Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Br J Haematol ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31945798

RESUMO

Multifactorial mechanisms leading to diminished platelet counts in immune thrombocytopaenia (ITP) might condition the ability of patients with ITP to respond to treatments. Examining their platelet and immune features, we aimed to detect singular characteristics of patients with ITP who do not respond to any treatment. We studied patients with chronic primary ITP who had been without treatment, or untreated (UT-ITP), for at least six months; included were responders to agonists of thrombopoietin receptors (TPO-RA), patients who showed no response to first- and second-line treatments (NR-ITP), and healthy controls. Platelets from NR-ITP patients exposed a reduced amount of sialic acid residues. Increased loss of platelet surface sialic acid residues was associated with increased platelet apoptosis. NR-ITP patients had an increased fraction of naive lymphocyte (L) B cells and a reduced LTreg (Lymphocyte T-regulator) subset. They also presented an anomalous monocyte and NK (Natural Killer) cells distribution. TPO-RA-treated patients seemed to recover an immune homeostasis similar to healthy controls. In conclusion, our results indicate a severe deregulation of the immune system of NR-ITP. The inverse correlation between loss of sialic acid and LTreg count suggests a potential relationship between glycan composition on the platelet surface and immune response, positing terminal sugar moieties of the glycan chains as aetiopathogenic agents in ITP.

2.
An. pediatr. (2003. Ed. impr.) ; 91(6): 394-400, dic. 2019. tab
Artigo em Espanhol | IBECS-Express | ID: ibc-ET2-4005

RESUMO

Introducción: La hemofilia es una enfermedad rara, por lo que su abordaje en Urgencias puede suponer un reto para los pediatras. Objetivos: Describir la frecuencia y motivos de consulta de los niños hemofílicos en Urgencias. Material y métodos: Estudio retrospectivo longitudinal realizado en Urgencias Pediátricas de un hospital de tercer nivel. Se incluyeron hemofílicos A y B, desde el nacimiento hasta los 16 años, que consultaron por cualquier motivo durante 6 años (2011-2016). Se analizaron: edad, tipo y gravedad de hemofilia, motivo de consulta, profilaxis domiciliaria frente a sangrados, pruebas complementarias, diagnóstico establecido, tratamiento y número de visitas a Urgencias. Resultados: Se analizaron 116 varones con un total de 604 visitas. La media de edad fue de 5,5 años y la mediana de 5,3. De ellos, 101 pacientes eran hemofílicos A (38 leves, 4 moderados, 59 graves) y 15 hemofílicos B (9 leves, 3 moderados, 3 graves). Los principales motivos de consulta (clasificados en triaje) fueron: problema musculoesquelético/traumático o sangrado (66,7%), causas no relacionadas con hemofilia (29%), sospecha de infección de catéter central (2,8%) y administración rutinaria de factor (1,5%). Se realizaron pruebas complementarias en 335 visitas (55,5%). Del total, 317 consultas (52,5%) requirieron factor; 103 episodios (17,1%) precisaron ingreso, cuyos principales motivos fueron: traumatismo craneoencefálico (35,9%), infección de catéter venoso central (13,6%), hemartrosis (8,7%), hematoma muscular (6,8%) y hematuria (5,8%). Conclusión: Los pacientes consultaron por causas habituales de la edad pediátrica, pero también lo hicieron por motivos específicos de su enfermedad; lo más frecuente fue el problema musculoesquelético/traumático o sangrado. El Servicio de Urgencias es un componente indispensable en su atención


Introduction: Haemophilia is a rare disease and its management can pose a challenge to Emergency Department paediatricians. Aim: To describe the frequency and reasons for consultation by haemophilic children in the ED. Materials and methods: Longitudinal retrospective study was conducted in a paediatric Emergency Department of a tertiary care hospital. The study included haemophiliacs A and B, ages 0 to 16 years old, and who had consulted the Emergency Department for whatever reason over a span of 6 years (2011-2016). The data analysed include: age, type and severity of haemophilia, reason for query, prophylactic status, complementary examinations, established diagnosis, treatment, and number of visits to the Emergency Department. Results: The analysis included 116 males with a total of 604 Emergency Department visits. The mean age was 5.5 years, and the median age was 5.3 years. A total of 101 patients were categorised as haemophiliac A (38 mild, 4 moderate, 59 severe), and 15 as haemophiliac B (9 mild, 3 moderate, 3 severe). The main reasons for initial Emergency Department visits (ranked by triage) were: musculoskeletal problems/injury or bleeding (66.7%), causes unrelated to haemophilia (29%), suspected central venous catheter related infection (2.8%), and routine clotting factor infusion (1.5%). Additional tests were conducted during 335 visits (55.5%). Factor replacement was undertaken in 317 visits (52.5%). A total of 103 episodes (17.1%) required hospital admission, due to: head trauma (35.9%), central venous catheter -related infection (13.6%), haemarthrosis (8.7%), muscle haematoma (6.8%), and haematuria (5.8%). Conclusion: Haemophilic patients went to the Emergency Department for common paediatric causes, but also requested consultation on specific problems related to haemophilia, with musculoskeletal problems/injury or bleeding being the main issues. The paediatric Emergency Department is an indispensable component of haemophilia care

