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1.
HIV Med ; 21(1): 30-42, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31589807

RESUMEN

OBJECTIVES: The aim of the study was to examine baseline neurocognitive impairment (NCI) prevalence and factors associated with NCI among patients enrolled in the Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study. METHODS: The NAMACO study is an ongoing, prospective, longitudinal, multicentre and multilingual (German, French and Italian) study within the Swiss HIV Cohort Study. Between 1 May 2013 and 30 November 2016, 981 patients ≥ 45 years old were enrolled in the study. All underwent standardized neuropsychological (NP) assessment by neuropsychologists. NCI was diagnosed using Frascati criteria and classified as HIV-associated or as related to other factors. Dichotomized analysis (NCI versus no NCI) and continuous analyses (based on NP test z-score means) were performed. RESULTS: Most patients (942; 96.2%) had viral loads < 50 HIV-1 RNA copies/mL. NCI was identified in 390 patients (39.8%): 263 patients (26.8%) had HIV-associated NCI [249 patients (25.4%) had asymptomatic neurocognitive impairment (ANI)] and 127 patients (13%) had NCI attributable to other factors, mainly psychiatric disorders. There was good correlation between dichotomized and continuous analyses, with NCI associated with older age, non-Caucasian ethnicity, shorter duration of education, unemployment and longer antiretroviral therapy duration. CONCLUSIONS: In this large sample of aging people living with HIV with well-controlled infection in Switzerland, baseline HIV-associated NCI prevalence, as diagnosed after formal NP assessment, was 26.8%, with most cases being ANI. The NAMACO study data will enable longitudinal analyses within this population to examine factors affecting NCI development and course.


Asunto(s)
Infecciones por VIH/epidemiología , VIH/fisiología , Trastornos Neurocognitivos/epidemiología , ARN Viral/genética , Factores de Edad , Comorbilidad , Femenino , Infecciones por VIH/psicología , Infecciones por VIH/virología , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Trastornos Neurocognitivos/etiología , Pruebas Neuropsicológicas , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Suiza/epidemiología , Carga Viral
2.
Thromb J ; 18: 17, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32922211

RESUMEN

Coronavirus disease 2019 (COVID-19) is associated with extreme inflammatory response, disordered hemostasis and high thrombotic risk. A high incidence of thromboembolic events has been reported despite thromboprophylaxis, raising the question of a more effective anticoagulation. First-line hemostasis tests such as activated partial thromboplastin time, prothrombin time, fibrinogen and D-dimers are proposed for assessing thrombotic risk and monitoring hemostasis, but are vulnerable to many drawbacks affecting their reliability and clinical relevance. Specialized hemostasis-related tests (soluble fibrin complexes, tests assessing fibrinolytic capacity, viscoelastic tests, thrombin generation) may have an interest to assess the thrombotic risk associated with COVID-19. Another challenge for the hemostasis laboratory is the monitoring of heparin treatment, especially unfractionated heparin in the setting of an extreme inflammatory response. This review aimed at evaluating the role of hemostasis tests in the management of COVID-19 and discussing their main limitations.

3.
HIV Med ; 2018 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-29932298

RESUMEN

OBJECTIVES: Dolutegravir (DTG) is a highly effective integrase inhibitor with a strong genetic resistance barrier and a potential role in simplified HIV maintenance treatment. We assessed the feasibility of DTG maintenance monotherapy and measured HIV reservoirs on DTG monotherapy. METHODS: An interventional, open-label, single-arm study including eight virologically suppressed HIV-1-infected patients switched to DTG 50 mg once daily for 24 weeks was performed. HIV-1 RNA levels in plasma and cerebrospinal and seminal fluids were measured at baseline and week 24, as well as HIV-1 DNA in peripheral cells and DTG concentrations in these compartments. RESULTS: HIV-1 RNA remained undetectable in all samples of blood, cerebrospinal fluid and sperm throughout the 24 weeks, except for one cerebrospinal fluid sample with a value of 28 HIV-1 RNA copies/mL at week 24. One patient discontinued the study because of a neurological side effect. There was no change in the mean HIV-1 DNA level between baseline and week 24. Plasma and cerebrospinal fluid DTG concentrations reached therapeutic levels in all patients in these two compartments. CONCLUSIONS: In this small sample of carefully selected patients, HIV-1 reservoirs were well controlled on DTG monotherapy over a period of 24 weeks. Viral suppression was also maintained throughout follow-up.

