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Sickle cell disease is an autosomal recessive, multisystem disorder, characterised by chronic haemolytic anaemia, painful episodes of vaso-occlusion, progressive organ failure and a reduced life expectancy. Sickle cell disease is the most common monogenetic disease, with millions affected worldwide. In well-resourced countries, comprehensive care programs have increased life expectancy of sickle cell disease patients, with almost all infants surviving into adulthood. Therapeutic options for sickle cell disease patients are however, still scarce. Predictors of sickle cell disease severity and a better understanding of pathophysiology and (epi)genetic modifiers are warranted and could lead to more precise management and treatment. This review provides an extensive summary of the pathophysiology and management of sickle cell disease and encompasses the characteristics, complications and current and future treatment options of the disease.
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Anemia Falciforme/complicações , Saúde Global , HumanosRESUMO
Essentials A pediatric pharmacogenetic dosing algorithm for acenocoumarol has not yet been developed. We conducted a multicenter retrospective follow-up study in children in the Netherlands. Body surface area and indication explained 45.0% of the variability in dose requirement. Adding the genotypes of VKORC1, CYP2C9 and CYP2C18 to the algorithm increased this to 61.8%. SUMMARY: Background The large variability in dose requirement of vitamin K antagonists is well known. For warfarin, pediatric dosing algorithms have been developed to predict the correct dose for a patient; however, this is not the case for acenocoumarol. Objectives To develop dosing algorithms for pediatric patients receiving acenocoumarol with and without genetic information. Methods The Children Anticoagulation and Pharmacogenetics Study was designed as a multicenter retrospective follow-up study in Dutch anticoagulation clinics and children's hospitals. Pediatric patients who used acenocoumarol between 1995 and 2014 were selected for inclusion. Clinical information and saliva samples for genotyping of the genes encoding cytochrome P450 (CYP) 2C9, vitamin K epoxide reductase complex subunit 1 (VKORC1), CYP4F2, CYP2C18 and CYP3A4 were collected. Linear regression was used to analyze their association with the log mean stable dose. A stable period was defined as three or more consecutive International Normalized Ratio measurements within the therapeutic range over a period of ≥ 3 weeks. Results In total, 175 patients were included in the study, of whom 86 had a stable period and no missing clinical information (clinical cohort; median age 8.9 years, and 49% female). For 80 of these 86 patients, genetic information was also available (genetic cohort). The clinical algorithm, containing body surface area and indication, explained 45.0% of the variability in dose requirement of acenocoumarol. After addition of the VKORC1, CYP2C9, and CYP2C18 genotypes to the algorithm, this increased to 61.8%. Conclusions These findings show that clinical factors had the largest impact on the required dose of acenocoumarol in pediatric patients. Nevertheless, genetic factors, and especially VKORC1, also explained a significant part of the variability.
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Acenocumarol/administração & dosagem , Anticoagulantes/administração & dosagem , Acenocumarol/análise , Acenocumarol/farmacocinética , Adolescente , Fatores Etários , Algoritmos , Anticoagulantes/análise , Anticoagulantes/farmacocinética , Variação Biológica Individual , Biotransformação/genética , Superfície Corporal , Criança , Pré-Escolar , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Estudos de Associação Genética , Humanos , Lactente , Masculino , Modelos Biológicos , Polimorfismo de Nucleotídeo Único , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Saliva/química , Trombofilia/tratamento farmacológico , Vitamina K/antagonistas & inibidoresRESUMO
Essentials The knowledge of quality and safety of acenocoumarol and phenprocoumon use in children is limited. We used data from a multicenter retrospective follow-up study in children in the Netherlands. The quality of anticoagulation control in the first month of use was low, but improved thereafter. No thromboembolic events occurred, however bleeding events occurred in 1-3 out of 10 patients. SUMMARY: Background The use of vitamin-K antagonists in pediatric patients is rare and information on the quality and safety of treatment with acenocoumarol and phenprocoumon is limited. Objectives To assess the quality, safety and effectiveness during the first year of acenocoumarol and phenprocoumon treatment in pediatric patients in the Netherlands. Methods The Children Anticoagulation and Pharmacogenetics Study (CAPS) was designed as a multicenter retrospective follow-up study. Patients who used acenocoumarol or phenprocoumon at an age of ≤ 18 years, were selected from four pediatric hospitals and one anticoagulation clinic in the Netherlands. The quality of treatment was assessed by calculating the percentage of time in therapeutic INR range (TTR) for the first month and for every 3 months of use during the first year of treatment. Effectiveness and safety were assessed by the number of thromboembolic and bleeding events. Results In total, 213 patients participated, of whom 187 (155 acenocoumarol; 32 phenprocoumon) were included in this analysis. The mean TTR was 47.0% and 51.4% in the first month of use for acenocoumarol and phenprocoumon, respectively. After the first 3 months the mean TTR for both VKAs was above 64%. In 14.6% (acenocoumarol) and 31.3% (phenprocoumon) of the patients a bleeding event occurred during the first year of treatment; no thromboembolic events were reported. Conclusions The quality of anticoagulation treatment was low during the first month of use and leaves room for improvement. After the first month it increased to an acceptable level. However, bleeding events occurred frequently during the first year.
