associated with risk for postoperative bleeding. Multivariate analysis revealed that fondaparinux thromboprophylaxis was identified as an independent risk factor of postoperative bleeding. Moreover, preoperative levels of D-dimer in patients with stage IV CRC were significantly higher than those with the other stages. The significant elevation in preoperative D-dimer was also observed in patients with stage II CRC compared to those with stage I CRC. Perioperative levels of D-dimer in patients with advanced disease-stage CRC (stages II, III, and IV) were significantly higher than those in patients with early disease-stage CRC. CONCLUSIONS: Fondaparinux administration and early disease-stage CRC appeared to be risk factors for postoperative bleeding in patients with pharmacological thromboprophylaxis undergoing surgical treatment for CRC. Patients' hypercoagulative condition depending on disease progression of CRC might be related to the occurrence of postoperative bleeding following CRC surgery.


Assuntos
Anticoagulantes/efeitos adversos , Neoplasias Colorretais/cirurgia , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Hemorragia Pós-Operatória/diagnóstico , Tromboembolia Venosa/prevenção & controle , Idoso , Anticoagulantes/administração & dosagem , Neoplasias Colorretais/patologia , Progressão da Doença , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Feminino , Fondaparinux/administração & dosagem , Fondaparinux/efeitos adversos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Hemorragia Pós-Operatória/epidemiologia , Hemorragia Pós-Operatória/etiologia , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia
6.
Am J Case Rep ; 20: 753-757, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31133634

RESUMO

BACKGROUND Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin therapy, characterized by thrombocytopenia and high risk for venous and arterial thrombosis. CASE REPORT We report an unusual case of acute stent thrombosis secondary to delayed HIT. A 74-year-old man with non-ST-segment elevation myocardial infarction had a coronary angiography which revealed 2-vessel disease. A bolus of unfractionated heparin (UFH) was administered at admission and he received fondaparinux during his hospitalization. We performed elective percutaneous coronary intervention (PCI) with stents to LAD and LCx. Two hours after PCI, the patient developed acute pulmonary edema, and repeat angiography revealed an occlusive thrombus in the ostial LAD and the LCx. A turbidimetric assay for the rapid detection of plasma anti-PF4/heparin antibodies was negative. After repeated unsuccessful attempts of balloon angioplasty and continuous thrombosis, the patient was transferred for emergency surgical revascularisation and was treated with additional UFH followed by enoxaparin. Platelets decreased gradually to 38 k/µl 7 days after surgery, at which time enoxaparin was replaced with fondaparinux. The subsequent HIT test results were positive. CONCLUSIONS HIT should be considered in patients with multiple recent exposures to anticoagulants, independent of the platelet count, if there are signs and symptoms of thrombosis.


Assuntos
Anticoagulantes/efeitos adversos , Heparina/efeitos adversos , Stents/efeitos adversos , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Trombose/etiologia , Idoso , Doença da Artéria Coronariana/terapia , Enoxaparina/efeitos adversos , Humanos , Masculino , Intervenção Coronária Percutânea/efeitos adversos , Trombose/diagnóstico , Trombose/terapia
7.
BMC Pharmacol Toxicol ; 20(1): 27, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31064405