4.
Transpl Infect Dis ; 20(4): e12898, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29668068

RESUMEN

BACKGROUND: There is lack of recent multicenter epidemiological data on invasive aspergillosis (IA) among solid organ transplant recipient (SOTr) in the mold-acting antifungal era. We describe the epidemiology and outcomes of IA in a contemporary cohort of SOTr using the Swiss Transplant Cohort Study. METHODS: All consecutive SOTr with proven or probable IA between 01.05.2008 and 31.12.2014 were included. A case-control study to identify IA predictors was performed: 1-case was matched with 3-controls based on SOT type, transplant center, and time post-SOT. RESULTS: Among 2868 SOTr, 70 (2.4%) patients were diagnosed with proven (N: 30/70, 42.9%) or probable (N: 40/70, 57.1%) IA. The incidence of IA was 8.3%, 7.1%, 2.6%, 1.3%, and 1.2% in lung, heart, combined, kidney, and liver transplant recipients, respectively, Galactomannan immunoassay was positive in 1/3 of patients tested. Only 33/63 (52.4%) of patients presented with typical pulmonary radiographic findings. Predictors of IA included: renal insufficiency, re-operation, and bacterial and viral infections. 12-week mortality was higher in liver (85.7%, 6/7) compared to other (15.9%, 10/63; P < .001) SOTr. CONCLUSIONS: Invasive aspergillosis remains a rare complication post-SOT, with atypical radiographic presentations and low positivity rates of biomarkers posing significant diagnostic challenges. Although overall mortality has decreased in SOTr, it remains high in liver SOTr.


Asunto(s)
Aspergillus/aislamiento & purificación , Terapia de Inmunosupresión/efectos adversos , Aspergilosis Pulmonar Invasiva/epidemiología , Trasplante de Órganos/efectos adversos , Adolescente , Adulto , Anciano , Biomarcadores/análisis , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Rechazo de Injerto/prevención & control , Humanos , Incidencia , Aspergilosis Pulmonar Invasiva/diagnóstico , Aspergilosis Pulmonar Invasiva/microbiología , Pulmón/diagnóstico por imagen , Pulmón/microbiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Radiografía , Factores de Riesgo , Suiza/epidemiología , Receptores de Trasplantes , Adulto Joven
5.
Am J Transplant ; 16(11): 3220-3234, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27105907

RESUMEN

The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study 112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six- and 12-week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio [HR]: 2.29; p-value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p-value = 0.017) were independent predictors for 6-week all-cause mortality, whereas the initial use of a voriconazole-based regimen showed a protective effect (HR: 0.34; p-value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy.


Asunto(s)
Rechazo de Injerto/mortalidad , Aspergilosis Pulmonar Invasiva/mortalidad , Fallo Renal Crónico/complicaciones , Trasplante de Riñón/mortalidad , Complicaciones Posoperatorias/mortalidad , Aspergillus , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Supervivencia de Injerto , Humanos , Agencias Internacionales , Aspergilosis Pulmonar Invasiva/etiología , Aspergilosis Pulmonar Invasiva/patología , Fallo Renal Crónico/cirugía , Pruebas de Función Renal , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Receptores de Trasplantes
6.
Am J Transplant ; 16(7): 2148-57, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26813515

RESUMEN

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case-control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09-90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08-10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04-339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63-456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group.


