RESUMO
BACKGROUND: Acute thrombocytopenia is a recognized side-effect of treatment with the fibrinogen receptor antagonist, abciximab, a chimeric (human/mouse) Fab fragment. The etiology of this complication is not fully understood. Generally, abciximab-induced thrombocytopenia occurs within a few hours of starting treatment with the drug. We have characterized a group of 13 patients who first developed thrombocytopenia 3-6 days after abciximab was discontinued. OBJECTIVE: To characterize clinical and serological aspects of this newly recognized clinical entity. PATIENTS AND METHODS: Clinical information was obtained from attending physicians and review of hospital records. Antibodies reactive with abciximab-coated platelets were characterized by flow cytometry. RESULTS: In each patient, IgG and/or IgM antibodies reactive with abciximab-coated platelets were identified. These antibodies could be distinguished from similar antibodies present in many normal persons by two criteria-they were relatively resistant to inhibition by normal Fab fragments, and they reacted preferentially with platelets coated with 7E3, the murine monoclonal antibody from which peptide sequences in abciximab are derived. Antibodies with these characteristics were not found in pretreatment serum from three of the thrombocytopenic patients or in patients given abciximab who did not develop thrombocytopenia. CONCLUSIONS: 'Delayed thrombocytopenia' after treatment with abciximab is caused by antibodies produced in response to the drug. These antibodies may be specific for murine peptide sequences in abciximab but could recognize other target epitopes on abciximab-coated platelets. Physicians administering abciximab should be aware of this potential complication of treatment, which usually occurs after discharge from hospital.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/imunologia , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Fragmentos Fab das Imunoglobulinas/imunologia , Trombocitopenia/induzido quimicamente , Abciximab , Idoso , Animais , Anticorpos/sangue , Anticorpos Heterófilos/sangue , Anticorpos Monoclonais/metabolismo , Formação de Anticorpos , Plaquetas/metabolismo , Hipersensibilidade a Drogas , Feminino , Citometria de Fluxo , Humanos , Fragmentos Fab das Imunoglobulinas/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombocitopenia/imunologiaRESUMO
Renal phosphate wasting related to a tumor (oncogenous osteomalacia) is a rare disorder usually associated with benign mesenchymal tumors. In this article, the authors describe a man with renal phosphate wasting and the syndrome of inappropriate antidiuretic hormone associated with small cell carcinoma. Chemotherapy markedly reduced tumor burden and was associated with normalization of renal phosphate handling and serum sodium. With recurrence, renal phosphate wasting and the syndrome of inappropriate antidiuretic hormone developed again, with the additional complication of hypercortisolism secondary to ectopic corticotropin production. The authors report the rare occurrence of renal phosphate wasting with small cell carcinoma (5 previously reported cases) and the unique co-existence of this paraneoplastic syndrome with the syndrome of inappropriate antidiuretic hormone and ectopic corticotropin production.
Assuntos
Hormônio Adrenocorticotrópico/metabolismo , Carcinoma de Células Pequenas/complicações , Síndrome de Secreção Inadequada de HAD/etiologia , Neoplasias Pulmonares/complicações , Osteomalacia/etiologia , Carcinoma de Células Pequenas/fisiopatologia , Feminino , Humanos , Síndrome de Secreção Inadequada de HAD/fisiopatologia , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteomalacia/fisiopatologiaRESUMO
Fifteen individuals among four generations of a family of English ancestry demonstrated elevated hemoglobin levels accompanied by leftward-shifted whole blood oxygen equilibrium curves. Five of the affected family members have required phlebotomies for relief of symptoms attributable to erythrocytosis. An abnormal hemoglobin or globin chain could not be isolated, but 43% of the beta chains of the affected individuals contained a Leu----Phe substitution at position 105 (G7). Oxygen equilibrium curves demonstrated a normal Bohr effect but decreased cooperativity.