RESUMO

BACKGROUND: Thromboprophylaxis dosing strategies using enoxaparin in elderly patients with renal disease are limited, while dose adjustments or monitoring of anti-Xa levels are recommended. We sought to evaluate the efficacy and safety of enoxaparin 20 mg versus 30 mg subcutaneously daily by comparing anti-Xa levels, thrombosis and bleeding. METHODS: We conducted a prospective, single-blinded, single-center randomized clinical trial including non-surgical patients, 70 years of age or older, with renal disease requiring thromboprophylaxis. Patients were randomized to receive either 20 mg or 30 mg of enoxaparin. The primary endpoint was peak anti-Xa levels on day 3. Secondary endpoints included trough anti-Xa levels on day 3, achievement of within range prophylactic target peak anti-Xa levels and the occurrence of hemorrhage, thrombosis, thrombocytopenia or hyperkalemia during hospitalization. RESULTS: Thirty-two patients were recruited and sixteen patients were randomized to each arm. Mean peak anti-Xa level was significantly higher in 30 mg arm (n = 13) compared to the 20 mg arm (n = 11) 0.26 ± 0.11, 95%CI (0.18-0.34), versus 0.14 ± 0.09, 95CI (0.08-0.19) UI/ml, respectively; p = 0.004. Mean trough anti-Xa level was higher in 30 mg arm (n = 10) compared to the 20 mg arm (n = 16), 0.06 ± 0.03, 95CI (0.04-0.08) versus 0.03 ± 0.03, 95CI (0.01-0.05) UI/ml, respectively; p = 0.044. Bleeding events reported in the 30 mg arm were one retroperitoneal bleed requiring multiple transfusions, and in the 20 mg arm one hematuria. No thrombotic events were reported. CONCLUSION: Peak anti-Xa levels provided by enoxaparin 20 mg were lower than the desired range for thromboprophylaxis in comparison to enoxaparin 30 mg. TRIAL REGISTRATION: The trial was retrospectively registered on ClinicalTrials.gov identifier: NCT03158792 . Registered: May 18, 2017.


Assuntos
Anticoagulantes/administração & dosagem , Enoxaparina/administração & dosagem , Fator Xa/análise , Insuficiência Renal/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Enoxaparina/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Insuficiência Renal/sangue , Método Simples-Cego , Trombose/prevenção & controle , Resultado do Tratamento
8.
J Thromb Thrombolysis ; 48(3): 387-393, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30945098

RESUMO

Current treatment dose of enoxaparin is based on total body weight (TBW), however dosage in obesity remains unclear. "Dose capping" commonly occurs if TBW > 100 kg minimising bleeding risk. However, this may result in under-dosing and increasing embolisation risk. The primary objective evaluated efficacy of current dosing strategies in obese patients and determined if resultant anti-Xa concentrations (aXaC) were therapeutic. The secondary objective was to investigate if an uncapped 0.75-0.85 mg/kg (TBW) twice daily dose, advocated by previous authors, results in therapeutic aXaC (0.5-1.0 IU/ml). This retrospective study included 133 patients with a median TBW of 128 kg, producing 59% therapeutic, 15% sub-therapeutic and 26% supra-therapeutic aXaC. Approximately 60% of patients in each dose group (< 0.75, 0.75-0.85 and > 0.85 mg/kg) had a therapeutic aXaC, however the percentage of sub-therapeutic versus supra-therapeutic was higher in the < 0.75 (27% vs 9%) and > 0.85 mg/kg (10% vs 34%) groups respectively. Most patients who weighed 100-119 kg (TBW) received doses > 0.85 mg/kg, however 32% had toxic aXaC. Those between 120 and 139 kg (TBW) had a high percentage of therapeutic aXaC (87%) when dosed < 0.75 mg/kg and a high percentage of supra-therapeutic aXaC (71%) when dosed > 0.85 mg/kg; although numbers were low. Dose reduction occurred in patients > 140 kg (TBW), however < 0.75 mg/kg resulted in higher percentage of sub-therapeutic aXaC (42%). Dosing at 0.75-0.85 mg/kg results in 62% of therapeutic, 14% sub-therapeutic and 24% supra-therapeutic aXaC. This appears to be a "safe" starting dose-range, however all obese patients should have aXaC monitoring due to high inter-patient variability.


Assuntos
Peso Corporal , Cálculos da Dosagem de Medicamento , Enoxaparina/administração & dosagem , Adulto , Enoxaparina/efeitos adversos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade , Estudos Retrospectivos
9.
Cochrane Database Syst Rev ; 3: CD010019, 2019 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-30839095

RESUMO

BACKGROUND: Pulmonary embolism (PE) is a common life-threatening cardiovascular condition, with an incidence of 23 to 69 new cases per 100,000 people each year. For selected low-risk patients with acute PE, outpatient treatment might provide several advantages over traditional inpatient treatment, such as reduction of hospitalisations, substantial cost savings, and improvements in health-related quality of life. This is an update of the review first published in 2014. OBJECTIVES: To compare the efficacy and safety of outpatient versus inpatient treatment in low-risk patients with acute PE for the outcomes of all-cause and PE-related mortality; bleeding; adverse events such as haemodynamic instability; recurrence of PE; and patients' satisfaction. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and AMED databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers, to 26 March 2018. We also undertook reference checking to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials of outpatient versus inpatient treatment of adults (aged 18 years and over) diagnosed with low-risk acute PE. DATA COLLECTION AND ANALYSIS: Two review authors selected relevant trials, assessed methodological quality, and extracted and analysed data. We calculated effect estimates using risk ratio (RR) with 95% confidence intervals (CIs), or mean differences (MDs) with 95% CIs. We used standardised mean differences (SMDs) to combine trials that measured the same outcome but used different methods. We assessed the quality of the evidence using GRADE criteria. MAIN RESULTS: One new study was identified for this 2018 update, bringing the total number of included studies to two and the total number of participants to 451. Both trials discharged patients randomised to the outpatient group within 36 hours of initial triage and both followed participants for 90 days. One study compared the same treatment regimens in both outpatient and inpatient groups, and the other study used different treatment regimes. There was no clear difference in treatment effect for the outcomes of short-term mortality (30 days) (RR 0.33, 95% CI 0.01 to 7.98, P = 0.49; low-quality evidence), long-term mortality (90 days) (RR 0.98, 95% CI 0.06 to 15.58, P = 0.99, low-quality evidence), major bleeding at 14 days (RR 4.91, 95% CI 0.24 to 101.57, P = 0.30; low-quality evidence) and at 90 days (RR 6.88, 95% CI 0.36 to 132.14, P = 0.20; low-quality evidence), minor bleeding (RR 1.08, 95% CI 0.07 to 16.79; P = 0.96, low-quality evidence), recurrent PE within 90 days (RR 2.95, 95% CI 0.12 to 71.85, P = 0.51, low-quality evidence), and participant satisfaction (RR 0.97, 95% CI 0.90 to 1.04, P = 0.39; moderate-quality evidence). We downgraded the quality of the evidence because the CIs were wide and included treatment effects in both directions, the sample sizes and numbers of events were small, and because the effect of missing data and the absence of publication bias could not be verified. PE-related mortality, and adverse effects such as haemodynamic instability and compliance, were not assessed by the included studies. AUTHORS' CONCLUSIONS: Currently, only low-quality evidence is available from two published randomised controlled trials on outpatient versus inpatient treatment in low-risk patients with acute PE. The studies did not provide evidence of any clear difference between the interventions in overall mortality, bleeding and recurrence of PE.


Assuntos
Assistência Ambulatorial , Enoxaparina/uso terapêutico , Hospitalização , Embolia Pulmonar/terapia , Doença Aguda , Adulto , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Intervalos de Confiança , Enoxaparina/efeitos adversos , Hemorragia/epidemiologia , Humanos , Embolia Pulmonar/mortalidade , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Rivaroxabana/efeitos adversos , Rivaroxabana/uso terapêutico
10.
Orthop Traumatol Surg Res ; 105(3): 497-501, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30878232

RESUMO

INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening condition associated with heparin administration. Many orthopaedic units routinely prescribe low-molecular-weight heparins as thromboprophylaxis after hip and knee arthroplasty. HYPOTHESIS: We postulated that routine platelet monitoring following heparin administration is of no clinical benefit. We therefore asked: firstly, what was the rate of thrombocytopenia in a large population of patients undergoing lower limb arthroplasty? Secondly, did this rate justify routine platelet monitoring? MATERIALS AND METHODS: Unless contraindicated, all patients (n=1999, 53.05% female, mean age 69.23 years) at a UK district general hospital undergoing hip and knee arthroplasty were given daily prophylactic enoxaparin. Platelet counts were obtained between the 8th and 10th postoperative days and compared to preoperative baseline. A > 50% fall in platelet count was classified as "possible HIT". The minimal acceptable risk of thrombocytopenia was defined using The American College of Chest Physicians (ACCP) 2012 guidelines, which recommend monitoring platelet counts in patients receiving heparin where the expected risk of HIT is>1% and by descriptive cost-benefit analysis based on the cost of routine platelet monitoring in the clinical setting. RESULTS: Complete results were available for 1361 (68.1%) patients, comprising: 653 primary hips, 22 revision hips, 1 hip resurfacing, 665 primary knees, 19 revision knees and 1 unicompartmental knee replacement. Mean platelet level was 281.9×109/L preoperatively and 527.83×109/L postoperatively. Forty-four patients (3.2%) experienced a postoperative fall in platelet levels. However, no patient experienced a drop in platelets to less than 50% of the preoperative value. DISCUSSION: The incidence of HIT in the elective arthroplasty population is low. Therefore, routine postoperative monitoring of platelets is not necessary in this population of patients. LEVEL OF EVIDENCE: II, prospective study.


Assuntos
Anticoagulantes/efeitos adversos , Artroplastia de Quadril , Artroplastia do Joelho , Enoxaparina/efeitos adversos , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Idoso , Anticoagulantes/uso terapêutico , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Enoxaparina/uso terapêutico , Feminino , Hospitais de Distrito , Hospitais Gerais , Humanos , Masculino , Contagem de Plaquetas , Complicações Pós-Operatórias/prevenção & controle , Período Pós-Operatório , Estudos Prospectivos , Trombocitopenia/sangue , Reino Unido , Tromboembolia Venosa/prevenção & controle
11.
Drugs ; 79(3): 291-302, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30719631

RESUMO

Acutely ill hospitalized medical patients remain at high thromboembolic risk for several weeks after discharge. Previous trials with extended-duration thromboprophylaxis using enoxaparin, apixaban, and rivaroxaban failed to achieve acceptable net clinical benefit, largely due to excess of major bleeding. Betrixaban is a novel factor Xa inhibitor with unique pharmacokinetic properties, including low renal clearance, long half-life, and low peak-to-trough ratio. The phase III APEX trial (N = 7513) compared a betrixaban 160 mg loading dose followed by 80 mg once daily for 35-42 days, with enoxaparin 40 mg once daily for 6-14 days; the betrixaban dose was reduced for renal impairment or a concomitant strong P-glycoprotein (P-gp) inhibitor. The primary efficacy endpoint of composite thrombotic events was not different between treatment arms in cohort 1 (D-dimer ≥ 2 × upper limit of normal). Subsequent exploratory analyses showed a statistically significant difference favoring betrixaban for symptomatic venous thromboembolism and net clinical benefit in the overall population. For the primary safety outcome, betrixaban did not significantly increase major bleeding compared with enoxaparin. Based on available data from the APEX trial and subanalyses, the use of betrixaban in patients similar to those enrolled in the APEX trial can reduce the risk of thromboembolic events without increasing the risk of major bleeding. Patients who may benefit more from betrixaban therapy include those with elevated D-dimer, history of venous thromboembolism, hospitalized for ischemic stroke, hospitalized for heart failure with N-terminal pro-B-type natriuretic peptide ≥ 1975 ng/L, or two or more VTE risk factors. Reduced-dose betrixaban does not appear to provide the same clinical utility as full-dose betrixaban.


Assuntos
Anticoagulantes/uso terapêutico , Benzamidas/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Piridinas/uso terapêutico , Tromboembolia Venosa/prevenção & controle , Anticoagulantes/efeitos adversos , Benzamidas/efeitos adversos , Quimioterapia Combinada , Enoxaparina/efeitos adversos , Enoxaparina/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Hemorragia/induzido quimicamente , Hospitalização , Humanos , Piridinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/terapia , Resultado do Tratamento
12.
Thromb Res ; 176: 1-7, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30743065

RESUMO

BACKGROUND/OBJECTIVES: Hospital acquired venous thromboembolism in children is associated with significant morbidity/mortality. Prevention strategies include sequential compression devices and prophylactic anticoagulation but these interventions carry risk and are poorly studied in children. Objectives were to evaluate primary thromboprophylaxis use in hospitalized children over time and the associated bleeding risk. MATERIALS AND METHODS: Retrospective study of hospitalized patients aged 10-18 years within the Pediatric Health Information System administrative database from January 2008-September 2015. Factors associated with thromboprophylaxis receipt and bleeding were identified using generalized linear mixed effects models. RESULTS: Of 1,075,383 hospitalizations, 10,544 (1%) received prophylactic enoxaparin and 58,768 (5%) received mechanical compression. Mechanical thromboprophylaxis increased slightly over time (4.3% in 2008, 6.2% in 2015), enoxaparin use did not (0.8% in 2008, 1.2% in 2015). Patients aged 16-18 were more likely than younger children (10-12) to receive pharmacologic (adjusted odds ratio [aOR] 3.1, 95% confidence interval [CI] 2.9-3.3) or mechanical thromboprophylaxis (aOR 2.9, 95% CI 2.9-3). Patients on rehabilitation medical service were more likely to receive prophylactic enoxaparin (aOR 53, 95% CI 44.1-64.5). 5.6% (589/10,544) of patients receiving enoxaparin prophylaxis had bleeding. Thromboprophylaxis use by hospital varied with a range of 0.25-3.3% for enoxaparin and 2-26.2% for mechanical compression. CONCLUSION: Thromboprophylaxis is infrequently utilized in hospitalized children. Pharmacologic prophylaxis with enoxaparin remains low and has not substantially increased over time. Significant variability exists across hospitals and services in the administration of both mechanical and pharmacologic thromboprophylaxis highlighting the need for further evidence to standardize practice.


Assuntos
Anticoagulantes/uso terapêutico , Enoxaparina/uso terapêutico , Trombólise Mecânica , Tromboembolia/prevenção & controle , Adolescente , Anticoagulantes/efeitos adversos , Criança , Enoxaparina/efeitos adversos , Feminino , Hemorragia/etiologia , Humanos , Masculino , Trombólise Mecânica/efeitos adversos , Trombólise Mecânica/métodos , Estudos Retrospectivos , Tromboembolia/terapia , Resultado do Tratamento
13.
Thromb Haemost ; 119(3): 461-466, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30650446

RESUMO

The double-blind, randomized, AMPLIFY trial compared 6 months' treatment with apixaban (10 mg twice daily for 7 days and 5 mg twice daily thereafter) versus conventional treatment (subcutaneous enoxaparin [1 mg/kg twice daily for ≥ 5 days] overlapped and followed by warfarin [international normalized ratio = 2.0-3.0]) in patients with acute venous thromboembolism (VTE). This post hoc analysis of AMPLIFY compared outcomes among those taking or not taking concomitant anti-platelet therapy. The primary efficacy outcome was recurrent VTE or VTE-related death; the principal safety outcome was major bleeding. Of 5,365 (apixaban, n = 2,676; enoxaparin/warfarin, n = 2,689) randomized patients, 813 (apixaban, n = 402 [15%]; enoxaparin/warfarin, n = 411 [15%]) took concomitant anti-platelet therapy, of which 92% consisted of low-dose aspirin. Rates of VTE or VTE-related death were similar whether or not anti-platelet agents were taken (apixaban: 3.6 and 2.0%; enoxaparin/warfarin: 3.0 and 2.6%; anti-platelet use: relative risk [RR], 1.23; 95% confidence interval [CI], 0.58-2.62; no anti-platelet use: RR, 0.77; 95% CI, 0.52-1.13); interaction p-value = 0.299. Major bleeding rates were threefold higher in those taking versus those not taking anti-platelet agents (apixaban: 1.2 and 0.4%; enoxaparin/warfarin: 4.1 and 1.4%; anti-platelet use: RR, 0.30; 95% CI, 0.11-0.81; no anti-platelet use: RR, 0.31; 95% CI, 0.15-0.63); interaction p-value = 0.924. Concomitant anti-platelet therapy produced a proportionally similar increase in major bleeding in patients randomized to apixaban or conventional therapy, but there were fewer major bleeds with apixaban. Therefore, the overall safety of apixaban over conventional therapy was maintained in patients receiving anti-platelet therapy. Clinicaltrials.gov: NCT00643201.


Assuntos
Anticoagulantes/administração & dosagem , Enoxaparina/administração & dosagem , Inibidores do Fator Xa/administração & dosagem , Inibidores da Agregação de Plaquetas/administração & dosagem , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Tromboembolia Venosa/tratamento farmacológico , Varfarina/administração & dosagem , Adulto , Idoso , Anticoagulantes/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Enoxaparina/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Tromboembolia Venosa/sangue , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/mortalidade , Varfarina/efeitos adversos
14.
Br J Clin Pharmacol ; 85(3): 570-579, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30511379

RESUMO

AIMS: Linear immunoglobin A (IgA) bullous dermatosis is a rare autoimmune dermatosis considered spontaneous or drug-induced (DILAD). We assessed all DILAD cases, determined the imputability score of drugs and highlighted suspected drugs. METHODS: Data for patients with DILAD were collected retrospectively from the French Pharmacovigilance network (from 1985 to 2017) and from physicians involved in the Bullous Diseases French Study Group and the French Investigators for Skin Adverse Reactions to Drugs. Drug causality was systematically determined by the French imputability method. RESULTS: Of the 69 patients, 42% had mucous membrane involvement, 20% lesions mimicking toxic epidermal necrolysis (TEN), 21% eosinophil infiltrates and 10% keratinocytes necrosis. Direct immunofluorescence, in 80%, showed isolated linear IgA deposits. Vancomycin (VCM) was suspected in 39 cases (57%), 11 had TEN-like lesions, as compared with three without VCM suspected. Among the 33 patients with a single suspected drug, 85% had an intrinsic imputability score of I4. Among them, enoxaparin, minocycline and vibramycin were previously unpublished. For all patients, the suspect drug was withdrawn; 15 did not receive any treatment. First-line therapy for 31 patients was topical steroids. Among the 60 patients with available follow-up, 52 achieved remission, 10 without treatment. Four patients experienced relapse, four died and five had positive accidental rechallenges. CONCLUSIONS: There is no major clinical difference between DILAD and idiopathic linear IgA bullous dermatosis, but the former features a higher prevalence of patients mimicking TEN. VCM, suspected in more than half of the cases, might be responsible for more severe clinical presentations. We report three new putative drugs.


Assuntos
Monitoramento de Medicamentos/estatística & dados numéricos , Dermatose Linear Bolhosa por IgA/epidemiologia , Farmacovigilância , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Bases de Dados Factuais/estatística & dados numéricos , Diagnóstico Diferencial , Doxiciclina/efeitos adversos , Enoxaparina/efeitos adversos , Feminino , França/epidemiologia , Humanos , Dermatose Linear Bolhosa por IgA/induzido quimicamente , Dermatose Linear Bolhosa por IgA/diagnóstico , Masculino , Pessoa de Meia-Idade , Minociclina/efeitos adversos , Prevalência , Estudos Retrospectivos , Índice de Gravidade de Doença , Síndrome de Stevens-Johnson/diagnóstico , Vancomicina/efeitos adversos , Adulto Jovem
16.
Am J Emerg Med ; 37(1): 174.e5-174.e6, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30274763

RESUMO

Clinical practice guidelines recommend protamine sulfate for reversal of enoxaparin associated bleeds dependent on the time from last administration and dose of enoxaparin. We present a case of a hemodynamically unstable patient with an enoxaparin induced abdominal wall hematoma/hemorrhage and the previous enoxaparin administration 21.5 h prior to presentation with a therapeutic anti-Xa assay (0.8 IU/mL) upon assessment in the emergency department. Along with resuscitative efforts, an interdisciplinary team collaborated to administer protamine sulfate 50 mg intravenous once (0.5 mg per 1 mg of enoxaparin) to reverse the therapeutic anticoagulation. Our case demonstrates the importance of monitoring renal function and the potential for accumulation of enoxaparin in patients with renal dysfunction leading to prolonged therapeutic anti-Xa assays. With the availability of anti-Xa assays, future reversal recommendations of enoxaparin associated bleeds using protamine sulfate should include the initial anti-Xa assay as a guide for the dosing regimen.


Assuntos
Anticoagulantes/efeitos adversos , Enoxaparina/efeitos adversos , Hematoma/induzido quimicamente , Hematoma/tratamento farmacológico , Antagonistas de Heparina/uso terapêutico , Protaminas/uso terapêutico , Parede Abdominal/diagnóstico por imagem , Idoso , Esquema de Medicação , Serviço Hospitalar de Emergência , Feminino , Hematoma/complicações , Hematoma/diagnóstico por imagem , Humanos , Insuficiência Renal Crônica/complicações , Fatores de Tempo , Tomografia Computadorizada por Raios X
17.
Eur J Neurol ; 26(2): 333-341, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30308696

RESUMO

BACKGROUND AND PURPOSE: Early pharmacological deep vein thrombosis (DVT) prophylaxis is recommended by guidelines, but rarely started within 48 h. We aimed to analyze the effect of early (within 48 h) versus late (>48 h) DVT prophylaxis on hematoma expansion (HE) and outcome in patients with spontaneous intracerebral hemorrhage (ICH). METHODS: We analyzed 134 consecutive patients admitted to a tertiary neurointensive care unit with diagnosed spontaneous ICH, without previous anticoagulation, severe coagulopathy, hematoma evacuation, early withdrawal of therapy or ineligibility for DVT prophylaxis according to our institutional protocol. Significant late HE was defined as ≥6 mL increase of hematoma volume between neuroimaging within 48 h and day 3-6. Multivariate analysis was performed to identify risk factors for late HE, poor 3-month outcome (modified Rankin Scale score ≥ 4) and mortality. RESULTS: Patients had a median Glasgow Coma Scale score of 14 [interquartile range (IQR), 10-15], ICH volume of 11 (IQR, 5-24) mL and were 71 (IQR, 61-76) years old. A total of 56% (n = 76) received early DVT prophylaxis, 37% (n = 50) received late DVT prophylaxis and 8 (6%) had unknown bleeding onset. Patients with early DVT prophylaxis had smaller ICH volume [9.5 (IQR, 4-18.5) vs. 17.5 (IQR, 8-29) mL, P = 0.038] and were more often comatose (26% vs. 10%, P = 0.025). Significant late HE [n = 5/134 (3.7%)] was associated with larger initial ICH volume (P = 0.02) and lower thrombocyte count (P = 0.03) but not with early DVT prophylaxis (P = 0.36). Early DVT prophylaxis was not associated with worse outcome. CONCLUSION: Significant late HE is uncommon and DVT prophylaxis within 48 h of symptom onset may be safe in selected patients with ICH.


Assuntos
Anticoagulantes/uso terapêutico , Hemorragia Cerebral/complicações , Enoxaparina/uso terapêutico , Hematoma/etiologia , Trombose Venosa/prevenção & controle , Idoso , Anticoagulantes/efeitos adversos , Enoxaparina/efeitos adversos , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Terapia Trombolítica/efeitos adversos , Trombose Venosa/tratamento farmacológico
18.
J Int Med Res ; 47(1): 225-234, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30259770

RESUMO

OBJECTIVE: This study was performed to evaluate the efficacy of daily subcutaneous enoxaparin 20 mg in patients with renal failure. METHODS: This retrospective cohort study included nonsurgical patients aged ≥18 years with a creatinine clearance rate of <30 mL/minute who were prescribed enoxaparin 20 mg subcutaneously (SC) daily for ≥3 days. The main outcome measures were the occurrence of a venous thromboembolic event (VTE) and bleeding events. RESULTS: One hundred sixty patients were identified. VTE occurred in 9 patients (5.6%), and bleeding events occurred in 37 (23.1%). Multivariable analysis showed that an age of >75 years was significantly associated with an increased risk of bleeding, while a creatinine clearance rate of 15 to 29 mL/minute was significantly associated with a lower risk of bleeding. CONCLUSION: In patients with renal failure, enoxaparin 20 mg SC daily resulted in a 5.6% incidence of VTE, which is similar to the previously published acceptable incidence of VTE in patients with normal renal function receiving enoxaparin 40 mg SC daily. The incidence of major bleeding events was 10%, which is lower than that previously published in the literature.


Assuntos
Anticoagulantes/administração & dosagem , Enoxaparina/administração & dosagem , Hemorragia/etiologia , Insuficiência Renal/terapia , Tromboembolia Venosa/etiologia , Adolescente , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Creatinina/sangue , Esquema de Medicação , Enoxaparina/efeitos adversos , Feminino , Hemorragia/diagnóstico , Hemorragia/fisiopatologia , Humanos , Injeções Subcutâneas , Masculino , Análise Multivariada , Projetos Piloto , Diálise Renal/métodos , Insuficiência Renal/sangue , Insuficiência Renal/patologia , Estudos Retrospectivos , Resultado do Tratamento , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/fisiopatologia
19.
Eur J Gastroenterol Hepatol ; 31(1): 34-42, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30188408

RESUMO

BACKGROUND AND OBJECTIVE: Portal vein thrombosis (PVT) is a common complication in cirrhosis, and when complete, it increases morbidity and mortality in liver transplant candidates. The aim of the study was to assess the hemostatic status, as well as clinical characteristics of thrombus and patients, as predictors of therapeutic efficacy of anticoagulation for the treatment of PVT in cirrhotics. PATIENTS AND METHODS: Patients with cirrhosis consecutively treated for PVT with enoxaparin were enrolled. All patients underwent evaluation of coagulation status and thrombophilia screening. Thrombus characteristics and extension were evaluated at baseline and during follow-up. Anticoagulation was continued until recanalization or up to 12 months. Variables correlated with the response to anticoagulation were used to create a predictive score that was validated in an external multicenter cohort. RESULTS: A total of 65 patients were included and had partial PVT in most cases (72%). Treatment with enoxaparin resulted in an overall response rate of 66% (43/65) after a median time of 4.4 months and 76% (33/43) within the first 6 months. At multivariate analysis, efficacy of anticoagulation correlated with the severity of liver disease, complete verus partial PVT, age of the thrombus, and time interval from treatment start (<6 months). The areas under the curve of the statistical model for predicting the response to anticoagulation were 0.84 and 0.76 for the training (n=65) and validation (n=60) cohorts, respectively. CONCLUSION: Early diagnosis and early treatment are key factors for the successful management of PVT in cirrhosis, so that screening of PVT and prompt start of anticoagulant treatment should be mandatory.


Assuntos
Anticoagulantes/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Técnicas de Apoio para a Decisão , Enoxaparina/uso terapêutico , Cirrose Hepática/complicações , Veia Porta , Trombose Venosa/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Biomarcadores/sangue , Testes de Coagulação Sanguínea , China , Diagnóstico Precoce , Enoxaparina/efeitos adversos , Feminino , Humanos , Itália , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Masculino , Pessoa de Meia-Idade , Veia Porta/diagnóstico por imagem , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Trombose Venosa/sangue , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologia
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