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PURPOSE: Radical cystectomy is associated with bleeding and high transfusion rates, presenting challenges in patient management. This study investigated the prophylactic use of tranexamic acid during radical cystectomy. METHODS: All consecutive patients treated with radical cystectomy at a tertiary care university center were included from a prospectively maintained database. After an institutional change in the cystectomy protocol patients received 1 g of intravenous bolus of tranexamic acid as prophylaxis. To prevent bias, propensity score matching was applied, accounting for differences in preoperative hemoglobin, neoadjuvant chemotherapy, tumor stage, and surgeon experience. Key outcomes included transfusion rates, complications, and occurrence of venous thromboembolism. RESULTS: In total, 420 patients were included in the analysis, of whom 35 received tranexamic acid. After propensity score matching, 32 patients and 32 controls were matched with regard to clinicopathologic characteristics. Tranexamic acid significantly reduced the number of patients who received transfusions compared to controls (19% [95%-Confidence interval = 8.3; 37.1] vs. 47% [29.8; 64.8]; p = 0.033). Intraoperative and postoperative transfusion rates were lower with tranexamic acid, though not statistically significant (6% [1.5; 23.2] vs. 19% [8.3; 37.1], and 16% [6.3; 33.7] vs. 38% [21.9; 56.1]; p = 0.257 and p = 0.089, respectively). The occurrence of venous thromboembolism did not differ significantly between the groups (9% [2.9; 26.7] vs. 3% [0.4; 20.9]; p = 0.606). CONCLUSION: Prophylactic tranexamic administration, using a simplified preoperative dosing regimen of 1 g as a bolus, significantly lowered the rate of blood transfusion after cystectomy. This exploratory study indicates the potential of tranexamic acid in enhancing outcomes of open radical cystectomy.
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Antifibrinolíticos , Pérdida de Sangre Quirúrgica , Transfusión Sanguínea , Cistectomía , Puntaje de Propensión , Ácido Tranexámico , Neoplasias de la Vejiga Urinaria , Humanos , Ácido Tranexámico/uso terapéutico , Ácido Tranexámico/administración & dosificación , Cistectomía/métodos , Masculino , Femenino , Transfusión Sanguínea/estadística & datos numéricos , Antifibrinolíticos/uso terapéutico , Antifibrinolíticos/administración & dosificación , Persona de Mediana Edad , Anciano , Pérdida de Sangre Quirúrgica/prevención & control , Neoplasias de la Vejiga Urinaria/cirugía , Estudios Retrospectivos , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiologíaRESUMEN
Background: The American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) have introduced an internationally shared framework for variant classification in genetic disorders. FVII deficiency is a rare inherited autosomal recessive bleeding disorder with sparse data concerning ACMG classification. Methods: To develop an approach which may improve the utility of molecular genetic test results, 129 patients with FVII deficiency were retrospectively assigned to six subgroups for exploratory analysis: F7 gene wildtype (group 1), ACMG 1 (benign variant) or ACMG 2 (likely benign variant), only (group 2), ACMG 3 (variant of uncertain significance) ± ACMG 1-2 heterozygous or not classified variant (group 3), ACMG 4 (likely pathogenic variant), or ACMG 5 (pathogenic variant) single heterozygous ± ACMG 1-3 single heterozygous (group 4), ACMG 4-5 homozygous or ≥2 ACMG 4-5 heterozygous or ≥1 ACMG 4-5 heterozygous plus either ACMG 1 c.1238G>A modifying variant homozygous or ≥2 ACMG 1-3 (group 5), FVII deficiency and another bleeding disorder (group 6). Results: Eleven of 31 patients (35.5%) in group 5 had abnormal ISTH-BS (n = 7) and/or history of substitution with recombinant factor VIIa (n = 5) versus 4 of 80 patients (5.0%, n = 1 abnormal ISTH-BS, n = 3 substitution) in groups 1 (n = 2/22), 2 (n = 1/29), 3 (n = 0/9), and 4 (n = 1/20). Four of 18 patients (22.2%) with FVII deficiency and another bleeding disorder (group 6) had an abnormal ISTH-BS (n = 2) and/or history of substitution with recombinant factor VIIa (n = 3). Conclusion: Patients with a homozygous ACMG 4-5 variant or with specific combinations of heterozygous ACMG 4-5 ± ACMG 1-3 variants exhibited a high-risk bleeding phenotype in contrast to the remaining patients without another bleeding disorder. This result may serve as a basis to develop a genotype/phenotype prediction model in future studies.
