RESUMEN
Venous thromboembolism (VTE) is a preventable disease, yet it is one of the leading causes of death among patients with cancer. Improving risk stratification mechanisms will allow us to personalize thrombo-prophylaxis strategies. We sought to evaluate Collagen and Thrombin Activated Platelets (COAT-platelets) as well as protein C and factor VIII as biomarkers predictive of cancer-associated thrombosis in a prospective cohort of patients with cancer. Protein C was selected as a candidate based on bioinformatics prediction. Blood samples were collected before chemotherapy. All specimen processing was blinded to clinical data. Surveillance and adjudication of the main outcome of VTE was performed for up to 1 year. We used Cox proportional hazard regression to measure the association of biomarkers and incident events using SAS 9.2 for all statistical analysis. Death was modeled as a competing event. Among 241 patients followed for an average of 10.4 months, 15% died and 13% developed a VTE. COAT-platelets were not predictive of VTE. Low levels of pre-chemotherapy protein C (<118%) (HR 2.5; 95% CI 1.1-5.5) and high baseline factor VIII (>261% I) (HR 3.0; 95% CI 1.1-8.0) were predictive of VTE after adjusting for age, Khorana prediction risk, metastatic disease and D dimer. In addition, low protein C was predictive of overall mortality independent of age, metastatic disease and functional status (HR 2.8; 95% CI 1.3-6.0). Addition of these biomarkers to cancer-VTE risk prediction models may add to risk stratification and patient selection to optimize thrombo-prophylaxis.
Asunto(s)
Factor VIII/análisis , Neoplasias/complicaciones , Proteína C/análisis , Tromboembolia Venosa/etiología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Activación Plaquetaria , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Tromboembolia Venosa/sangreRESUMEN
BACKGROUND: The benefit of combined mechanical and pharmacologic methods for venous thromboembolism prevention after abdominal surgery has not been clearly established. OBJECTIVES: To compare the efficacy and safety of fondaparinux in conjunction with intermittent pneumatic compression vs. intermittent pneumatic compression alone in this context. PATIENTS AND METHODS: This was a randomized, double-blind, placebo-controlled superiority trial. Patients aged at least 40 years undergoing abdominal surgery were randomized to receive either fondaparinux 2.5 mg or placebo s.c. for 5-9 days, starting 6-8 h postoperatively. All patients received intermittent pneumatic compression. The primary efficacy outcome was venous thromboembolism up to day 10. The main safety outcomes were major bleeding and all-cause mortality. Follow-up lasted 32 days. RESULTS: Of the 1309 patients randomized, 842 (64.3%) were evaluable for efficacy. The venous thromboembolism rate was 1.7% (7/424) in the fondaparinux-treated patients and 5.3% (22/418) in the placebo-treated patients (odds ratio reduction 69.8%; 95% confidence interval 27.9-87.3; P = 0.004). Fondaparinux significantly reduced the proximal deep vein thrombosis rate from 1.7% (7/417) to 0.2% (1/424; P = 0.037). Major bleeds occurred in 1.6% (10/635) and 0.2% (1/650) of fondaparinux-treated and placebo-treated patients, respectively (P = 0.006), none being fatal or involving a critical organ. By day 32, eight patients (1.3%) receiving fondaparinux and five (0.8%) receiving placebo had died. CONCLUSIONS: In patients undergoing abdominal surgery and receiving intermittent pneumatic compression, fondaparinux 2.5 mg reduced the venous thromboembolism rate by 69.8% as compared to pneumatic compression alone, with a low bleeding risk as compared to placebo.