Asunto(s)
Funcionamiento Retardado del Injerto/etiología , Rechazo de Injerto/etiología , Aspergilosis Pulmonar Invasiva/etiología , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Estudios de Casos y Controles , Funcionamiento Retardado del Injerto/patología , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/patología , Supervivencia de Injerto , Humanos , Aspergilosis Pulmonar Invasiva/patología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Receptores de Trasplantes
7.
HIV Med ; 17(4): 280-8, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26268702

RESUMEN

OBJECTIVES: The aim of this study was to quantify loss to follow-up (LTFU) in HIV care after delivery and to identify risk factors for LTFU, and implications for HIV disease progression and subsequent pregnancies. METHODS: We used data on pregnancies within the Swiss HIV Cohort Study from 1996 to 2011. A delayed clinical visit was defined as > 180 days and LTFU as no visit for > 365 days after delivery. Logistic regression analysis was used to identify risk factors for LTFU. RESULTS: A total of 695 pregnancies in 580 women were included in the study, of which 115 (17%) were subsequent pregnancies. Median maternal age was 32 years (IQR 28-36 years) and 104 (15%) women reported any history of injecting drug use (IDU). Overall, 233 of 695 (34%) women had a delayed visit in the year after delivery and 84 (12%) women were lost to follow-up. Being lost to follow-up was significantly associated with a history of IDU [adjusted odds ratio (aOR) 2.79; 95% confidence interval (CI) 1.32-5.88; P = 0.007] and not achieving an undetectable HIV viral load (VL) at delivery (aOR 2.42; 95% CI 1.21-4.85; P = 0.017) after adjusting for maternal age, ethnicity and being on antiretroviral therapy (ART) at conception. Forty-three of 84 (55%) women returned to care after LTFU. Half of them (20 of 41) with available CD4 had a CD4 count < 350 cells/µL and 15% (six of 41) a CD4 count < 200 cells/µL at their return. CONCLUSIONS: A history of IDU and detectable HIV VL at delivery were associated with LTFU. Effective strategies are warranted to retain women in care beyond pregnancy and to avoid CD4 cell count decline. ART continuation should be advised especially if a subsequent pregnancy is planned.


Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Trastornos Relacionados con Sustancias/epidemiología , Adulto , Estudios de Cohortes , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , Humanos , Perdida de Seguimiento , Atención Posnatal/estadística & datos numéricos , Embarazo , Análisis de Regresión , Factores de Riesgo , Suiza/epidemiología , Carga Viral , Adulto Joven
8.
Clin Infect Dis ; 61(4): 619-22, 2015 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-25977268

RESUMEN

Donor PTX3 polymorphisms were shown to influence the risk of invasive aspergillosis among hematopoietic stem cell transplant recipients. Here, we show that PTX3 polymorphisms are independent risk factors for invasive mold infections among 1101 solid organ transplant recipients, thereby strengthening their role in mold infection pathogenesis and patients' risk stratification.


Asunto(s)
Proteína C-Reactiva/genética , Hongos/aislamiento & purificación , Huésped Inmunocomprometido , Micosis/genética , Micosis/inmunología , Trasplante de Órganos/efectos adversos , Polimorfismo Genético , Componente Amiloide P Sérico/genética , Femenino , Humanos , Masculino , Estudios Prospectivos
9.
Lupus ; 24(11): 1161-8, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25862730