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Disseminated intravascular coagulation in sepsis is associated with microvascular thrombosis and organ dysfunction. It was expected that prothrombotic disposition such as factor V Leiden (FVL) mutation would worsen clinical outcome. Astonishingly, clinical trial and animal experimental data indicate that FVL can be associated with improved survival. This study investigated the effect of FVL on the response to endotoxin of the coagulation and fibrinolytic system in humans. Fourteen healthy male subjects without FVL and 15 healthy males with heterozygous FVL received an intravenous bolus dose of endotoxin, 2 ng/kg of body weight. Blood samples were drawn before and 1, 2, 4, 6, and 24 hours after administration of the endotoxin. Injection of endotoxin led to a more pronounced increase in soluble fibrin in patients with FVL than in controls. Patients with FVL displayed a more sustained increase in plasmin-plasmin inhibitor complex after 4, 6, and 24 hours. Patients with FVL mutation also displayed higher levels of D-dimer and fibrinogen-fibrin degradation products in plasma after 24 hours. Patients with FVL generate higher levels of soluble fibrin, which may serve as cofactor in tissue plasminogen activator-induced plasminogen activation, leading to a more sustained activation of fibrinolysis with production of more fibrinogen- and fibrin-degradation products.
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Endotoxemia/sangre , Factor V/fisiología , Fibrina/biosíntesis , Fibrinólisis/genética , Adulto , Anciano , Activación Enzimática , Factor V/genética , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Fibrinolisina/análisis , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Plasminógeno/metabolismo , Solubilidad , Factores de Tiempo , Adulto Joven , alfa 2-Antiplasmina/análisisRESUMEN
INTRODUCTION: There are no published data on the status of endogenous activated protein C (APC) in pulmonary embolism (PE), and no data on the effect of drotrecogin alfa (activated) (DAA) given in addition to therapeutic dose enoxaparin. METHODS: In this double-blind clinical trial, 47 patients with computed tomography (CT)-confirmed acute submassive PE treated with 1 mg/kg body weight of enoxaparin twice daily were randomized to groups receiving a 12-hour intravenous infusion of 6, 12, 18, or 24 µg/kg/hour of DAA or a placebo. Blood samples were drawn before starting DAA infusion, after 4, 8 and 12 hours (at the end of the infusion period), and on treatment days 2, 3, 4, 5 and 6. RESULTS: Initial endogenous plasma activated protein C (APC) levels were 0.36 ± 0.48 ng/ml (<0.10 to 1.72 ng/ml) and remained in the same range in the placebo group. APC levels in patients treated with DAA were 13.67 ± 3.57 ng/ml, 32.71 ± 8.76 ng/ml, 36.13 ± 7.60 ng/ml, and 51.79 ± 15.84 ng/ml in patients treated with 6, 12, 18, and 24 µg/kg/hour DAA, respectively. In patients with a D-dimer level >4 mg/L indicating a high level of acute fibrin formation and dissolution, DAA infusion resulted in a more rapid drop in soluble fibrin, D-dimer, and fibrinogen/fibrin degradation products (FDP) levels, compared to enoxaparin alone. There was a parallel decline of soluble fibrin, D-dimer, FDP, and plasmin-plasmin inhibitor complex (PPIC) in response to treatment with enoxaparin ± DAA, with no evidence of a systemic profibrinolytic effect of the treatment. CONCLUSIONS: In patients with acute submassive PE endogenous APC levels are low. DAA infusion enhances the inhibition of fibrin formation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00191724.
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Coagulación Sanguínea/efectos de los fármacos , Enoxaparina/uso terapéutico , Fibrinólisis/efectos de los fármacos , Fibrinolíticos/uso terapéutico , Proteína C/metabolismo , Embolia Pulmonar/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteína C/uso terapéutico , Embolia Pulmonar/sangre , Embolia Pulmonar/diagnóstico por imagen , Radiografía , Proteínas Recombinantes/uso terapéutico , Resultado del Tratamiento , Adulto JovenRESUMEN
We analyzed data for women who received fondaparinux for ≥7 days during pregnancy. The study retrospectively included women who received fondaparinux pre-, peri- and/or postpartum for ≥7 days for prophylaxis/venous thromboembolism (VTE) treatment at German specialist centers (2004-2010). Data on pregnancy, VTE risk factors, anticoagulant treatment, pregnancy outcome and adverse events were extracted from medical records. 120 women (mean age 31.5 years) were included. Among 84 women with prior pregnancies, 41.0% had ≥1 abortion. Anticoagulation was indicated for prophylaxis in 92.5% cases, including 82.5% women with an elevated VTE risk (82.8% thrombophilia, 34.2% VTE history). All women received low-molecular-weight heparin (LMWH) as first-line therapy; 3 also unfractionated heparin. Treatment changed to fondaparinux, due to heparin allergy (41.7%) or heparin-induced thrombocytopenia (10.0%). Fondaparinux was generally well tolerated. Adverse events included bleeding events (n = 5), abortion (n = 2), premature births (n = 2), stillbirth (n = 1), arrested labors (n = 2), injection site erythema (n = 4) and unspecified drug hypersensitivity (n = 6). No VTE events or increased liver enzymes occurred during treatment. In this retrospective study, fondaparinux was effective and well tolerated. Trial registration: ClinicalTrials.gov NCT01004939.
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Fondaparinux/uso terapéutico , Tromboembolia Venosa/tratamiento farmacológico , Adulto , Estudios de Cohortes , Femenino , Fondaparinux/farmacología , Humanos , Masculino , Periodo Posparto , Embarazo , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: The cobas h 232 point-of-care analyzer by Roche is the instrument successor of the Cardiac reader allowing the quantitative determination of troponin T, creatine kinase MB, myoglobin, NT-proBNP and D-dimer. METHODS: In this study 1329 patients with acute coronary syndromes, heart failure, thromboembolic or other diseases and 945 healthy donors were assessed. Comparisons versus central laboratory methods were carried out with 2379 samples from these individuals; out of these, 1591 samples gave quantitative results within the measuring range and were included in the evaluation. RESULTS: The point-of-care assays for creatine kinase MB, myoglobin, NT-proBNP and D-dimer were within a relative bias range of -5.9 to +6.9% compared to the laboratory assay. The troponin T assay showed a bias of -11.0% and after change of the calibration procedure of +1.9%. None of the five point-of-care assays had a relative difference between the new system and the precursor device that was higher than +5.0%. Within-series coefficients of variation of patient samples were found in a range from 4.8 to 14.8%. No significant interference was observed with lipemic, hemolytic and icteric blood or at different hematocrit values. CONCLUSIONS: Due to its good analytical agreement with the laboratory methods and with its precursor device, the cobas h 232 system can be reliably used to support on-site decision making for cardiovascular patients in acute and non-acute settings.
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Cardiopatías/diagnóstico , Sistemas de Atención de Punto/normas , Tromboembolia/diagnóstico , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/diagnóstico , Calibración , Forma MB de la Creatina-Quinasa/sangre , Diseño de Equipo , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Cardiopatías/sangre , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico , Humanos , Masculino , Mioglobina/sangre , Péptido Natriurético Encefálico/sangre , Variaciones Dependientes del Observador , Fragmentos de Péptidos/sangre , Valores de Referencia , Reproducibilidad de los Resultados , Tromboembolia/sangre , Troponina T/sangreRESUMEN
BACKGROUND: Expression of cellular adhesion molecules on leukocytes plays a key role in coronary artery disease (CAD). The aim of the present study was to assess whether atorvastatin therapy has an impact on the expression of cellular adhesion molecules on leukocytes in patients with normocholesterolemic CAD. PATIENTS AND METHODS: In 54 patients with CAD and atorvastatin treatment and 54 CAD patients without atorvastatin therapy, expression of CD40L, CD11a, CD11b, CD54, CD62L and CD41 on leukocytes was measured using flow cytometry. All patients were normocholesterolemic. RESULTS: Atorvastatin treatment led to a significantly lower expression of CD40L, CD11b and CD54 on monocytes (p<0.05) and neutrophils (p<0.05). Expression of CD11a was significantly lower on monocytes (p<0.05) in atorvastatin-treated patients. CONCLUSION: The present results indicate that atorvastatin apparently improves chronic inflammation and may have a beneficial effect on hemostasis by reducing the expression of cellular adhesion molecules on leukocytes.
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Moléculas de Adhesión Celular/metabolismo , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Ácidos Heptanoicos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Leucocitos/efectos de los fármacos , Pirroles/uso terapéutico , Anciano , Atorvastatina , Antígeno CD11a/metabolismo , Antígeno CD11b/metabolismo , Ligando de CD40/metabolismo , Colesterol/sangre , Enfermedad de la Arteria Coronaria/sangre , Femenino , Citometría de Flujo , Humanos , Molécula 1 de Adhesión Intercelular/metabolismo , Selectina L/metabolismo , Leucocitos/metabolismo , Masculino , Persona de Mediana Edad , Glicoproteína IIb de Membrana Plaquetaria/metabolismoRESUMEN
BACKGROUND: Treatment with HMG-CoA reductase inhibitors (statins) reduces the morbidity and mortality of coronary artery disease (CAD). In addition to their lipid-lowering actions, pleiotropic effects of statins have been demonstrated. OBJECTIVE: The aim of the present study was to assess if atorvastatin therapy has an impact on haemostasis, fibrinolysis and inflammation in normocholesterolaemic patients with CAD. METHODS: Fifty-four patients with CAD who had received atorvastatin treatment for at least 8 weeks (mean dosage 30 mg/day) and 54 patients with CAD who had not received atorvastatin therapy were selected from a larger prospective, randomized, double-blind study for inclusion in this post hoc analysis. Patients were matched by their total cholesterol levels. All patients were normocholesterolaemic. RESULTS: In the atorvastatin-treated patients significantly lower plasma levels of thrombin-antithrombin complexes (p < 0.05), plasminogen activator inhibitor-1 activity (PAI-1) [p < 0.05], soluble vascular cell adhesion molecule-1 (p < 0.05), soluble platelet selectin (p < 0.05) and high-sensitivity C-reactive protein (p < 0.05) were measured compared with patients not on atorvastatin therapy. Additionally, a strong trend towards lower soluble intercellular adhesion molecule-1 plasma levels was detected in patients treated with atorvastatin. No differences were found in tissue-type plasminogen activator antigen, plasmin-plasmin inhibitor complexes, fibrinogen, D-dimer and activated factor XII values. CONCLUSION: Atorvastatin appears to have an effect on coagulation activation, fibrinolysis and inflammation in patients with CAD. Reduction in PAI-1 and reduced thrombin formation may have an impact on cardiovascular morbidity and mortality in patients with CAD.
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Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Ácidos Heptanoicos/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Pirroles/farmacología , Anciano , Atorvastatina , Enfermedad de la Arteria Coronaria/fisiopatología , Método Doble Ciego , Femenino , Fibrinólisis/efectos de los fármacos , Hemostasis/efectos de los fármacos , Humanos , Inflamación/tratamiento farmacológico , Inflamación/etiología , Masculino , Persona de Mediana Edad , Inhibidor 1 de Activador Plasminogénico/sangre , Ensayos Clínicos Controlados Aleatorios como Asunto , Trombina/efectos de los fármacosRESUMEN
Severe dengue was perceived as one clinical disease entity until the WHO 2009 classification stratified it into severe vascular leakage, severe bleeding, and severe organ dysfunction. The objectives of this study were to investigate the potential use of severe dengue categories as endpoints for intervention research. 271 patients with severe dengue among 1734 confirmed dengue patients were followed prospectively in this hospital-based observational study in Latin America and Asia. We compared the distribution of severe dengue categories according to gender and age (below/above 15y), and determined the relative frequency and the overlap of severe dengue categories in the same patients. In a next step, we extended the analysis to candidate moderate severity categories, based on recently suggested definitions which were adapted for our purposes. Severe vascular leakage occurred in 244 (90%), severe bleeding in 39 (14%), and severe organ dysfunction in 28 (10%) of 271 severe dengue patients. A higher frequency of severe leakage was seen in children or adolescents (<15y) compared to adults. More than 80% of the severe leakage cases, and 30-50% of the cases with severe bleeding or severe organ dysfunction, were defined as severe on the basis of that feature alone. In 136 out of 213 patients with severe leakage alone, neither moderate bleeding manifestation nor hepatic involvement was recorded. On the other hand, moderate leakage manifestations were detected in 4 out of 12 cases that were classified as severe based on bleeding alone. A major proportion of severe dengue patients exhibited clinical manifestations of severe vascular leakage only, which may constitute a useful endpoint for intervention research or pathophysiology studies. Severe bleeding and severe organ manifestation were recorded less frequently and exhibited a higher degree of overlap with severe leakage. Severe bleeding without leakage may be associated with individual predisposition or the presence of comorbidities. More detailed assessments are needed to explore this hypothesis. Candidate moderate disease endpoints were investigated and need to be further validated.
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Hospitalización , Dengue Grave/clasificación , Dengue Grave/patología , Adolescente , Factores de Edad , Asia , Niño , Femenino , Hospitales , Humanos , Incidencia , Pacientes Internos , América Latina , Masculino , Estudios Prospectivos , Adulto JovenRESUMEN
A 30-year-old female experienced three miscarriages in early pregnancy. Extensive laboratory screening showed a low plasma fibrinogen level of approximately l g/l detected by PT-derived fibrinogen assay. The fibrinogen level in the immunological assay was 3 g/l. The functional Clauss assay yielded an intermediate result of 1.78 g/l. During her fourth and fifth pregnancy, the patient received fibrinogen concentrates (Haemocomplettan, CLS Behring, Marburg, Germany), starting with 4 grams of human fibrinogen, followed by 2 grams every second day until the 15(th) week of pregnancy. The further course of these pregnancies was uneventful. SDS-PAGE and immunoblotting showed doublet bands in the positions of the high-molecular weight (HMW)- and low-molecular-weight (LMW)-fibrinogen, a single LMW' fibrinogen band, plus additional bands with higher molecular weight than HMW-fibrinogen, which were also reactive with anti-human serum albumin (HSA) antiserum. These bands correspond to variant fibrinogen conjugated with albumin. Reduced SDS-PAGE and immunoblotting using polyclonal anti-fibrinopeptide A antiserum disclosed one additional Aalpha-chain band with lower molecular weight. Amplification and sequencing of exon 5 of the alpha gene indicated heterozygosity for a novel single nucleotide deletion at codon Aalpha494 (C1537delA). His494 is replaced by Pro and this is followed by 23 (LMKLPSSTLPQLEKHSQ VSSHLC) new amino acids before premature truncation after Cys517, yielding a free C-terminal cysteine, which may link with albumin. This new fibrinogen mutation, leads to a balanced array of homo- and heterodimeric fibrinogen molecules, some of which are conjugated to albumin.
