PHLEBOTOMY THERAPY IN HEREDITARY HEMOCHROMATOSIS

最近可用的遗传测试（HFE基因中C282 Y突变的纯合性）用于诊断遗传性血色病（HH）已经重新关注这种疾病，并导致在铁负荷较小的年轻受试者中进行诊断。然而，由于缺乏简单的生理实验室监测指南，HH的放血治疗仍然受到阻碍。此外，尽管许多HH受试者符合同种异体献血的标准，但由于所获得的血液未用于同种异体输血，因此认为放血疗法是浪费。最近的法规变化现在允许在制定从HH受试者获得的血液的输血政策方面增加灵活性。在过去12年进行的研究中，我们开发了一种简单的、基于生理学的静脉切开术指南，作为使用适当血色病患者血液进行同种异体输血的方案的基础。DTM中的前瞻性研究表明，红细胞平均红细胞体积（MCV）是一种精确测量的造血铁可用性生理指标，当与血红蛋白结合测量时，可提供诱导和维持放血期间管理患者所需的所有信息。每周开始放血，当MCV下降至基线以下5%至10%且血红蛋白和MCV同时下降时，转为较低频率间隔。在维持性静脉切开术期间，血红蛋白的目标是大于13 g/dL，MCV保持在基线以下5%至10%（通常为85至90（3）。所有患者在平均38次静脉切开术和去除9.0克铁后均获得稳定的、无症状的铁缺乏状态。在诱导治疗期间，MCV在较长时间内保持稳定，然后以平稳、一致的方式下降，表明铁限制性红细胞生成开始。转铁蛋白饱和度在静脉切开术期间变化很大，但在稳定的MCV靶向维持期间保持在40%以下。铁蛋白值对评估铁耗竭或维持性静脉切开术的速度没有帮助。中位稳定维持间隔为7.5周（范围6至16周），相当于平均每日铁去除量为35至67（g/kg）。本研究中的数据表明，红细胞MCV是HH患者静脉切开术治疗的生理性、廉价指南。与标准的、更昂贵的测量（如铁蛋白水平）相比，MCV准确地预测铁的消耗，防止转铁蛋白饱和度过度反弹，并根据每个患者指导维护。的个体铁吸收。MCV引导的静脉切开术指南，沿着扩展的血液流变学和肝脏评价，形成了正在开发的大型综合方案的核心，以最佳地管理血色素沉着症患者的静脉切开术，同时利用适当患者的血液进行同种异体输血。

The recent availability of a genetic test (homozygosity for the C282Y mutation in the HFE gene) for the diagnosis of hereditary hemochromatosis (HH) has focused renewed attention on this disorder and has resulted in the diagnosis being made in younger subjects with smaller iron burdens. However, phlebotomy therapy in HH remains hampered by lack of simple, physiologic laboratory monitoring guides. In addition, phlebotomy therapy has been perceived as wasteful because the blood obtained has not been not used for allogeneic transfusion although many HH subjects meet standards for allogeneic blood donation. Recent regulatory changes now allow increased flexibility in establishing policies for transfusion of blood obtained from HH subjects. In studies performed over the last 12 years, we have developed a simple, physiologically based phlebotomy guide as the basis for a protocol to utilize blood from appropriate hemochromatosis patients for allogeneic transfusion. Prospective studies in the DTM have shown that the red cell mean corpuscular volume (MCV), a physiologic, precisely measured indicator of erythopoietic iron availability, when measured in conjunction with the hemoglobin, provides all the information necessary to manage patients during induction as well as maintenance phlebotomy. Phlebotomy was started weekly and transitioned to less frequent intervals when the MCV decreased to 5 to 10 percent below baseline and the hemoglobin and MCV were decreasing n concert. During maintenance phlebotomy, the hemoglobin was targeted at greater than 13 g/dL and the MCV was kept at 5 to 10 percent below baseline (generally 85 to 90 (3). A stable, asymptomatic, iron-depleted state was obtained in all patients after a median of 38 phlebotomies and removal of 9.0 grams of iron. The MCV was stable for a prolonged period during induction therapy, and then decreased in a smooth, consistent manner, indicating the onset of iron-limited erythropoiesis. Transferrin saturation varied considerably during phlebotomy, but remained below 40 percent during stable MCV-targeted maintenance. Ferritin values were not useful to assess the pace of iron depletion or maintenance phlebotomy. The median stable maintenance interval was 7.5 (range 6 to 16) weeks, corresponding to an average daily iron removal of 35 to 67(g/kg. The data in this study indicate that the red cell MCV is a physiologic, inexpensive guide to phlebotomy therapy in patients with HH. In contrast to standard, more expensive measurements such as ferritin levels, the MCV accurately predicts iron depletion, prevents excessive rebound transferrin saturation and guides maintenance according to each patient?s individual iron absorption. The MCV-guided phlebotomy guideline, along with extended rheumatologic and hepatic evaluations, forms the core of a large, omnibus protocol being developed to optimally manage phlebotomy in hemochromatosis patients while utilizing blood from appropriate patients for allogeneic transfusion.