3.
An Pediatr (Barc) ; 91(6): 394-400, 2019 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-31171477

RESUMO

INTRODUCTION: Haemophilia is a rare disease and its management can pose a challenge to Emergency Department paediatricians. AIM: To describe the frequency and reasons for consultation by haemophilic children in the ED. MATERIALS AND METHODS: Longitudinal retrospective study was conducted in a paediatric Emergency Department of a tertiary care hospital. The study included haemophiliacs A and B, ages 0 to 16 years old, and who had consulted the Emergency Department for whatever reason over a span of 6 years (2011-2016). The data analysed include: age, type and severity of haemophilia, reason for query, prophylactic status, complementary examinations, established diagnosis, treatment, and number of visits to the Emergency Department. RESULTS: The analysis included 116 males with a total of 604 Emergency Department visits. The mean age was 5.5 years, and the median age was 5.3 years. A total of 101 patients were categorised as haemophiliac A (38 mild, 4 moderate, 59 severe), and 15 as haemophiliac B (9 mild, 3 moderate, 3 severe). The main reasons for initial Emergency Department visits (ranked by triage) were: musculoskeletal problems/injury or bleeding (66.7%), causes unrelated to haemophilia (29%), suspected central venous catheter related infection (2.8%), and routine clotting factor infusion (1.5%). Additional tests were conducted during 335 visits (55.5%). Factor replacement was undertaken in 317 visits (52.5%). A total of 103 episodes (17.1%) required hospital admission, due to: head trauma (35.9%), central venous catheter -related infection (13.6%), haemarthrosis (8.7%), muscle haematoma (6.8%), and haematuria (5.8%). CONCLUSION: Haemophilic patients went to the Emergency Department for common paediatric causes, but also requested consultation on specific problems related to haemophilia, with musculoskeletal problems/injury or bleeding being the main issues. The paediatric Emergency Department is an indispensable component of haemophilia care.

4.
Blood Coagul Fibrinolysis ; 30(3): 111-119, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30958454

RESUMO

: Arthrocentesis of an acute hemarthrosis in hemophilia remains a controversial issue. The purpose of this study is to define the role that joint aspiration can play in the recovery from acute hemarthrosis in patients with hemophilia. The study sample included 33 hemophilic patients (55 joints) with acute elbow, knee, and ankle hemarthrosis as confirmed by ultrasonography. Patients were distributed into a treatment group and a control group. Patients in the first group were subjected to joint aspiration, whereas patients in the second were not. Arthrocentesis was carried out immediately after diagnosis of acute hemarthrosis in liquid phase. Patients were infused with the deficient coagulation factor and were instructed to observe relative rest until resolution of hemarthrosis. The following parameters were analyzed: time to full resolution of hemarthrosis (determined by ultrasonography), duration of treatment with the deficient coagulation factor, time to pain relief, time to recovery of prebleed range of motion, and time to resumption of school/work (all of these measured in days). The joints treated with joint aspiration exhibited a significantly faster resolution of bleeding (fewer days). In addition, this group required fewer days of pharmacological treatment, with faster achievement of functional recovery and resumption of school/work activities. No complications were observed. This study shows that joint aspiration under hemostatic cover and in strictly aseptic conditions is a well-tolerated technique that makes the recovery of acute hemarthrosis of hemophilic patients faster.


