Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 10 de 10
Filtrar
1.
Haemophilia ; 27(2): e221-e229, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33595163

RESUMEN

INTRODUCTION: Recurrent joint bleeds in haemophilia patients often cause musculoskeletal changes leading to functional capacity impairment. AIM: In this study, we assessed the effects of aquatic activities performed to improve functional capacity in these patients. METHODS: The interventional protocol consisted of 24 hydrotherapy sessions during three months, in comparison with 24 swimming sessions. The pre- and post-intervention assessment consisted of Functional Independence Score, haemophilia joint health score (HJHS), Pediatric Haemophilia Activities List (PedHAL), surface electromyography (SEMG) of thigh muscles to assess muscle electric activity, and load cell on extensor and flexor thigh muscles to evaluate muscular strength. RESULTS: Forty-seven haemophilia patients were enrolled in this study, and 32 (23 severe haemophilia A, one moderate haemophilia A and 8 severe haemophilia B), median age 12y (6 to 40y), concluded the aquatic intervention. We observed a statistically significant increase with substantial improvement in functional capacity in the pre- and post-intervention evaluation of hydrotherapy in comparison with the swimming protocol, with HJHS (p = .006 and p = .001 respectively), PedHAL (Sum score) (p = .022 and p = .001) and score FISH (p = .021). The swimming group revealed significant improvements in muscular strength, in all muscles tested (p = .005 and p = .001). SEMG signal amplitude reached significantly higher levels in all muscles evaluated after both interventions except for the vastus medialis (right) in the hydrotherapy group. CONCLUSION: Our results concluded that both swimming and hydrotherapy were associated with physical improvement in haemophilia patients; however, only hydrotherapy lead to a more significant improvement in functional capacity.


Asunto(s)
Hemofilia A , Niño , Hemartrosis , Hemofilia A/complicaciones , Hemofilia A/terapia , Hemorragia , Humanos , Fuerza Muscular , Estudios Prospectivos
2.
N Engl J Med ; 376(5): 429-439, 2017 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-27959701

RESUMEN

BACKGROUND: The up-regulation of P-selectin in endothelial cells and platelets contributes to the cell-cell interactions that are involved in the pathogenesis of vaso-occlusion and sickle cell-related pain crises. The safety and efficacy of crizanlizumab, an antibody against the adhesion molecule P-selectin, were evaluated in patients with sickle cell disease. METHODS: In this double-blind, randomized, placebo-controlled, phase 2 trial, we assigned patients to receive low-dose crizanlizumab (2.5 mg per kilogram of body weight), high-dose crizanlizumab (5.0 mg per kilogram), or placebo, administered intravenously 14 times over a period of 52 weeks. Patients who were receiving concomitant hydroxyurea as well as those not receiving hydroxyurea were included in the study. The primary end point was the annual rate of sickle cell-related pain crises with high-dose crizanlizumab versus placebo. The annual rate of days hospitalized, the times to first and second crises, annual rates of uncomplicated crises (defined as crises other than the acute chest syndrome, hepatic sequestration, splenic sequestration, or priapism) and the acute chest syndrome, and patient-reported outcomes were also assessed. RESULTS: A total of 198 patients underwent randomization at 60 sites. The median rate of crises per year was 1.63 with high-dose crizanlizumab versus 2.98 with placebo (indicating a 45.3% lower rate with high-dose crizanlizumab, P=0.01). The median time to the first crisis was significantly longer with high-dose crizanlizumab than with placebo (4.07 vs. 1.38 months, P=0.001), as was the median time to the second crisis (10.32 vs. 5.09 months, P=0.02). The median rate of uncomplicated crises per year was 1.08 with high-dose crizanlizumab, as compared with 2.91 with placebo (indicating a 62.9% lower rate with high-dose crizanlizumab, P=0.02). Adverse events that occurred in 10% or more of the patients in either active-treatment group and at a frequency that was at least twice as high as that in the placebo group were arthralgia, diarrhea, pruritus, vomiting, and chest pain. CONCLUSIONS: In patients with sickle cell disease, crizanlizumab therapy resulted in a significantly lower rate of sickle cell-related pain crises than placebo and was associated with a low incidence of adverse events. (Funded by Selexys Pharmaceuticals and others; SUSTAIN ClinicalTrials.gov number, NCT01895361 .).


