Brittenham G M, Griffith P M, Nienhuis A W, McLaren C E, Young N S, Tucker E E, Allen C J, Farrell D E, Harris J W
Department of Medicine, Case Western Reserve University, Cleveland, OH.
N Engl J Med. 1994 Sep 1;331(9):567-73. doi: 10.1056/NEJM199409013310902.
To determine whether deferoxamine prevents the complications of transfusional iron overload in thalassemia major, we evaluated 59 patients (30 were female and 29 male; age range, 7 to 31 years) periodically for 4 to 10 years or until death.
At each follow-up visit, we performed a detailed clinical and laboratory evaluation and measured hepatic iron stores with a noninvasive magnetic device.
The body iron burden as assessed by magnetic measurement of hepatic iron stores was closely correlated (R = 0.89, P < 0.001) with the ratio of cumulative transfusional iron load to cumulative deferoxamine use (expressed in millimoles of iron per kilogram of body weight, in relation to grams of deferoxamine per kilogram, transformed into the natural logarithm). Each increase of one unit in the natural logarithm of the ratio (transfusional iron load to deferoxamine use) was associated with an increased risk of impaired glucose tolerance (relative risk, 19.3; 95 percent confidence interval, 4.8 to 77.4), diabetes mellitus (relative risk, 9.2; 95 percent confidence interval, 1.8 to 47.7), cardiac disease (relative risk, 9.9; 95 percent confidence interval, 1.9 to 51.2), and death (relative risk, 12.6; 95 percent confidence interval, 2.4 to 65.4). All nine deaths during the study occurred among the 23 patients who had begun chelation therapy later and used less deferoxamine in relation to their transfusional iron load (P < 0.001).
The early use of deferoxamine in an amount proportional to the transfusional iron load reduces the body iron burden and helps protect against diabetes mellitus, cardiac disease, and early death in patients with thalassemia major.
为了确定去铁胺是否能预防重型地中海贫血患者输血性铁过载的并发症，我们对59例患者（30例女性，29例男性；年龄范围7至31岁）进行了为期4至10年的定期评估，直至其死亡。
在每次随访时，我们进行了详细的临床和实验室评估，并使用无创磁性装置测量肝脏铁储存量。
通过磁性测量肝脏铁储存量评估的机体铁负荷与累计输血铁负荷与累计去铁胺使用量的比值密切相关（R = 0.89，P < 0.001）（以每千克体重铁的毫摩尔数表示，相对于每千克去铁胺的克数，转换为自然对数）。该比值（输血铁负荷与去铁胺使用量）自然对数每增加一个单位，糖耐量受损风险增加（相对风险为19.3；95%置信区间为4.8至77.4）、糖尿病风险增加（相对风险为9.2；95%置信区间为1.8至47.7）、心脏病风险增加（相对风险为9.9；95%置信区间为1.9至51.2）以及死亡风险增加（相对风险为12.6；95%置信区间为2.4至65.4）。研究期间的所有9例死亡均发生在23例开始螯合治疗较晚且相对于其输血铁负荷使用较少去铁胺的患者中（P < 0.001）。
早期使用与输血铁负荷成比例的去铁胺可减轻机体铁负荷，并有助于预防重型地中海贫血患者患糖尿病、心脏病和早期死亡。