Assuntos
Artrocentese/métodos , Hemartrose/terapia , Hemofilia A/complicações , Articulações/patologia , Doença Aguda , Adulto , Articulação do Tornozelo , Articulação do Cotovelo , Feminino , Hemartrose/cirurgia , Humanos , Articulação do Joelho , Masculino , Fatores de Tempo , Resultado do Tratamento
5.
Haemophilia ; 25(3): 500-508, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30664313

RESUMO

INTRODUCTION: Haemophilic arthropathy (osteoarthritis secondary to haemophilia) of the ankle may result in painful hindfoot malalignment. PURPOSE: To analyse hindfoot alignment in subjects with haemophilic arthropathy of the ankle and evaluate the response (improvement of pain, function and alignment) to the orthotic treatment prescribed in patients with malalignment. METHODS: The study included 163 patients with haemophilia, all of them over 16 years of age. Hindfoot alignment and footprint were analysed in patients with and without haemophilic arthropathy of the ankle (as determined by the Pettersson score). Response to the use of an orthosis was evaluated at 6 months by means of the AOFAS Ankle-Hindfoot Scale. RESULTS: Fifty-six (59.5%) patients with haemophilic arthropathy presented with concomitant  hindfoot malalignment. The most common abnormality was a valgus alignment combined with a neutral footprint. In 14 cases, valgus was associated with a pes planus or a pes cavus. Only 5 patients without haemophilic arthropathy (7.2%) presented with some form of malalignment. The differences between the groups were statistically significant. The probability of having malalignment increased with the degree of arthropathy. Patients with haemophilic arthropathy and malalignment were treated with an orthosis, with insoles as the most commonly used alternative (86%). Such treatment significantly improved patients' pain and function-related scores on the AOFAS Ankle-Hindfoot Scale. CONCLUSION: Given the high rates of valgus malalignment in subjects with haemophilic arthropathy of the ankle, and the good response rates obtained following individualised orthotic treatment, it seems reasonable to routinely evaluate hindfoot alignment in this group of patients.


Assuntos
Articulação do Tornozelo/cirurgia , Pé/patologia , Hemartrose/diagnóstico , Hemartrose/cirurgia , Aparelhos Ortopédicos , Adolescente , Adulto , Articulação do Tornozelo/patologia , Diagnóstico Precoce , Feminino , Hemartrose/patologia , Humanos , Masculino , Adulto Jovem
6.
Haemophilia ; 25(1): 144-153, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30444298

RESUMO

AIM: The use of musculoskeletal ultrasound (MSK-US) following protocols for haemophilic arthropathy and the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) score can help standardize monitoring in haemophilia. This study evaluated the joint status (elbows, knees and ankles) of patients with haemophilia B (HB) in Spain using MSK-US and the HEAD-US score. METHODS: Haemophilia B patients ≥14 years old were included in this observational, multicentre, cross-sectional study, regardless of their clinical condition, HB severity and treatment received. Two blinded observers were involved in image acquisition and scoring in each centre. RESULTS: Eighty-two patients from 12 centres were enrolled: 27% mild HB, 23% moderate, 50% severe HB. Mean age was 38.9 ± 16.4 years, 60% were treated on demand (OD) and 40% were on prophylaxis. HEAD-US was zero in all joints in 28.6% OD patients and 36.4% on prophylaxis. Mean scores significantly worsened with HB severity, except for the left knee. Patients on primary and secondary prophylaxis had significantly better joint health vs OD patients in all joints, except the right ankle. Among OD patients, those with severe disease presented significantly worse scores in all HEAD-US items related to permanent damage. CONCLUSION: Joint status of HB patients in Spain is influenced by severity and treatment modality, related to the development of arthropathy, which appears prevalent in OD patients with severe HB. Routine assessment with an imaging tool such as ultrasound and HEAD-US system may help to improve joint health by personalizing and adjusting treatment in this population.


Assuntos
Hemofilia B/patologia , Artropatias/diagnóstico , Articulações/diagnóstico por imagem , Sinovite/diagnóstico , Adolescente , Adulto , Estudos Transversais , Humanos , Artropatias/patologia , Modelos Logísticos , Pessoa de Meia-Idade , Razão de Chances , Índice de Gravidade de Doença , Espanha , Sinovite/patologia , Ultrassonografia , Adulto Jovem
7.
Thromb Haemost ; 118(4): 734-744, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29554698