Asunto(s)
Anemia de Células Falciformes/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Selectina-P/antagonistas & inhibidores , Dolor/prevención & control , Adolescente , Adulto , Anemia de Células Falciformes/complicaciones , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales Humanizados , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Hidroxiurea/uso terapéutico , Masculino , Persona de Mediana Edad , Selectina-P/inmunología , Dolor/etiología , Calidad de Vida , Adulto Joven
4.
Haematologica ; 100(4): 466-71, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25596272

RESUMEN

Hemoglobin SC disease is a very prevalent hemoglobinopathy; however, very little is known about this condition specifically. There appears to be an increased risk of thromboembolic events in hemoglobin SC disease, but studies evaluating the hemostatic alterations are lacking. We describe the findings of a cross-sectional observational study evaluating coagulation activation markers in adult patients with hemoglobin SC, comparing them with those in sickle cell anemia patients and healthy controls. A total of 56 hemoglobin SC and 39 sickle cell anemia patients were included in the study, all in steady state, and 27 healthy controls. None of the patients was taking hydroxyurea. Hemoglobin SC patients had a significantly up-regulated relative expression of tissue factor, as well as elevations in thrombin-antithrombin complex and D-dimer, in comparison to controls (P<0.01). Hemoglobin SC patients had lower tissue factor expression, and thrombin-antithrombin complex and D-dimer levels when compared to sickle cell anemia patients (P<0.05). Markers of endothelial activation (soluble thrombomodulin and soluble vascular cell adhesion molecule-1) and inflammation (tumor necrosis factor-alpha) were both significantly elevated in hemoglobin SC patients when compared to controls, being as high as the levels seen in patients with sickle cell anemia. Overall, in hemoglobin SC patients, higher hemolytic activity and inflammation were associated with a more intense activation of coagulation, and hemostatic activation was associated with two very prevalent chronic complications seen in hemoglobin SC disease: retinopathy and osteonecrosis. In summary, our results demonstrate that hemoglobin SC patients have a hypercoagulable state, although this manifestation was not as intense as that seen in sickle cell anemia.


Asunto(s)
Coagulación Sanguínea , Enfermedad de la Hemoglobina SC/sangre , Trombofilia/sangre , Adulto , Biomarcadores/sangre , Estudios Transversales , Células Endoteliales/metabolismo , Femenino , Expresión Génica , Enfermedad de la Hemoglobina SC/complicaciones , Enfermedad de la Hemoglobina SC/diagnóstico , Enfermedad de la Hemoglobina SC/genética , Hemólisis , Humanos , Mediadores de Inflamación , Leucocitos/metabolismo , Masculino , Persona de Mediana Edad , Tromboplastina/genética
5.
Haematologica ; 100(6): 730-9, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25769545

RESUMEN

As hypoxia-induced inflammatory angiogenesis may contribute to the manifestations of sickle cell disease, we compared the angiogenic molecular profiles of plasma from sickle cell disease individuals and correlated these with in vitro endothelial cell-mediated angiogenesis-stimulating activity and in vivo neovascularization. Bioplex demonstrated that plasma from patients with steady-state sickle cell anemia contained elevated concentrations of pro-angiogenic factors (angiopoietin-1, basic fibroblast growth factor, vascular endothelial growth factor, vascular endothelial growth factor-D and placental growth factor) and displayed potent pro-angiogenic activity, significantly increasing endothelial cell proliferation, migration and capillary-like structure formation. In vivo neovascularization of Matrigel plugs was significantly greater in sickle cell disease mice than in non-sickle cell disease mice, consistent with an up-regulation of angiogenesis in the disease. In plasma from patients with hemoglobin SC disease without proliferative retinopathy, anti-angiogenic endostatin and thrombospondin-2 were significantly elevated. In contrast, plasma from hemoglobin SC individuals with proliferative retinopathy had a pro-angiogenic profile and more significant effects on endothelial cell proliferation and capillary formation than plasma from patients without retinopathy. Hydroxyurea therapy was associated with significant reductions in plasma angiogenic factors and inhibition of endothelial cell-mediated angiogenic mechanisms and neovascularization. Thus, individuals with sickle cell anemia or hemoglobin SC disease with retinopathy present a highly angiogenic circulating milieu, capable of stimulating key endothelial cell-mediated angiogenic mechanisms. Combination anti-angiogenic therapy to prevent the progression of unregulated neovascularization and associated manifestations in sickle cell disease, such as pulmonary hypertension, may be indicated; furthermore, the benefits and drawbacks of the potent anti-angiogenic effects of hydroxyurea should be clarified.


Asunto(s)
Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/tratamiento farmacológico , Antidrepanocíticos/farmacología , Células Endoteliales/metabolismo , Hidroxiurea/farmacología , Neovascularización Patológica/sangre , Adolescente , Adulto , Animales , Antidrepanocíticos/uso terapéutico , Células Endoteliales/efectos de los fármacos , Femenino , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Hidroxiurea/uso terapéutico , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Persona de Mediana Edad , Neovascularización Patológica/tratamiento farmacológico , Adulto Joven
6.
Br J Haematol ; 158(6): 788-97, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22775554

