RESUMO
BACKGROUND: Drug-induced immune haemolytic anaemia (DIIHA) is caused by various drugs or their metabolites. Cephalosporins are associated with haemolytic anaemia but multi-organ failure is rarely described. CASE DESCRIPTION: We report the case of a 57-year-old female who was diagnosed with neuroborreliosis and treated with ceftriaxone. The patient developed severe DIIHA. Massive intravascular haemolysis led to shock and acute renal failure, necessitating mechanical ventilation and dialysis. Treatment with ceftriaxone was discontinued and glucocorticoids were prescribed. The patient recovered slowly but fully. CONCLUSION: Ceftriaxone-induced immune haemolytic anaemia is a rare but potentially fatal condition.
Assuntos
Anemia Hemolítica/induzido quimicamente , Antibacterianos/efeitos adversos , Ceftriaxona/efeitos adversos , Insuficiência de Múltiplos Órgãos/induzido quimicamente , Anemia Hemolítica/imunologia , Antibacterianos/uso terapêutico , Ceftriaxona/uso terapêutico , Feminino , Hidratação , Glucocorticoides/uso terapêutico , Humanos , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/imunologiaRESUMO
In chronic lymphocytic leukemia (CLL), strategies to overcome drug resistance due to p53 dysfunction are highly needed. Platinum-based compounds such as cisplatinum (CDDP) are active in fludarabine-refractory CLL through a largely unknown mechanism. We analyzed the mechanism of action of CDDP in the context of p53 dysfunctionality. In vitro treatment with CDDP did not induce death in quiescent CLL cells, but did induce apoptosis in CD40-ligand (and CpG) stimulated and proliferating cells, irrespective of p53 function. In the p53 dysfunctional prolymphocytic cell-line MEC1, CDDP treatment resulted in apoptosis, cell cycle arrest and ABL1-dependent expression of TAp73, CDKN1A, PUMA and BID. TAp73 RNA-interference decreased sensitivity to CDDP. Finally, both in vitro stimulated CLL cells and lymph node (LN) derived CLL cells showed increased TAp73 expression in comparison with quiescent peripheral blood derived cells. Activity of CDDP may therefore be mediated by TAp73, especially in the context of activation such as occurs in the LN microenvironment.