Asunto(s)
Abdomen/cirugía , Anticoagulantes/uso terapéutico , Aparatos de Compresión Neumática Intermitente , Polisacáridos/uso terapéutico , Procedimientos Quirúrgicos Operativos/efectos adversos , Tromboembolia/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Método Doble Ciego , Femenino , Fondaparinux , Humanos , Masculino , Persona de Mediana Edad , Placebos , Polisacáridos/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Thromboplastin reagents are used to conduct prothrombin time (PT) clotting tests to monitor oral anticoagulant therapy and screen for clotting factor deficiencies. Thromboplastins made from purified, recombinant tissue factor are generally more sensitive to changes in plasma factor (F) VII levels than are thromboplastins prepared from tissue extracts. This may be problematic as FVII's short plasma half-life can result in day-to-day fluctuation during oral anticoagulant therapy. We hypothesized that trace contamination of tissue-derived thromboplastins with FVII(a) blunts sensitivity to plasma FVII levels. METHODS: Traces of purified FVIIa were added to thromboplastin reagents prepared using recombinant human tissue factor and the effect on sensitivity to individual clotting factors was quantified in PT clotting assays. RESULTS AND CONCLUSIONS: Adding 5-100 pm FVIIa not only decreased thromboplastin sensitivity to plasma FVII, it surprisingly increased sensitivity to plasma levels of FV, FX and prothrombin. In addition, traces of FVIIa interacted with changes in the salt content and phospholipid composition of recombinant thromboplastins to further modulate their sensitivities to individual clotting factors. These results help explain how thromboplastin reagents of differing composition exhibit differing sensitivities to individual clotting factor levels. Implications of our results for monitoring oral anticoagulant therapy and other uses of the PT assay are discussed.
Asunto(s)
Factores de Coagulación Sanguínea/metabolismo , Factor VIIa/fisiología , Tiempo de Protrombina/normas , Tromboplastina/metabolismo , Anticoagulantes/farmacocinética , Monitoreo de Drogas , Factor V/metabolismo , Factor VII/metabolismo , Factor X/metabolismo , Humanos , Indicadores y Reactivos , Protrombina/metabolismoRESUMEN
BACKGROUND: Tissue factor is the active ingredient in thromboplastin reagents used to perform prothrombin time (PT) clotting tests to monitor oral anticoagulant therapy and to screen for clotting factor deficiencies. Thromboplastins are complex mixtures prepared from extracts of brain or placenta, although newer thromboplastins contain recombinant tissue factor incorporated into phospholipid vesicles. Thromboplastins can vary widely in their sensitivity to reductions in the levels of vitamin K-dependent clotting factors. A system to compensate for this, the International Sensitivity Index (ISI) and International Normalized Ratio (INR), has revolutionized the monitoring of oral anticoagulant therapy. The INR system is also sometimes used to monitor coagulopathies in patients with sepsis or liver failure, applications for which it was not originally designed and for which it has not been rigorously validated. OBJECTIVES: To better understand thromboplastin performance, we systematically investigated which properties of recombinant thromboplastins influence their sensitivities to changes in the levels of specific clotting factors. RESULTS: We now report that relative sensitivities to changes in the plasma levels of factors V, VII, X (FV, FVII, FX) and prothrombin are differentially influenced by a recombinant thromboplastin's content of phospholipid and sodium chloride. Furthermore, thromboplastins of similar ISI values may exhibit quite different sensitivities to each of these clotting factors. CONCLUSIONS: Differing sensitivities of thromboplastin reagents to individual clotting factor levels have implications for monitoring of oral anticoagulant therapy and interpreting results of the PT assay.