RESUMEN

Chronic vascular inflammation and endothelial activation may initiate vaso-occlusion in sickle cell disease (SCD). TNFSF14 (CD258; LIGHT), a recently-identified pro-thrombotic and pro-inflammatory tumour necrosis factor (TNF)-superfamily cytokine, has a potent activating effect on endothelial cells. We evaluated whether TNFSF14 production is altered in SCD and whether platelets contribute to this production. TNFSF14 was measured in platelet-free plasma from healthy-control individuals (CON), steady-state sickle cell anaemia (SCA), SCA on hydroxycarbamide therapy (SCAHC) and haemoglobin SC (HbSC) patients. Mean plasma TNFSF14 was significantly increased in SCA, SCAHC and HbSC, compared to CON individuals. In SCA/SCAHC patients, plasma TNFSF14, showed no correlation with haematological variables, but was significantly correlated with serum lactate dehydrogenase and inflammatory markers (CD40LG , IL8 and ICAM1). Platelet-membrane TNFSF14 expression was significantly augmented on SCA platelets, and correlated with platelet activation; furthermore, measurement of platelet TNFSF14 release indicated that platelets may be a major source of circulating TNFSF14 in SCA. Interestingly, high plasma TNFSF14 was significantly associated with elevated tricuspid regurgitant velocity (≥2·5 m/s) in a population of SCA/SCAHC patients. The pro-inflammatory and atherogenic cytokine, TNFSF14, could contribute to endothelial activation and inflammation in SCA; future investigations may confirm whether this protein contributes to major clinical complications of the disease, such as pulmonary hypertension, and represents a potential therapeutic target.


Asunto(s)
Anemia de Células Falciformes/sangre , Plaquetas/metabolismo , Miembro 14 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/sangre , Adolescente , Adulto , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/patología , Biomarcadores , Endotelio Vascular/patología , Femenino , Genotipo , Hemoglobina C/genética , Enfermedad de la Hemoglobina C/sangre , Enfermedad de la Hemoglobina C/genética , Humanos , Hidroxiurea/uso terapéutico , Mediadores de Inflamación/sangre , Masculino , Persona de Mediana Edad , Activación Plaquetaria , Miembro 14 de Receptores del Factor de Necrosis Tumoral/sangre , Rasgo Drepanocítico/sangre , Rasgo Drepanocítico/genética , Trombofilia/etiología , Trombofilia/metabolismo , Miembro 14 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/genética , Miembro 14 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/fisiología , Adulto Joven
7.
J Thromb Haemost ; 19(9): 2275-2286, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34018665

RESUMEN

BACKGROUND: The optimum second-line treatment or best sequence of treatments for immune thrombocytopenia (ITP) are yet to be determined. Our institution has accumulated extensive experience regarding the use of dapsone as second-line therapy for ITP. OBJECTIVES: We aimed to assess the efficacy rate and safety of dapsone treatment in ITP patients. PATIENTS/METHODS: Here we report our experience in a retrospective study, including 122 patients, with a median treatment duration with dapsone of 6 months and a median follow-up period of 3.4 years. RESULTS: The overall response rate in this cohort was 66%, including 24% of complete responses. Among responders, in 24% a relapse occurred while on treatment. Therefore, a sustained response was observed in 51% of patients. Interestingly, 81% of the responders maintained the response after the interruption of treatment, for a median time of 26 months. Side effects were reported in 16% of the patients in this cohort and treatment was interrupted due to side effects in 11% of patients. The main cause in these cases was hemolytic anemia and methemoglobinemia. Reductions in hemoglobin levels during the use of dapsone were seen in 94% of the patients. Responders presented significantly greater reductions in their hemoglobin levels than nonresponders did: median hemoglobin drop of 1.9 g/dl vs. 1.2 g/dl (p = .004). CONCLUSIONS: Our findings suggest that dapsone has adequate efficacy and is well tolerated. Although the mechanism of action is still unclear, our observation that the degree in the drop of hemoglobin is greater in responders suggest a possible role of the blockage of the reticuloendothelial system in the therapeutic effect of the drug.


Asunto(s)
Dapsona , Púrpura Trombocitopénica Idiopática , Humanos , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Inducción de Remisión , Estudios Retrospectivos , Esplenectomía , Resultado del Tratamiento
8.
Clin Appl Thromb Hemost ; 24(3): 477-482, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28393617

RESUMEN

Although deep vein thrombosis (DVT) recurrence is a common late complication of the disease, there are few predictive markers to risk-stratify patients long-term after the thrombotic event. The accuracy of residual vein thrombosis (RVT) in this context is controversial, possibly due to a lack of a standardized methodology. The objective of the study was to evaluate the accuracy of RVT echogenicity as a predictive marker of late DVT recurrence. To evaluate the accuracy of RVT echogenicity as a predictive marker of late DVT recurrence. This prospective study included patients with history of DVT in the past 33 months. Ultrasound examination was performed to detect the presence of RVT, and its echogenicity was determined by calculating the grayscale median (GSM) of the images. Blood samplings were taken for plasma D-dimer levels. Patients were followed-up for 28 months and the primary end point was DVT recurrence. Deep vein thrombosis recurrence was confirmed or excluded by ultrasound during the follow-up. Fifty-six patients were included, of which 10 presented DVT recurrence during the follow-up. D-dimer levels above 630 ng/mL conferred higher risk for recurrence with a negative predictive value of 94%. The absence of RVT was a protective marker for recurrence with a negative predictive value of 100%. Also, the presence of hypoechoic RVT, determined by GSM values below 24, positively predicted 75% of DVT recurrences. Our results suggest that the persistence of RVT and, particularly, the presence of hypoechoic thrombi (GSM < 24) are predictive markers of the risk of DVT recurrence. Residual vein thrombosis echogenicity, by GSM analysis, could represent a new strategy for the evaluation of recurrence risk in patients with DVT.


Asunto(s)
Ultrasonografía , Trombosis de la Vena/diagnóstico por imagen , Adulto , Anciano , Estudios de Cohortes , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Recurrencia , Ultrasonografía/métodos
9.
Blood Coagul Fibrinolysis ; 27(6): 673-8, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26825621

RESUMEN

Postthrombotic syndrome (PTS) may affect 50% of patients with deep venous thrombosis, 5-10% of them may present severe manifestations. The causes for PTS development and severity have not been well established. This study evaluated whether PTS may be associated with the presence, and echogenicity, of the residual vein thrombosis (RVT). We included patients with a history of deep venous thrombosis in the past 58 months. These patients were further evaluated for PTS diagnosis, clinical comorbidities, plasma levels of D-dimer, serum levels of C-reactive protein and for the presence of RVT. Particularly, RVT was detected by ultrasound examination and the residual thrombi echogenicity was determined by grayscale median (GSM). Fifty-six patients were included, of which 41 presented PTS. Mild PTS was detected in 23 patients, moderate PTS in 11 and severe PTS in seven patients. Patients with severe PTS showed higher body mass index, higher abdominal circumference and higher C-reactive protein levels when compared with the other patients (P = 0.007, P = 0.002, P = 0.02, respectively). The ultrasound-generated GSM was significantly lower in patients with severe PTS compared with patients with mild-moderate PTS or no PTS (median = 24, 35 and 41, respectively; P = 0.04). A GSM value less than 25, which was consistent with a hypoechoic RVT, was the best cut-off value to discriminate patients with severe PTS from those with mild or moderate PTS and those without PTS. RVT is a common finding among patients with PTS and the echogenicity of the RVT may impact the severity of PTS.


Asunto(s)
Síndrome Postrombótico/diagnóstico por imagen , Trombosis de la Vena/diagnóstico por imagen , Adulto , Biomarcadores/sangre , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Estudios Transversales , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Síndrome Postrombótico/sangre , Síndrome Postrombótico/complicaciones , Síndrome Postrombótico/etiología , Factores de Riesgo , Índice de Severidad de la Enfermedad , Ultrasonografía , Trombosis de la Vena/sangre , Trombosis de la Vena/complicaciones , Trombosis de la Vena/patología , Circunferencia de la Cintura
10.
Blood Coagul Fibrinolysis ; 23(2): 172-4, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22246165

RESUMEN

New portable devices for the measurement of the prothrombin time and the international normalized ratio (INR) from capillary blood samples have demonstrated to have good correlation with classic laboratory methods in multiple clinical settings. In this study, we evaluated the performance of the point-of-care device CoaguChek XS (CoaguChek XS; Roche Diagnostics, Basel, Switzerland), comparing the INR results with the standard laboratory method (automatic coagulometer) in an outpatient anticoagulation clinic. Results were compared by linear regression and Bland-Altman plot. Two hundred paired results were collected from 170 patients in a period of 90 days. The main indications for anticoagulation were prophylaxis of venous thromboembolic events, atrial fibrillation and prosthetic heart valves. Mean INR results obtained with the portable device and with the standard laboratory method were 2.22 ±â€Š0.70 and 2.30 ±â€Š0.77, respectively. The proportion of patients with supratherapeutic INRs was 13.5%. The CoaguChek XS monitor tended to underestimate the INR on average by 0.08 U. The correlation coefficient (R) between the two methods was 0.91 (P < 0.0001). The CoaguChek XS device is suitable for INR monitoring in patients in outpatient oral anticoagulation clinics.


Asunto(s)
Sistemas de Atención de Punto , Tiempo de Protrombina/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Anticoagulantes/envenenamiento , Sobredosis de Droga , Humanos , Relación Normalizada Internacional/instrumentación , Relación Normalizada Internacional/métodos , Persona de Mediana Edad , Tiempo de Protrombina/instrumentación , Warfarina/administración & dosificación , Warfarina/envenenamiento , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA