RESUMEN
Postoperative bleeding following cardiac surgeries is still an issue that deranges the medical resources and cost. The oral and injection administrations of blood coagulation protein, Factor VII (FVII), is effective to stop the bleeding. However, its short half-life has limited the effectiveness of this treatment and frequent FVII intake may distress the patients. Instead, incorporating FVII into synthetic biodegradable polymers such as polycaprolactone (PCL) that is commonly used in drug delivery applications should provide a solution. Therefore, this study aimed to immobilize FVII on PCL membranes through a cross-linkage polydopamine (PDA) grafting as an intermediate layer. These membranes are intended to provide a solution for cardiac bleeding in coagulating blood and sealing the sutured region. The membranes were evaluated in terms of its physio-chemical properties, thermal behavior, FVII release profile and biocompatibility properties. The ATR-FTIR was used to analyze the chemical functionalities of the membranes. Further validation was done with XPS where the appearances of 0.45 ± 0.06% sulfur composition and C-S peak have confirmed the immobilization of FVII on the PCL membranes. The cross-linked FVIIs were viewed in spherical immobilization on the PCL membranes with a size range between 30 and 210 nm. The surface roughness and hydrophilicity of the membranes were enhanced with a slight shift of melting temperature. The PCL-PDA-FVII0.03 and PCL-PDA-FVII0.05 membranes, with wide area of FVII immobilization released approximately only 22% of FVII into the solution within 60 days period and, it is found that the PCL-PDA-FVIIx membranes projected the Higuchi release model with non-Fickian anomalous transport. While the cytotoxic and hemocompatibility analyses showed advance cell viability, identical coagulation time and low hemolysis ratio on the PCL-PDA-FVIIx membranes. The erythrocytes were viewed in polyhedrocyte coagulated structure under SEM visualization. These results validate the biocompatibility of the membranes and its ability to prolong blood coagulation, thus highlighting its potential application as cardiac bleeding sealant.
Asunto(s)
Coagulantes , Factor VII , Humanos , Factor VII/análisis , Polímeros/químicaRESUMEN
BACKGROUND: Vitamin K has long been regarded as a procoagulant drug by physicians, and concerns have been raised with regard to its effects on hemostasis. Although many studies have shown that vitamin K supplementation is safe for thrombotic events, the effect of vitamin K supplementation on the activities of vitamin K dependent procoagulation factors in healthy individuals is not available. OBJECTIVES: This study aimed to investigate whether vitamin K2 supplementation at recommended doses affects the activity of vitamin K dependent procoagulation factors in healthy individuals without any anticoagulation treatment. DESIGN: Forty healthy volunteers between 25 and 40âyears of age were recruited. Menaquinone-7 (MK-7) was administrated at 90âµg for 30âdays. Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and blood coagulation factors II, VII, IX, and X activities and Protein induced by vitamin K absence or antagonist-II (PIVKA-II) were measured on days 0 and 30 after MK-7 administration. RESULTS: PT, APTT, and TT showed no significant differences on day 30 when compared with baseline. The activities of coagulation factors II, VII, IX, and X on day 30 showed no significant differences with those at baseline. PIVKA-II levels were unchanged after 30âdays of MK-7 supplementation. CONCLUSIONS: MK-7 supplementation at recommended dosage does not affect vitamin K-dependent coagulation factors' coagulation activity, and does not enhance the carboxylation of prothrombin in healthy individuals. This indicated that MK-7 administration does not alter hemostatic balance in healthy populations without anticoagulation treatment.
Asunto(s)
Factores de Coagulación Sanguínea/efectos de los fármacos , Suplementos Dietéticos/normas , Vitamina K 2/farmacología , Adulto , Antifibrinolíticos/farmacología , Antifibrinolíticos/uso terapéutico , Factores de Coagulación Sanguínea/análisis , Suplementos Dietéticos/estadística & datos numéricos , Factor IX/análisis , Factor IX/efectos de los fármacos , Factor VII/análisis , Factor VII/efectos de los fármacos , Factor X/análisis , Factor X/efectos de los fármacos , Femenino , Voluntarios Sanos/estadística & datos numéricos , Humanos , Masculino , Tiempo de Tromboplastina Parcial/métodos , Tiempo de Tromboplastina Parcial/estadística & datos numéricos , Protrombina/análisis , Protrombina/efectos de los fármacos , Tiempo de Protrombina/métodos , Tiempo de Protrombina/estadística & datos numéricos , Tiempo de Trombina/métodos , Tiempo de Trombina/estadística & datos numéricos , Vitamina K 2/uso terapéuticoRESUMEN
During warfarin management, variability in prothrombin time-based international normalized ratio (PT-INR) is caused, in part, by clinically inconsequential fluctuations in factor VII (FVII). The new factor II and X (Fiix)-prothrombin time (Fiix-PT) and Fiix-normalized ratio (Fiix-NR), unlike PT-INR, are only affected by reduced FII and FX. We assessed the incidence of thromboembolism (TE) and major bleeding (MB) in all 2667 patients on maintenance-phase warfarin managed at our anticoagulation management service during 30 months; 12 months prior to and 18 months after replacing PT-INR monitoring with Fiix-NR monitoring. Months 13 to 18 were predefined as transitional months. Using 2-segmented regression, a breakpoint in the monthly incidence of TE became evident 6 months after test replacement, that was followed by a 56% reduction in incidence (from 2.82% to 1.23% per patient-year; P = .019). Three-segmented regression did not find any significant trend in TE incidence (slope, +0.03) prior to test replacement; however, during months 13 to 18 and 19 to 30, the incidence of TE decreased gradually (slope, -0.12; R2 = 0.20; P = .007). The incidence of MB (2.79% per patient-year) did not differ. Incidence comparison during the 12-month Fiix and PT periods confirmed a statistically significant reduction (55-62%) in TE. Fiix monitoring reduced testing, dose adjustments, and normalized ratio variability and prolonged testing intervals and time in range. We conclude that ignoring FVII during Fiix-NR monitoring in real-world practice stabilizes the anticoagulant effect of warfarin and associates with a major reduction in TEs without increasing bleeding.
Asunto(s)
Anticoagulantes/uso terapéutico , Monitoreo de Drogas/métodos , Factor VII/análisis , Factor X/análisis , Hemorragia/inducido químicamente , Protrombina/análisis , Tromboembolia/prevención & control , Trombofilia/tratamiento farmacológico , Warfarina/uso terapéutico , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Anticoagulantes/farmacología , Fibrilación Atrial/complicaciones , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Islandia/epidemiología , Relación Normalizada Internacional , Análisis de Series de Tiempo Interrumpido , Quimioterapia de Mantención , Masculino , Tiempo de Protrombina , Riesgo , Tromboembolia/epidemiología , Trombofilia/sangre , Trombofilia/epidemiología , Warfarina/efectos adversos , Warfarina/farmacologíaRESUMEN
BACKGROUND/AIMS: This study aimed to provide supporting evidence for prevention and prognostic evaluation of bleeding complications in the early stage by exploring the risk and predicting factors in patients with acute-on-chronic liver failure (ACLF). MATERIALS AND METHODS: A total of 101 hospitalized patients with ACLF were retrospectively included from January 1, 2014 to December 31, 2015. The patients were divided into bleeding (n=38) and nonbleeding groups (n=63). Demographic data and laboratory tests were recorded and compared between the two groups. The incidence, risk factors, and prognosis of bleeding complications among patients with ACLF were investigated. RESULTS: A total of 38 cases (37.62%) had bleeding complications: 26 (25.74%) were spontaneous and 12 (11.88%) were postprocedural. Patients with bleeding complications had lower platelet (p=0.008), fibrinogen (p<0.001), factor V (p=0.001), and factor VII (p=0.026) levels; higher serum creatinine levels (p=0.004); and a higher proportion of cirrhosis (p=0.013). Logistic regression analysis showed that cirrhosis (odds ratio=3.251, p=0.046), fibrinogen level (odds ratio=0.352, p=0.007), and factor VII level (odds ratio=0.951, p=0.011) contributed to the development of bleeding complications. A subgroup analysis of invasive manipulation-induced bleeding complications showed lower levels of factors V (p=0.018) and VII (p=0.021) in the postprocedural bleeding group. Follow-up studies showed that the nonbleeding group had a higher survival rate than the bleeding group at day 90 (73.33% versus 51.85%, p=0.040). CONCLUSION: Liver cirrhosis, lower levels of fibrinogen, and major coagulation factor activity in patients with ACLF were associated with an elevated risk of bleeding events during hospitalization, which further impaired the 90-day survival rate.
Asunto(s)
Insuficiencia Hepática Crónica Agudizada/sangre , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/mortalidad , Virus de la Hepatitis B , Hepatitis B/sangre , Insuficiencia Hepática Crónica Agudizada/complicaciones , Insuficiencia Hepática Crónica Agudizada/virología , Adulto , Anciano , Factores de Coagulación Sanguínea/análisis , Factor VII/análisis , Femenino , Fibrinógeno/análisis , Hemorragia Gastrointestinal/virología , Hepatitis B/complicaciones , Hepatitis B/virología , Hospitalización/estadística & datos numéricos , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
INTRODUCTION: Inherited factor VII deficiency is the most common autosomal recessive inherited bleeding disorder, with an estimated incidence of one per 500 000 cases in the general population. Bleeding manifestations correlate poorly with circulating FVII levels. During pregnancy, increases in FVII levels can occur in women with mild-moderate FVII deficiencies but not in those with severe deficiency. AIM: We present five pregnant patients with FVII deficiency and describe the management during their pregnancies and peripartum periods. METHODS: Retrospective analysis of six pregnancies in five women with FVII deficiency followed during pregnancy and delivery at an academic medical centre between January 2013 and December 2019. RESULTS: Of the five patients, two had severe, one with moderate and two with mild FVII deficiency. Early postpartum haemorrhage (PPH) occurred in two patients. One of the two severe FVII-deficient patients had PPH with a laceration at delivery despite replacement therapy with recombinant factor VII. The other PPH occurred in a patient with mild FVII deficiency who delivered twins by caesarean section under general anaesthesia. Neuraxial anaesthesia was utilized in only one woman with mild deficiency whose FVII level normalized at the end of the pregnancy. CONCLUSIONS: Management of delivery for women with FVII deficiency should be addressed on a case-by-case basis at centres with expertise in rare bleeding disorders, maternal foetal medicine and obstetric anaesthesiology. These management discussions should factor the patient's bleeding history, third trimester PT, FVII level, multiple gestation and mode of delivery.
Asunto(s)
Deficiencia del Factor VII/congénito , Deficiencia del Factor VII/tratamiento farmacológico , Factor VII/análisis , Hemorragia/prevención & control , Manejo de Atención al Paciente/métodos , Hemorragia Posparto/etiología , Adulto , Trastornos de la Coagulación Sanguínea Heredados/epidemiología , Trastornos de la Coagulación Sanguínea Heredados/etnología , Cesárea/métodos , Cesárea/estadística & datos numéricos , Factor VII/uso terapéutico , Deficiencia del Factor VII/sangre , Deficiencia del Factor VII/complicaciones , Femenino , Hemorragia/etiología , Humanos , Incidencia , Periodo Periparto , Hemorragia Posparto/epidemiología , Embarazo , Complicaciones Hematológicas del Embarazo , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Factor VII deficiency is the most common of the rare coagulation deficiencies. A hemorrhagic syndrome may occur in patients with FVII deficiency below 20%, although no correlation exist between the plasma FVII activity level (FVII:C) and the bleeding risk. Therefore, the management of surgery in patients with FVII deficiency remains challenging. Laboratory monitoring of FVII:C level may be helpful but should be interpreted with caution, because the dosage of FVII:C level may vary depending on the origin of the thromboplastin used. Herein, we report the case of the management of a woman who had been fortuitously diagnosed during pregnancy with FVII deficiency due to FVII variant Padua, which have induced discrepant results between two different laboratories.
Asunto(s)
Deficiencia del Factor VII/diagnóstico , Deficiencia del Factor VII/genética , Factor VII/genética , Factor VII/metabolismo , Complicaciones Hematológicas del Embarazo/diagnóstico , Tromboplastina/metabolismo , Adulto , Sustitución de Aminoácidos , Coagulación Sanguínea/genética , Pruebas de Coagulación Sanguínea , Factor VII/análisis , Deficiencia del Factor VII/sangre , Femenino , Humanos , Hallazgos Incidentales , Recién Nacido , Mutación Missense , Embarazo , Complicaciones Hematológicas del Embarazo/genética , Tromboplastina/análisisRESUMEN
Human endothelial cells (ECs) synthesize, store, and secrete von Willebrand factor multimeric strings and coagulation factor (F) VIII. It is not currently known if ECs produce other coagulation factors for active participation in coagulation. We found that 3 different types of human ECs in primary culture produce clotting factors necessary for FX activation via the intrinsic (FVIII-FIX) and extrinsic (tissue factor [TF]-FVII) coagulation pathways, as well as prothrombin. Human dermal fibroblasts were used as comparator cells. TF, FVII, FIX, FX, and prothrombin were detected in ECs, and TF, FVII, FIX, and FX were detected in fibroblasts. In addition, FVII, FIX, FX, and prothrombin were detected by fluorescent microscopy in EC cytoplasm (associated with endoplasmic reticulum and Golgi proteins). FX activation occurred on human umbilical vein EC surfaces without the addition of external coagulation proteins, proteolytic enzymes, or phospholipids. Tumour necrosis factor, which suppresses the generation of activated protein C and increases TF, augmented FX activation. Fibroblasts also produced TF, but (in contrast to ECs) were incapable of activating FX without the exogenous addition of FX and had a marked increase in FX activation following the addition of both FX and FVII. We conclude that human ECs produce their own coagulation factors that can activate cell surface FX without the addition of exogenous proteins or phospholipids.
Asunto(s)
Coagulación Sanguínea , Factor X/metabolismo , Fibroblastos/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Línea Celular , Citoplasma/metabolismo , Factor IX/análisis , Factor IX/metabolismo , Factor VII/análisis , Factor VII/metabolismo , Factor VIII/análisis , Factor VIII/metabolismo , Fibroblastos/citología , Células Endoteliales de la Vena Umbilical Humana/citología , Humanos , Microscopía Fluorescente , Cultivo Primario de Células , Protrombina/análisis , Protrombina/metabolismo , Piel/citología , Tromboplastina/análisis , Tromboplastina/metabolismoRESUMEN
BACKGROUND: Cholesteryl ester transfer protein (CETP) plays an important role in lipoprotein metabolism. Previous studies have suggested that the CETP TaqI B1/B2 allele is associated with the risk of venous thrombosis (VT). AIM: To investigate the associations between genetically determined CETP concentrations and 22 hemostatic factors in healthy individuals, and the risk of a first VT event, in a large VT case-control study. METHODS: Analyses were performed in the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis (MEGA) case-control study. CETP unweighted/weighted genetic risk scores (GRSs) were derived from three single-nucleotide polymorphisms that were identified from a recent genome-wide association study on serum CETP concentrations. The associations between CETP GRSs and 22 hemostatic factors (procoagulant/anticoagulant and fibrinolytic factors) were assessed by linear regression from an additive model in controls (n = 2813). The associations between CETP GRSs and the risk of a first VT were assessed by logistic regression analyses in 3950 VT cases and 4765 controls. RESULTS: In the controls (median age, 49 years; 53% women), both unweighted and weighted GRSs showed that factor VII activity was negatively associated with the genetically determined CETP concentration (weighted GRS ß -3.08 IU/dL per µg/mL genetically determined CETP, 95% confidence interval -5.73 to -0.42). No association was observed with the risk of a first VT. CONCLUSIONS: Genetically determined CETP concentrations only showed a weak negative association with factor VII activity. However, this did not lead to an association with the risk of a first VT.
Asunto(s)
Proteínas de Transferencia de Ésteres de Colesterol/genética , Polimorfismo de Nucleótido Simple , Trombosis de la Vena/genética , Adolescente , Adulto , Anciano , Alelos , Proteínas Sanguíneas/análisis , Estudios de Casos y Controles , Factor VII/análisis , Femenino , Estudios de Asociación Genética , Hemostasis , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Embolia Pulmonar/sangre , Embolia Pulmonar/epidemiología , Embolia Pulmonar/genética , Riesgo , Trombosis de la Vena/sangre , Trombosis de la Vena/epidemiología , Adulto JovenRESUMEN
Canine inherited factor VII deficiency is a mild-to-moderate, inherited coagulopathy that affects several breeds of dog. We identified 2 polymorphisms near the disease-causing F7 gene mutation, one of which interfered with testing in several Beagles by causing allele dropout of the normal, wild-type allele. In the absence of an external proficiency program among veterinary genetic testing laboratories, implementation of an internal proficiency program, which requires 2 independent methods for genotyping dogs at any given locus, was further enhanced by ensuring minimally non-overlapping primer pairs between the 2 assays. After redesign of our clinical tests, all dogs were re-examined, and the correct genotypes were identified. These changes ensure higher accuracy in future testing of the F7 mutation.
Asunto(s)
Pruebas Diagnósticas de Rutina/veterinaria , Enfermedades de los Perros/diagnóstico , Deficiencia del Factor VII/veterinaria , Factor VII/genética , Pruebas Genéticas/veterinaria , Ensayos de Aptitud de Laboratorios/métodos , Polimorfismo Genético , Alelos , Animales , Secuencia de Bases , Pruebas Diagnósticas de Rutina/métodos , Perros , Factor VII/análisis , Deficiencia del Factor VII/diagnóstico , Pruebas Genéticas/métodos , GenotipoRESUMEN
Cerebral thrombosis disease is a worldwide problem, with high rates of morbidity, disability, and mortality. Magnetic resonance imaging diffusion-weighted imaging was used as an important early diagnostic method for cerebral thrombotic diseases; however, its diagnosis time is 2 h after onset. In this study, we designed EGFP-EGF1-NP-Fe3O4 for earlier diagnosis of cerebral thrombosis by taking advantage of EGFP-EGF1 fusion protein, in which EGF1 can bind with tissue factor and enhanced green fluorescent protein has previously been widely used as a fluorescent protein marker. EGFP-EGF1-NP-Fe3O4 or NP-Fe3O4 reaches the highest concentration in the infarction areas in 1 h. To evaluate the targeting ability of EGFP-EGF1-NP-Fe3O4, a fluorochrome dye, Dir, was loaded into the nanoparticle. As shown by the in vivo organ multispectral fluorescence imaging, Dir-loaded EGFP-EGF1-NP-Fe3O4 exhibited higher fluorescence than those of model rats treated with Dir-loaded NP-Fe3O4. Coronal frozen sections and transmission electron microscope further showed that EGFP-EGF1-NP-Fe3O4 was mainly accumulated in the tissue factor exposure region of brain. The data indicated that the EGFP-EGF1-NP-Fe3O4 targeted cerebral thrombosis and might be applied in the early diagnosis of intracranial thrombosis.
Asunto(s)
Encéfalo/diagnóstico por imagen , Factor VII/análisis , Proteínas Fluorescentes Verdes/análisis , Trombosis Intracraneal/diagnóstico por imagen , Nanopartículas de Magnetita/análisis , Animales , Diagnóstico Precoz , Masculino , Imagen Óptica/métodos , Dominios Proteicos , Ratas Sprague-Dawley , Proteínas Recombinantes de Fusión/análisis , Tromboplastina/análisisRESUMEN
BACKGROUND: The initial rise in INR following warfarin is attributed to rapid decline in coagulation factor VII (F7). The R353Q polymorphism in F7 accounts for approximately 1/3 of the variability in F7 activity (FVIIc). OBJECTIVE: Evaluate the role of R353Q in the initial response to warfarin. METHODS: Twenty-eight healthy, males, carrying CYP2C9*1/*1 (n = 14), CYP2C9*1/*2 (n = 4) or CYP2C9*1/*3 (n = 10) genotypes, received single 20 mg warfarin. S&R-warfarin concentrations, INR, and FVIIc were monitored periodically for 7 days. RESULTS: Baseline and maximal INR were 5.6% and 33.5% higher among carriers of the RQ (n = 12) as compared with those carrying the RR (n = 16) genotype (p = 0.032, p = 0.003, respectively). Baseline and nadir FVIIc were 21.6% and 42.0% lower among subjects carrying the RQ as compared with carriers of the RR genotype (p = 0.001, p = 0.007 respectively). In multiple regression analysis, R353Q predicted 36.6% of the variability in peak INR whereas 20.2%, 9.9%, and 5.9% were attributed to VKORC1 genetic polymorphism, cholesterol concentration, and S Warfarin concentration after 24 h, respectively. CONCLUSIONS: R353Q genetic polymorphism plays a key role in determining the initial response to warfarin. The incorporation of this genetic variant into warfarin loading algorithm should be further investigated.
Asunto(s)
Anticoagulantes/sangre , Coagulación Sanguínea/genética , Factor VII/análisis , Polimorfismo de Nucleótido Simple , Warfarina/sangre , Adulto , Anticoagulantes/administración & dosificación , Arginina/genética , Citocromo P-450 CYP2C9/genética , Monitoreo de Drogas , Genotipo , Glutamina/genética , Humanos , Relación Normalizada Internacional , Modelos Lineales , Masculino , Análisis Multivariante , Vitamina K Epóxido Reductasas/genética , Warfarina/administración & dosificación , Adulto JovenRESUMEN
RATIONALE: Congenital factor VII (FVII) deficiency is a rare coagulopathy. There are little clinical data for congenital FVII deficiency and no evidence-based medicine guidelines for treatment. PATIENT CONCERNS: A 48-year-old woman with gallbladder stones suffered from intermittent abdominal pain for 2 months that was accompanied by an abnormally prolonged prothrombin time. DIAGNOSES: The woman was diagnosed as having cholecystolithiasis with cholecystitis and congenital FVII deficiency. INTERVENTION: Preoperative evaluation confirmed the necessity of recombinant activated factor VII (rFVIIa) replacement therapy. We monitored the plasma factor VII activity (FVII:C) and coagulation function, determined the half-life of rFVIIa in the patient, and administered personalized rFVIIa replacement therapy. OUTCOMES: Laparoscopic cholecystectomy was performed successfully, and the patient recovered well without any complications. LESSONS: The clinical manifestations and severity of bleeding in patients with congenital FVII deficiency can vary widely. The history of massive bleeding and plasma FVII:C are the decisive factors when implementing a replacement therapy. The actual half-life of rFVIIa can be determined from intensive monitoring results of plasma FVII:C at the beginning of replacement therapy, which could further guide the personalization of rFVIIa replacement therapy.
Asunto(s)
Deficiencia del Factor VII/diagnóstico , Factor VIIa/uso terapéutico , Cuidados Preoperatorios/métodos , Pruebas de Coagulación Sanguínea/métodos , Factor VII/análisis , Deficiencia del Factor VII/tratamiento farmacológico , Femenino , Hemorragia/etiología , Hemorragia/prevención & control , Humanos , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéuticoRESUMEN
Cigarette smoking has been shown to be associated with changes in coagulation factors in the circulation and the subsequent thrombosis development. In this study, the impact of waterpipe smoking on the levels of fibrinogen, factor VII (FVII), and factor VIII (FVIII) was investigated. In addition, the effects of waterpipe smoking were compared to those of cigarette smoking and never smokers. A total of 80 male smokers (40 cigarette smokers and 40 waterpipe smokers) and 40 apparently healthy never smokers were recruited in the study. Both waterpipe smoking and cigarette smoking induced significant increases in the plasma levels of fibrinogen, factor VII, and factor VIII (p < 0.01). The magnitude of the increase in fibrinogen levels induced by waterpipe smoking was higher than that induced by cigarette smoking (p < 0.01), while similar increases were observed in other factors (p > 0.05). In addition, in the waterpipe group, the magnitude of the increase in fibrinogen and factor VIII was higher in the smokers with more than 3 years of use (p < 0.05). In conclusion, similar to cigarette smoking, waterpipe smoking modulates the levels of coagulation factors, suggesting its thrombotic potential.
Asunto(s)
Factor VIII/análisis , Factor VII/análisis , Fibrinógeno/análisis , Fumar en Pipa de Agua , Adolescente , Adulto , Estudios de Casos y Controles , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Anabolic androgenic steroid (AAS) abusers are considered at increased risk of cardiovascular morbidity and mortality. We hypothesized that current and former AAS abuse would induce a procoagulant shift in the haemostatic balance. METHODS: Men 18 to 50 years of age were included as current AAS abusers, former AAS abusers or controls. Morning blood samples were collected after overnight fasting. Thrombin generation (lag time, time to peak, peak height, and endogenous thrombin potential [ETP]) and coagulation factor II (prothrombin), VII and X, antithrombin, protein C, free protein S and tissue factor pathway inhibitor (TFPI) were assessed. Groups were compared by ANOVA or Kruskal-Wallis test and probabilities were corrected for multiple comparisons. Associations were evaluated using linear regression models. RESULTS: ETP was increased around 15% in current (n = 37) and former (n = 33) AAS abusers compared with controls (n = 30; p < 0.001). Prothrombin and factor X were increased ≥10% in AAS abusers and prothrombin was a predictor of ETP (p < 0.0005). Lag time and time to peak were increased 10 to 30% in current AAS abusers (p < 0.001) and associated with higher concentrations of TFPI, antithrombin, protein C and protein S (p < 0.0005; = 0.005). Multivariate linear regression, with all coagulation inhibitors as covariates, identified TFPI to be independently associated with lag time and time to peak (p < 0.0005). CONCLUSION: Thrombin generation is augmented in current and former AAS abusers, reflecting a procoagulant state, with altered concentrations of coagulation proteins. Prospective studies are needed to clarify whether these findings translate into an increased thrombotic risk in AAS abusers potentially even after cessation.
Asunto(s)
Andrógenos/efectos adversos , Coagulantes/sangre , Esteroides/efectos adversos , Trastornos Relacionados con Sustancias/sangre , Adolescente , Adulto , Coagulación Sanguínea , Pruebas de Coagulación Sanguínea , Consumidores de Drogas , Factor VII/análisis , Factor X/análisis , Humanos , Modelos Lineales , Lipoproteínas/sangre , Masculino , Persona de Mediana Edad , Proteína C/análisis , Proteína S/análisis , Protrombina/análisis , Trastornos Relacionados con Sustancias/rehabilitación , Trombina/análisis , Trombosis , Adulto JovenRESUMEN
BACKGROUND: International normalized ratio (INR) and partial thromboplastin time (PTT) are used interchangeably to diagnose acute traumatic coagulopathy but reflect disparate activation pathways. In this study, we identified injury/patient characteristics and coagulation factors that drive contact pathway, tissue factor pathway (TF), and common pathway dysfunction by examining injured patients with discordant coagulopathies. We hypothesized that patients with INR/PTT discordance reflect differing phenotypes representing contact versus tissue factor pathway perturbations and that characterization will provide targets to guide individualized resuscitation. METHODS: Plasma samples were prospectively collected from 1,262 critically injured patients at a single Level I trauma center. Standard coagulation measures and an extensive panel of procoagulant and anticoagulant factors were assayed and analyzed with demographic and outcome data. RESULTS: Fourteen percent of patients were coagulopathic on admission. Among these, 48% had abnormal INR and PTT (BOTH), 43% had isolated prolonged PTT (PTT-CONTACT), and 9% had isolated elevated INR (INR-TF). PTT-CONTACT and BOTH had lower Glasgow Coma Scale score than INR-TF (p < 0.001). INR-TF had decreased factor VII activity compared with PTT-CONTACT, whereas PTT-CONTACT had decreased factor VIII activity compared with INR-TF. All coagulopathic patients had factor V deficits, but activity was lowest in BOTH, suggesting an additive downstream effect of disordered activation pathways. Patients with PTT-CONTACT received half as much packed red blood cell and fresh frozen plasma as did the other groups (p < 0.001). Despite resuscitation, mortality was higher for coagulopathic patients; mortality was highest in BOTH and higher in PTT-CONTACT than in INR-TF (71%, 60%, 41%; p = 0.04). CONCLUSIONS: Discordant phenotypes demonstrate differential factor deficiencies consistent with dysfunction of contact versus tissue factor pathways with additive effects from common pathway dysfunction. Recognition and treatment of pathway-specific factor deficiencies driving different coagulopathic phenotypes in injured patients may individualize resuscitation and improve outcomes. LEVEL OF EVIDENCE: Prognostic/epidemiological study, level II.
Asunto(s)
Trastornos de la Coagulación Sanguínea/etiología , Heridas y Lesiones/complicaciones , Adulto , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/diagnóstico , Trastornos de la Coagulación Sanguínea/terapia , Transfusión Sanguínea/estadística & datos numéricos , Factor VII/análisis , Factor VIII/análisis , Femenino , Escala de Coma de Glasgow , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Tiempo de Tromboplastina Parcial , Resucitación , Centros Traumatológicos , Heridas y Lesiones/sangre , Adulto JovenRESUMEN
BACKGROUND: The role of factor VII (FVII) as a risk factor in myocardial infarction (MI) has been the subject of numerous studies. However, it remains uncertain whether the FVII levels are associated with development of MI. METHODS: The subjects were 4142 men and women whose activated FVII (FVIIa) and FVII coagulant (FVIIc) levels were measured in the Jichi Medical School Cohort Study. Subjects were divided into tertiles by FVIIa and FVIIc levels, and Cox's proportional hazard model was used to calculate hazard ratios (HRs) for MI. RESULTS: The multivariate-adjusted HRs (95% confidential interval [CI]) for FVIIa in men were 0.67 (0.67-1.78) in tertile 2 (T2), and 0.52 (0.17-1.60) in T3. In women, the multivariate-adjusted HRs (95% CI) were 0.18 (0.02-1.60) in T2, and 0.39 (0.07-2.20) in T3. The multivariate-adjusted HRs (95% CI) for FVIIc in men were 0.54 (0.21-1.36) in T2, and 0.20 (0.04-0.91) in T3. In women, the multivariate-adjusted HRs (95% CI) were 0.44 (0.07-2.85) in T2, and 0.35 (0.06-2.22) in T3. We used T1 as a reference for all measures. CONCLUSION: Our findings revealed a significant association between low FVIIc level and incidence of MI in men. The FVIIa and FVIIc levels were inversely related to increased MI risk, but did not reach statistical significance. Future studies are needed to confirm this association.
Asunto(s)
Factor VII/análisis , Infarto del Miocardio/sangre , Infarto del Miocardio/epidemiología , Adulto , Anciano , Femenino , Humanos , Incidencia , Japón/epidemiología , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de RiesgoRESUMEN
INTRODUCTION: A paucity of data exists on the incidence, diagnosis and treatment of bleeding in women with inherited factor VII (FVII) deficiency. AIM: Here we report results of a comprehensive analysis from two international registries of patients with inherited FVII deficiency, depicting the clinical picture of this disorder in women and describing any gender-related differences. METHODS: A comprehensive analysis of two fully compatible, international registries of patients with inherited FVII deficiency (International Registry of Factor VII deficiency, IRF7; Seven Treatment Evaluation Registry, STER) was performed. RESULTS: In our cohort (N = 449; 215 male, 234 female), the higher prevalence of mucocutaneous bleeds in females strongly predicted ensuing gynaecological bleeding (hazard ratio = 12.8, 95% CI 1.68-97.6, P = 0.014). Menorrhagia was the most prevalent type of bleeding (46.4% of patients), and was the presentation symptom in 12% of cases. Replacement therapies administered were also analysed. For surgical procedures (n = 50), a receiver operator characteristic analysis showed that the minimal first dose of rFVIIa to avoid postsurgical bleeding during the first 24 hours was 22 µg kg(-1) , and no less than two administrations. Prophylaxis was reported in 25 women with excellent or effective outcomes when performed with a total weekly rFVIIa dose of 90 µg kg(-1) (divided as three doses). CONCLUSION: Women with FVII deficiency have a bleeding disorder mainly characterized by mucocutaneous bleeds, which predicts an increased risk of ensuing gynaecological bleeding. Systematic replacement therapy or long-term prophylaxis with rFVIIa may reduce the impact of menorrhagia on the reproductive system, iron loss and may avoid unnecessary hysterectomies.
Asunto(s)
Coagulantes/uso terapéutico , Deficiencia del Factor VII/tratamiento farmacológico , Factor VIIa/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antifibrinolíticos/uso terapéutico , Niño , Preescolar , Estudios de Cohortes , Factor VII/análisis , Femenino , Hemorragia/epidemiología , Hemorragia/prevención & control , Humanos , Lactante , Masculino , Menorragia/epidemiología , Persona de Mediana Edad , Fenotipo , Modelos de Riesgos Proporcionales , Curva ROC , Proteínas Recombinantes/uso terapéutico , Sistema de Registros , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Obesity is an important venous thrombosis (VT) risk factor but the reasons for this are unclear. MATERIALS AND METHODS: In a cohort of 20,914 individuals aged 45 and older without prior VT, we calculated the relative risk (RR) of VT over 12.6years follow-up according to baseline body size measures, and studied whether associations were mediated by biomarkers of hemostasis and inflammation that are related to adiposity. RESULTS: Greater levels of all body size measures (weight, height, waist, hip circumference, calf circumference, body-mass index, waist-hip ratio, fat mass and fat-free mass) were associated with increased risk of VT, with 4th versus 1st quartile RRs of 1.5-3.0. There were no multiplicative interactions of biomarkers with obesity status. Adjustment for biomarkers associated with VT risk and body size (factors VII and VIII, von Willebrand factor, partial thromboplastin time, D-dimer, C-reactive protein and factor XI) only marginally lowered, or did not impact, the RRs associated with body size measures. CONCLUSIONS: Greater body size, by multiple measures, is a risk factor for VT. Associations were not mediated by circulating levels of studied biomarkers suggesting that body size relates to VT because of physical factors associated with blood flow, not the hypercoagulability or inflammation associated with adiposity.
Asunto(s)
Hemostasis , Inflamación/complicaciones , Obesidad/complicaciones , Trombosis de la Vena/etiología , Anciano , Biomarcadores/sangre , Tamaño Corporal , Proteína C-Reactiva/análisis , Estudios de Cohortes , Factor VII/análisis , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Estudios de Seguimiento , Humanos , Inflamación/sangre , Masculino , Persona de Mediana Edad , Obesidad/sangre , Factores de Riesgo , Trombosis de la Vena/sangre , Relación Cintura-Cadera , Factor de von Willebrand/análisisRESUMEN
OBJECTIVE: Inflammatory/hemostatic biomarkers are associated with coronary heart disease events, but relationships in asymptomatic midlife women are uncertain. We evaluated separately whether high-sensitivity C-reactive protein (hsCRP), fibrinogen, plasminogen-activator inhibitor 1, tissue plasminogen activator antigen, and circulating factor VII (factor VIIc) were associated with coronary artery calcification (CAC) in healthy midlife women. METHODS: A cross-sectional study was performed of participants from the Study of Women's Health Across the Nation. Logistic and Tobit regression was used to assess associations between log-transformed biomarkers, and CAC presence (CAC > 0) and extent. Effect modification by race/ethnicity was evaluated. RESULTS: The study included 372 women (mean age 51.3 y; 35.2% African-American). All biomarkers were positively associated with CAC presence and extent (Pâ<â0.001 for all), adjusting for Framingham risk score, site, race/ethnicity, menopause status, income, and education. Additional adjustment for body mass index explained all associations except for factor VIIc, which remained associated with CAC extent only (Pâ=â0.02). Final adjustment for insulin resistance, family history of cardiovascular disease, and cardiovascular medication use produced similar results. Associations between hsCRP, and CAC presence and extent were modified by race/ethnicity (Pâ<â0.05). Log(hsCRP) was positively associated with CAC presence (odds ratio 3.25; 95% CI, 1.53-6.90; Pâ=â0.002; per 1 log unit increase) and CAC extent (ßâ=â19.66; SEâ=â7.67; Pâ=â0.01; per 1 log unit increase) in African-Americans only. CONCLUSIONS: Inflammatory/hemostatic biomarkers were associated with CAC through obesity, except for factor VIIc. Among African-American women only, hsCRP was independently associated with CAC, suggesting that hsCRP may have a role in coronary heart disease prevention in African-American midlife women.
Asunto(s)
Negro o Afroamericano , Enfermedad de la Arteria Coronaria/sangre , Inflamación/sangre , Calcificación Vascular/sangre , Población Blanca , Salud de la Mujer , Biomarcadores , Proteína C-Reactiva/análisis , Enfermedad de la Arteria Coronaria/etnología , Estudios Transversales , Factor VII/análisis , Femenino , Fibrinógeno/análisis , Hemostasis/fisiología , Humanos , Persona de Mediana Edad , Obesidad/sangre , Inhibidor 1 de Activador Plasminogénico/sangre , Activador de Tejido Plasminógeno/sangre , Calcificación Vascular/etnologíaRESUMEN
INTRODUCTION: Production of very low-density lipoprotein (VLDL) is increased in states of metabolic syndrome, leading to hypertriglyceridemia. However, metabolic syndrome is often associated with non-alcoholic fatty liver disease, which leads to liver fibrosis and inflammation that may decrease VLDL production. In this study, we aim to determine the interactive impact on VLDL profiles from insulin resistance, impairment in liver synthetic function and inflammation. METHODS: We examined cross-sectional associations of insulin sensitivity, inflammation, and liver synthetic function with VLDL particle (VLDL-P) concentration and size among 1,850 older adults in the Cardiovascular Health Study. RESULTS: Indices for high insulin sensitivity and low liver synthetic function were associated with lower concentrations of VLDL-P. In addition, insulin resistance preferentially increased concentration of large VLDL and was associated with mean VLDL size. Indices for inflammation however demonstrated a nonlinear relationship with both VLDL-P concentration and VLDL size. When mutually adjusted, one standard deviation (SD) increment in Matsuda index and C-reactive protein (CRP) were associated with 4.9 nmol/L (-8.2 to -1.5, p=0.005) and 6.3 nmol/L (-11.0 to -1.6, p=0.009) lower VLDL-P concentration respectively. In contrast, one-SD increment in factor VII, a marker for liver synthetic function, was associated with 16.9 nmol/L (12.6-21.2, p<0.001) higher VLDL-P concentration. Furthermore, a one-SD increment in the Matsuda index was associated with 1.1 nm (-2.0 to -0.3, p=0.006) smaller mean VLDL size, whereas CRP and factor VII were not associated with VLDL size. CONCLUSION: Insulin sensitivity, inflammation and markers for liver synthetic function differentially impact VLDL-P concentration and VLDL size. These results underscore the complex effects of insulin resistance and its complications on VLDL production.