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Factores de Coagulación Sanguínea/metabolismo , Fosfolípidos/metabolismo , Tromboplastina/metabolismo , Adolescente , Adulto , Anticoagulantes/uso terapéutico , Coagulación Sanguínea/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ingeniería de Proteínas , Tiempo de Protrombina , Proteínas Recombinantes/químicaRESUMEN
BACKGROUND: Recombinant human soluble thrombomodulin (ART-123) is composed of the active, extracellular, domain of thrombomodulin. ART-123 binds to thrombin and this complex converts protein C into the natural anticoagulant activated protein C. This study was performed to identify an effective and safe dose of ART-123 for prevention of venous thromboembolism after elective, unilateral total hip replacement. METHODS AND RESULTS: An open-label, sequential, dose-ranging study was performed in which 312 patients received either 0.3 mg kg(-1) or 0.45 mg kg(-1) of ART-123, subcutaneously, 2-4 h after surgery (day 1). Those who received 0.3 mg kg(-1) were given a second dose of 0.3 mg kg(-1) on day 6, and the first 29 of these patients also used intermittent pneumatic compression devices. Those who received 0.45 mg kg(-1) were not given a second dose. Primary efficacy outcome was all deep vein thrombosis on mandatory bilateral venography performed on day 9 +/- 2 and symptomatic venous thromboembolism up to day 11. Primary safety outcome was major bleeding up to day 11. Among patients who did not use intermittent pneumatic compression, venous thromboembolism occurred in 3.4% of 116 evaluable patients in the 0.3 mg kg(-1) group and 0.9% of 111 patients in the 0.45 mg kg(-1) group. Major bleeding occurred in 1.4% of 139 patients in the 0.3 mg kg(-1) group and 6.3% of 144 patients in the 0.45 mg kg(-1) group. CONCLUSION: ART-123 is a highly effective antithrombotic agent that should be directly compared with current methods of prophylaxis in patients who have major orthopedic surgery.
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Artroplastia de Reemplazo de Cadera/efectos adversos , Complicaciones Posoperatorias , Proteínas Recombinantes/farmacología , Tromboembolia/prevención & control , Trombomodulina/química , Trombosis de la Vena/prevención & control , Anciano , Vendajes , Relación Dosis-Respuesta a Droga , Ensayo de Inmunoadsorción Enzimática , Femenino , Fibrinolíticos/farmacología , Hemoglobinas/metabolismo , Hemorragia , Humanos , Masculino , Persona de Mediana Edad , Flebografía , Proteína C/metabolismo , Factores de Tiempo , Resultado del TratamientoRESUMEN
Sex steroids negatively regulate B lymphopoiesis in adult mice. Paradoxically, lymphocytes arise during fetal life, when estrogen levels are high and maternal lymphopoiesis is suppressed. Here we demonstrate that embryonic B lymphopoiesis was unaffected by estrogen, but sensitive to glucocorticoids. Both fetal and adult precursors contained glucocorticoid receptor transcripts, but only adult precursors expressed estrogen receptor alpha and beta together with the androgen receptor. Fetal hematopoietic cells did not efficiently acquire functional estrogen receptors after transplantation to irradiated adult mice. Sex steroid receptors were also expressed in a stage- and developmental age-dependent fashion in human precursors. A developmental switch in responsiveness of hematopoietic cells to sex steroids may be essential for formation of the immune system.
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Linfocitos/metabolismo , Receptores de Estrógenos/metabolismo , Factores de Edad , Animales , Secuencia de Bases , Cartilla de ADN , Trasplante de Tejido Fetal , Citometría de Flujo , Humanos , Trasplante de Hígado , Ratones , Ratones Endogámicos C57BL , Técnicas de Cultivo de Órganos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Estrógenos/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Human B lineage lymphocyte precursors in chimeric nonobese diabetic/SCID mice transplanted with umbilical cord blood cells were directly compared with those present in normal bone marrow. All precursor subsets were represented and in nearly normal proportions. Cell cycle activity and population dynamics were investigated by staining for the Ki-67 nuclear Ag as well as by incorporation experiments using 5-bromo-2'-deoxyuridine. Again, this revealed that human B lymphopoiesis in chimeras parallels that in normal marrow with respect to replication and progression through the lineage. Moreover, sequencing of Ig gene rearrangement products showed that a diverse repertoire of V(H) genes was utilized by the newly formed lymphocytes but there was no evidence for somatic hypermutation. The newly formed B cells frequently acquired the CD5 Ag and had a short life span in the periphery. Thus, all molecular requirements for normal B lymphocyte formation are present in nonobese diabetic/SCID mice, but additional factors are needed for recruitment of B cells into a fully mature, long-lived pool. The model can now be exploited to learn about species restricted and conserved environmental cues for human B lymphocyte production.
