RESUMEN
Aim: To compare freeze-dried and fresh platelet-rich plasma (PRP) preparations, in a pre-clinical study. Materials & methods: 30 Wistar male rats were used to compare and characterize human PRP which was applied at the perilesional area in an acute wound model, evaluated by macroscopical and histological analysis. Results: Despite the increased growth factor concentration after the freeze-drying process, no change in the healing kinetics was observed in vivo. Nevertheless, a significant increased number of myofibroblasts was demonstrated in comparison with the fresh PRP group. We also demonstrated a significant increased percentage of blood vessels in comparison with controls in both the superficial and deep epidermis. Conclusion: These results encourage randomized clinical trials to evaluate the effectiveness of freeze-dried PRP for skin ulcer treatment.
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Conservación de la Sangre , Criopreservación , Plasma Rico en Plaquetas , Cicatrización de Heridas , Heridas y Lesiones/terapia , Enfermedad Aguda , Animales , Humanos , Masculino , Ratas , Ratas WistarRESUMEN
BACKGROUND: Promising results with platelet-rich plasma (PRP) in androgenetic alopecia that could be associated with platelet number and growth factor levels were described. OBJECTIVE: Analyze the platelet countand growth factor levels in PRP and their correlation with hair growth parameters evaluated by using the TrichoScan (Tricholog GmbH, Freiburg, Germany). METHODS: A total of 26 patients were randomized to receive 4 subcutaneous injections of PRP or saline. Hair growth, hair density, and percentage of anagen hairs were evaluated by using the TrichoScan method before injection, 15 days after the last injection, and again 3 months after the last injection. Growth factors (platelet-derived growth factor, epidermal growth factor, and vascular endothelial growth factor) were measured by the Luminex method (Millipore, Bedford, MA). RESULTS: We demonstrated a significant increase in hair count (P = .0016), hair density (P = .012) and percentage of anagen hairs (P = .007) in the PRP group versus in the control group, without correlation with platelet counts or quantification of the growth factors in PRP. LIMITATIONS: Other growth factors that could be related to response to PRP were not evaluated. CONCLUSION: Our data favor the use of PRP as a therapeutic alternative in the treatment of androgenetic alopecia. The lack of association between platelet count, platelet-derived growth factor, epidermal growth factor, and vascular endothelial growth factor levels and clinical improvement suggest that other mechanisms could be involved in this response.
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Alopecia/terapia , Cabello/crecimiento & desarrollo , Péptidos y Proteínas de Señalización Intercelular/análisis , Recuento de Plaquetas , Plasma Rico en Plaquetas/química , Plasma Rico en Plaquetas/citología , Adulto , Dermoscopía , Método Doble Ciego , Factor de Crecimiento Epidérmico/análisis , Cabello/diagnóstico por imagen , Humanos , Masculino , Factor de Crecimiento Derivado de Plaquetas/análisis , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/análisis , Adulto JovenRESUMEN
PURPOSE: The purpose was to investigate the presence of hypercoagulability in the very early phase of the host response to an infection in the clinical course of sepsis and septic shock. MATERIAL AND METHODS: Twenty-four patients with chemotherapy-associated febrile neutropenia were evaluated at baseline, at the time of fever onset, and 48 hours thereafter using the thrombin generation test, a more physiological and global assay of hemostasis. RESULTS: The rate of thrombin generation was decreased and no signals of systemic hypercoagulability could be observed during the first 48 hours of sepsis. Moreover, patients that evolved to septic shock presented a more significant impairment in thrombin generation than those with noncomplicated sepsis. CONCLUSIONS: Patients with sepsis and febrile neutropenia present an impairment in thrombin generation from very early stages of their disease course. These results suggest that the procoagulant in vitro alterations described during sepsis do not necessarily translate into a clinically relevant systemic hypercoagulable state. These findings could help explain why treatment with systemic anticoagulants did not translate to clinical benefits in human sepsis and highlight the need for a better understanding of the hemostatic alterations in sepsis before new treatments targeting coagulation activation are developed.
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Neutropenia Febril Inducida por Quimioterapia/fisiopatología , Sepsis/fisiopatología , Trombina/biosíntesis , Adolescente , Adulto , Biomarcadores , Pruebas de Coagulación Sanguínea , Neutropenia Febril Inducida por Quimioterapia/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Puntuaciones en la Disfunción de Órganos , Sepsis/sangre , Choque Séptico/sangre , Factores de Tiempo , Adulto JovenRESUMEN
Increased levels of factor VIII (FVIII) are a prevalent and independent risk factor for deep venous thrombosis (DVT). After a median of 10 years of the first DVT, we evaluated FVIII coagulation levels in 55 patients with DVT of the lower limbs and previous high levels of FVIII and in 74 controls. Subsequently, we analyzed the presence of post-thrombotic syndrome (PTS) in patients and its relationship with FVIII levels. After a median of 10 years of the first DVT, the FVIII levels were still significantly higher in patients when compared to controls (P < .001). Patients with severe PTS showed increased levels of FVIII when compared to patients with moderate or absent PTS (P < .001). We demonstrated a persistent increase in FVIII levels in a subset of patients with DVT, but in a lower magnitude after 10 years of the first DVT episode. Moreover, we observed a significant association between increased FVIII levels and severe PTS.
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Factor VIII/metabolismo , Síndrome Postrombótico/sangre , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndrome Postrombótico/patología , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Septic shock is the most feared complication of chemotherapy-induced febrile neutropenia. So far, there are no robust biomarkers that can stratify patients to the risk of sepsis complications. The VEGF-A axis is involved in the control of microvascular permeability and has been involved in the pathogenesis of conditions associated with endothelial barrier disruption such as sepsis. sFlt-1 is a soluble variant of the VEGF-A receptor VEGFR-1 that acts as a decoy receptor down-regulating the effects of VEGF-A. In animal models of sepsis, sFlt-1 was capable to block the barrier-breaking negative effects of VEGF-A and to significantly decrease mortality. In non-neutropenic patients, sFlt-1 has been shown to be a promising biomarker for sepsis severity. METHODS: We prospectively evaluated concentrations of sFlt-1 and VEGF-A at different time-points during febrile neutropenia, and evaluated the association of these levels with sepsis severity and septic shock development. RESULTS: Neutropenic patients that evolved with septic shock (n = 10) presented higher levels of sFlt-1 and VEGF-A measured 48 hours after fever onset than patients with non-complicated sepsis (n = 31) and levels of these biomarkers correlated with sepsis severity scores. Estimation of the diagnostic accuracy of sFlt-1 levels for the discrimination of patients that evolved to septic shock yielded promising results in our study population. DISCUSSION: Our data suggest that sFlt-1 and VEGF-A could be useful biomarkers for sepsis severity in patients with febrile neutropenia. In addition, the kinetics of sFlt-1 release in patients that evolve to septic shock suggest that the sFlt-1 could be a salvage compensatory mechanism in patients with septic shock, but that the magnitude of the sFlt-1 release observed in human sepsis is not sufficient to reproduce the beneficial anti-VEGF-A effects observed in animal models of sepsis.
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Neutropenia/complicaciones , Choque Séptico/complicaciones , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neutropenia/sangre , Pronóstico , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Choque Séptico/sangre , Choque Séptico/diagnóstico , Factores de Tiempo , Factor A de Crecimiento Endotelial Vascular/sangre , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Adulto JovenRESUMEN
The aim of this study was to assess the incidence and risk factors for recurrent venous thromboembolism (VTE) in a Hispanic population. We prospectively followed 343 patients after a first episode of objectively proven VTE. We excluded all patients with VTE at unusual sites, older than 70 years old, with neoplasia, liver or renal chronic disease and antiphospholipid syndrome. Predictors for recurrence were evaluated by Cox model. The probability of recurrent VTE was estimated by the method of Kaplan-Meier. The cumulative probability of recurrent VTE was 19.1% in 5 years and 30.0% in 10 years. Male sex [relative risk (RR) 1.7, 95% confidence interval (CI) 1.0-2.8], spontaneous first VTE (RR 2.9, 95% CI 1.7-5.0) and FII G20210A mutation (RR 4.2, 95% CI 1.9-9.4) were independent risk factors for recurrent VTE. The fibrinogen, coagulation factors VIII, IX, X and XI were measured in 200 patients and were not associated to thrombotic recurrence risk. This study indicates that the incidence of recurrent VTE is high in Hispanics and depends on clinical and laboratory findings. In this population, FII G20210A mutation may represent a specific risk factor for recurrence. The inclusion of different ethnic populations in epidemiological studies of VTE as well as new approaches to the management of anticoagulation therapy in Hispanics is warranted.
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Hispánicos o Latinos , Tromboembolia Venosa/etnología , Adolescente , Adulto , Anciano , Factores de Coagulación Sanguínea/análisis , Femenino , Humanos , Incidencia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Probabilidad , Estudios Prospectivos , Protrombina/genética , Recurrencia , Factores de Riesgo , Factores Sexuales , Factores de Tiempo , Tromboembolia Venosa/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Febrile neutropenia carries a high risk of sepsis complications, and the identification of biomarkers capable to identify high risk patients is a great challenge. Angiopoietins (Ang -) are cytokines involved in the control microvascular permeability. It is accepted that Ang-1 expression maintains endothelial barrier integrity, and that Ang-2 acts as an antagonizing cytokine with barrier-disrupting functions in inflammatory situations. Ang-2 levels have been recently correlated with sepsis mortality in intensive care units. METHODS: We prospectively evaluated concentrations of Ang-1 and Ang-2 at different time-points during febrile neutropenia, and explored the diagnostic accuracy of these mediators as potential predictors of poor outcome in this clinical setting before the development of sepsis complications. RESULTS: Patients that evolved with septic shock (n = 10) presented higher levels of Ang-2 measured 48 hours after fever onset, and of the Ang-2/Ang-1 ratio at the time of fever onset compared to patients with non-complicated sepsis (n = 31). These levels correlated with sepsis severity scores. CONCLUSIONS: Our data suggest that imbalances in the concentrations of Ang-1 and Ang-2 are independent and early markers of the risk of developing septic shock and of sepsis mortality in febrile neutropenia, and larger studies are warranted to validate their clinical usefulness. Therapeutic strategies that manipulate this Ang-2/Ang-1 imbalance can potentially offer new and promising treatments for sepsis in febrile neutropenia.