Predictors of early mortality after rabbit antithymocyte globulin as first-line treatment in severe aplastic anemia.

Despite being recommended as first-line immunosuppressive therapy in severe aplastic anemia (SAA), horse antithymocyte globulin (ATG) is still unavailable in many countries outside the USA. Rabbit ATG is more lymphocytoxic than horse ATG, and this might result in a higher incidence of severe infections and early mortality. This study was designed to identify the risk factors for early mortality and overall survival (OS) after rabbit ATG in patients with SAA. We retrospectively reviewed 185 patients with SAA who underwent rabbit ATG and cyclosporine. The incidence of death in 3 months following rabbit ATG therapy was 15.1% (28/185). Early mortality was mainly related to infectious complications, despite adequate antibiotic and/or antifungal treatment. Age > 35 years (odds ratio [OR] 5.06, P = 0.001) and baseline absolute neutrophil count (ANC) ≤ 0.1 × 109/L (OR 7.64, P < 0.001) were independent risk factors for early mortality after immunosuppressive therapy with this agent. Hematological response at 6 months was observed in only 29.7% of all patients. OS at 1 year after rabbit ATG was 75.3%; and age > 35 years (OR 1.88, P = 0.03), baseline ANC ≤ 0.1 × 109/L (OR 2.65, P < 0.001), and lack of response to rabbit ATG (OR 11.40, P < 0.001) were independently associated with mortality. Alternative strategies are needed for the treatment of SAA patients in countries were horse ATG is unavailable, particularly for those at high risk for early mortality after rabbit ATG due to a higher age and very low pre-treatment neutrophil count.

Oral anticoagulation therapy in children.

Treatment of thromboembolic complications in children has been the subject of considerable research in the last decade. Recommendations for oral anticoagulant therapy in children have been extrapolated from adult clinical trials. Coumarin derivatives are the preeminent oral antithrombotic agents used in children. Warfarin, acenocoumarol and phenprocoumon are the vitamin K antagonists used in children with thrombotic complications in different countries according to their experience and familiarity within a country or region. Prospective studies from Canada and Argentina propose guidelines for administering and monitoring warfarin and acenocoumarol therapy in children. These studies highlight the difficulty of their use in pediatric patients. Infants younger than 12 months of age require increased doses to achieve and maintain the therapeutic target INR, adjustments of loading dose to achieve the target INR faster with no overshooting, more frequent INR testing and dose adjustments, and fewer INR in the target range. The current indications for oral anticoagulants in children with thrombotic complications, the side effects of these agents and the reversal of the anticoagulant effect are discussed.