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BACKGROUND: Preoperative identification of patients with haemostasis abnormalities leading to an increased bleeding risk was based on routine haemostasis tests: prothrombin time (PT), activated prothrombin time (aPTT), and platelet count. Because of their low predictive performance, guidelines recommend replacing them with structured bleeding risk questionnaires, but none is validated in this population. OBJECTIVES: To assess the diagnostic accuracy of 3 strategies, performed at the pre-anaesthesia visit before scheduled interventions, to identify patients with haemostasis abnormalities leading to an increased bleeding risk PATIENTS AND METHODS: Multicenter study in 7 French academic hospitals, involving patients scheduled for surgical intervention, without antiplatelet/anticoagulant treatment. The 3 strategies consisted of 1-a structured screening questionnaire; 2-PT, aPTT, and platelet count ordered in selected patients; 3-systematic PT, aPTT, and platelet count. The reference standard comprised von Willebrand factor activity/antigen, factors VIII, IX, and XI, platelet-function analyser, and, when required, FII, FV, FX, and FVII and haemostasis consultation. RESULTS: Eighteen (1.2%) of 1484 patients had a haemostasis abnormality leading to an increased bleeding risk according to reference standard. In the overall cohort, sensitivity of the questionnaire-based strategy was 50% (95%CI, 26-74; specificity 87% (95%CI, 85-88); sensitivity was 0 (95%CI, 0-41) in men vs 82% (95%CI, 48- 98) in women. For selective routine tests, sensitivity was 33% (95%CI, 13-59) and specificity 97% (95% CI, 96-98). Corresponding values for systematic routine tests were 44% (95%CI, 22-69) and 93% (95%CI, 91-94). CONCLUSIONS: Sensitivity was low for all 3 strategies investigated. The structured screening questionnaire had clinically acceptable diagnostic accuracy only in women.
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Gabapentin, a structural analog of gamma-aminobutyric acid, is used to treat peripheral neuropathic pain. Here we report the first case of platelet function disorder associated with gabapentin treatment in a 44-year-old woman without a history of bleeding. She presented with mucocutaneous bleeding approximately 1 month after initiation of gabapentin and platelet function tests showed no aggregation to arachidonic acid and epinephrine, a defective response to ADP and a slightly decreased response to collagen. Gabapentin's imputability was supported by the fact that all platelet functions were normalized 6 days after drug discontinuation, with the simultaneous disappearance of bleedings.
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Plaquetas/efectos de los fármacos , Gabapentina/efectos adversos , Hemorragia/inducido químicamente , Pruebas de Función Plaquetaria/métodos , Adulto , Femenino , Gabapentina/farmacología , HumanosRESUMEN
INTRODUCTION: Severe haemophilia is a rare disease characterised by spontaneous bleeding from early childhood, which may lead to various complications, especially in joints. It is nowadays possible to avoid these complications thanks to substitutive therapies for which the issue of adherence is major. The transition from adolescence to adulthood in young people with severe haemophilia is a critical period as it is associated with a high risk of lack of adherence to healthcare, which might have serious consequences on daily activities and on quality of life. METHODS AND ANALYSIS: We present the protocol for a cross-sectional, observational, multicentric study to assess the differences between adolescents and young adults with severe haemophilia in France through the transition process, especially on adherence to healthcare. This study is based on a mixed methods design, with two complementary and consecutive phases, comparing data from a group of adolescents (aged 14-17 years) with those from a group of young adults (aged 20-29 years). The quantitative phase focuses on the determinants (medical, organisational, sociodemographic and social and psychosocial and behavioural factors) of adherence to healthcare (considered as a marker of the success of transition). The qualitative phase explores participants' views in more depth to explain and refine the results from the quantitative phase. Eligible patients are contacted by the various Haemophilia Treatment Centres participating in the French national registry FranceCoag. ETHICS AND DISSEMINATION: The study was approved by the French Ethics Committee and by the French National Agency for Medicines and Health Products Safety (number: 2016-A01034-47). Study findings will be disseminated to the scientific and medical community in peer-reviewed journals and presented at scientific meetings. Results will be popularised to be communicated via the French association for people with haemophilia to participants and to the general public. TRIAL REGISTRATION NUMBER: NCT02866526; Pre-results.
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Hemofilia A/terapia , Transición a la Atención de Adultos , Cumplimiento y Adherencia al Tratamiento/estadística & datos numéricos , Rendimiento Académico , Adolescente , Adulto , Actitud Frente a la Salud , Estudios Transversales , Relaciones Familiares , Femenino , Francia , Hemofilia A/psicología , Humanos , Masculino , Satisfacción del Paciente , Factores Protectores , Investigación Cualitativa , Calidad de Vida , Factores de Riesgo , Clase Social , Cumplimiento y Adherencia al Tratamiento/psicología , Adulto JovenRESUMEN
BACKGROUND: Tissue factor (TF), the main initiator of blood coagulation, is also a signaling protein that regulates cancer progression. TF synthesis was recently shown to be affected by tumor suppressor genes (TSGs) in tumor cell lines. We therefore studied TF gene (F3) expression and the status of genes coding for tumor protein p53 (TP53), phosphatase and tensin homolog (PTEN), and serine/threonine kinase 11 (STK11) in non-small cell lung cancer (NSCLC). Heparanase (HPSE) gene expression was also measured because this endo-beta-D-glucuronidase was recently shown to enhance TF gene expression. METHODS: TF and heparanase mRNA expression was measured by real-time PCR in 53 NSCLC tumors. Exons 5-8 of TP53 were sequenced from genomic DNA. Mutations of PTEN and STK11 were screened by multiplex ligation-dependent probe amplification. RESULTS: TF mRNA levels were significantly higher in T(3)-T(4) tumors (P = 0.04) and in stages III-IV of NSCLC (P = 0.03). Mutations of TP53, STK11, and PTEN were identified in 20 (37.7%), 21 (39%), and 20 (37.7%) of tumors, respectively. TF expression was higher in mutated TP53 (TP53(Mut)) (P = 0.02) and PTEN(Mut) (P = 0.03) samples. Moreover, TF mRNA increased from 2700 copies (no mutation) to 11 6415 when 3 TSG were mutated. Heparanase gene expression did not differ according to TF gene (F3) expression or TSG mutation. The median survival time was shorter in patients with tumor TF mRNA levels above median values (relative risk 2.2; P = 0.03, multivariate analysis) and when TP53 was mutated (relative risk 1.8; P = 0.02). CONCLUSIONS: These results provide clear evidence that combined oncogene events affecting TSG dramatically increase TF gene expression in lung tumors. Moreover, this study suggests that TF gene expression could be used as a prognostic marker in NSCLC.