RESUMEN
Dense granule disorder is one of the most common platelet abnormalities, resulting from dense granule deficiency or secretion defect. This study was aimed to evaluate the clinical usefulness of the flow cytometric combination of mepacrine uptake/release assay and CD63 expression detection in the management of patients with suspected dense granule disorder. Over a period of 5 years, patients with abnormal platelet aggregation and/or reduced adenosine triphosphate (ATP) secretion suggestive of dense granule disorder were consecutively enrolled. The flow cytometric assays were systematically performed to further investigate dense granule functionality. Among the 26 included patients, 18 cases showed impaired mepacrine uptake/release and reduced CD63 expression on activated platelets, consistent with δ-storage pool deficiency (SPD). Another seven patients showed decrease in mepacrine release and CD63 expression but mepacrine uptake was normal, indicating secretion defect rather than δ-SPD. Unfortunately, ATP secretion could not be measured in 7 out of the 26 patients due to insufficient sample and/or severe thrombocytopenia. This test combination provides a rapid and effective method to detect the heterogeneous abnormalities of platelet dense granule by distinguishing between storage and release defects. This combination is particularly advantageous for severely thrombocytopenic patients and pediatric patients in which only minimal sample is required.
Asunto(s)
Plaquetas/metabolismo , Citometría de Flujo/métodos , Deficiencia de Almacenamiento del Pool Plaquetario/diagnóstico , Quinacrina/metabolismo , Tetraspanina 30/metabolismo , Adenosina Trifosfato/metabolismo , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Activación Plaquetaria , Agregación Plaquetaria , Recuento de Plaquetas , Pruebas de Función Plaquetaria/métodos , Deficiencia de Almacenamiento del Pool Plaquetario/metabolismo , Quinacrina/farmacocinética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
The ristocetin cofactor activity assay (VWF:RCo) is the reference method for assessing von Willebrand factor (VWF) activity but remains difficult to perform, and the coefficient of variation of the method is high (about 20-30%). This study evaluated and compared the performance for measuring the VWF activity of two newly commercialised assays [VWF:Ac Innovance (VWF:Ac) and VWF:RCo Acustar (VWF:RCo Acu)] with the reference VWF:RCo aggregation in 123 pathological plasma samples. The correlation and concordance between both new tests (VWF:RCo-Acu and VWF:Ac) and the reference VWF:RCo were good. The results of the VWF activity to VWF antigen ratio were also comparable whatever the method for the classification of VWF deficiency in all patients. Our results showed that both new tests could replace the "gold standard" VWF:RCo in aggregometry with several benefits: they are fully automated, easier and faster to perform, better adapted to emergency situations if necessary.
Asunto(s)
Pruebas de Coagulación Sanguínea/métodos , Enfermedades de von Willebrand/sangre , Factor de von Willebrand/análisis , Factor de von Willebrand/inmunología , Automatización , Coagulación Sanguínea , Calibración , Estudios de Casos y Controles , Colágeno/química , Ensayo de Inmunoadsorción Enzimática , Humanos , Agregación Plaquetaria , Estudios Prospectivos , Valores de Referencia , Reproducibilidad de los Resultados , Ristocetina/sangre , Sensibilidad y Especificidad , Enfermedades de von Willebrand/diagnóstico , Factor de von Willebrand/metabolismoRESUMEN
Taking in charge the delivery of pregnant women with inherited major deficiency of factor VII (FVII) is poorly reported in literature. We report here the haemorrhagic prophylaxis of delivery by recombinant activated FVII (rFVIIa) in a 27-year-old women, gravida 1, para 0, with major deficiency FVII by missense mutation (p.Arg337Cys). Her parents, first germen, presented a FVII deficiency. She has four brothers and three sisters, of which only one brother has major FVII deficiency with hemorrhagic diathesis in childhood (hematochezia). At her birth, because of dystocia, a right sterno-cleido-mastoid muscle hematoma and left clavicle fracture occurred. The FVII concentration was 0.08âU/mL. At the age of fifteen, a surgery of appendicitis was performed with substitution by FVII from plasma donors without any haemorrhagic complication. Because of anatomic specificity (bifid uterus and vagina), caesarean was planned. After reviewing of the literature, caesarean was performed at 38th week of gestation with haemorrhagic prophylaxis consisting in administration of rFVIIa (eptacog alfa) at a dose of 20âµg/kg, 30âmin before surgery, then every 3âh during 48âh. No haemorrhagic complication occurred. Thrombosis prophylaxis was ensured by enoxaparin (4000âUI a day subcutaneously started 6âh after surgery for 5âdays). Clinical examination of the newborn was normal. In future, modalities of taking in charge have to be evaluated by prospective studies involving a sufficiently numerous group of woman with FVII major deficiency, or by retrospective studies with the means of national or European registers.
Asunto(s)
Cesárea , Quimioprevención/métodos , Deficiencia del Factor VII/tratamiento farmacológico , Factor VIIa/uso terapéutico , Hemorragia Posoperatoria/prevención & control , Complicaciones Hematológicas del Embarazo/tratamiento farmacológico , Adulto , Cesárea/efectos adversos , Parto Obstétrico/efectos adversos , Deficiencia del Factor VII/sangre , Deficiencia del Factor VII/complicaciones , Deficiencia del Factor VII/genética , Femenino , Humanos , Complicaciones del Trabajo de Parto/prevención & control , Linaje , Embarazo , Complicaciones Hematológicas del Embarazo/genética , Proteínas Recombinantes/uso terapéutico , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: The aim of this study was to assess the consumption of anti-haemophilic drugs by adults and children with severe haemophilia A or B (residual activity of FVIII or FIX < or =2%) and to quantify the average direct medical costs. METHOD: A retrospective multicentre cost-of-illness study from the perspective of French national health insurance system. The costs include only the use of clotting factors. MAIN OUTCOME MEASURE: Consumption was expressed in UI/kg/year and costs in euros/kg/year. RESULTS: From January 1, 2001 to December 31, 2002, data from 81 adults and 30 children with severe haemophilia A (n = 92) or B (n = 19) and included in the "SNH" were collected and analysed. A coagulation factor inhibitor was present in 10 patients (9%). Four of them were high responders. Mean age and body weight were respectively 28 +/- 17 years and 58 +/- 24 kg. Except for one adult patient, all (99%) had outpatient treatment, 44 patients (40%) were hospitalized and treated by recombinant or/and plasma-derived FVIII or FIX or/and rFVIIa. Overall median annual consumption of anti-haemophilic drugs per patient was estimated at 1,333 UI/kg, with a median cost-of-illness of 1,156 euros/kg. Patients with severe haemophilia B consumed more than patients with severe haemophilia A, though not significantly (P = 0.096), with a median of 2,167 vs. 1,100 UI/kg/year and a median cost of 1,760 vs. 917 euros/kg/year (P = 0.13). Children consumed respectively more than adults (P = 0.008), with a median of 3,204 vs. 1,106 UI/kg/year and a median cost of 2,614 vs. 913 euros/kg/year (P = 0.012). The median cost for patients with an inhibitor was 3,291 euros/kg/year, approximately threefold higher than that of patients without an inhibitor (926 euros/kg/year) (P = 0.022). CONCLUSION: It suggests a higher consumption and cost of anti-haemophilic drugs among children when compared to adults. Haemophilia B patients did not consume significantly more than haemophilia A patients, whereas the consumption and cost for patients with or without inhibitors differed significantly.
Asunto(s)
Costo de Enfermedad , Hemofilia A/economía , Hemofilia A/terapia , Hemofilia B/economía , Hemofilia B/terapia , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Preescolar , Recolección de Datos , Costos de los Medicamentos , Economía Farmacéutica , Factor IX/economía , Factor IX/uso terapéutico , Factor VIII/economía , Factor VIII/uso terapéutico , Femenino , Francia/epidemiología , Hemofilia A/tratamiento farmacológico , Hemofilia B/tratamiento farmacológico , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/economía , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Factores SocioeconómicosRESUMEN
Factor VII (FVII) is a plasma glycoprotein that plays a key role in the initiation of blood coagulation cascade. Inherited FVII deficiency is a rare autosomal recessive disorder with a wide heterogeneous clinical pattern. The severe form may be associated with intracranial haemorrhages occurring closely to birth with a high mortality rate. In the present article, we report two novel cases of neonatal intracerebral bleeding associated with FVII activity levels below 1% of normal. FVII genotyping investigations revealed particular genotypes including the deleterious Cys135Arg mutation and a novel Ser52Stop nonsense mutation at the homozygous state. Both mutations, through different mechanisms, are expected to be inconsistent with the production of functional FVII. These putative mechanisms are discussed through a review of the literature on phenotypic and genotypic characteristics of cerebral haemorrhages in severe inherited FVII deficiency.
Asunto(s)
Hemorragia Cerebral/etiología , Deficiencia del Factor VII/genética , Factor VII/genética , Secuencia de Bases , Hemorragia Cerebral/genética , Codón sin Sentido , ADN/química , ADN/genética , Análisis Mutacional de ADN , Exones/genética , Deficiencia del Factor VII/complicaciones , Femenino , Genotipo , Homocigoto , Humanos , Recién Nacido , Mutación PuntualRESUMEN
Inherited factor VII (FVII) deficiency is a rare autosomal disorder characterized by a weak relationship between FVII activity (FVII:C) and operative bleeding risk. We report a retrospective study of 17 patients with a FVII:C below 0.1 IU/ml, in whom surgery was performed without any replacement therapy. Clinical and biological data were analysed to establish predictive criteria for bleeding tendency. We found that systematic preoperative replacement therapy may not be necessary for 'minor' surgical procedures, for patients suffering from inherited FVII deficiency, unless the clinical history includes severe haemorrhagic symptoms such as haemarthrosis, severe haematomas (even of soft tissue) or abundant epistaxis.