RESUMEN

OBJECTIVES: Health-related quality of life (HRQoL) has not been fully explored in antiphospholipid syndrome (APS); therefore, we compared HRQoL between APS patients and the general population and assessed the impact of thromboembolic history. METHODS: HRQoL was measured in a multicentre cohort study by the Medical Outcomes Study Short-Form 36 (MOS-SF-36) questionnaire. HRQoL scores were compared to the French general population norms. Factors significantly associated with an impaired HRQoL were identified. RESULTS: A total of 115 patients with aPL and/or systemic lupus erythematosus (SLE) were included (mean age 42.7 ± 14.1 years old, 86 women). In 53 patients APS was diagnosed. Compared to general population norms, patients with APS had an impaired HRQoL. SLE-associated APS patients had the worst HRQoL scores (physical component summary (PCS)=40.8 ± 10.6; mental component summary (MCS)=40.6 ± 16.5) in comparison with SLE or aPL patients without thromboembolic history. In APS patients, history of arterial thrombosis significantly impaired HRQoL (PCS score: 42.2 ± 9.4 vs 49.2 ± 8.5; MCS score: 33.9 ± 13.7 vs 44.6 ± 10.3). CONCLUSION: Compared to the general population, APS patients experienced a lower HRQoL. In these patients, a history of arterial thrombosis significantly impaired HRQoL. Therefore, measurements of HRQoL should be included in APS patient management to assess the burden of the disease from a patient's perspective and to provide patients with the support they need.


Asunto(s)
Síndrome Antifosfolípido/fisiopatología , Adulto , Síndrome Antifosfolípido/psicología , Estudios de Cohortes , Femenino , Estado de Salud , Humanos , Lupus Eritematoso Sistémico/fisiopatología , Lupus Eritematoso Sistémico/psicología , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Calidad de Vida , Factores de Riesgo , Encuestas y Cuestionarios , Trombosis/fisiopatología
10.
Rev Med Suisse ; 9(372): 315-8, 320, 2013 Feb 06.
Artículo en Francés | MEDLINE | ID: mdl-23469399

RESUMEN

Polycythaemia vera, essential thrombocythemia and primary myelofibrosis are stem cell-derived clonal haemopathies classified in the group of myeloproliferative neoplasms. Their clinical course may be complicated by both arterial and venous (sometimes in unusual sites) thrombotic events. Although general risk factors contribute to the prevalence of thrombotic events in this population, some other risk factors are specifically associated with the myeloproliferative neoplasms. The treatment options are aspirin, anticoagulation, cytoreduction and phlebotomies.


Asunto(s)
Neoplasias de la Médula Ósea/complicaciones , Medicina General , Trastornos Mieloproliferativos/complicaciones , Trombosis/etiología , Humanos , Factores de Riesgo , Trombosis/epidemiología
11.
Adv Clin Chem ; 114: 151-223, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37268332

RESUMEN

D-dimer containing species are soluble fibrin degradation products derived from plasmin-mediated degradation of cross-linked fibrin, i.e., 'D-dimer'. D-dimer can hence be considered a biomarker of in vivo activation of both coagulation and fibrinolysis, the leading clinical application in daily practice of which is ruling out venous thromboembolism (VTE). D-dimer has been further evaluated for assessing the risk of VTE recurrence and helping define optimal duration of anticoagulation treatment in VTE, for diagnosing disseminated intravascular coagulation (DIC), and for screening those at enhanced risk of VTE. D-dimer assays should however be performed as intended by regulatory agencies, as their use outside these indications might make them a laboratory-developed test (LDT). This narrative review is aimed at: (1) reviewing the definition of D-dimer, (2) discussing preanalytical variables affecting D-dimer measurement, (3) reviewing and comparing the assays performance and some postanalytical variables (e.g., different units and age-adjusted cutoffs), and (4) discussing the interest of D-dimer measurement across different clinical settings, including pregnancy, cancer, and coronavirus disease 2019 (COVID-19).


Asunto(s)
COVID-19 , Coagulación Intravascular Diseminada , Tromboembolia Venosa , Embarazo , Femenino , Humanos , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Productos de Degradación de Fibrina-Fibrinógeno/uso terapéutico , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamiento farmacológico , COVID-19/diagnóstico , Coagulación Intravascular Diseminada/diagnóstico , Pruebas de Coagulación Sanguínea
12.
Circulation ; 124(2): 215-24, 2011 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-21690492