RESUMO

Etiopathogenesis of myelodysplastic syndrome (MDS) might cause per se an anomalous haemostasis that can be even more deteriorated by thrombocytopaenia. So, evaluation of haemostasis in patients with MDS rises as a necessity.This work aimed to characterize haemostasis in non-bleeder MDS patients with a platelet count similar to healthy controls to establish differences between the two groups not related to thrombocytopaenia.Thromboelastometry in samples from MDS patients suggested the existence of at least two antagonistic processes: one of them giving a hypocoagulable pattern (prolonged clotting time and lower α angle) and another conferring a procoagulant profile (decreased fibrinolysis). Hypocoagulable state might be due to a decreased ability of platelets to be stimulated and to the presence in plasma of a factor/s that prolonged the time to initiate thrombin generation. This factor/s might be antibodies as this effect was observed in samples from MDS patients with an associated autoimmune-inflammatory condition.Otherwise, hypercoagulable state seemed to rely on an increased presence of red cell- and monocyte-derived microparticles and to the increased exposure of phosphatidylserine that served as scaffold for binding of coagulation factors.We concluded that haemostasis in MDS patients is a complex process influenced by more factors than platelet count.


Assuntos
Hemostasia , Síndromes Mielodisplásicas/sangue , Adulto , Idoso , Automação , Coagulação Sanguínea , Fatores de Coagulação Sanguínea/metabolismo , Testes de Coagulação Sanguínea , Plaquetas/metabolismo , Caspases/metabolismo , Micropartículas Derivadas de Células/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/metabolismo , Fosfatidilserinas/química , Contagem de Plaquetas , Plasma Rico em Plaquetas/metabolismo , Estudos Prospectivos , Tromboelastografia , Trombina/metabolismo
8.
Recurso na Internet em Espanhol | LIS - Localizador de Informação em Saúde, LIS-ES-CIUD | ID: lis-LISBR1.1-46032

RESUMO

Guía que mediante un sencillo sistema de preguntas y respuestas trata de aclarar las dudas más habituales que se les plantean a los pacientes con hemofilia a la hora de planificar su viaje. Se estructura en tres partes: antes, durante y después del viaje. Incluye una lista de comprobación al final de la guía con el fin de facilitar la recopilación de todo lo necesario.


Assuntos
Hemofilia A , Saúde do Viajante
9.
Int J Hematol ; 106(4): 508-516, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28667351

RESUMO

Eltrombopag is safe and effective in primary chronic ITP. However, lack of clinical trials avoids a clear demonstration of its utility in newly diagnosed and persistent ITP. Our aim here is to report Spanish results for this type of patients. We retrospectively evaluated 220 adult primary ITP patients. According to standard definition, patients were allocated to newly diagnosed (n = 30), persistent (n = 30), and chronic (n = 160) ITP. Groups were homogenous regarding most relevant parameters. 180 (90%) of 220 patients achieved a platelet response (R) with 167 (75.9%) complete responses (CR) after a 15-month follow-up. No statistical significant differences among groups but a trend towards a greater efficacy in newly diagnosed ITP were observed (93.3% of responses with 86.7% of CR). Efficacy in persistent ITP (83.3% of responses with 80.0% of CR) and chronic ITP (79.4% of responses with 73.1% of CR) was similar. 70 patients (31.8%) experienced adverse events. 15 of them were grade 3-4. Most common adverse effects were headache and hepatobiliary laboratory abnormalities (HBLAs). One persistent ITP had a venous thrombosis and one chronic ITP had grade II myelofibrosis. We consider Eltrombopag use for the early stage ITP as effective and safe as it is in chronic ITP.


Assuntos
Benzoatos/administração & dosagem , Hidrazinas/administração & dosagem , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/administração & dosagem , Idoso , Benzoatos/efeitos adversos , Doença Crônica , Seguimentos , Humanos , Hidrazinas/efeitos adversos , Pessoa de Meia-Idade , Pirazóis/efeitos adversos
10.
Thromb Haemost ; 117(1): 66-74, 2017 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-27734074

RESUMO

Currently, molecular diagnosis of haemophilia A and B (HA and HB) highlights the excess risk-inhibitor development associated with specific mutations, and enables carrier testing of female relatives and prenatal or preimplantation genetic diagnosis. Molecular testing for HA also helps distinguish it from von Willebrand disease (VWD). Next-generation sequencing (NGS) allows simultaneous investigation of several complete genes, even though they may span very extensive regions. This study aimed to evaluate the usefulness of a molecular algorithm employing an NGS approach for sequencing the complete F8, F9 and VWF genes. The proposed algorithm includes the detection of inversions of introns 1 and 22, an NGS custom panel (the entire F8, F9 and VWF genes), and multiplex ligation-dependent probe amplification (MLPA) analysis. A total of 102 samples (97 FVIII- and FIX-deficient patients, and five female carriers) were studied. IVS-22 screening identified 11 out of 20 severe HA patients and one female carrier. IVS-1 analysis did not reveal any alterations. The NGS approach gave positive results in 88 cases, allowing the differential diagnosis of mild/moderate HA and VWD in eight cases. MLPA confirmed one large exon deletion. Only one case did have no pathogenic variants. The proposed algorithm had an overall success rate of 99 %. In conclusion, our evaluation demonstrates that this algorithm can reliably identify pathogenic variants and diagnose patients with HA, HB or VWD.


