RESUMO
To determine whether survival of patients with beta-thalassemia major has been prolonged by management that utilizes hypertransfusion and chelation with deferoxamine, we analyzed longevity by the Kaplan-Meier product-limit method. Group 1 patients (n = 71) followed between 1960 and 1976 with a low-transfusion regimen (pretransfusion hemoglobin level 7 to 8 gm/dl) and no chelation had an estimated median age of survival of 17.4 years, whereas it was 31.0 years for group 2 subjects (n = 80), who began hypertransfusion between 1976 and 1978 (pretransfusion hemoglobin level 10.5 to 11.5 gm/dl) and chelation with deferoxamine (20 to 60 mg/kg per day) (p less than 0.0001). For 70 patients who were treated with hypertransfusion and deferoxamine, we had data to calculate the ratio of total milligrams of transfusional iron to cumulative grams of deferoxamine. The 24 patients who died had a total iron burden of greater than 1.05 gm/kg; the ratio for them exceeded 31. These patients were characterized by poor compliance with chelation or by late start of therapy, with inability to receive enough deferoxamine before death. Death was preceded by arrhythmia requiring therapy in all but one, and by cardiac failure in all. Of 41 similarly iron-loaded survivors, 33 had a ratio of less than 31; only three had an arrhythmia, and five had cardiac failure. We conclude that treatment with deferoxamine, when used in amounts proportional to iron burden, delayed cardiac complications and improved longevity.
Assuntos
Desferroxamina/uso terapêutico , Talassemia/tratamento farmacológico , Adolescente , Adulto , Transfusão de Sangue , Carga Corporal (Radioterapia) , Terapia por Quelação , Criança , Pré-Escolar , Terapia Combinada , Humanos , Ferro/metabolismo , Talassemia/metabolismo , Talassemia/mortalidade , Talassemia/terapiaRESUMO
Transfusion requirements for 1978 were compiled for 79 patients with thalassemia major (ages 1 to 29 years) who were maintained at hemoglobin concentrations of greater than 10 gm/dl. In 46 patients with intact spleens, the mean transfusion requirement was 258 ml/kg/year, and there was a clear increase with age. The transfusion history prior to 1978 had no influence on the increase of transfusion requirement with age. In contrast, in 33 splenectomized patients, the mean transfusion requirement was 203 ml/kg/year and it did not increase with age. Urinary iron excretion in response to deferoxamine increased with age, with no obvious difference between splenectomized and nonsplenectomized patients. The ability to achieve iron balance with a daily dose of 20 mg/kg of deferoxamine was a function of the transfusion requirement splenectomized patients with lower blood requirements generally achieved negative iron balance, whereas nonsplenectomized patients did not. We conclude that the spleen should be removed when the transfusion requirement exceeds 250 ml/kg/year, which usually occurs between 6 and 8 years of age. In young patients with intact spleens, a higher dose of deferoxamine may be use in order to prevent hemosiderosis.
Assuntos
Esplenectomia , Talassemia/terapia , Adolescente , Adulto , Fatores Etários , Transfusão de Sangue , Criança , Pré-Escolar , Desferroxamina/uso terapêutico , Humanos , Lactente , Ferro/metabolismo , Ferro/urina , Talassemia/tratamento farmacológicoRESUMO
Thirty-three prospectively studied neonates born to mothers using methadone plus other drugs developed significant thrombocytosis by the second week of life compared to platelet counts performed during the first week. This increase persisted for over 16 weeks, with a further short-lived significant peak at 10 weeks of age. Platelet counts exceeding 1,000,000/mm3 were found in seven infants. Thrombocytosis was not related to withdrawal symptoms or treatment (phenobarbital or paregoric). No thrombocytosis was found in 36 normal control infants up to eight weeks of life. Twenty-eight of the study group infants were evaluated for circulating platelet aggregates. Thirteen patients had a normal aggregate index and a mean platelet count of 468,000/mm3; 15 patients had increased aggregates and mean platelet count of 754,000/mm3. The risk for increased circulating platelet aggregates correlated directly with an increase in platelet count. Thrombocytosis and increased circulating platelet aggregates may be factors in the pathogenesis of the focal infarcts, and subarachnoid and germinal plate hemorrhages, described at autopsy in infants of addicted mothers.