RESUMEN

BACKGROUND: Heart valve disease (HVD) is frequent in patients with systemic lupus erythematosus (SLE), and the role of antiphospholipid antibodies (aPL) is controversial. Thus, our objective was to estimate the risk of HVD, including Libman-Sacks endocarditis, associated with aPL in patients with SLE. METHODS AND RESULTS: Studies were selected if they investigated the association between aPL and HVD in SLE patients and if aPL-negative patients were included for comparison. Data sources were MEDLINE, Embase, Cochrane Library, hand search, contact with investigators, and reference lists of studies, without language restrictions. Data on study and patient characteristics, risk estimates, and study quality were independently extracted by 2 investigators. Pooled effect estimates were obtained by using the DerSimonian-Laird method. Of 234 identified abstracts, 23 primary studies (15 cross-sectional, 7 cohort, 1 case-control) met inclusion criteria, including 1656 SLE patients and 508 cases of HVD. Compared with SLE patients without aPL (n=988), the overall pooled odds ratios for HVD and Libman-Sacks endocarditis in aPL-positive patients (n=668) were 3.13 (95% confidence interval, 2.31 to 4.24) and 3.51 (95% confidence interval, 1.93 to 6.38), respectively. The risk of HVD depending on aPL subtypes was the highest for lupus anticoagulant at 5.88 (95% confidence interval, 2.92 to 11.84) and IgG anticardiolipin antibodies at 5.63 (95% confidence interval, 3.53 to 8.97). CONCLUSIONS: Overall, the presence of aPL in SLE patients is significantly associated with an increased risk for HVD including Libman-Sacks endocarditis. The risk conferred by IgG anticardiolipin antibodies is as strong as by lupus anticoagulant. Systematic echocardiographic examinations in SLE patients with aPL should be performed.


Asunto(s)
Anticuerpos Anticardiolipina/sangre , Enfermedades de las Válvulas Cardíacas/sangre , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Inmunoglobulina G/sangre , Inhibidor de Coagulación del Lupus/sangre , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/diagnóstico por imagen , Estudios de Casos y Controles , Estudios de Cohortes , Estudios Transversales , Ecocardiografía/métodos , Endocarditis/sangre , Endocarditis/diagnóstico por imagen , Endocarditis/etiología , Femenino , Enfermedades de las Válvulas Cardíacas/etiología , Humanos , Lupus Eritematoso Sistémico/complicaciones , MEDLINE , Masculino , Factores de Riesgo
13.
Lupus ; 21(7): 725-6, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22635213

RESUMEN

We conducted a prospective study of anticardiolipin antibody (aCL) testing, performed in our university hospital. Among 6321 consecutive patients tested for both IgG and IgM aCL, 91 patients with medium or high positivity (>99th percentile) had a subsequent confirmatory test. Among them, 53 had a persistent positivity at 12 weeks. In this real world setting, patients with transient positivity had lower values than patients with persistent positivity.


Asunto(s)
Anticuerpos Anticardiolipina/sangre , Síndrome Antifosfolípido/diagnóstico , Adulto , Anciano , Síndrome Antifosfolípido/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo
14.
Lupus ; 21(7): 758-60, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22635224

RESUMEN

Our objective was to study acquired Activated Protein C (APC) resistance in patients with antiphospholipid antibodies (aPL) using a thrombin generation based assay. We compared patients with and without lupus (systemic lupus erythematosus, SLE). A parameter summarizing APC inhibition of thrombin generation with increasing APC concentrations (IC(50)-APC) was increased in all patient groups compared to controls: median values were 15.3 (interquartile range, IQR, 9.7 to 34.0) in patients with primary antiphospholipid syndrome (APS), 27.3 (IQR 23.5 to 43.5) in patients with SLE without APS, 64.1 (IQR 25.9 to 65.0) in patients with SLE/APS compared to 10.4 [IQR 8.5 to 15.8] in controls, respectively p = 0.003, p = 0.0001 and p = 0.0001. In conclusion, patients with SLE and primary APS displayed a hypercoagulable state characterized by APC resistance.


Asunto(s)
Resistencia a la Proteína C Activada/inmunología , Anticuerpos Antifosfolípidos/sangre , Síndrome Antifosfolípido/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Resistencia a la Proteína C Activada/metabolismo , Síndrome Antifosfolípido/metabolismo , Estudios de Casos y Controles , Humanos , Lupus Eritematoso Sistémico/metabolismo , Estudios Prospectivos , Trombina/metabolismo
15.
Vox Sang ; 102(4): 354-61, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22092160

RESUMEN

BACKGROUND AND OBJECTIVES: Several pathogen inactivation methods currently applied to therapeutic plasma may result in products with different hemostatic properties. This study aims at evaluating and comparing the hemostatic potential of different therapeutic plasma preparations currently available in France. MATERIALS AND METHODS: We studied three types of pathogen-reduced plasma for transfusion (MB/light, Amotosalen/UVA, industrial S/D plasma). Quarantine, non-pathogen-reduced plasma, was used as a control. This study compared more specifically the content in FVIII, fibrinogen (clottable and antigen assays) and ADAMTS-13 and evaluated the intrinsic hemostatic properties using a thrombin generation test [Calibrated Automated Thrombogram (CAT)] at high and low concentrations of tissue factor to assess the maximum quantity of thrombin generated or the contribution of FVIII and FIX in the amplification phase of thrombin generation, respectively. RESULTS: The median FVIII concentration was >70 IU/dl for each preparation. Endogenous thrombin potential values were significantly different among the methods of plasma preparation (P<0·001) but were all in the range of the values measured in donors' plasma. Control by the thrombomodulin-activated protein C system was preserved in all preparations (>50% inhibition of endogenous thrombin potential). Fibrinogen concentrations were all within normal range but fibrinogen levels were lower in the plasmas treated with photochemical methods. ADAMTS-13 levels were preserved. CONCLUSION: The hemostatic potential appears well preserved in all therapeutic plasmas tested but there are some differences between preparations, the clinical relevance of which remains to be elucidated.


Asunto(s)
Hemostasis , Plasma , Trombina/biosíntesis , Proteínas ADAM/sangre , Proteína ADAMTS13 , Factor VIII/análisis , Fibrinógeno/análisis , Francia , Humanos , Plasma/química , Plasma/microbiología
16.
Cerebrovasc Dis ; 33(6): 574-8, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22710855

RESUMEN

BACKGROUND AND PURPOSE: Aspirin is the most commonly used antiplatelet treatment during the acute phase of cerebral ischemic events. It inhibits the production of thromboxane (TX) A(2), a powerful platelet activator. Despite this protection, early ischemic recurrences are frequent and considered clinical failures of this therapy. Only a few trials have focused on the use of antiplatelet therapy during this phase, and none has described the laboratory effect of the first dose of aspirin given after an ischemic cerebral event. However, this study may help clinicians to understand the mechanisms of early recurrences, and to design new therapeutic strategies, in particular for patients already treated with a daily dose of aspirin. METHOD: We studied laboratory parameters of the first 300-mg oral dose of aspirin given within 48 h after an ischemic cerebral event. Two blood samples were taken from all of the patients: the first during the third hour following aspirin intake (T1) and the second during the twenty-fourth hour (T2). For patients already treated with a daily dose of aspirin, a supplementary sample was taken before aspirin intake (T0). Platelet reactivity was studied on the basis of serum TXB(2) levels, a metabolite of TXA(2), and light transmission aggregometry after stimulation of platelet-rich plasma by arachidonic acid and by two concentrations of collagen, i.e. 2 µg/ml (Col2), dependent on the TXA(2) pathway, and 20 µg/ml (Col20), independent of the TXA(2) pathway. Results with Col2 were related to results with Col20 (Col2/20 ratio) to limit the impact of variations induced by the effects of preanalytical conditions. RESULTS: Fifty patients were included. TXB(2) values (p < 0.001) and relative values of the Col2/20 ratio (p = 0.037) were significantly higher at T2 compared to T1. For patients already treated with aspirin, TXB(2) levels (p < 0.001) were significantly lower at T1 compared to T0, and the Col2/20 ratio tended to decrease (p = 0.096). CONCLUSION: Platelet reactivity recovers within 24 h following the first 300-mg oral dose of aspirin during the acute phase of a cerebral ischemic event as demonstrated by an increase in TXB(2) levels, and the Col2/20 ratio, at T2 compared to T1. This would favor early ischemic recurrences. However, for patients already treated with aspirin, this dose is able to decrease TXB(2) levels and to complete the inhibition of the TXA(2) pathway, which shows the utility of this prescription in this case.


Asunto(s)
Aspirina/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Enfermedad Aguda , Administración Oral , Anciano , Aspirina/administración & dosificación , Plaquetas/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/administración & dosificación , Tromboxanos/biosíntesis , Factores de Tiempo
17.
Pathol Biol (Paris) ; 59(2): 122-6, 2011 Apr.
Artículo en Francés | MEDLINE | ID: mdl-20570055

RESUMEN

OBJECTIVES: The objective was to evaluate the good use of fluoroquinolones in a hospital with a relevance review in the context of an approach to evaluation of professional practices at the regional level initiated by the Antibiolor network. METHOD: In February 2008, in each volunteer service, practitioners filled out a standardized form indicating indication, the name of the fluoroquinolone, route of administration and duration of treatment, retrospectively from 20 medical records on the last 3 months. Each one was analyzed by a binomial (doctors and pharmacists) according to the local Antibioguide. The degree of compliance requirements has been appreciated by a global index of adequacy of therapeutic consisting of six criteria. RESULTS: Eighteen units of Nancy's hospital filled 475 cards. The most frequent indications were pulmonary infections (38 %; 181/475) and urinary (23 %; 111/475). The fluoroquinolone indication was non-conform for 28 % of the cards (133/475). When the fluoroquinolone indication was justified, the association with another antibiotic was considered non-compliant in 20 % of cases (70/342), the choice of the molecule in 18 % (62/342), duration of treatment in 17 % (57/342), the dose in 13 % (45/342) and route of administration in 9 % (30/342). The requirements were entirely conform in 34 % of cases (160/475). CONCLUSION: The results were communicated to each participating service with corrective actions and then this experience has been repeated in May 2009.


Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Prescripciones de Medicamentos/estadística & datos numéricos , Fluoroquinolonas/uso terapéutico , Hospitales Universitarios/estadística & datos numéricos , Prescripción Inadecuada/estadística & datos numéricos , Anciano , Antibacterianos/administración & dosificación , Infecciones Bacterianas/epidemiología , Quimioterapia Combinada , Utilización de Medicamentos/estadística & datos numéricos , Femenino , Fluoroquinolonas/administración & dosificación , Francia/epidemiología , Adhesión a Directriz , Departamentos de Hospitales , Registros de Hospitales , Humanos , Masculino , Auditoría Médica , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/epidemiología , Estudios Retrospectivos , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/epidemiología
18.
Br J Dermatol ; 161(1): 181-3, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19545295

RESUMEN

Nonbacterial purpura fulminans (PF) is rare, usually follows viral infection in young children, and is characterized by specific coagulation disorders, requiring specific therapy. Following a transient rash, a 2-year-old previously healthy girl developed PF without haemodynamic impairment. Laboratory data revealed disseminated intravascular coagulation and a severe transient protein S deficiency. Antiprotein S autoantibodies and active human herpesvirus-6 (HHV6) replication were demonstrated. Purpuric skin lesions spread very rapidly despite broad-spectrum antibiotics and right leg amputation. Plasmapheresis and intravenous immunoglobulins gave complete clinical recovery and normalization of protein S level within 10 days, with progressive clearance of antiprotein S autoantibodies. Transient severe protein S deficiencies have previously been reported in patients with nonbacterial PF, usually after varicella infection. This is the first documented case of PF after HHV6 infection.


Asunto(s)
Enfermedades Autoinmunes/complicaciones , Púrpura Fulminante/virología , Infecciones por Roseolovirus/complicaciones , Amputación Quirúrgica , Enfermedades Autoinmunes/terapia , Preescolar , Coagulación Intravascular Diseminada/etiología , Femenino , Heparina/uso terapéutico , Herpesvirus Humano 6/aislamiento & purificación , Herpesvirus Humano 6/fisiología , Humanos , Inmunoglobulinas/uso terapéutico , Pierna/cirugía , Plasmaféresis/métodos , Reacción en Cadena de la Polimerasa , Proteína S/análisis , Deficiencia de Proteína S/etiología , Deficiencia de Proteína S/terapia , Púrpura Fulminante/terapia , Resultado del Tratamiento , Replicación Viral
19.
J Mal Vasc ; 34(1): 16-25, 2009 Feb.
Artículo en Francés | MEDLINE | ID: mdl-19110389

RESUMEN

Aspirin is the first-line oral antiplatelet drug to prevent thromboembolic arterial occlusions. Aspirin irreversibly inhibits cyclooxygenase (COX) 1 involved in the platelet production of thromboxane (TX) A(2), an inducer of vasoconstriction and a platelet activating agent. Recurrent vascular events despite aspirin intake, combined with laboratory evidence of poor antiplatelet effect, suggested what has been called "aspirin resistance". For clarity's sake a real aspirin resistance would be the absence of COX1 inhibition due to intrinsic platelet factors (which has never been reported). What has been described is (expected) variability. COX1 inhibition can be insufficient to modify TX-dependent platelet behaviour. Other agonists, the production of which does not involve COX1, can stimulate TX-receptors. The antiplatelet effect of aspirin can be insufficient for pharmacokinetic or pharmacodynamic reasons, the latter being further classified as TX-dependent or not. If platelets are so reactive that responses are more TX-independent than normally, then neither aspirin nor any drugs acting on this pathway can do the job. These mechanisms should be better understood and diagnosed, and this is the prerequisite for the development of newer antiplatelet agents.


Asunto(s)
Aspirina/farmacología , Plaquetas/fisiología , Inhibidores de Agregación Plaquetaria/farmacología , Aspirina/efectos adversos , Plaquetas/efectos de los fármacos , Clopidogrel , Resistencia a Medicamentos , Humanos , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/efectos adversos , Ticlopidina/análogos & derivados , Ticlopidina/farmacología
20.
Ann Biol Clin (Paris) ; 67(3): 343-8, 2009.
Artículo en Francés | MEDLINE | ID: mdl-19411238

RESUMEN

Erythema infectiosum (fifth disease) is the most common clinical presentation of acute parvovirus B19 infection in infancy. In healthy adults, most cases of infection are asymptomatic or accompanied by a flu-like syndrome like headaches and myalgia. Haematological manifestations are dominated by transient aplasia of erythroid progenitor cells which remains asymptomatic in most of non immunocompromised patients. Patients with sickle cell disease, thalassemia or other disorders associated with shortened red blood cell survival are at particular risk for marked anemia or red blood cell aplasia. In immunosuppressed patients, anemia may be chronic because of persistent viral load. Neutropenia, lymphopenia or thrombocytopenia have also been reported in acute parvovirus B19 infection. Mechanisms of these cytopenias are not yet elucidated. We present two patients with thrombopenia and/or neutropenia but without anemia due to acute parvovirus B19 infection.


Asunto(s)
Eritema Infeccioso/sangre , Eritema Infeccioso/diagnóstico , Neutropenia/virología , Infecciones por Parvoviridae/sangre , Infecciones por Parvoviridae/diagnóstico , Parvovirus B19 Humano/aislamiento & purificación , Trombocitopenia/virología , Adulto , Femenino , Humanos , Mielografía
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