Asunto(s)
Subgrupos de Linfocitos B/patología , Diabetes Mellitus Tipo 1/terapia , Hematopoyesis , Trasplante de Células Madre Hematopoyéticas , Inmunodeficiencia Combinada Grave/terapia , Animales , Antígenos de Diferenciación de Linfocitos B/biosíntesis , Antígenos de Diferenciación de Linfocitos B/genética , Médula Ósea/patología , Antígenos CD5/análisis , Ciclo Celular , Linaje de la Célula , Senescencia Celular , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/patología , Sangre Fetal/citología , Perfilación de la Expresión Génica , Reordenamiento Génico de Cadena Pesada de Linfocito B , Genes de Inmunoglobulinas , Supervivencia de Injerto , Humanos , Región Variable de Inmunoglobulina/genética , Ratones , Ratones Endogámicos NOD , Ratones SCID , Modelos Animales , Quimera por Radiación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Inmunodeficiencia Combinada Grave/sangre , Inmunodeficiencia Combinada Grave/inmunología , Inmunodeficiencia Combinada Grave/patología , Organismos Libres de Patógenos Específicos , Trasplante HeterólogoRESUMEN
BACKGROUND: With the best prophylactics now available, venous thromboembolism after total knee replacement remains substantial (25% to 27%). Recombinant nematode anticoagulant protein c2 (rNAPc2) is a potent inhibitor of factor VIIa/tissue factor complex that has the potential to reduce this risk. The present study was performed to determine an efficacious and safe dose of rNAPc2 for prevention of venous thromboembolism after elective, unilateral total knee replacement. METHODS AND RESULTS: This open-label, sequential dose-ranging study was conducted in 11 centers in Canada, Europe, and the United States. Five regimens were tested. Injections were administered subcutaneously on the day of surgery (day 1) and days 3, 5, and optionally, day 7. Primary efficacy outcome was a composite of overall deep vein thrombosis based on mandatory unilateral venography (day 7+/-2) and confirmed symptomatic venous thromboembolism recorded =48 hours after the last dose of rNAPc2. Primary safety outcome was major bleeding =72 hours after the last dose. An independent, blinded Central Adjudication Committee assessed all outcome events. Of 293 patients studied, 251 (86%) could be evaluated for primary efficacy analysis. A dosage of 3.0 microgram/kg administered within 1 hour after surgery provided the best observed results, with an overall deep vein thrombosis rate of 12.2%, a proximal deep vein thrombosis rate of 1.3%, and a major bleeding rate of 2.3%. CONCLUSIONS: A randomized, double-blind trial that compared rNAPc2 with current best prophylactics is warranted based on encouraging, first-reported clinical results for a factor VIIa/tissue factor inhibitor evaluated for thrombosis prophylaxis.