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Aborto Habitual/sangre , Aborto Habitual/genética , Fibrinógenos Anormales/genética , Albúmina Sérica/metabolismo , Adulto , Secuencia de Aminoácidos , Dimerización , Femenino , Fibrinógenos Anormales/química , Fibrinógenos Anormales/metabolismo , Variación Genética , Humanos , Datos de Secuencia Molecular , Peso Molecular , Mutación Puntual , EmbarazoRESUMEN
BACKGROUND: Low antithrombin levels may compromise the anticoagulant effect of heparin and heparin-related compounds, such as fondaparinux. METHODS: We compared the anticoagulant effect of 10 concentrations of fondaparinux added to plasma samples with normal range (n = 25, antithrombin 95.4% +/- 9.2%) and low antithrombin (n = 22, antithrombin 45.5% +/- 13.2%) levels, using the Heptest coagulation assay. RESULTS: Heptest clotting time was shorter at any given fondaparinux concentration in the antithrombin-deficient samples, indicating less anticoagulant effect than in the group with normal antithrombin levels. At a high fondaparinux concentration, a saturation effect is observed with no further increase in Heptest clotting time. Addition of antithrombin concentrates results in a shift of the dose-response curve. When antithrombin concentrate was added, Heptest clotting time increased up to a fondaparinux concentration of 10 microg/mL. CONCLUSIONS: In the conventional prophylactic and therapeutic dose range, not only treatment with antithrombin concentrates but also an increase in fondaparinux dose normalizes the anticoagulant effect. A saturation effect is observed at high fondaparinux concentrations. Higher levels of antithrombin lead to an exaggerated effect of fondaparinux on Heptest.
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Anticoagulantes/farmacología , Antitrombinas/metabolismo , Polisacáridos/farmacología , Antitrombinas/química , Coagulación Sanguínea/efectos de los fármacos , Pruebas de Coagulación Sanguínea , Relación Dosis-Respuesta a Droga , Fondaparinux , Heparina/química , Humanos , Análisis de Regresión , Resultado del TratamientoRESUMEN
In patients with von Willebrand disease (VWD), replacement therapy may be indicated in the case of spontaneous bleeding, surgical interventions and injuries/trauma or as a prophylaxis of spontaneous bleeding episodes. The deficient von Willebrand factor (VWF) is replaced with or without factor VIII (FVIII). Dual VWF/FVIII concentrates can be beneficial in the case of low FVIII level, while repeated dosing may lead to very high FVIII levels, with a potential thrombogenic effect in individual VWD patients. An excessive FVIII:C increase can be limited by using a VWF product with a low level of FVIII, achieving a haemostatic adequate FVIII:C increase after 6 to 12 hours. Replacement therapy in patients with VWD shall be individualised considering VWD type, history and risk of bleeding and risk of thrombosis, as well as indication and the individually variable VWF and FVIII increase. Deviations from the dosages and minimum trough levels mentioned in guidelines or recommendations can be considered in justified cases. The objective of this review is to provide recommendations for specific constellations of replacement therapy based on the VWD-specific guidelines available in Europe, the available evidence, own experiences and the consensus of the interdisciplinary German author group.