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Acenocumarol/administração & dosagem , Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Femprocumona/administração & dosagem , Tromboembolia/tratamento farmacológico , Acenocumarol/efeitos adversos , Administração Oral , Adolescente , Fatores Etários , Anticoagulantes/efeitos adversos , Criança , Pré-Escolar , Monitoramento de Medicamentos/métodos , Feminino , Fidelidade a Diretrizes/normas , Hemorragia/induzido quimicamente , Humanos , Lactente , Coeficiente Internacional Normatizado , Masculino , Países Baixos , Femprocumona/efeitos adversos , Guias de Prática Clínica como Assunto/normas , Padrões de Prática Médica/normas , Indicadores de Qualidade em Assistência à Saúde/normas , Estudos Retrospectivos , Tromboembolia/sangue , Tromboembolia/diagnóstico , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Hereditary spherocytosis (HS) is a heterogeneous hemolytic anemia treated with splenectomy in patients suffering from severe or moderate disease. Total splenectomy, however, renders patients vulnerable to overwhelming postsplenectomy infection despite preventive measures. Although subtotal splenectomy has been advocated as an alternative to total splenectomy, long-term follow-up data are scarce. We investigated how often hematologic recurrences requiring secondary total splenectomy occurred. PROCEDURE: With a follow-up of at least 5 years, we analyzed the data of 12 patients, aged 11 years maximum (median 6.5 years), who had undergone intended subtotal splenectomy, and 9 patients (median age 11.9 years), who had undergone total splenectomy. We compared their hematologic results and searched for factors associated with secondary spleen surgery. RESULTS: Hemolysis was reduced after subtotal splenectomy and absent after total splenectomy. Subtotal splenectomy was not successful in three children because no functional splenic remnant remained after 6 months (one conversion at surgery; one necrosis of splenic remnant; one early secondary splenectomy). Four children required secondary splenectomy after a median of 5 years for hematologic recurrence. In the remaining five patients, a functional splenic remnant was present for at least 5.5 years. The median time to secondary total splenectomy after intended subtotal splenectomy was 5.2 years. In all patients requiring secondary total splenectomy, increased reticulocyte levels within 2 years indicated hematologic recurrence. CONCLUSIONS: Subtotal splenectomy can be an alternative for total splenectomy in young patients with HS. It allows for hematologic improvement and may preserve splenic immune function for as many as 5 years.
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Hemólise , Recuperação de Função Fisiológica , Esferocitose Hereditária , Esplenectomia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Esferocitose Hereditária/sangue , Esferocitose Hereditária/cirurgiaRESUMO
Treatment adherence in haemophilia is strongly associated with quality of life and the cost-benefit of treatment. Therefore, it is important to quantify and monitor it. This study aimed to validate a translation of the VERITAS-Pro cross-culturally and analyse treatment adherence in a Dutch population of paediatric haemophilia patients. Children aged 1-18 years with haemophilia were included from three Haemophilia Treatment Centres, on prophylactic clotting factor replacement therapy for more than 1 year. Parents and adolescents were analysed separately. The adherence scale for prophylactic therapy (VERITAS-Pro) was translated according to international guidelines. This instrument contains a total of six subscales ('Time', 'Dose', 'Plan', 'Remember', 'Skip' and 'Communicate') each with four items. Lower scores reflect higher adherence. Overall response rate was 85%, leading to a study population of 60 children. Mean age was 10 years (SD 4.1). Internal consistency reliability: Mean Cronbach's alphas were adequate (>0.70) for total score and the subscales 'Skip' and 'Communicate'. Item-own subscale correlations were stronger than most item-other subscale correlations. Convergent validity: Total scores were higher for non-adherent participants compared with adherent participants according to patient infusion logs (n = 48; P < 0.05). Test-retest correlations: Significant for all scales except 'Dose' (n = 58; P < 0.01). This study demonstrates applicability of VERITAS-Pro outside the United States, as total score and most subscales effectively quantified treatment adherence in a Dutch paediatric population on prophylactic therapy. Non-adherent respondents' total scores were significantly higher, demonstrating the ability of VERITAS-Pro to identify non-adherent individuals.
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Fatores de Coagulação Sanguínea/uso terapêutico , Hemofilia A/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Autoadministração/normas , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Países Baixos , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e Questionários , Estados UnidosRESUMO
Higher self-efficacy in chronic disease patients is associated with higher development of self-management skills and increased quality-of-life. Quantification and monitoring of self-efficacy is therefore of importance. Self-efficacy in haemophilia patients has received little attention due to lack of standardized scales. To validate the novel Haemophilia-specific Self-Efficacy Scale (HSES) in haemophilia patients on prophylactic home treatment, haemophilia patients aged 1-18 years on prophylactic treatment ≥1 year were included from three Dutch Haemophilia Treatment Centres. The HSES consists of 12 items, relating to perceptions of the ability to function on a day-to-day basis with regard to patient's disease. Retest was performed in a subsample. Validity was proven by the General Self-Efficacy Scale and by the health-related quality-of-life assessment tool Haemo-QoL. Data were analysed from 53 children (response 75%), with a mean age of 9.8 years (SD 4.0). Mean total scale score of HSES was 55.5 (SD 4.7; range 38-60), with a ceiling effect of 17%. The HSES showed adequate internal consistency (Cronbach's alpha 0.72) and good test-retest reliability (Intra-Class-Correlation coefficient 0.75; P < 0.01; n = 37). The convergent validity was adequate as haemophilia-specific self-efficacy correlated significantly with general self-efficacy (r = 0.38; P < 0.01). High HSES scores correlated significantly with quality-of-life as measured by the Haemo-QoL (r = -0.42; P ≤ 0.01). The novel HSES is a reliable and valid tool to assess self-efficacy in paediatric haemophilia patients on prophylactic home treatment. High self-efficacy correlated with higher quality-of-life, further underlining the importance to standardly assess, monitor and improve self-efficacy.
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Hemofilia A/psicologia , Psicometria/métodos , Autoeficácia , Adolescente , Criança , Humanos , MasculinoRESUMO
The aim of this study was to determine the effect of radial extracorporeal shock-wave therapy (rESWT) on patients with chronic tendinitis of the rotator cuff. This was a randomised controlled trial in which 82 patients (mean age 47 years (24 to 67)) with chronic tendinitis diagnosed clinically were randomly allocated to a treatment group who received low-dose rESWT (three sessions at an interval 10 to 14 days, 2000 pulses, 0.11 mJ/mm(2), 8 Hz) or to a placebo group, with a follow-up of six months. The patients and the treating orthopaedic surgeon, who were both blinded to the treatment, evaluated the results. A total of 44 patients were allocated to the rESWT group and 38 patients to the placebo group. A visual analogue scale (VAS) score for pain, a Constant-Murley (CMS) score and a simple shoulder test (SST) score significantly improved in both groups at three and six months compared with baseline (all p ≤ 0.012). The mean VAS was similar in both groups at three (p = 0.43) and six months (p = 0.262). Also, the mean CMS and SST scores were similar in both groups at six months (p = 0.815 and p = 0.834, respectively). It would thus seem that low-dose rESWT does not reduce pain or improve function in patients chronic rotator cuff tendinitis compared with placebo treatment.
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Ondas de Choque de Alta Energia/uso terapêutico , Manejo da Dor/métodos , Manguito Rotador/fisiopatologia , Articulação do Ombro/patologia , Tendinopatia/terapia , Adulto , Idoso , Doença Crônica , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Medição da Dor , Estudos Prospectivos , Manguito Rotador/patologia , Articulação do Ombro/fisiopatologia , Resultado do Tratamento , Adulto JovemRESUMO
With the introduction of prophylaxis, restricting children with haemophilia to participate in physical activities was no longer necessary. Subsequently, many studies report on improved physical functioning in children and adolescents with haemophilia. However, little is known about psychological aspects such as perceived competence and impact of disease. Therefore, the aims of this study were to explore: (i) perceived competence, (ii) perceived impact of illness, and (iii) analyse associations between perceived competence and demographic factors, disease-related factors and joint status in young haemophiliacs in the Netherlands. Fifty-four children (age 8-12 years) and 72 adolescents (12-18 years) with haemophilia participated in this cross-sectional, multi-centre, explorative study. Measurements included perceived competence (Self Perception Profile for Children/Adolescents; range 6-24/5-20), impact of disease (Revised Perception Illness Experience; range 1-5), demographic factors, disease-related factors, joint status and functional status. Mean (SD) scores for perceived competence in the children ranged from 17.3 (±4.0) to 19.6 (±4.0), and for adolescents from 13.3 (±2.4) to 15.7 (±2.8) points. In general, scores were comparable with those of healthy peers, but children with haemophilia had a lower global self-worth score and competence in close friendship was lower for adolescents when compared with those of healthy peers. Mean (SD) scores for impact of disease ranged from 1.2 (±0.4) to 2.3 (±0.8) in children and from 1.3 (±0.4) to 2.0 (±0.8) in adolescents. Severe haemophilia, prophylactic medication, high impact of disease and a shorter walking distance showed a weak to moderate association with perceived competence. Children and adolescents with haemophilia in general have a perceived competence that is nearly comparable with that of healthy peers, with the exception of a lower global self-worth in children and a lower competence for close friendship in adolescents. Haemophiliacs seem to perceive their disease as having relatively low impact on their life. Severe disease, prophylactic treatment and low functional status seemed to be associated with lower perceived competence.
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Atividades Cotidianas , Avaliação da Deficiência , Hemofilia A/fisiopatologia , Hemofilia B/fisiopatologia , Autoeficácia , Adolescente , Criança , Estudos Transversais , Feminino , Hemofilia A/psicologia , Hemofilia B/psicologia , Humanos , Masculino , Países Baixos , Qualidade de Vida , Amplitude de Movimento Articular , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Von Willebrand disease (VWD) is the most frequent inherited bleeding disorder. Whether VWD is associated with health-related quality of life (HR-QoL) in children is unknown. OBJECTIVES: This nationwide cross-sectional study measured HR-QoL in children with moderate or severe VWD. Our primary aim was to compare HR-QoL of VWD patients with that of reference populations. Additionally, we studied the impact of bleeding phenotype and VWD type on HR-QoL. METHODS: HR-QoL was assessed with the Infant/Toddler QoL Questionnaire (0-5 years) and Child Health Questionnaire (6-15 years), and compared with reference population scores. Multivariate analysis was used to evaluate the influence of type of VWD and bleeding phenotype on HR-QoL scores. RESULTS: Preschool children (0-5 years, n = 46) with VWD had lower HR-QoL scores for general health perceptions and parental time than reference populations. School children (6-15 years, n = 87) with VWD had lower scores for physical functioning, role functioning - emotional/behavioral, general health perceptions, and physical summary. Type of VWD was associated with HR-QoL in school children for bodily pain, general health perceptions, parental emotion, family activities, and physical summary. Scores of children with type 3 VWD were, on average, 15 points lower than those of the reference population on the above-mentioned scales. A more severe bleeding phenotype was associated with a lower score on 11/15 physical, emotional and social scales. CONCLUSION: HR-QoL is lower in VWD children than in reference populations, in particular in school children. The negative impact of VWD is sensitive to type of VWD and bleeding phenotype; as well as physical scales, emotional and social scales are affected.
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Doenças de von Willebrand/fisiopatologia , Doenças de von Willebrand/psicologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Emoções , Feminino , Hemorragia/sangue , Humanos , Lactente , Recém-Nascido , Masculino , Países Baixos , Avaliação de Resultados em Cuidados de Saúde , Fenótipo , Qualidade de Vida , Sociologia , Inquéritos e Questionários , Doenças de von Willebrand/sangue , Doenças de von Willebrand/classificaçãoRESUMO
Thrombosis is a multifactorial disorder. Congenital disorders of glycosylation (CDG) are one of the known risk factors for its occurrence. These disorders result in glycosylation defects of glycoproteins, including those of the (anti-)coagulation system. CDG-Ib can specifically be treated with mannose, as illustrated by the case of a 4-year-old girl in whom deep venous thrombosis was the presenting symptom after a common viral infection. The diagnosis was made after recurrent episodes of thrombo-embolism and consumptive coagulopathy. After treatment with mannose no such episodes recurred. The pathophysiology of CDG as a risk factor for thrombotic disease is discussed.
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Erros Inatos do Metabolismo dos Carboidratos/complicações , Manose/uso terapêutico , Tromboembolia/tratamento farmacológico , Fatores de Coagulação Sanguínea/análise , Erros Inatos do Metabolismo dos Carboidratos/metabolismo , Pré-Escolar , Feminino , Glicosilação/efeitos dos fármacos , Humanos , Recidiva , Tromboembolia/etiologia , Tromboembolia/metabolismoRESUMO
The aim of this pilot study was to investigate the effects of the transition from paediatric to adult health care services in haemophilia patients and their parents. We compared pretransition children (n = 9) and their parents (n = 18) to posttransition patients (n = 8) and their parents (n = 21). Pre- and posttransition patients did not differ in self-rated health-related quality of life (QoL) or worries about the transition. Fathers of posttransition patients rated their son's QoL as poorer than those of pretransition patients (P = 0.034) and indicated higher levels of illness-related distress than fathers of pretransition patients (P = 0.034). The findings indicate that the transition affects parents more than patients. Moreover, we found gender differences in parental worries about the transition. The findings indicate that programmes designed to facilitate the transition in haemophilic patients should also address the patients' parents.
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Atitude Frente a Saúde , Continuidade da Assistência ao Paciente , Saúde da Família , Hemofilia A/terapia , Pais/psicologia , Adolescente , Serviços de Saúde do Adolescente , Adulto , Ansiedade/etiologia , Feminino , Indicadores Básicos de Saúde , Hemofilia A/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Satisfação do Paciente , Projetos Piloto , Psicometria , Qualidade de Vida , Fatores Sexuais , Estresse Psicológico/psicologia , Adulto JovemRESUMO
3 pregnant women, aged 27, 33 and 31 years respectively, were carriers of haemophilia A. The first patient had a caesarean section without prior measurement or substitution of factor VIII. She gave birth to a healthy boy, but developed severe diffuse abdominal bleeding after a few hours. The second patient had a normal level of factor VIII, and lived 100 km away from the nearest haemophilia treatment centre. Ultrasound investigation revealed a female foetus. She gave birth in the local hospital. The third patient was pregnant with a male foetus, but refused further prenatal investigation. Contrary to medical advice she gave birth at home. For carriers of haemophilia, there are several options for prenatal diagnosis and managing labour and delivery. Early referral is advised and the need for adequate counselling is explained. It is important to have an experienced haemophilia treatment centre nearby, where haematologists, gynaecologists, geneticists and paediatricians cooperate in caring for pregnant carriers of haemophilia.
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Acessibilidade aos Serviços de Saúde , Hemofilia A/complicações , Obstetrícia/métodos , Complicações Hematológicas na Gravidez/prevenção & controle , Resultado da Gravidez , Adulto , Parto Obstétrico/métodos , Gerenciamento Clínico , Feminino , Hemofilia A/prevenção & controle , Humanos , Recém-Nascido , Masculino , Obstetrícia/normas , GravidezRESUMO
A 5-year-old boy presented with fever and fatigue after a holiday in northern Italy. On physical examination a marked splenomegaly was found. Laboratory investigations showed a pancytopenia as well as several markers suggesting an autoimmune disease. The splenomegaly and pancytopenia continued to progress despite treatment with prednisolone and intravenous immunoglobulins. One and a half years after presentation, the spleen had grown to such an extent that it was causing mechanical problems. Splenectomy was performed for diagnostic and therapeutic purposes. Histological investigation of the spleen showed amastigotes of Leishmania. PCR confirmed the diagnosis visceral leishmaniasis. Leishmaniasis is too often considered to be a tropical disease only. In recent years it has frequently been seen in southern European countries around the Mediterranean Sea.
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Leishmaniose Visceral/diagnóstico , Esplenomegalia/diagnóstico , Esplenomegalia/parasitologia , Pré-Escolar , Diagnóstico Diferencial , Febre de Causa Desconhecida/etiologia , Humanos , Leishmaniose Visceral/complicações , Masculino , Pancitopenia/diagnóstico , Pancitopenia/etiologia , Esplenomegalia/cirurgiaRESUMO
Anaemia was diagnosed in four adopted children during a standard screening examination 1-4 weeks after arrival. Further investigation revealed a number of causes which could then be specifically treated. The children were a girl aged 14 months from China with iron-deficiency anaemia, a boy aged 16 months from Nigeria with sickle cell anaemia, a girl aged 5 from Haiti who had alpha-thalassaemia, and a boy aged 7 from Brazil with spherocytosis. Iron deficiency is the most common cause of anaemia in childhood. However, in adopted children from sub-tropical areas other causes of anaemia like haemoglobinopathies or erythrocyte membrane defects should be borne in mind, particularly as a history of disease and family history are often lacking. Additional investigations may be necessary. An incorrect diagnosis of iron deficiency may result in ongoing and unjustified iron supplementation leading to harmful iron accumulation in thalassaemia and a delay in the correct treatment in sickle cell anemia or spherocytosis which could carry considerable risk.
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Anemia Ferropriva/diagnóstico , Anemia Falciforme/diagnóstico , Anemia/etiologia , Esferocitose Hereditária/diagnóstico , Talassemia alfa/diagnóstico , Adoção/etnologia , Anemia/epidemiologia , Anemia/etnologia , Anemia Ferropriva/complicações , Anemia Ferropriva/epidemiologia , Anemia Ferropriva/terapia , Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia , Anemia Falciforme/terapia , Brasil/etnologia , Criança , Pré-Escolar , China/etnologia , Diagnóstico Diferencial , Feminino , Haiti/etnologia , Humanos , Lactente , Masculino , Programas de Rastreamento , Nigéria/etnologia , Esferocitose Hereditária/complicações , Esferocitose Hereditária/epidemiologia , Esferocitose Hereditária/terapia , Talassemia alfa/complicações , Talassemia alfa/epidemiologia , Talassemia alfa/terapiaRESUMO
4 children, a boy aged 10 years and 3 girls aged 3, 3, and 16 years, suffering from chronic or refractory autoimmune haemolytic anaemia (AIHA), who were dependent on high doses of steroids and were refractory to immunosuppressants, were treated with rituximab at a dose of 375 mg/m2 once a week for 3 or 4 weeks as an alternative to splenectomy. Rituximab is a monoclonal anti-CD20 antibody that prevents the production ofautoantibodies by selective destruction of B-lymphocytes. Haemoglobin levels increased and the parameters of chronic haemolysis (reticulocyte count, lactate dehydrogenase activity, bilirubin concentration) decreased to normal values. 3 patients were taken off corticosteroids completely; 1 of these was also no longer dependent on blood transfusions. Circulating B-lymphocytes were absent for 6 to 15 months after the treatment and the rituximab was well-tolerated. During the treatment, immunoglobulins were substituted and infectious complications were not seen. Rituximab was valuable in the treatment of chronic or refractory AIHA and eliminated the need for splenectomy. 1 patient did not respond to rituximab.
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Anemia Hemolítica Autoimune/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Fatores Imunológicos/uso terapêutico , Adolescente , Anemia Hemolítica Autoimune/imunologia , Anticorpos Monoclonais Murinos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Rituximab , Esplenectomia , Resultado do TratamentoRESUMO
Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by intravascular haemolysis, nocturnal haemoglobinuria, thrombotic events, serious infections and bone marrow failure. This acquired disease, caused by a deficiency of glycosylphosphatidylinositol (GPI) anchored proteins on the haematopoietic cells, is rare in children. We describe 11 Dutch paediatric PNH patients (median age: 12 years, range 9-17 years) diagnosed since 1983, seven cases associated with aplastic anaemia (AA), four with myelodysplastic syndrome (MDS). Presenting symptoms were haemorrhagic diathesis (n = 10), palor/tiredness (n = 8), dark urine (n = 1), fever (n = 1) and serious weight loss (n = 1). Treatment consisted of prednisolone (n = 7), anti-thymocyte globulin (n = 3) and/or androgens (n = 5). Eventually, five patients received a bone marrow transplantation (BMT) (three matched unrelated donors/two matched family donors), of whom four are still alive. PNH, diagnosed by immunophenotypic GPI-linked anchor protein analysis, should be considered in all children with AA or MDS. BMT should be considered as a therapeutic option in every paediatric PNH patient with BM failure.