Asunto(s)
Enfermedades de von Willebrand/genética , Factor de von Willebrand/genética , Adolescente , Alelos , Exones , Factor VIII/análisis , Factor VIII/uso terapéutico , Femenino , Frecuencia de los Genes , Humanos , Tiempo de Tromboplastina Parcial , Polimorfismo de Nucleótido Simple , Enfermedades de von Willebrand/diagnóstico , Enfermedades de von Willebrand/tratamiento farmacológico , Factor de von Willebrand/análisis , Factor de von Willebrand/uso terapéuticoRESUMEN
We performed a prospective, randomized, open study in 109 outpatients under chronic anticoagulation with acenocoumarine, presenting with International Normalized Ratios (INRs) > or = 6.0 and no or minor bleeding. All the patients withheld one dose of acenocoumarine; in addition, a treated group also received 1 mg oral vitamin K1. We aimed at a post-intervention INR < 6.0, with a target zone of 2.0-4.0. The INRs were lowered from a mean of 8.1 +/- 1.7 to 4.9 +/- 2.5 in the controls (P = 0.0000) and from 8.4 +/- 2.4 to 3.3 +/- 3 in the treated patients (P = 0.0000). There were no differences in the percentage of patients with post-intervention INRs < 6.0 or within the therapeutic zone. One-third of the treated patients and only 2% of the controls reached INRs < 2.0 (P = 0.0003). Oral vitamin K1 offered no advantage to the simple discontinuation of one dose of acenocoumarine. A substantial number of treated patients were consequently exposed to under-anticoagulation.
Asunto(s)
Acenocumarol/efectos adversos , Anticoagulantes/efectos adversos , Vitamina K 1/administración & dosificación , Acenocumarol/uso terapéutico , Administración Oral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Factores de Coagulación Sanguínea/efectos de los fármacos , Factores de Coagulación Sanguínea/metabolismo , Quimioterapia Combinada , Femenino , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Vitamina K 1/normasRESUMEN
BACKGROUND AND OBJECTIVES: Difficulties in identifying the coexistence of neutralizing anti-factor VIII antibodies (anti-fVIII) and lupus anticoagulant (LA) are mainly due to the interference of LA on anti-fVIII assays. Our aim was to reveal the presence of anti-fVIII using a system that is not affected by LA. DESIGN AND METHODS: We developed an enzyme-linked immunosorbent assay (ELISA) method that uses phospholipid-free recombinant factor VIII as the antigen. A monoclonal anti-fVIII was tested as a positive control, excluding non-specific binding by using two unrelated monoclonal antibodies. The ELISA was performed on hemophilic plasmas with anti-fVIII and negative LA (n=12) or without inhibitors (n=12). Two hemophilic plasmas with LA and presumably anti-fVIII were also assayed. Positive LA (n=12) and normal (n=10) plasmas were tested as negative controls. RESULTS: All (12/12) plasmas with anti-fVIII and 5/12 hemophilic plasmas without inhibitors were positive; LA and normal plasma controls were negative. INTERPRETATION AND CONCLUSIONS: Results presented here show that LA does not interfere with the anti-fVIII ELISA: However, the assay detects both neutralizing and non-neutralizing anti-fVIII antibodies, therefore a neutralizing effect must be confirmed through functional tests.