Asunto(s)
Anticoagulantes/administración & dosificación , Artroplastia de Reemplazo de Rodilla , Factor VIIa/antagonistas & inhibidores , Proteínas del Helminto/administración & dosificación , Complicaciones Posoperatorias/prevención & control , Trombosis de la Vena/prevención & control , Anciano , Artroplastia de Reemplazo de Rodilla/efectos adversos , Canadá , Relación Dosis-Respuesta a Droga , Europa (Continente) , Femenino , Proteínas del Helminto/efectos adversos , Hemorragia/inducido químicamente , Humanos , Inyecciones Subcutáneas , Modelos Logísticos , Masculino , Oportunidad Relativa , Medición de Riesgo , Tasa de Supervivencia , Tromboplastina/antagonistas & inhibidores , Estados Unidos , Trombosis de la Vena/etiologíaRESUMEN
Protein S is a vitamin K-dependent protein with anticoagulant properties. Case series have reported reduced plasma concentrations in patients with arterial thromboses, while other studies have reported increased levels in patients with coronary heart disease (CHD). The present study sought to clarify the relation between free protein S and risk of CHD. A prospective survey was conducted of 3000 men aged 50 to 61 years, free of clinical CHD at baseline. Free protein S was measured by commercial immunoassay. End-points recorded were sudden coronary death, first nonfatal and fatal myocardial infarction (MI), surgical intervention for symptomatic, angiographically demonstrated CHD, and all-causes mortality. Statistical analysis employed univariate incidence rate ratios followed by Cox proportional hazards regression. There were 168 CHD events recorded during 21,000 person-years of risk. Mean free protein S concentration was 6% higher in those who developed CHD than in the remainder, the crude hazard ratio (HR) for a one standard deviation (S.D.) increase in free protein S being 1.25 (95% CI, 1.08-1.25). Free protein S was associated with cholesterol concentration and other conventional CHD risk factors. In multivariate regression analysis, after adjustment for conventional CHD risk factors a 1 S.D. increase in free protein S was associated with a HR of 1.15 (0.98-1.35) for CHD, of borderline conventional statistical significance. This association of free protein S with risk of CHD may reflect effects of plaque-destabilising inflammatory activity on protein S levels.
Asunto(s)
Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/etiología , Proteína S/análisis , Análisis de Varianza , Estudios de Cohortes , Enfermedad Coronaria/sangre , Humanos , Inmunoensayo , Incidencia , Lípidos/sangre , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Patients undergoing hip or knee joint replacement are at risk for venous thromboembolic complications for up to twelve weeks postoperatively. We evaluated the efficacy and safety of a prolonged post-hospital regimen of enoxaparin, a low-molecular-weight heparin, in this patient population. METHODS: Following elective total hip or knee replacement, 968 patients received subcutaneous enoxaparin (30 mg twice daily) for seven to ten days, and 873 were then randomized to receive three weeks of double-blind outpatient treatment with either enoxaparin (40 mg once daily) or a placebo. The primary efficacy end point was the prevalence of objectively confirmed venous thromboembolism or symptomatic pulmonary embolism during the double-blind phase of treatment. RESULTS: Of the 873 randomized patients, 435 underwent elective total hip replacement and 438 underwent elective total knee replacement. Enoxaparin was superior to the placebo in reducing the prevalence of venous thromboembolism in patients treated with hip replacement: 8.0% (eighteen) of the 224 patients treated with enoxaparin had venous thromboembolism compared with 23.2% (forty-nine) of the 211 patients treated with the placebo (p < 0.001; odds ratio, 3.62; 95% confidence interval, 2.00 to 6.55; relative risk reduction, 65.5%). Enoxaparin had no significant benefit in the patients treated with knee replacement: thirty-eight (17.5%) of the 217 patients treated with enoxaparin had venous thromboembolism compared with forty-six (20.8%) of the 221 patients treated with the placebo (p = 0.380; odds ratio, 1.24; 95% confidence interval, 0.76 to 2.02; relative risk reduction, 15.9%). Symptomatic pulmonary embolism developed in three patients, one with a hip replacement and two with a knee replacement; all had received the placebo. There was no significant difference in the prevalence of hemorrhagic episodes or other types of toxicity between the enoxaparin and placebo-treated groups. CONCLUSIONS: Prolonging enoxaparin thromboprophylaxis following hip replacement for a total of four weeks provided therapeutic benefit, by reducing the prevalence of venous thromboembolism, without compromising safety. A similar benefit was not observed in patients treated with knee replacement.
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Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Enoxaparina/administración & dosificación , Fibrinolíticos/administración & dosificación , Complicaciones Posoperatorias/prevención & control , Tromboembolia/prevención & control , Trombosis de la Vena/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Enoxaparina/uso terapéutico , Fibrinolíticos/uso terapéutico , Humanos , Persona de Mediana Edad , Periodo Posoperatorio , Estudios ProspectivosRESUMEN
OBJECTIVE: To test the hypothesis that thrombomodulin (TM) may be a target for lupus anticoagulant (LAC) antibodies. METHODS: A recombinant soluble form of TM was produced and used as an antigen for an ELISA to detect antibodies to TM (TMAB). Sixty-one samples from 58 patients identified by the coagulation laboratory as having a LAC and 200 patients with unexplained thrombosis were evaluated along with 201 healthy controls. RESULTS: Eighteen (30%) of the 58 patients with a LAC and 20 (10%) of 200 patients with unexplained thrombosis had antibodies to TM. Similar antibodies were found in only 4 (2%) of 201 normal controls. TMAB show selectivity for TM lacking chondroitin sulfate, but do not otherwise have an immunodominant region. The IgG from 6 patients with TMAB was purified, and it bound TM in our ELISA. Three of the 6 IgG fractions inhibited protein C activation 40% to 70% compared to no inhibition in 7 healthy controls. CONCLUSION: Some patients with LAC and unexplained thrombosis have antibodies to TM that may arise in response to TM that has been altered and lost its chondroitin sulfate attachment. Antibodies to TM may be an important risk factor for inflammation and thrombosis in these patients.
Asunto(s)
Anticuerpos/inmunología , Inhibidor de Coagulación del Lupus/inmunología , Trombomodulina/inmunología , Trombosis/inmunología , Adulto , Anciano , Anticuerpos/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inhibidor de Coagulación del Lupus/sangre , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/inmunología , Trombosis/sangreRESUMEN
BACKGROUND: Compression ultrasonography has a high negative predictive value for deep vein thrombosis in symptomatic outpatients. Limited data are available on factors influencing positive predictive value. The objective of this study was to evaluate the positive predictive value of compression ultrasonography according to the anatomic site of vein noncompressibility. METHODS: We performed a prospective cohort study of 756 consecutive outpatients with suspected first-episode deep vein thrombosis. Compression ultrasonography was performed at the initial visit: results were abnormal if a noncompressible segment was identified or normal if all segments were fully compressible. Venography was performed in patients with abnormal compression ultrasonography results. Positive predictive value was determined according to the site of noncompressibility: common femoral vein only, popliteal vein only, or both sites. Venography was the reference standard for the presence of deep vein thrombosis. RESULTS: Positive predictive value was 16.7% (95% confidence interval, 0.4%-64.1%) for noncompressibility isolated to the common femoral vein compared with 91.3% (95% confidence interval, 72.0%-98.9%) for the popliteal vein only and 94.4% (95% confidence interval, 72.7%-99.9%) for both sites (P<.001). Of 15 patients with isolated noncompressibility of the common femoral vein, 8 (53%) had pelvic neoplasm or abscess compared with 2 (5%) of 42 with noncompressibility of the popliteal vein only and 6 (13%) of 47 with noncompressibility of both sites (P<.001). CONCLUSIONS: The positive predictive value of noncompressibility isolated to the common femoral vein is too low to be used alone as the diagnostic end point for giving anticoagulant therapy. Noncompressibility isolated to the common femoral vein is a diagnostic marker for pelvic disease.
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Vena Femoral/diagnóstico por imagen , Vena Poplítea/diagnóstico por imagen , Trombosis de la Vena/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Reacciones Falso Positivas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Flebografía , Valor Predictivo de las Pruebas , Estudios Prospectivos , UltrasonografíaRESUMEN
A young Native American woman presented with ischemia of the left lower limb resulting from embolic occlusion of the left common iliac artery and left femoral artery. The source of her emboli was aortic thrombus. The only underlying abnormality responsible for her hypercoagulability appeared to be hyperhomocysteinemia.
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Enfermedades de la Aorta/complicaciones , Arteriopatías Oclusivas/etiología , Embolia/etiología , Arteria Femoral/patología , Hiperhomocisteinemia/complicaciones , Arteria Ilíaca/patología , Trombosis/complicaciones , Femenino , Humanos , Isquemia/etiología , Persona de Mediana EdadAsunto(s)
Trombosis de la Vena/etiología , Anticuerpos Antifosfolípidos/fisiología , Anticoagulantes/farmacología , Anticonceptivos Orales/efectos adversos , Terapia de Reemplazo de Estrógeno/efectos adversos , Factor V/genética , Humanos , Inhibidor de Coagulación del Lupus/fisiología , Mutación Puntual/genética , Proteína C/fisiología , Deficiencia de Proteína C/complicaciones , Deficiencia de Proteína S/complicaciones , Protrombina/genética , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/tratamiento farmacológico , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/tratamiento farmacológico , Trombosis de la Vena/fisiopatologíaRESUMEN
Orgaran (danaparoid sodium injection) is a novel antithrombotic agent. Early studies suggest that this compound may be beneficial in preventing deep vein thrombosis in predisposed patients. This multicenter, randomized, assessor blinded, clinical trial compared subcutaneous danaparoid with warfarin for the prevention of deep vein thrombosis in patients undergoing hip replacement surgery. Bilateral venography was used to detect thrombi. Patients also underwent follow-up examinations 1, 2, and 3 months after discontinuation of the study to determine the after effects of treatment. Nearly 27% of patients who received warfarin and 14.6% of patients who received danaparoid developed deep vein thrombosis, a risk reduction of 46%. The absolute difference in the incidence of deep vein thrombosis was 12.3% in favor of danaparoid. The incidence of venographically documented proximal deep vein thrombosis was 1.5% for danaparoid and 4.1% for warfarin. These results demonstrate that danaparoid is more effective than warfarin in preventing deep vein thrombosis following hip replacement surgery. The preoperative administration of danaparoid does not increase surgical blood loss compared with warfarin.
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Anticoagulantes/uso terapéutico , Artroplastia de Reemplazo de Cadera , Sulfatos de Condroitina/uso terapéutico , Dermatán Sulfato/uso terapéutico , Heparitina Sulfato/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Trombosis de la Vena/prevención & control , Warfarina/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Pérdida de Sangre Quirúrgica/prevención & control , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Método Simple Ciego , Resultado del Tratamiento , Trombosis de la Vena/etiologíaRESUMEN
The PFA-100 system is a platelet function analyzer designed to measure platelet-related primary hemostasis. The instrument uses two disposable cartridges: a collagen/epinephrine (CEPI) and a collagen/ADP (CADP) cartridge. Previous experience has shown that CEPI cartridges detect qualitative platelet defects, including acetylsalicylic acid (ASA)-induced abnormalities, while CADP cartridges detect only thrombocytopathies and not ASA use. In this seven-center trial, 206 healthy subjects and 176 persons with various platelet-related defects, including 127 ASA users, were studied. The platelet function status was determined by a platelet function test panel. Comparisons were made as to how well the defects were identified by the PFA-100 system and by platelet aggregometry. The reference intervals for both cartridges, testing the 206 healthy subjects, were similar to values described in smaller studies in the literature [mean closure time (CT) 132 s for CEPI and 93 s for CADP]. The use of different lot numbers of cartridges or duplicate versus singleton testing revealed no differences. Compared with the platelet function status, the PFA-100 system had a clinical sensitivity of 94.9% and a specificity of 88.8%. For aggregometry, a sensitivity of 94.3% and a specificity of 88.3% were obtained. These values are based on all 382 specimens. A separate analysis of sensitivity by type of platelet defect, ASA use versus congenital thrombocytopathies, revealed for the PFA-100 system a 94.5% sensitivity in identifying ASA users and a 95.9% sensitivity in identifying the other defects. For aggregometry, the values were 100% for ASA users and 79.6% for congenital defects. Analysis of concordance between the PFA-100 system and aggregometry revealed no difference in clinical sensitivity and specificity between the systems (p > 0.9999). The overall agreement was 87.5%, with a Kappa index of 0.751. The two tests are thus equivalent in their ability to identify normal and abnormal platelet defects. Testing 126 subjects who took 325 mg ASA revealed that the PFA-100 system (CEPI) was able to detect 71.7% of ASA-induced defects with a positive predictive value of 97.8%. The overall clinical accuracy of the system, calculated from the area under the ROC curve, was 0.977. The data suggest that the PFA-100 system is highly accurate in discriminating normal from abnormal platelet function. The ease of operation of the instrument makes it a useful tool to use in screening patients for platelet-related hemostasis defects.
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Trastornos de las Plaquetas Sanguíneas/sangre , Pruebas de Función Plaquetaria/instrumentación , Adolescente , Adulto , Anciano , Aspirina/farmacología , Tiempo de Sangría , Trastornos de las Plaquetas Sanguíneas/diagnóstico , Plaquetas/efectos de los fármacos , Diseño de Equipo , Femenino , Hemostasis/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Agregación Plaquetaria/efectos de los fármacos , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Trombastenia/sangre , Trombastenia/diagnóstico , Enfermedades de von Willebrand/sangre , Enfermedades de von Willebrand/diagnósticoRESUMEN
BACKGROUND: Ultrasonography using vein compression accurately detects proximal deep venous thrombosis in symptomatic outpatients. Repeated testing is required for patients with normal results at presentation, but the optimal management of such patients is uncertain. OBJECTIVE: To test the safety of withholding anticoagulation in outpatients suspected of having first-episode deep venous thrombosis who have normal results on simplified compression ultrasonography at presentation and on a single repeated test done 5 to 7 days later. DESIGN: Prospective cohort study. SETTING: Noninvasive vascular laboratories at a university teaching hospital and a Veterans Administration medical center. PATIENTS: 405 consecutive outpatients suspected of having first-episode deep venous thrombosis. INTERVENTION: Ultrasonography was performed at presentation. The common femoral and popliteal veins were assessed for compressibility. If the result was normal, anti-coagulation was withheld and testing was repeated 5 to 7 days later. Anticoagulation was withheld from all patients whose results remained normal according to compression ultrasonography, regardless of their symptoms. The safety of this approach was tested by follow-up lasting 3 months. MEASUREMENTS: Objective testing was done during follow-up in all patients with symptoms or signs of venous thromboembolism. The outcome measure was symptomatic venous thrombosis or pulmonary embolism during follow-up, confirmed by objective testing. RESULTS: Ultrasonography had normal results in 335 patients (83%) and abnormal results in 70 (17%). None of the patients with normal results died of pulmonary embolism. Venous thromboembolism occurred during follow-up in 2 patients with normal ultrasonographic results (0.6% [95% CI, 0.07% to 2.14%]) and in 4 patients with abnormal results (5.7% [CI, 1.58% to 13.99%]) (P = 0.009). CONCLUSIONS: It is safe to withhold anticoagulation in outpatients suspected of having first-episode deep venous thrombosis if results of simplified compression ultrasonography are normal at presentation and on a single repeated test done 5 to 7 days later.
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Tromboflebitis/diagnóstico por imagen , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Protocolos Clínicos , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados , Tromboflebitis/tratamiento farmacológico , Ultrasonografía/métodosRESUMEN
We have examined factor VIIa levels in consecutive consenting patients undergoing coronary angiography (n = 702) to determine if levels are related to the presence of coronary arterial narrowing and to the degree and extent of that narrowing. Both men and women with clinically defined coronary artery disease (> or = 50% stenosis in at least 1 vessel) had factor VIIa levels that were similar to men and women with less stenosis or normal coronary arteries.