Assuntos
Algoritmos , Fator IX/genética , Fator VIII/genética , Hemofilia A/diagnóstico , Hemofilia A/genética , Hemofilia B/diagnóstico , Hemofilia B/genética , Sequenciamento de Nucleotídeos em Larga Escala , Técnicas de Diagnóstico Molecular , Mutação , Fator de von Willebrand/genética , Análise Mutacional de DNA , Diagnóstico Diferencial , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Hemofilia A/sangue , Hemofilia B/sangue , Heterozigoto , Humanos , Masculino , Reação em Cadeia da Polimerase Multiplex , Fenótipo , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
11.
Blood Coagul Fibrinolysis ; 27(7): 737-744, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27116081

RESUMO

The World Federation of Hemophilia and the National Hemophilia Foundation encourage people with haemophilia (PWH) to participate in routine physical activity. The benefits of physical activity for PWH include improvements in joint, bone, and muscle health. Accordingly, a number of studies suggest that levels of physical activity among PWH are similar to those of their healthy peers, especially among individuals who began prophylaxis at an early age (≤3 years). Importantly, several studies found either no increased risk or only a transient increase in risk of bleeding with more intensive physical activity compared with less intensive physical activity. Data on optimal prophylaxis regimens for PWH who participate in physical/sporting activities; however, remain sparse. Long-acting recombinant factor VIII Fc fusion protein (rFVIIIFc) and recombinant factor IX Fc fusion protein (rFIXFc) demonstrated efficacy for the prevention and treatment of bleeding episodes in Phase 3 clinical trials of participants with haemophilia A and B, respectively, with most individuals able to maintain or increase their physical activities. This manuscript reviews the current literature that describes physical activity in PWH. Additionally, case studies are presented to provide supplemental information to clinicians illustrating the use of rFVIIIFc and rFIXFc in physically active patients with haemophilia A and B, respectively. These case reports demonstrate that it is possible for patients to be physically active and maintain good control of their haemophilia with extended interval prophylactic dosing using rFVIIIFc or rFIXFc.


Assuntos
Exercício/fisiologia , Fator IX/uso terapêutico , Fator VIII/uso terapêutico , Hemofilia A/tratamento farmacológico , Hemofilia A/terapia , Hemofilia A/complicações , Humanos
12.
Thromb Haemost ; 115(5): 872-95, 2016 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-26842562

RESUMO

Prophylaxis with the blood clotting factor, factor VIII (FVIII) is ineffective for individuals with haemophilia A and high-titre inhibitors to FVIII. Prophylaxis with the FVIII bypassing agents activated prothrombin complex concentrates (aPCC; FEIBA® Baxalta) or recombinant activated factor VII (rFVIIa; Novo-Seven®, Novo Nordisk) may be an effective alternative. It was our aim to develop evidence -and expert opinion- based guidelines for prophylactic therapy for patients with high-titre inhibitors to FVIII. A panel of nine Spanish haematologists undertook a systematic review of the literature to develop consensus-based guidance. Particular consideration was given to prophylaxis in patients prior to undergoing immune tolerance induction (ITI) (a process of continued exposure to FVIII that can restore sensitivity for some patients), during the ITI period and for those not undergoing ITI or for whom ITI had failed. These guidelines offer guidance for clinicians in deciding which patients might benefit from prophylaxis with FVIII bypassing agents, the most appropriate agents in various clinical settings related to ITI, doses and dosing regimens and how best to monitor the efficacy of prophylaxis. The paper includes recommendations on when to interrupt or stop prophylaxis and special safety concerns during prophylaxis. These consensus guidelines offer the most comprehensive evaluation of the clinical evidence base to date and should be of considerable benefit to clinicians facing the challenge of managing patients with severe haemophilia A with high-titre FVIII inhibitors.


Assuntos
Fatores de Coagulação Sanguínea/uso terapêutico , Fator VIII/antagonistas & inibidores , Fator VIIa/uso terapêutico , Hemofilia A/terapia , Consenso , Medicina Baseada em Evidências , Fator VIII/imunologia , Hemofilia A/sangue , Hemofilia A/imunologia , Humanos , Imunossupressão/métodos , Proteínas Recombinantes/uso terapêutico , Prevenção Secundária , Espanha
13.
Blood ; 127(14): 1761-9, 2016 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-26755710

RESUMO

A global phase 3 study evaluated the pharmacokinetics, efficacy, and safety of recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 63 previously treated male patients (12-61 years) with severe hemophilia B (factor IX [FIX] activity ≤2%). The study included 2 groups: group 1 patients received routine prophylaxis once every 7 days for 26 weeks, followed by either 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively; group 2 patients received on-demand treatment of bleeding episodes for 26 weeks and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks. The mean terminal half-life of rIX-FP was 102 hours, 4.3-fold longer than previous FIX treatment. Patients maintained a mean trough of 20 and 12 IU/dL FIX activity on prophylaxis with rIX-FP 40 IU/kg weekly and 75 IU/kg every 2 weeks, respectively. There was 100% reduction in median annualized spontaneous bleeding rate (AsBR) and 100% resolution of target joints when subjects switched from on-demand to prophylaxis treatment with rIX-FP (P< .0001). The median AsBR was 0.00 for all prophylaxis regimens. Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection. No patient developed an inhibitor, and no safety concerns were identified. These results indicate rIX-FP is safe and effective for preventing and treating bleeding episodes in patients with hemophilia B at dosing regimens of 40 IU/kg weekly and 75 IU/kg every 2 weeks. This trial was registered at www.clinicaltrials.gov as #NCT0101496274.


Assuntos
Albuminas/administração & dosagem , Albuminas/farmacocinética , Fator IX/administração & dosagem , Fator IX/farmacocinética , Hemofilia B/sangue , Hemofilia B/prevenção & controle , Adolescente , Adulto , Albuminas/efeitos adversos , Criança , Fator IX/efeitos adversos , Hemofilia B/patologia , Hemorragia/sangue , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/farmacocinética
14.
Eur J Haematol ; 96(5): 461-74, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26714021

RESUMO

INTRODUCTION: Patients with severe haemophilia and inhibitors against factor VIII who require surgery need a prophylactic approach to prevent bleeding complications. Scientific evidence to decide the best prophylactic treatment is very limited and mainly based on retrospective or case series. AIMS: To develop evidence- and expert opinion-based guidelines for prophylactic therapy for patients with haemophilia and inhibitors undergoing surgery. METHODS: A panel of nine Spanish haematologists undertook a systematic review of the literature and selected publications providing relevant information regarding the prophylactic management of patients with haemophilia and inhibitors undergoing dental extraction, minor surgery or major surgery. RESULTS: Although evidence is very limited, the panel considers that it seems advisable that prophylaxis should be given in most cases with a bypassing agent (aPCC or rFVIIa) and should start immediately before minor or major surgery. Patients should be closely monitored to enable dose/product modification as needed. CONCLUSION: It is necessary to communicate clinical experience in a detailed way in order to ensure optimal schemes of prophylaxis for patients with haemophilia and inhibitors. Development of objective outcomes to evaluate efficacy is crucial.


Assuntos
Fator VIII/imunologia , Hemofilia A/complicações , Hemofilia A/imunologia , Hemorragia/etiologia , Hemorragia/prevenção & controle , Isoanticorpos/imunologia , Pré-Medicação , Fatores Etários , Gerenciamento Clínico , Fator VIII/efeitos adversos , Fator VIII/uso terapêutico , Fator VIIa/administração & dosagem , Fator VIIa/efeitos adversos , Fator VIIa/efeitos dos fármacos , Hemofilia A/tratamento farmacológico , Hemorragia/diagnóstico , Hemorragia/cirurgia , Humanos , Procedimentos Ortopédicos , Guias de Prática Clínica como Assunto , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/efeitos dos fármacos , Retratamento , Procedimentos Cirúrgicos Operatórios/métodos , Tempo para o Tratamento
15.
Eur J Haematol ; 97(3): 297-302, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26709028

