Assuntos
Hemartrose/terapia , Hemofilia A/complicações , Hemofilia A/terapia , Doenças Musculoesqueléticas/terapia , Doença Aguda , Tornozelo/cirurgia , Artrodese , Síndromes Compartimentais/etiologia , Síndromes Compartimentais/terapia , Terapia por Exercício , Hemartrose/cirurgia , Humanos , Doenças Musculoesqueléticas/etiologia , Doenças Musculoesqueléticas/cirurgia , SucçãoRESUMO
Skin necrosis and priapism are unusual complications of warfarin therapy. We report a teenager with warfarin-associated skin necrosis and priapism who was subsequently found to be a compound heterozygote for protein C deficiency and a heterozygote for the factor V Leiden mutation.
Assuntos
Anticoagulantes/efeitos adversos , Toxidermias/etiologia , Priapismo/induzido quimicamente , Varfarina/efeitos adversos , Adolescente , Toxidermias/complicações , Toxidermias/patologia , Fator V/genética , Humanos , Masculino , Necrose , Priapismo/complicações , Deficiência de Proteína C/complicações , Trombofilia/genéticaRESUMO
OBJECTIVES: To evaluate safety, efficacy, and outcome after combination thrombolytic and anticoagulant therapy. STUDY DESIGN: An open nonrandomized clinical protocol with prospective standardized monitoring and data collection. Children with a documented first episode of deep vein thrombosis were treated with urokinase 4400 U/kg load and per hour with unfractionated heparin at 10 U/kg/h. At 48 hours heparin infusions were increased to achieve a therapeutic level for 5 days. Children were given therapeutic warfarin for at least 3 months. Outcome was assessed at 48 hours and > or =1 year with history, physical examination, high-resolution imaging, and Doppler ultrasonography +/- impedance and photo plethysmography. RESULTS: Thirty-two children were treated. There was 1 thrombotic death, 1 nonfatal thrombus progression, and 1 pulmonary embolism. At 48 hours half of the children showed substantial clot lysis, and on follow-up these children had complete resolution and had no symptoms. Three children with poor early clot lysis had recurrent thromboemboli, pulmonary embolism, or both, 2 had limb pain and swelling, and 2 had asymptomatic swelling. Two children had minor bleeding, whereas systemic reactions were common. CONCLUSIONS: Combination therapy in children (urokinase and unfractionated heparin) was safe and efficacious. A prospective, randomized, controlled study in children is needed.
Assuntos
Anticoagulantes/uso terapêutico , Fibrinolíticos/uso terapêutico , Terapia Trombolítica , Trombose Venosa/tratamento farmacológico , Adolescente , Anticoagulantes/efeitos adversos , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Fibrinolíticos/efeitos adversos , Seguimentos , Humanos , Lactente , Masculino , Pletismografia/métodos , Estudos Prospectivos , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/estatística & dados numéricos , Resultado do Tratamento , Ultrassonografia , Trombose Venosa/sangue , Trombose Venosa/diagnóstico por imagemRESUMO
OBJECTIVE: The objective of this study was to determine the cause of purpura fulminans, disseminated intravascular coagulation, or thrombosis in seven children with varicella. All children were found to have a lupus anticoagulant and acquired protein S deficiency. Thrombosis in five children was associated with presumed or documented infection with streptococcus. STUDY DESIGN: Coagulation tests included determinations of the activated partial thromboplastin time, the prothrombin time, the dilute Russell viper venom time, the prothrombin F 1 + 2 fragment, the C4b-binding protein (C4b), total and free protein S antigen, and clotting activities of factors II, V, VII, and X and of protein C and protein S. Autoantibodies to phospholipids, cardiolipin, and protein S were determined in enzyme-linked immunosorbent assays. RESULTS: All children had a lupus anticoagulant and acquired protein S deficiency. Thrombosis in five children was associated with presumed or documented infection with streptococcus. All children transiently expressed free protein S deficiency, elevated levels of IgG, IgM, or both binding to protein S, the lupus anticoagulant, and increased concentration of the F 1+2 fragment. Four children also had antiphospholipid or anticardiolipin antibodies. In one child a purified IgG fraction cross-reacted with both protein S and a specific varicella antigen. CONCLUSIONS: A subset of children with varicella infection, some of whom are coinfected with streptococcus, are prone to development of a lupus anticoagulant and an autoantibody to protein S, which results in acquired free protein S deficiency. Such children are at risk of having life-threatening thrombotic events.
Assuntos
Varicela/complicações , Vasculite por IgA/etiologia , Inibidor de Coagulação do Lúpus/análise , Deficiência de Proteína S/etiologia , Trombose/etiologia , Anticorpos Antifosfolipídeos/análise , Testes de Coagulação Sanguínea , Estudos de Casos e Controles , Criança , Pré-Escolar , Coagulação Intravascular Disseminada/etiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Masculino , Fatores de Risco , Infecções Estreptocócicas/complicações , Streptococcus pyogenesRESUMO
OBJECTIVE: To determine whether resistance to activated protein C caused by the factor V Leiden mutation (Arg506 to Gln) is associated with thrombosis occurring during childhood. STUDY DESIGN: Children with thrombosis were screened for activated protein C resistance. Children found resistant to activated protein C had DNA analysis for the factor V Leiden mutation. Family members of the children with activated protein C resistance were similarly studied. RESULTS: Three of fourteen children examined had abnormal normalized activated protein C sensitivity ratios. One child had protein S deficiency. The children had hyperlipidemia. Molecular confirmation of the factor V Leiden mutation was obtained for all three children. Family members of each of the three children were affected. CONCLUSIONS: Children have thromboses in association with the factor V Leiden mutation, as do adults. This mutation may be identified as an isolated risk factor or in association with other risk factors for thrombosis.
Assuntos
Fator V/genética , Trombose/genética , Adolescente , Adulto , Testes de Coagulação Sanguínea , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Mutação , Linhagem , Proteína C/metabolismo , Fatores de Risco , Trombose/sangue , Trombose/epidemiologiaRESUMO
We hypothesized that magnetic resonance imaging (MRI) would improve clinical and plain-radiograph assessments of children with hemophilic arthropathy. Thirteen children, aged 7 to 16 years, with severe factor VIII deficiency and one or more target joints were identified. A target joint was defined as a joint into which hemorrhage had occurred at least twice a month for at least the previous 6 months. After review of history, examination, and plain radiography, a recommendation regarding synovectomy or prophylaxis with factor VIII concentrate was made for each target joint. The MRI of each target joint was then reviewed. Fourteen target joints (three elbows, three knees, eight ankles) were evaluated. On the basis of clinical and plain-radiograph data, synovectomy was recommended for five and prophylaxis for seven joints. Discontinuation of prophylaxis was recommended for two ankles in one child. The MRI examination confirmed that four of five potential synovectomy candidates had markedly hypertrophied synovium and could benefit from surgery; one of five was excluded from synovectomy because synovial hypertrophy was minimal. Two of seven children recommended for prophylaxis were given substantially altered plans after MRI. In all, approximately 40% of joint assessments were modified as a result of the MRI findings. We conclude that MRI should be included in the evaluation of some children with hemophilic arthropathy.
Assuntos
Hemofilia A/complicações , Artropatias/complicações , Artropatias/patologia , Imageamento por Ressonância Magnética , Adolescente , Criança , Hemofilia A/patologia , HumanosRESUMO
We report a case of progressive encephalitis caused by varicella-zoster virus (VZV) in an adolescent with hemophilia and acquired immunodeficiency syndrome but without cutaneous signs of VZV infection. Magnetic resonance imaging of the brain demonstrated an abnormally increased periventricular signal in T2-weighted images. Infection with VZV was proved by in situ hybridization and immunofluorescence staining of brain tissue, which showed histologic evidence of herpesvirus infection. Encephalitis caused by infection with VZV is a potentially treatable complication of acquired immunodeficiency syndrome and requires a high index of suspicion for diagnosis.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Encefalite/complicações , Hemofilia A/complicações , Herpes Zoster/complicações , Adolescente , Encéfalo/patologia , Encefalite/diagnóstico , Encefalite/microbiologia , Encefalite/patologia , Herpes Zoster/diagnóstico , Herpesvirus Humano 3/isolamento & purificação , Humanos , Imuno-Histoquímica , MasculinoRESUMO
Severe deficiencies of protein C, a pivotal coagulation-regulatory protein, have been reported in neonates as an apparently transient condition. In this prospective study, cord blood was collected at 193 deliveries and assays of protein C were correlated with clinical status, other coagulation results, and outcome. Protein C levels of less than 0.1 unit/ml were found most frequently in preterm infants with respiratory distress, infants of diabetic mothers, and infants of twin gestations. Levels of protein C correlated with levels of factor VIII activity but did not correlate with markers of consumptive coagulopathy. A protein C level less than 0.1 unit/ml was significantly correlated with the subsequent onset of thrombosis, even when the effects of gestational age and birth weight were excluded. Low cord blood levels of protein C may reflect delayed maturation or increased turnover in certain infants and appear to convey an independent risk of thrombosis, but the critical concentration of protein C necessary to maintain neonatal hemostasis is not known.
Assuntos
Coagulação Intravascular Disseminada/epidemiologia , Deficiência de Proteína C , Trombose/epidemiologia , Antitrombina III/análise , Proteínas Sanguíneas/análise , Proteínas de Transporte/sangue , Colorado/epidemiologia , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/etiologia , Sangue Fetal/química , Glicoproteínas/sangue , Cofator II da Heparina/análise , Humanos , Recém-Nascido , Prevalência , Proteína C/análise , Proteína C/antagonistas & inibidores , Proteína S , Fatores de Risco , Trombose/sangue , Trombose/etiologiaAssuntos
Proteínas Inativadoras do Complemento , Glicoproteínas , Deficiência de Proteína/complicações , Púrpura/etiologia , Adulto , Fatores Etários , Testes de Coagulação Sanguínea , Proteínas Sanguíneas/análise , Proteínas de Transporte/análise , Feminino , Homozigoto , Humanos , Imunoeletroforese Bidimensional , Recém-Nascido , Masculino , Proteína C/análise , Deficiência de Proteína/sangue , Deficiência de Proteína/genética , Púrpura/sangue , Púrpura/tratamento farmacológico , Varfarina/uso terapêuticoRESUMO
Eleven infants initially seen in the neonatal period had levels of protein C suggestive of homozygous protein C deficiency but as an apparently acquired condition. Family studies failed to document parental carrier status, the clinical course was not typical of that reported with homozygous protein C deficiency, and protein C levels increased in all restudied infants, six of whom received heparin anticoagulation. No infant had evidence of vitamin K deficiency. Care is advised in the evaluation of infants with low levels of protein C. Parental blood studies, delayed testing, and serial assays can help to establish the correct diagnosis.