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Factor VIII/uso terapéutico , Terapia de Reemplazo de Hormonas/métodos , Factor de von Willebrand/uso terapéutico , Combinación de Medicamentos , Factor VIII/farmacología , Humanos , Enfermedades de von Willebrand/terapia , Factor de von Willebrand/farmacologíaRESUMEN
During surgery and childbirth, patients with hereditary antithrombin (AT) deficiency are at high risk for thrombosis, and heparin prophylaxis may not be sufficiently efficacious. In these patients, exogenous AT may be used in association with heparin. A recombinant human AT (generic name: antithrombin alfa) has been developed. This multi-center study assessed the efficacy and safety of prophylactic intravenous administration of antithrombin alfa to hereditary AT deficient patients in high risk situations, including elective surgery, childbirth, or cesarean section. Antithrombin alfa was administered prior to and during the high risk period for restoration and maintenance of AT activity at 100% of normal. Heparin, low-molecular-weight heparin, and/or vitamin K antagonists were used according to standard of care. The primary efficacy endpoint was the incidence of acute deep vein thrombosis (DVT) from baseline up to day 30 post dosing as assessed by independent central review of duplex ultrasonograms and/or venograms. Safety was assessed based on adverse events (AEs) and laboratory evaluations. Five surgical and nine obstetrical hereditary AT deficiency patients received antithrombin alfa for a mean period of seven days. No clinically overt DVT occurred. Central review of ultrasonograms identified signs of acute DVT in two out of 13 evaluable patients. No antithrombin alfa-related AEs were reported. No patient developed anti-antithrombin alfa antibodies. In conclusion, this study suggests that antithrombin alfa is a safe and effective alternative to human plasma-derived AT for treating hereditary AT deficiency patients at high risk for thromboembolic events.
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Anticoagulantes/administración & dosificación , Antitrombinas/administración & dosificación , Trastornos de la Coagulación Sanguínea Heredados/tratamiento farmacológico , Trombosis de la Vena/prevención & control , Adulto , Anciano , Anticoagulantes/efectos adversos , Antitrombinas/efectos adversos , Antitrombinas/deficiencia , Antitrombinas/genética , Artroplastia de Reemplazo de Cadera/efectos adversos , Coagulación Sanguínea/efectos de los fármacos , Trastornos de la Coagulación Sanguínea Heredados/sangre , Trastornos de la Coagulación Sanguínea Heredados/complicaciones , Trastornos de la Coagulación Sanguínea Heredados/genética , Cesárea/efectos adversos , Parto Obstétrico/efectos adversos , Esquema de Medicación , Europa (Continente) , Femenino , Heparina/uso terapéutico , Humanos , Infusiones Intravenosas , Masculino , Mamoplastia/efectos adversos , Persona de Mediana Edad , Flebografía , Estudios Prospectivos , Proteínas Recombinantes/administración & dosificación , Factores de Tiempo , Resultado del Tratamiento , Ultrasonografía Doppler Dúplex , Estados Unidos , Trombosis de la Vena/sangre , Trombosis de la Vena/etiología , Trombosis de la Vena/genética , Trombosis de la Vena/patologíaRESUMEN
Point of care assays for various analytes have been established in critical care, including blood gas analysis, glucose, electrolytes, and markers for cardiac ischemia. Coagulation assays can also be adapted to the critical care environment by using whole blood as sample material and instruments optimized for point of care analysis. Available assays include the conventional coagulation assays, such as prothrombin time and activated partial thromboplastin time, fibrinogen, assays for monitoring of anticoagulant drugs, global coagulation assays based on thrombelastography and viscosimetry, platelet function assays, and D-dimer assays. The main problem in point of care coagulation diagnostics is quality control. Point of care coagulation assays help in rapidly establishing a diagnosis, clarifying causes of bleeding, and monitoring therapy. Thrombelastography and similar assays extend the scope of coagulation diagnostics by visualizing the process of clot formation and extending the observation period to provide an estimate of clot stability versus mechanical and proteolytic attack.
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Pruebas de Coagulación Sanguínea , Hemorragia/diagnóstico , Sistemas de Atención de Punto , Tiempo de Sangría , Coagulación Sanguínea/fisiología , Enfermedad Crítica , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Pruebas de Función Plaquetaria , TromboelastografíaRESUMEN
Reports have been published on blood coagulation disturbances by valproate therapy. In the present prospective trial, blood samples were drawn before valproate therapy, after 6 weeks of therapy, after more than 6 weeks and after longer than 6 months of valproate therapy from 23 children newly treated with valproate. Two children developed thrombocytopenia, and six children with initial normal von Willebrand factor showed acquired von Willebrand's disease. Fibrinogen levels dropped below the lower limit in 12 patients and subnormal factor XIII plasma levels were observed in 17% of patients. No patient developed signs of hemorrhage. Eight percent of patients developed valproate-induced thrombocytopenia. Reduction in platelets did not reach statistic significance. Thrombelastography showed a 47% incidence of altered platelet function. We found a statistically significant, positive correlation between clotting time of collagen extrinsic pathway inhibitor and, accordingly, adenosindiphosphate and valproate level. Plasmatic coagulation investigations showed a significant decrease of prothrombin time. Activated partial thromboplastin time measurements also showed significant prolongation with valproate. Activity of von Willebrand factor antigen and von Willebrand factor ristocetin cofactor significantly decreased. Factor XIII activity significantly decreased after valproate therapy for longer than 6 months (17% of children). Fibrinogen was significantly reduced. In the coagulatory system a decrease in the main antiprotease antithrombin III activity was observed. Blood coagulation disturbances are common in patients with valproate, but rarely become clinically symptomatic. Acquired von Willebrand's disease and hypofibrinogenemia may become relevant in patients with surgery or trauma. Particular attention should be paid to factor-XIII deficiency, which is especially seen with valproate therapy.
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Anticonvulsivantes/efectos adversos , Trombocitopenia/sangre , Trombocitopenia/inducido químicamente , Ácido Valproico/efectos adversos , Enfermedades de von Willebrand/sangre , Enfermedades de von Willebrand/inducido químicamente , Anticonvulsivantes/administración & dosificación , Plaquetas/metabolismo , Niño , Preescolar , Factor XIII/análisis , Femenino , Fibrinógeno/análisis , Humanos , Masculino , Estudios Prospectivos , Tromboelastografía/métodos , Ácido Valproico/administración & dosificación , Factor de von Willebrand/análisis , Factor de von Willebrand/inmunologíaRESUMEN
D-dimer is an indicator for in vivo fibrin formation, reflecting the formation of fibrin crosslinked by factor XIIIa. D-dimer assays are frequently used in emergency situations, such as diagnosis of venous thrombosis and pulmonary embolism, or disseminated intravascular coagulation. In these conditions, short sample turnaround times are essential. The PATHFAST D-dimer assay allows rapid quantitative measurement of D-dimer in plasma and whole blood. The study shows an excellent correlation between whole blood and plasma measurement of D-dimer both in the high range, as well as in the normal range. Intra-assay and inter-assay coefficients of variation (CV) were below 10%. The upper limit of normal (ULN = mean value measured in 100 samples from healthy blood donors + 2 x S.D.) was approximately 1 microg/ml FEU, using the assay-specific calibration. The maximal value measured in 20 replicates of calibrator 1 containing no D-dimer antigen was 0.00052 microg/ml FEU, and this 10-fold lower than the declared detection limit of 0.005 microg/ml FEU. In conclusion, the PATHFAST D-dimer assay is the first automated fully quantitative D-dimer assay, which can use plasma and whole blood as sample materials in parallel.
Asunto(s)
Productos de Degradación de Fibrina-Fibrinógeno/análisis , Sangre , Calibración , Humanos , Plasma , Juego de Reactivos para Diagnóstico , Reproducibilidad de los ResultadosRESUMEN
INTRODUCTION: Rapid reversal of anticoagulant effect from the use of vitamin K antagonists (VKA) is essential when acute bleeding or emergency surgery occurs. Prothrombin complex concentrates (PCCs) produce a more rapid effect with a better clinical outcome, and do not cause volume overload as compared with fresh-frozen plasma (FFP). Octaplex is a modern, double virus safeguarded PCC with balanced content of vitamin K-dependent coagulation factors, which ensures fast onset of action and efficacious treatment, i.e. rapid correction of international normalized ratio (INR). MATERIALS AND METHODS: The main purpose of this study was to demonstrate that Octaplex, when individually dosed, efficiently corrects INR to pre-determined levels in patients under oral anticoagulation who have bleeding complications or are undergoing invasive procedures. To measure the efficacy response, the INR achieved after PCC application per patient was calculated as geometric mean of three measurements within 1 h post-infusion. RESULTS: Sixty patients received a median total Octaplex dose of 41.1 (15.3-83.3) IU/kg body weight (bw). Of 56 patients evaluable in terms of efficacy, 51 (91%) showed a response as pre-defined in the protocol and in 52 (93%) the INR decreased to a value below 1.4 within one hour after dosing. The median INR declined from 2.8 (1.5-9.5) to 1.1 (1.0-1.9) within 10 min. All prothrombin complex coagulation factors recovered in parallel. Three patients had minor adverse drug reactions. One patient showed a non-symptomatic parvovirus B19 seroconversion. No thrombotic side effects were observed. CONCLUSIONS: Octaplex is efficacious and safe in immediate correction of dosage-dependent INR in patients with VKA-related deficiency of prothrombin complex coagulation factors.
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Anticoagulantes/efectos adversos , Factores de Coagulación Sanguínea/administración & dosificación , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológico , Relación Normalizada Internacional , Adulto , Anciano , Anciano de 80 o más Años , Factores de Coagulación Sanguínea/farmacología , Femenino , Hemorragia/prevención & control , Humanos , Masculino , Cuidados Preoperatorios/métodos , Resultado del Tratamiento , Vitamina K/antagonistas & inhibidoresRESUMEN
INTRODUCTION: In patients with chronic hypercholesterolemia, the CD40-CD40L dyad is upregulated, contributing to the initiation and progression of atherosclerosis. Our aim was to describe the role of postprandial lipemia and inflammatory stimulation on platelet and monocyte activation and CD40-ligand (CD40L) levels. METHODS AND RESULTS: Before and 2 h after consumption of a defined fatty meal, whole blood samples of 31 healthy subjects were incubated with endotoxin (LPS). CD40-ligand and CD62P expression on platelets, tissue-factor expression on monocytes and platelet-monocyte aggregates were measured with flow cytometry. Soluble CD40-ligand plasma levels were measured with an ELISA. After the meal, serum triglyceride levels increased from 137.6+/-60.5 mg/dl to 201.5+/-75.0 mg/dl. Expression of CD40L and CD62P on platelets and plasma levels of soluble CD40L were significantly decreased. No significant changes after the meal were observed concerning tissue factor expression on monocytes and platelet-monocyte aggregates. Addition of LPS showed no significant effect concerning CD40L or CD62P expression on platelets, whereas the amount of platelet-monocyte aggregates significantly increased under LPS stimulation after the fatty meal. CONCLUSIONS: Acute alimenatry lipemia leads to a decreased expression of CD40L on platelets and a reduced plasma level of sCD40L, suggesting an increased turnover in the CD40L system. CONDENSED ABSTRACT: Before and after a fatty meal, blood samples of 31 healthy subjects were incubated with LPS. After the meal, expression of CD40L and CD62P on platelets and plasma levels of soluble CD40L were significantly decreased. Addition of LPS showed no effect concerning CD40L or CD62P expression, whereas the amount of platelet-monocyte aggregates significantly increased under LPS stimulation after the fatty meal.
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Plaquetas/metabolismo , Antígenos CD40/biosíntesis , Ligando de CD40/metabolismo , Regulación de la Expresión Génica , Hiperlipidemias/metabolismo , Adulto , Anciano , Femenino , Humanos , Hipercolesterolemia/sangre , Inflamación , Selectina L/biosíntesis , Lipopolisacáridos/metabolismo , Masculino , Persona de Mediana Edad , Periodo Posprandial , Tromboplastina/metabolismoRESUMEN
Recombinant factor VIIa (rFVIIa) is increasingly used outside the labeled indications for treatment of life-threatening bleeding episodes after failure of the respective standard therapy. An interdisciplinary group of experts summarizes the state of knowledge of the use of rFVIIa in gastroenterology and hepatology, thrombocytopenia and -pathia, coagulation factor deficiencies, von Willebrand's disease, periinterventional bleeding without specific bleeding diathesis, drug-induced bleeding, disseminated intravascular coagulation, and neonatology. The most commonly used dose is 90 microg/kg body weight rFVIIa as bolus, if necessary followed by additional injections at intervals of 2-3 h. In factor VII deficiency lower dosages of 15-30 microg/kg body weight of rFVIIa are given every 4-6 h, whereas higher doses of 150-200 microg/kg body weight are used in neonates.
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Medicina Basada en la Evidencia , Deficiencia del Factor VII/tratamiento farmacológico , Factor VIIa/administración & dosificación , Hemorragia/tratamiento farmacológico , Adulto , Niño , Aprobación de Drogas , Deficiencia del Factor VII/sangre , Alemania , Hemorragia/sangre , Hemorragia/etiología , Humanos , Proteínas Recombinantes/administración & dosificaciónRESUMEN
D-dimer assays are efficient in the exclusion diagnostics of deep vein thrombosis (DVT) in patients without severe concomitant diseases. We have determined diagnostic sensitivity and specificity of a new point-of-care rapid assay for quantitative determination of D-dimer in heparinized whole blood in outpatients with suspected DVT. In 19 participating centers, 637 patients were included in the study, of which 77 were excluded, the majority because of inadequate documentation of analytical quality control measures. DVT was diagnosed in 223 of the remaining 560 patients by duplex ultrasound examination. The POC D-dimer assay showed a high sensitivity of 96.9% for the diagnosis of DVT and a high specificity of 60.8% at a pre-specified cutoff of 0.5 microg/ml. For Tina-quant D-dimer, sensitivity was slightly lower at 94.9%, with a specificity of 64.8%. The VIDAS D-dimer assay showed a sensitivity of 98.2%, but specificity was 40.7%. The area under the curve (AUC +/- standard error, 95% confidence interval) was 0.879 +/- 0.019 (0.845-0.909) for POC D-dimer, 0.908 +/- 0.016 (0.877-0.934) for Tina-quant D-dimer, and 0.895 +/- 0.018 (0.862-0.922) forVIDAS D-dimer. Differences were not statistically significant. The new whole blood POC D-dimer assay is a reliable tool for exclusion of DVT in symptomatic outpatients, displaying a comparable diagnostic performance as VIDAS D-dimer and Tina-quant D-dimer assays.