RESUMO

BACKGROUND: Eltrombopag is effective and safe in chronic immune thrombocytopenia (ITP). However, clinical trials may not accurately reflect what happens in clinical practice. We evaluated the efficacy and safety of eltrombopag in primary chronic ITP in a real-world setting. METHODS: A total of 164 primary patients with chronic ITP from 40 Spanish centers, who had been treated with eltrombopag, were retrospectively evaluated. RESULTS: The median age of our cohort (72% women) was 63 yr (interquartile range, IQR, 45-75 yr). The median time with ITP diagnosis was 81 months (IQR, 30-192 months). The median number of therapies prior to eltrombopag was 3 (IQR, 2-4). At the time of eltrombopag start, 45 patients (30%) were receiving concomitant treatment for ITP. Forty-six patients (30%) had bleeding signs/symptoms the month before the treatment started. The median platelet count at eltrombopag initiation was 22 × 10(9) /L (IQR, 8-39 × 10(9) /L). A total of 135 patients (88.8%) achieved a platelet response. The median time to platelet response was 12 d (95% CI, 9-13 d). Maintained platelet response rate during the 15-month period under examination was 75.2%. Twenty-eight patients (18.4%) experienced adverse events, mainly grades 1-2. CONCLUSION: Eltrombopag is highly effective and well tolerated in unselected patients with primary chronic ITP.


Assuntos
Benzoatos/uso terapêutico , Hidrazinas/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/uso terapêutico , Idoso , Benzoatos/administração & dosagem , Benzoatos/efeitos adversos , Doença Crônica , Feminino , Humanos , Hidrazinas/administração & dosagem , Hidrazinas/efeitos adversos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/imunologia , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Retratamento , Estudos Retrospectivos , Espanha , Resultado do Tratamento
16.
Br J Haematol ; 169(1): 111-6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25521630

RESUMO

The thrombopoietin receptor agonists (THPO-RAs), romiplostim and eltrombopag, are effective and safe in immune thrombocytopenia (ITP). However, the value of their sequential use when no response is achieved or when adverse events occur with one THPO-RA has not been clearly established. Here we retrospectively evaluated 51 primary ITP adult patients treated with romiplostim followed by eltrombopag. The median age of our cohort was 49 (range, 18-83) years. There were 32 women and 19 men. The median duration of romiplostim use before switching to eltrombopag was 12 (interquartile range 5-21) months. The reasons for switching were: lack of efficacy (n = 25), patient preference (n = 16), platelet-count fluctuation (n = 6) and side-effects (n = 4). The response rate to eltrombopag was 80% (41/51), including 67% (n = 35) complete responses. After a median follow-up of 14 months, 31 patients maintained their response. Efficacy was maintained after switching in all patients in the patient preference, platelet-count fluctuation and side-effect groups. 33% of patients experienced one or more adverse events during treatment with eltrombopag. We consider the use of eltrombopag after romiplostim for treating ITP to be effective and safe. Response to eltrombopag was related to the cause of romiplostim discontinuation.


Assuntos
Benzoatos/administração & dosagem , Benzoatos/efeitos adversos , Hidrazinas/administração & dosagem , Hidrazinas/efeitos adversos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Receptores Fc/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Trombopoetina/administração & dosagem , Trombopoetina/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue , Receptores de Trombopoetina/agonistas , Estudos Retrospectivos
17.
Am J Hematol ; 90(3): E40-3, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25400215

RESUMO

Eltrombopag is effective and safe in immune thrombocytopenia (ITP). Some patients may sustain their platelet response when treatment is withdrawn but the frequency of this phenomenon is unknown. We retrospectively evaluated 260 adult primary ITP patients (165 women and 95 men; median age, 62 years) treated with eltrombopag after a median time from diagnosis of 24 months. Among the 201 patients who achieved a complete remission (platelet count >100 × 10(9) /l), eltrombopag was discontinued in 80 patients. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n = 33), platelet count >400 × 10(9) /l (n = 29), patient's request (n = 5), elevated aspartate aminotransferase (n = 3), diarrhea (n = 3), thrombosis (n = 3), and other reasons (n = 4). Of the 49 evaluable patients, 26 patients showed sustained response after discontinuing eltrombopag without additional ITP therapy, with a median follow-up of 9 (range, 6-25) months. These patients were characterized by a median time since ITP diagnosis of 46.5 months, with 4/26 having ITP < 1 year. Eleven patients were male and their median age was 59 years. They received a median of 4 previous treatment lines and 42% were splenectomized. No predictive factors of sustained response after eltrombopag withdrawal were identified. Platelet response following eltrombopag cessation may be sustained in an important percentage of adult primary ITP patients who achieved CR with eltrombopag. However, reliable markers for predicting which patients will have this response are needed.


Assuntos
Benzoatos/administração & dosagem , Eritropoese/efeitos dos fármacos , Hematínicos/administração & dosagem , Hidrazinas/administração & dosagem , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/administração & dosagem , Adulto , Idoso , Plaquetas/efeitos dos fármacos , Plaquetas/patologia , Doença Crônica , Esquema de Medicação , Monitoramento de Medicamentos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/patologia , Púrpura Trombocitopênica Idiopática/cirurgia , Receptores de Trombopoetina/agonistas , Receptores de Trombopoetina/genética , Receptores de Trombopoetina/metabolismo , Recidiva , Indução de Remissão , Estudos Retrospectivos , Esplenectomia , Resultado do Tratamento
19.
Hum Mol Genet ; 22(9): 1903-10, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23372042

RESUMO

Human genetic variation contributes to differences in susceptibility to HIV-1 infection. To search for novel host resistance factors, we performed a genome-wide association study (GWAS) in hemophilia patients highly exposed to potentially contaminated factor VIII infusions. Individuals with hemophilia A and a documented history of factor VIII infusions before the introduction of viral inactivation procedures (1979-1984) were recruited from 36 hemophilia treatment centers (HTCs), and their genome-wide genetic variants were compared with those from matched HIV-infected individuals. Homozygous carriers of known CCR5 resistance mutations were excluded. Single nucleotide polymorphisms (SNPs) and inferred copy number variants (CNVs) were tested using logistic regression. In addition, we performed a pathway enrichment analysis, a heritability analysis, and a search for epistatic interactions with CCR5 Δ32 heterozygosity. A total of 560 HIV-uninfected cases were recruited: 36 (6.4%) were homozygous for CCR5 Δ32 or m303. After quality control and SNP imputation, we tested 1 081 435 SNPs and 3686 CNVs for association with HIV-1 serostatus in 431 cases and 765 HIV-infected controls. No SNP or CNV reached genome-wide significance. The additional analyses did not reveal any strong genetic effect. Highly exposed, yet uninfected hemophiliacs form an ideal study group to investigate host resistance factors. Using a genome-wide approach, we did not detect any significant associations between SNPs and HIV-1 susceptibility, indicating that common genetic variants of major effect are unlikely to explain the observed resistance phenotype in this population.


Assuntos
Resistência à Doença/genética , Estudo de Associação Genômica Ampla , Infecções por HIV/genética , Hemofilia A/genética , Adulto , Variações do Número de Cópias de DNA , Epistasia Genética , Fator VIII/uso terapêutico , Feminino , Deleção de Genes , Predisposição Genética para Doença , Soropositividade para HIV/genética , Heterozigoto , Homozigoto , Humanos , Modelos Logísticos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Receptores CCR5/genética , Receptores CCR5/metabolismo
20.
Blood ; 120(18): 3670-6, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-22915649

RESUMO

Rozrolimupab, a recombinant mixture of 25 fully human RhD-specific monoclonal antibodies, represents a new class of recombinant human antibody mixtures. In a phase 1 or 2 dose escalation study, RhD(+) patients (61 subjects) with primary immune thrombocytopenia received a single intravenous dose of rozrolimupab ranging from 75 to 300 µg/kg. The primary outcome was the occurrence of adverse events. The principal secondary outcome was the effect on platelet levels 7 days after the treatment. The most common adverse events were headache and pyrexia, mostly mild, and reported in 20% and 13% of the patients, respectively, without dose relationship. Rozrolimupab caused an expected transient reduction of hemoglobin concentration in the majority of the patients. At the dose of 300 µg/kg platelet responses, defined as platelet count ≥ 30 × 10(9)/L and an increase in platelet count by > 20 × 10(9)/L from baseline were observed after 72 hours and persisted for at least 7 days in 8 of 13 patients (62%). Platelet responses were observed within 24 hours in 23% of patients and lasted for a median of 14 days. Rozrolimupab was well tolerated and elicited rapid platelet responses in patients with immune thrombocytopenia and may be a useful alternative to plasma-derived products. This trial is registered at www.clinicaltrials.gov as #NCT00718692.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Imunoglobulina G/administração & dosagem , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Proteínas Recombinantes/administração & dosagem , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacocinética , Relação Dose-Resposta a Droga , Feminino , Humanos , Imunoglobulina G/efeitos adversos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacocinética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA