Porter J B, Abeysinghe R D, Marshall L, Hider R C, Singh S
Department of Clinical Haematology, University College, London, UK.
Blood. 1996 Jul 15;88(2):705-13.
The rapidity and duration of the response of non-transferrin-bound iron (NTBPI) to chelation therapy are largely unknown and have important implications for the design of optimal chelation regimens. Methodology was developed to measure simultaneously NTBPI, deferoxamine (DFO), and its major metabolite. NTBPI was present in all but 2 of 28 thalassaemia major (TM) patients who had received conventional subcutaneous DFO the previous night, suggesting a short duration of NTBPI clearance by DFO. The detailed kinetics of NTBPI were therefore studied in response to intravenous DFO at 50 mg/kg/27 h for 48 hours and compared in 17 regularly transfused TM and 8 untransfused thalassaemia intermedia (TI) patients to determine the influence of hypertransfusion and iron overload on NTBPI response. Before DFO infusion, NTBPI was present in all patients and was significantly higher in TI (4.52 +/- 0.53 mumol/L) than TM (2.92 +/- 0.03 mumol/L; P = .03). NTBPI values in TM correlated with transferrin saturation (r = .6, P = .03) but not with serum ferritin. Removal of NTBPI by intravenous DFO is in a biphasic manner. The initial rapid rate constant (alpha) was similar in TI (1.5 hour-1) and TM (1.6 hour-1), but the subsequent beta phase was slower (0.04 hour-1) in TI when compared with TM (0.4 hour-1, P = .002). Detectable NTBPI persisted during the beta phase, particularly in TI, despite an excess of plasma DFO also being present (steady state 8 mumol/L). On cessation of DFO infusion, NTBPI reappearance was rapid; the kinetics also being biphasic. The rapid initial rate constant (alpha = 2.5 hour-1) lasted less than 30 minutes and was approximately equal to the summation of the initial rate constant for removal of DFO (1.8 hour-1) and its major metabolite (0.6 hour-1). This was followed by a slower return to pretreatment levels, usually between 6 and 12 hours, which was faster in TI than in TM. This marked NTBPI lability supports the use of continuous rather than intermittent DFO in high risk patients.
非转铁蛋白结合铁（NTBPI）对螯合疗法的反应速度和持续时间在很大程度上尚不清楚，这对优化螯合方案的设计具有重要意义。已开发出同时测量NTBPI、去铁胺（DFO）及其主要代谢产物的方法。在28例重型地中海贫血（TM）患者中，除2例前一晚接受常规皮下DFO治疗的患者外，其余患者均存在NTBPI，这表明DFO清除NTBPI的持续时间较短。因此，研究了17例定期输血的TM患者和8例未输血的中间型地中海贫血（TI）患者在静脉注射50 mg/kg/27 h的DFO共48小时后NTBPI的详细动力学，以确定过度输血和铁过载对NTBPI反应的影响。在DFO输注前，所有患者均存在NTBPI，TI患者（4.52±0.53 μmol/L）的NTBPI显著高于TM患者（2.92±0.03 μmol/L；P = 0.03）。TM患者的NTBPI值与转铁蛋白饱和度相关（r = 0.6，P = 0.03），但与血清铁蛋白无关。静脉注射DFO清除NTBPI呈双相性。初始快速速率常数（α）在TI患者（1.5小时-1）和TM患者（1.6小时-1）中相似，但随后的β相在TI患者中比TM患者慢（0.04小时-1）（0.4小时-1，P = 0.002）。尽管血浆中也存在过量的DFO（稳态8 μmol/L），但在β相期间仍可检测到NTBPI，尤其是在TI患者中。在DFO输注停止后，NTBPI迅速重新出现；动力学也呈双相性。初始快速速率常数（α = 2.5小时-1）持续不到30分钟，大约等于DFO清除的初始速率常数（1.8小时-1）及其主要代谢产物（0.6小时-1）之和。随后是较慢地恢复到预处理水平，通常在6至12小时之间，TI患者比TM患者恢复得更快。这种显著的NTBPI不稳定性支持在高危患者中使用持续而非间歇性的DFO。
