RESUMEN

INTRODUCTION: Current guidelines recommend that the International Normalized Ratio (INR) be less than 1.5 prior to spine intervention. Recent studies have shown that an INR > 1.25 is associated worse outcomes following anterior cervical surgery. We sought to determine the risk of complications associated with an INR > 1.25 following elective posterior cervical surgery. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried. Patients undergoing elective posterior cervical surgery from 2012 to 2016 with an INR level within 24 h of surgery were included. Primary outcomes were hematoma requiring surgery, 30-day mortality, and transfusions within 72-hours. There were 815 patients in the INR ≤ 1 cohort (Cohort A), 410 patients in the 1 < INR ≤ 1.25 cohort (Cohort B), and 33 patients in the 1.25 < INR ≤ 1.5 cohort (Cohort C). RESULTS: Cohort C had a higher rate of transfusion (4% Cohort A; 6% Cohort B; 12% Cohort C; p = 0.028) and the rate of mortality within 30 days postoperatively trended toward significance (0.4% Cohort A; 0.5% Cohort B; 3% Cohort C; p = 0.094). There was no significant difference in the rate of postoperative hematoma formation requiring surgery (0.2% Cohort A; 0% Cohort B; 0% Cohort C; p = 0.58). On multivariate analysis, increasing INR was not associated with an increased risk of developing a major complication. CONCLUSION: An INR > 1.25 but ≤ 1.5 may be safe for posterior cervical surgery. An INR > 1.25 but ≤ 1.5 was associated with a significantly higher rate of transfusions. However, increasing INR was not significantly associated with increased risk of any of the major complications.

Asunto(s)

Vértebras Cervicales , Relación Normalizada Internacional , Complicaciones Posoperatorias , Humanos , Femenino , Vértebras Cervicales/cirugía , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Anciano , Resultado del Tratamiento , Estudios de Cohortes , Transfusión Sanguínea/estadística & datos numéricos , Hematoma/etiología , Hematoma/epidemiología , Adulto , Estudios Retrospectivos , Periodo Preoperatorio , Procedimientos Quirúrgicos Electivos/efectos adversos

RESUMEN

Renal function significantly influences the appropriate warfarin dosage. However, studies investigating the impact of genetic factors on warfarin dosage, considering renal function, are limited. This study aimed to assess the role of genetic polymorphisms in VKORC1, CYP2C9, CYP2C19, CYP4F2, GGCX, and APOE in warfarin dosage adjustment considering renal function. A total of 108 outpatients receiving warfarin treatment with controlled prothrombin time-targeted international normalized ratio (1.5-3.0) were included. Patient data, warfarin dosage, and laboratory results were collected from electronic medical records. Each SNP [VKORC1 rs9923231, CYP2C9 rs1057910, CYP4F2 rs2108622, CYP2C19* 2 (rs4244285) and* 3 (rs4986893), GGCX rs699664 and rs12714145, and APOE rs7421] was analyzed. Multiple regression analysis revealed estimated glomerular filtration rate as the most significant factor influencing warfarin dose (p <0.001) (ß = -0.445). VKORC1 rs9923231 AA, CYP4F2 rs2108622 CT/TT, GGCX rs12714145 CT/TT, and CYP2C9 rs1057910 AC carriers were associated with warfarin dose (p <0.001, 0.015, 0.020, 0.038 and ß = -0.317, 0.191, -0.188, -0.162, respectively); however, other genes showed no significant association. In conclusion, after adjusting for renal function, genetic factors of VKORC1 rs9923231, CYP4F2 rs2108622, GGCX rs12714145, and CYP2C9 rs1057910 were found to contribute to warfarin dosage, having impact in that order. In contrast, the contribution of other genes to warfarin dosage was absent or negligible.

Asunto(s)

Anticoagulantes , Polimorfismo de Nucleótido Simple , Warfarina , Humanos , Warfarina/administración & dosificación , Femenino , Masculino , Anticoagulantes/administración & dosificación , Anciano , Persona de Mediana Edad , Pueblo Asiatico/genética , Japón , Relación Normalizada Internacional , Relación Dosis-Respuesta a Droga , Tasa de Filtración Glomerular , Vitamina K Epóxido Reductasas/genética , Anciano de 80 o más Años , Familia 4 del Citocromo P450/genética , Genotipo , Adulto , Pueblos del Este de Asia

RESUMEN

BACKGROUND AND AIMS: The transition from compensated to decompensated cirrhosis is crucial, drastically reducing prognosis from a median survival of over 10 years to 2 years. There is currently an unmet need to accurately predict decompensation. We systematically reviewed and meta-analysed data regarding biomarker use to predict decompensation in individuals with compensated cirrhosis. METHODS: PubMed and EMBASE database searches were conducted for all studies from inception until February 2024. The study was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Quality of Prognosis Studies framework was used to assess the risk of bias. The meta-analysis was conducted with a random effects model using STATA software. RESULTS: Of the 652 studies initially identified, 63 studies (n=31 438 patients) were included in the final review, examining 49 biomarkers. 25 studies (40%) were prospective with the majority of studies looking at all-cause decompensation (90%). The most well-studied biomarkers were platelets (n=17), Model for End-Stage Liver Disease (n=17) and albumin (n=16). A meta-analysis revealed elevated international normalised ratio was the strongest predictor of decompensation, followed by decreased albumin. However, high statistical heterogeneity was noted (l2 result of 96.3%). Furthermore, 21 studies were assessed as having a low risk of bias (34%), 26 (41%) moderate risk and 16 (25%) high risk. CONCLUSIONS: This review highlights key biomarkers that should potentially be incorporated into future scoring systems to predict decompensation. However, future biomarker studies should be conducted with rigorous and standardised methodology to ensure robust and comparable data.

Asunto(s)

Biomarcadores , Cirrosis Hepática , Humanos , Biomarcadores/sangre , Cirrosis Hepática/sangre , Cirrosis Hepática/complicaciones , Pronóstico , Progresión de la Enfermedad , Albúmina Sérica/análisis , Albúmina Sérica/metabolismo , Relación Normalizada Internacional , Valor Predictivo de las Pruebas

RESUMEN

Importance: Millions of people take vitamin K antagonists (VKAs). Some people who need urgent surgical procedures require rapid VKA reversal to prevent excessive intraoperative bleeding. Objective: To evaluate the hemostatic noninferiority of an investigational 4-factor prothrombin complex concentrate (4F-PCC) to a control 4F-PCC for rapid VKA reversal before urgent surgery. Design, Setting, and Participants: This phase 3, double-blind, noninferiority randomized clinical trial (LEX-209) was conducted in 24 hospitals in the US, Russia, Georgia, Belarus, Ukraine, and Romania from June 7, 2017, through November 8, 2021; the study was stopped in February 2022. Participants were adult patients taking VKA who had an international normalized ratio (INR) of 2 or higher and needed urgent surgery with a substantial bleeding risk (≥50 mL). Patients were randomized 1:1 to a single infusion of either the investigational 4F-PCC or the control 4F-PCC. Data analysis followed intention-to-treat and per-protocol approaches. Interventions: Single intravenous infusion was dosed by body weight and baseline INR. A dose of 25, 35, or 50 IU/kg of investigational 4F-PCC or control 4F-PCC was administered for baseline INR of 2 to less than 4, 4 to 6, or over 6, respectively. Main Outcome and Measure: The primary end point was hemostatic efficacy at surgery end. An independent adjudication board, blinded to the 4F-PCC treatment allocation, assessed hemostatic efficacy using an objective 4-point scale. Results: A total of 208 patients (median [range] age, 67.5 [31-92] years; 118 males [56.7%]) received the investigational (n = 105) or the control (n = 103) 4F-PCC. The median (range) dose was 25 (16-50) IU/kg in the investigational group and 25 (15-50) IU/kg in the control group, with a median (range) infusion time of 12 (8-50) minutes and 13 (7-30) minutes and a median (range) time from infusion to surgery start of 1.42 (0.25-15.25) hours and 1.50 (0.42-18.50) hours, respectively. Baseline median (range) INR was 3.05 (1.97-21.10) in the investigational group and 3.00 (2.00-11.30) in the control group. In the intention-to-treat analysis, the investigational 4F-PCC was noninferior to the control 4F-PCC, resulting in effective hemostasis in 94.3% of patients vs 94.2% of patients (proportion difference, 0.001; 95% CI, -0.080 to 0.082; P < .001), meeting the prespecified noninferiority margin of 0.15. An INR of 1.5 or lower at 30 minutes after infusion occurred in 78.1% of patients in the investigational group vs 71.8% of patients in the control group (proportion difference, 0.063; 95% CI, -0.056 to 0.181). Thrombotic events (2.9% vs 0%, respectively) and mortality (4.8% vs 1.0%, respectively) were no different than expected for 4F-PCC use. One patient in each treatment group discontinued due to adverse events (cardiac disorders unrelated to 4F-PCC). Conclusions and Relevance: This randomized clinical trial found that the investigational 4F-PCC was hemostatically noninferior to the control 4F-PCC for rapid VKA reversal in patients needing urgent surgery with considerable bleeding risk; the safety profile of these two 4F-PCCs was similar. These results support the investigational 4F-PCC as a therapeutic option for surgical patients requiring rapid VKA reversal. Trial Registration: ClinicalTrials.gov Identifier: NCT02740335.

Asunto(s)

Factores de Coagulación Sanguínea , Vitamina K , Humanos , Masculino , Femenino , Factores de Coagulación Sanguínea/uso terapéutico , Factores de Coagulación Sanguínea/administración & dosificación , Persona de Mediana Edad , Anciano , Método Doble Ciego , Vitamina K/antagonistas & inhibidores , Vitamina K/uso terapéutico , Pérdida de Sangre Quirúrgica/prevención & control , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Relación Normalizada Internacional , Adulto

RESUMEN

BACKGROUND: Poor anticoagulation management of warfarin may lead to patient admission, prolonged hospital stays, and even death due to anticoagulation-related adverse events. Traditional non-web-based outpatient clinics struggle to provide ideal anticoagulation management services for patients, and there is a need to explore a safer, more effective, and more convenient mode of warfarin management. OBJECTIVE: This study aimed to compare differences in the quality of anticoagulation management and clinical adverse events between a web-based management model (via a smartphone app) and the conventional non-web-based outpatient management model. METHODS: This study is a prospective cohort research that includes multiple national centers. Patients meeting the nadir criteria were split into a web-based management group using the Alfalfa app or a non-web-based management group with traditional outpatient management, and they were then monitored for a 6-month follow-up period to collect coagulation test results and clinical events. The effectiveness and safety of the 2 management models were assessed by the following indicators: time in therapeutic range (TTR), bleeding events, thromboembolic events, all-cause mortality events, cumulative event rates, and the distribution of the international normalized ratio (INR). RESULTS: This national multicenter cohort study enrolled 522 patients between June 2019 and May 2021, with 519 (99%) patients reaching the follow-up end point, including 260 (50%) in the non-web-based management group and 259 (50%) in the web-based management group. There were no observable differences in baseline characteristics between the 2 patient groups. The web-based management group had a significantly higher TTR than the non-web-based management group (82.4% vs 71.6%, P<.001), and a higher proportion of patients received effective anticoagulation management (81.2% vs 63.5%, P<.001). The incidence of minor bleeding events in the non-web-based management group was significantly higher than that in the web-based management group (12.1% vs 6.6%, P=.048). Between the 2 groups, there was no statistically significant difference in the incidence of severe bleeding and thromboembolic and all-cause death events. In addition, compared with the non-web-based management group, the web-based management group had a lower proportion of INR in the extreme subtreatment range (17.6% vs 21.3%) and severe supertreatment range (0% vs 0.8%) and a higher proportion in the treatment range (50.4% vs 43.1%), with statistical significance. CONCLUSIONS: Compared with traditional non-web-based outpatient management, web-based management via the Alfalfa app may be more beneficial because it can enhance patient anticoagulation management quality, lower the frequency of small bleeding events, and improve INR distribution.

Asunto(s)

Anticoagulantes , Relación Normalizada Internacional , Internet , Warfarina , Humanos , Warfarina/uso terapéutico , Warfarina/efectos adversos , Estudios Prospectivos , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Hemorragia , Aplicaciones Móviles , Estudios de Cohortes

RESUMEN

A woman in her mid-20s, a known case of congenital afibrinogenaemia, presented with abdominal pain and distension. She was diagnosed with decompensated liver cirrhosis due to Budd-Chiari syndrome. She underwent deceased donor liver transplantation. Preoperatively, her serum fibrinogen level was undetectable and prothrombin time and international normalised ratio (INR) were unrecordable. Intraoperatively, she was given thromboelastography-guided human fibrinogen concentrate. Postoperatively, her fibrinogen, prothrombin time and INR normalised rapidly. This report summarises the rare occurrence of a complication of hypercoagulability (Budd-Chiari syndrome) in the setting of congenital hypocoagulability (congenital afibrinogenaemia). In this report, we discuss the simultaneous management of these two clinical problems and the curative role of liver transplantation.

Asunto(s)

Afibrinogenemia , Síndrome de Budd-Chiari , Trasplante de Hígado , Humanos , Síndrome de Budd-Chiari/etiología , Afibrinogenemia/complicaciones , Femenino , Adulto , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Fibrinógeno/uso terapéutico , Relación Normalizada Internacional

RESUMEN

Warfarin-related nephropathy (WRN) is defined as acute kidney injury subsequent to excessive anticoagulation with warfarin. Patients with mechanical prosthetic valves require long-term anticoagulant therapy. Nonetheless, warfarin remains the sole available option for anticoagulant therapy. Consequently, patients with mechanical prosthetic valves constitute a special group among the entire anticoagulant population. The present study recorded two cases of patients who had undergone mechanical prosthetic valve surgery and were receiving warfarin therapy. They presented to the hospital with gross hematuria and progressive creatinine levels. Notably, their international normalized ratio (INR) did not exceed three. Subsequent renal biopsies confirmed WRN with IgA nephropathy. The two patients continued to receive warfarin as anticoagulation therapy and were prescribed oral corticosteroids and cyclophosphamide, which resulted in improved renal function during the follow-up. Based on a review of all relevant literature and the present study, we proposed a new challenge: must elevated INR levels be one of the criteria for clinical diagnosis of WRN? Perhaps some inspiration can be drawn from the present article.

Asunto(s)

Anticoagulantes , Warfarina , Humanos , Warfarina/efectos adversos , Anticoagulantes/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Relación Normalizada Internacional , Anciano , Glomerulonefritis por IGA , Biopsia , Lesión Renal Aguda/inducido químicamente , Riñón/patología , Riñón/efectos de los fármacos , Ciclofosfamida/efectos adversos , Corticoesteroides/uso terapéutico , Corticoesteroides/efectos adversos , Corticoesteroides/administración & dosificación

RESUMEN

OBJECTIVE: Both chronic kidney disease and its main treatment, hemodialysis (HD), are associated with hematological abnormalities. However, little is known about how starting hemodialysis when already in end-stage renal disease (ESRD) affects hematological parameters. This study investigated the effect of HD on hematological and coagulation markers among ESRD patients. METHODS: A retrospective study was carried out on 43 HD-ESRD patients from January to December 2022. The data were collected from Sabt Alalaya General Hospital in Belgarn, Saudi Arabia. Using GraphPad Prism, multiple unpaired t-tests were utilized to compare hematological and coagulation markers between the patients and healthy subjects. RESULTS: The 43 HD-ESRD patients (46.5% male and 53.5% female) ranged in age from 20 to 89 years. The data obtained from our analysis unsurprisingly revealed significant variation in hematological parameters and coagulation patterns among HD-ESRD patients. Most notably, there were gradual and significant changes in platelet, MCV, MPV, and INR values during the assessment time. CONCLUSION: This investigation verified the possible occurrence of macrocytosis and thrombotic conditions among patients with ESRD who undergo HD. It is recommended to closely observe patients undergoing this procedure, with a specific focus on platelet, MCV, MPV, and INR levels as potential indications.

Asunto(s)

Relación Normalizada Internacional , Fallo Renal Crónico , Diálisis Renal , Humanos , Femenino , Fallo Renal Crónico/sangre , Fallo Renal Crónico/terapia , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana Edad , Proyectos Piloto , Adulto , Anciano , Estudios Retrospectivos , Anciano de 80 o más Años , Plaquetas , Adulto Joven , Índices de Eritrocitos , Arabia Saudita/epidemiología , Coagulación Sanguínea/fisiología

RESUMEN

BACKGROUND: Spinal muscular atrophy (SMA) is a progressive neurodegenerative disorder that can be treated with intrathecal nusinersen, an antisense oligonucleotide. In addition to efficacy, safety is a determining factor in the success of any therapy. Here, we aim to assess the safety of nusinersen therapy in paediatric patients with SMA. METHODS: Laboratory data of paediatric patients with SMA who received nusinersen between October 2019 and May 2022 were retrospectively analysed. RESULTS: During the observation period, 46 infants and children aged 2.9 months to 13.6 years received a total of 213 nusinersen doses without safety concerns. Inflammatory markers were stable throughout the study. International normalized ratio was increased by 0.09 per injection. Urea levels were increased by 0.108 mmol/L, and cystatin C decreased by 0.029 mg/L per injection. There were no significant changes in platelet count, activated partial thrombin time, creatinine levels or liver enzyme levels during treatment. The cerebrospinal fluid (CSF) leukocyte count remained stable, and total protein increased by 24.038 mg/L per injection. CONCLUSION: Our data showed that nusinersen therapy is generally safe in children with SMA. Laboratory monitoring did not identify any persistent or significantly abnormal findings. CSF protein should be monitored to gain more insights.

Asunto(s)

Oligonucleótidos , Humanos , Oligonucleótidos/uso terapéutico , Lactante , Preescolar , Niño , Estudios Retrospectivos , Masculino , Femenino , Adolescente , Inyecciones Espinales , Atrofia Muscular Espinal/tratamiento farmacológico , Atrofia Muscular Espinal/sangre , Relación Normalizada Internacional

RESUMEN

OBJECTIVES: This study aimed to evaluate the safety and efficacy of therapeutic plasma exchange (TPE) in pediatric acute liver failure (PALF). METHODS: All children aged 2-18 years with PALF were included. The intervention cohort included a subset of PALF patients undergoing complete three sessions of TPE, whereas the matching controls were derived by propensity score matching from the patient cohort who did not receive any TPE. Propensity matching was performed based on the international normalized ratio (INR), grade of hepatic encephalopathy (HE), age, bilirubin, and ammonia levels. The primary outcome measure was native liver survival (NLS) in the two arms on day 28. RESULTS: Of the total cohort of 403 patients with PALF, 65 patients who received TPE and 65 propensity-matched controls were included in analysis. The 2 groups were well balanced with comparable baseline parameters. On day 4, patients in the TPE group had significantly lower INR (P = 0.001), lower bilirubin (P = 0.008), and higher mean arterial pressure (MAP) (P = 0.033) than controls. The NLS was 46.15% in the TPE arm and 26.15% in the control arm. The overall survival (OS) was 50.8% in the TPE arm and 35.4% in the control arm. Kaplan-Meier survival analysis showed a significantly higher NLS in patients receiving TPE than controls (P = 0.001). On subgroup analysis, NLS benefit was predominantly seen in hepatitis A-related and indeterminate PALF. CONCLUSION: TPE improved NLS and OS in a propensity-matched cohort of patients with PALF. Patients receiving TPE had lower INR and bilirubin levels and higher MAP on day 4.

Asunto(s)

Fallo Hepático Agudo , Intercambio Plasmático , Puntaje de Propensión , Humanos , Niño , Intercambio Plasmático/métodos , Fallo Hepático Agudo/terapia , Fallo Hepático Agudo/mortalidad , Preescolar , Femenino , Adolescente , Masculino , Bilirrubina/sangre , Encefalopatía Hepática/terapia , Relación Normalizada Internacional , Hígado , Resultado del Tratamiento , Estudios Retrospectivos

RESUMEN

Different dosing strategies exist to initiate warfarin, most commonly fixed warfarin dosing (FWD), clinical warfarin dosing (CWD), and genetic-guided warfarin dosing (GWD). Landmark trials have shown GWD to be superior when compared to FWD in the EU-PACT trial or CWD in the GIFT trial. COAG trial did not show differences between GWD and CWD. We aim to compare the anticoagulation quality outcomes of CWD and FWD. This is a prospective cohort study with a retrospective comparator. Recruited subjects in the CWD (prospective) arm were initiated on warfarin according to the clinical dosing component of the algorithm published in www.warfarindosing.org. The primary efficacy outcome was the percentage time in the therapeutic range (PTTR) from day 3 to 6 till day 28 to 35. The study enrolled 122 and 123 patients in the CWD and FWD, respectively. The PTTR did not differ statistically between CWD and FWD (62.2 ± 26.2% vs. 58 ± 25.4%, p = 0.2). There was also no difference between both arms in the percentage of visits with extreme subtherapeutic international normalized ratio (INR) (<1.5; 15 ± 18.3% vs. 16.8 ± 19.1%, p = 0.44) or extreme supratherapeutic INR (>4; 7.7 ± 14.7% vs. 7.5 ± 12.4%, p = 0.92). We conclude that CWD did not improve the anticoagulation quality parameters compared to the FWD method.

Asunto(s)

Anticoagulantes , Relación Normalizada Internacional , Warfarina , Humanos , Warfarina/administración & dosificación , Anticoagulantes/administración & dosificación , Femenino , Masculino , Anciano , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Coagulación Sanguínea/efectos de los fármacos , Algoritmos , Relación Dosis-Respuesta a Droga , Monitoreo de Drogas/métodos , Monitoreo de Drogas/normas , Resultado del Tratamiento , Anciano de 80 o más Años

RESUMEN

BACKGROUND: Little is known how individual time-in-therapeutic-range (TTR) impacts the effectiveness and safety of warfarin therapy compared to direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF). OBJECTIVE: To compare the effectiveness and safety of standard dose DOACs to warfarin in patients with AF, while categorizing warfarin treated patients into quartiles based on their individual TTR. MATERIALS AND METHODS: We conducted a nationwide study including all patients with new-onset AF between 2011 and 2018 in Finland. Hazard ratios (HR) were calculated using Cox regression analysis with the inverse probability of treatment weighted method to assess the risks of ischaemic stroke (IS), intracranial haemorrhage (ICH) and mortality for users of apixaban (n = 12,426), dabigatran (n = 4545), rivaroxaban (n = 12,950) and warfarin (n = 43,548). RESULTS: The median TTR for warfarin users was 72%. Compared to the second best TTR quartile (reference), the risk of IS was higher in the two poorest TTR quartiles, and lower in the best TTR quartile and on rivaroxaban [2.35 (95% confidence interval, 1.85-2.85), 1.44 (1.18-1.75), 0.60 (0.47-0.77) and 0.72 (0.56-0.92)]. These differences were non-significant for apixaban and dabigatran. HR of ICH was 6.38 (4.88-8.35) and 1.87 (1.41-2.49) in the two poorest TTR groups, 1.44 (1.02-1.93) on rivaroxaban, and 0.58 (0.40-0.85) in the best TTR group compared to the reference group. Mortality was higher in the two poorest TTR groups and lowest in the best TTR group. CONCLUSIONS: The outcome was unsatisfactory in the two lowest TTR quartiles - in half of the patients treated with warfarin. The differences between the high TTR groups and standard dose DOACs were absent or modest.

Asunto(s)

Anticoagulantes , Fibrilación Atrial , Dabigatrán , Pirazoles , Piridonas , Rivaroxabán , Warfarina , Humanos , Warfarina/efectos adversos , Warfarina/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Masculino , Femenino , Anciano , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Finlandia/epidemiología , Rivaroxabán/efectos adversos , Rivaroxabán/administración & dosificación , Piridonas/administración & dosificación , Piridonas/efectos adversos , Piridonas/uso terapéutico , Persona de Mediana Edad , Pirazoles/administración & dosificación , Pirazoles/efectos adversos , Dabigatrán/efectos adversos , Dabigatrán/administración & dosificación , Administración Oral , Anciano de 80 o más Años , Estudios de Cohortes , Hemorragias Intracraneales/inducido químicamente , Hemorragias Intracraneales/epidemiología , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular Isquémico/prevención & control , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/etiología , Relación Normalizada Internacional , Resultado del Tratamiento

RESUMEN

The purpose of this paper is to study the genetic polymorphisms of related gene loci (CYP2C9*3, VKORC1-1639G > A) based on demographic and clinical factors, and use the maximum a posterior Bayesian method to construct a warfarin individualized dose prediction model in line with the Chinese Han population. Finally, the built model is compared and analyzed with the widely used models at home and abroad. In this study, a total of 5467 INR measurements are collected from 646 eligible subjects in our hospital, and the maximum a posterior Bayesian method is used to construct a warfarin dose prediction that conforms to the Chinese Han population on the basis of the Hamberg model. The model is verified and compared with foreign models. This study finds that body weight and concomitant use of amiodarone have a significant effect on the anticoagulant effect of warfarin. The model can provide an effective basis for individualized and rational dosing of warfarin in Han population more accurately. In the performance of comparison with different warfarin dose prediction models, the new model has the highest prediction accuracy, and the prediction percentage is as high as 72.56%. The dose predicted by the Huang model is the closest to the actual dose of warfarin. The population pharmacokinetics and pharmacodynamics model established in this study can better reflect the distribution characteristics of INR values after warfarin administration in the Han population, and performs better than the models reported in the literature.

Asunto(s)

Anticoagulantes , Citocromo P-450 CYP2C9 , Vitamina K Epóxido Reductasas , Warfarina , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticoagulantes/administración & dosificación , Anticoagulantes/farmacocinética , Teorema de Bayes , China , Citocromo P-450 CYP2C9/genética , Citocromo P-450 CYP2C9/metabolismo , Relación Normalizada Internacional , Vitamina K Epóxido Reductasas/genética , Warfarina/administración & dosificación , Warfarina/farmacocinética , Pueblos del Este de Asia

Asunto(s)

Algoritmos , Anticoagulantes , Warfarina , Warfarina/administración & dosificación , Humanos , Singapur , Anticoagulantes/administración & dosificación , Farmacogenética , Masculino , Relación Normalizada Internacional , Femenino , Citocromo P-450 CYP2C9/genética , Persona de Mediana Edad , Anciano , Vitamina K Epóxido Reductasas/genética

Asunto(s)

Relación Normalizada Internacional , Humanos , Anticoagulantes/uso terapéutico

RESUMEN

Warfarin remains the most prescribed oral anticoagulant of choice in atrial fibrillation (AF) patient in resource-limited settings. Despite evidence linking Time in Therapeutic Range (TTR) to patient outcomes, its use in clinical practice is not widespread. This prospective study explores the impact of a TTR-INR guided Warfarin adjustment protocol on TTR in AF patients. Conducted at the Warfarin clinic of King Chulalongkorn Memorial Hospital. TTR was calculated using the Rosendaal linear interpolation method at baseline, and then at 6 and 12 months post-protocol implementation. The primary outcome was the improvement in TTR following the protocol's implementation. The study analyzed 57 patients, with a mean age of 72 years and an even gender distribution. At baseline, 53% of patients had a TTR of less than 65%. However, TTR significantly improved from 65% at baseline to 80% after 12 months of protocol implementation (p < 0.001). Furthermore, there was a significant increase in the proportion of patients with a TTR of 65% or more, from 47 to 88% (p < 0.001). During the follow-up period in the first 12 months, three patients died, but no ischemic or major bleeding events occurred. The significant improvement in TTR after 12 months of protocol implementation suggests that this strategy could provide additional value in improving TTR and outcomes in AF patients receiving Warfarin.

Asunto(s)

Anticoagulantes , Fibrilación Atrial , Relación Normalizada Internacional , Warfarina , Humanos , Warfarina/administración & dosificación , Warfarina/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Masculino , Femenino , Anciano , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Estudios Prospectivos , Persona de Mediana Edad , Anciano de 80 o más Años , Resultado del Tratamiento , Monitoreo de Drogas/métodos

RESUMEN

BACKGROUND: The development of acute traumatic coagulopathy is associated with increased mortality and morbidity in patients with battlefield traumatic injuries. Currently, the incidence of acute traumatic coagulopathy in the Role 1 setting is unclear. METHODS: We queried the Prehospital Trauma Registry (PHTR) module of the Department of Defense Trauma Registry (DoDTR) for all encounters from inception through May 2019. The PHTR captures data on Role 1 prehospital care. Data from the PHTR was linked to the DoDTR to analyze laboratory data and patient outcomes using descriptive statistics. We defined coagulopathy as an international normalized ratio (INR) of ≥1.5 or platelet count ≤150×109/L. RESULTS: A total of 595 patients met the inclusion criteria; 36% (212) met our definition for coagulopathy, with 31% (185) carrying low platelet numbers, 11% (68) showing an elevated INR, and 7% (41) with both. The baseline (no coagulopathy) cohort had a mean INR of 1.10 (95% CI 1.09-1.12) versus 1.38 (95% CI 1.33-1.43) in the coagulopathic cohort. The mean platelet count was 218 (95% CI 213-223) ×109/L in the baseline cohort versus 117 (95% CI 110-125) ×109/L in the coagulopathic cohort. CONCLUSIONS: Our findings indicate a high incidence of coagulopathy in trauma patients. Approximately one-third of wounded patients had laboratory evidence of coagulopathy upon presentation to a forward medical care facility. Advanced diagnostic facilities are therefore needed to facilitate early diagnosis of acute traumatic coagulopathy. Blood products with a long shelf life can aid in early correction.

Asunto(s)

Trastornos de la Coagulación Sanguínea , Servicios Médicos de Urgencia , Relación Normalizada Internacional , Sistema de Registros , Resucitación , Humanos , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/epidemiología , Incidencia , Masculino , Adulto , Resucitación/métodos , Femenino , Servicios Médicos de Urgencia/estadística & datos numéricos , Heridas y Lesiones/complicaciones , Heridas y Lesiones/terapia , Heridas y Lesiones/epidemiología , Recuento de Plaquetas , Personal Militar/estadística & datos numéricos , Estados Unidos/epidemiología

RESUMEN

Prothrombin time (PT) and its derivative international normalized ratio (INR) are frequently ordered to assess the coagulation system. Plasma transfusion to treat incidentally abnormal PT/INR is a common practice with low biological plausibility and without credible evidence, yet INR targets appear in major clinical guidelines and account for the majority of plasma use at many institutions. In this article, we review the historical origins of INR targets. We recount historical milestones in the development of the PT, discovery of vitamin K antagonists (VKAs), motivation for INR standardization, and justification for INR targets in patients receiving VKA therapy. Next, we summarize evidence for INR testing to assess bleeding risk in patients not on VKA therapy and plasma transfusion for treating mildly abnormal INR to prevent bleeding in these patients. We conclude with a discussion of the parallels in misunderstanding of historic PT and present-day INR testing with lessons from the past that might help rationalize plasma transfusion in the future.

Asunto(s)

Anticoagulantes , Coagulación Sanguínea , Hemorragia , Relación Normalizada Internacional , Tiempo de Protrombina , Vitamina K , Humanos , Relación Normalizada Internacional/historia , Historia del Siglo XX , Vitamina K/antagonistas & inhibidores , Historia del Siglo XXI , Coagulación Sanguínea/efectos de los fármacos , Anticoagulantes/uso terapéutico , Anticoagulantes/historia , Hemorragia/historia , Hemorragia/sangre , Tiempo de Protrombina/historia , Transfusión de Componentes Sanguíneos/historia , Historia del Siglo XIX , Valor Predictivo de las Pruebas , Monitoreo de Drogas/historia , Plasma

RESUMEN

BACKGROUND: To explore the risk factors for postoperative abnormal coagulation (PAC) and establish a predictive model for patients with normal preoperative coagulation function who underwent hepatectomy. MATERIALS AND METHODS: A total of 661 patients with normal preoperative coagulation function who underwent hepatectomy between January 2015 and December 2021 at the First Affiliated Hospital of Sun Yat-sen University were divided into two groups: the postoperative abnormal coagulation group (PAC group, n = 362) and the normal coagulation group (non-PAC group, n = 299). Univariate and multivariate logistic analyses were used to identify the risk factors for PAC. RESULTS: The incidence of PAC in 661 patients who underwent hepatectomy was 54.8% (362/661). The least absolute shrinkage and selection operator (LASSO) method was used for multivariate logistic regression analysis. The preoperative international normalized ratio (INR), intraoperative succinyl gelatin infusion and major hepatectomy were found to be independent risk factors for PAC. A nomogram for predicting the PAC after hepatectomy was constructed. The model presented a receiver operating characteristic (ROC) curve of 0.742 (95% confidence interval (CI): 0.697-0.786) in the training cohort. The validation set demonstrated a promising ROC of 0.711 (95% CI: 0.639-0.783), and the calibration curve closely approximated the true incidence. Decision curve analysis (DCA) was performed to assess the clinical usefulness of the predictive model. The risk of PAC increased when the preoperative international normalized ratio (INR) was greater than 1.025 and the volume of intraoperative succinyl gelatin infusion was greater than 1500 ml. CONCLUSION: The PAC is closely related to the preoperative INR, intraoperative succinyl gelatin infusion and major hepatectomy. A three-factor prediction model was successfully established for predicting the PAC after hepatectomy.

Asunto(s)

Trastornos de la Coagulación Sanguínea , Hepatectomía , Complicaciones Posoperatorias , Humanos , Hepatectomía/efectos adversos , Femenino , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Factores de Riesgo , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/epidemiología , Trastornos de la Coagulación Sanguínea/diagnóstico , Estudios Retrospectivos , Adulto , Anciano , Relación Normalizada Internacional , Nomogramas , Incidencia , Coagulación Sanguínea/fisiología , Periodo Preoperatorio

RESUMEN

Warfarin, a widely utilized anticoagulant, is paramount for preventing thromboembolic events in patients with mechanical heart valve replacements. However, its narrow therapeutic index can lead to over-anticoagulation and overdose, resulting in serious health risks. This study examines the efficacy of human prothrombin complex concentrate (PCC) in managing warfarin overdose, in comparison with traditional treatments. A retrospective analysis was conducted on 162 adults who presented with warfarin overdose (INR > 5.0) at a tertiary care hospital between 2016 and 2020. Participants were divided into 2 groups-those treated with PCC (n = 57) and those treated with conventional methods (n = 105), including vitamin K and fresh frozen plasma. The primary outcome was the rate of reaching the target (International Normalized Ratio) INR within 24 hours. Secondary outcomes included transfusion requirements, thromboembolic events, adverse reactions, 30-day mortality, and length of hospital stay. PCC demonstrated significant efficacy, with 89.5% of patients achieving the target INR within 24 hours, compared to 64.8% in the control group (P < .05). The PCC group also had reduced transfusion requirements and a shorter average hospital stay. There was no significant difference in thromboembolic events or adverse reactions between the 2 groups, and the reduced 30-day mortality in the PCC group was not statistically significant. Human prothrombin complex concentrate is associated with rapid reaching the target INR, decreased transfusion needs, and shortened hospitalization, making it a promising option for warfarin overdose management. While the results are encouraging, larger, multicenter, randomized controlled trials are necessary to further validate these findings and optimize PCC administration protocols.

Asunto(s)

Anticoagulantes , Factores de Coagulación Sanguínea , Sobredosis de Droga , Relación Normalizada Internacional , Warfarina , Humanos , Warfarina/efectos adversos , Warfarina/uso terapéutico , Factores de Coagulación Sanguínea/uso terapéutico , Factores de Coagulación Sanguínea/administración & dosificación , Femenino , Masculino , Estudios Retrospectivos , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Persona de Mediana Edad , Sobredosis de Droga/tratamiento farmacológico , Sobredosis de Droga/terapia , Anciano , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/métodos , Tromboembolia/prevención & control , Adulto , Resultado del Tratamiento , Transfusión Sanguínea/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Vitamina K/uso terapéutico