Prospective Studies Of Phlebotomy Therapy In Hereditary Hemochromatosis

血色素沉着症患者通过基于互联网的信息和给地区医生的信件进行招募。无论受试者是否符合同种异体捐献标准，均免费提供综合护理和静脉切开术治疗。以12.5 g/dL的血红蛋白（美国献血的调节阈值）作为进行静脉切开术的阈值，以平均红细胞体积（MCV）和铁蛋白的下降为指导治疗终点。截至2007年8月31日，324名铁超载患者连续入组。该研究最常见的转诊途径是自我转诊，这是由患者在互联网上发起的搜索产生的。74%的受试者是HFE基因C282Y突变纯合子，75%符合同种异体捐献的资格标准，52%是以前的献血者。在MCV达到低于基线3%的目标终点（此时铁蛋白低于30mcg /L，转铁蛋白饱和度低于30%）之前，进行中位25周或双周抽血（范围7-99）。维持治疗期间将MCV维持在这一水平所需的中位放血间隔为10-12周。血色素沉着症捐献是安全的：在5000例捐献中没有发生输血传播疾病因子的血清转换事件。截至2007年9月，血色素沉着症捐献者每年捐献800单位的红细胞，占NIH临床中心收集的同种异体使用单位的11%，另外每年有200单位的红细胞从不符合标准捐献者资格标准的捐献者那里提供给研究使用。家庭成员的筛选和咨询是通过集中在血液中心的护理方便。在这项研究开展的6年里，研究结果在会议和医学文献中广为传播，全国范围内建立血色素沉着症捐献项目的血液中心的数量从26个增加到76个。我们的数据表明，血色素沉着症患者可以安全而显著地增加异体血液供应。在血液中心提供静脉切开术治疗，不受保险报销或是否适合捐赠的考虑，可以改善获得护理的机会，并消除不完全风险披露的动机。

Persons with hemochromatosis were recruited via Internet-based information and letters to area physicians. Comprehensive care and phlebotomy therapy were offered free of charge regardless of whether subjects met criteria for allogeneic donation. Hemoglobin of 12.5 g/dL, the regulatory threshold for blood donation in the U.S., was used as the threshold for performing phlebotomy, and decreases in the mean corpuscular volume (MCV) and ferritin were used to guide the endpoints of therapy. 324 subjects with iron overload were consecutively enrolled as of August 31, 2007. The most common route of referral to the study was self-referral, resulting from patient-initiated searches performed on the Internet. 74% of subjects were homozygous for the C282Y mutation in the HFE gene, 75% met eligibility criteria for allogeneic donation, and 52% were previous blood donors. A median of 25 weekly or biweekly phlebotomies (range 7-99) were performed before the MCV reached the targeted endpoint of 3% below baseline, at which time the ferritin was less than 30 mcg/L and the transferrin saturation less than 30%. The median phlebotomy interval necessary to keep the MCV at this level during maintenance therapy was 10-12 weeks. Hemochromatosis donations were safe: no incident seroconversions for agents of transfusion-transmissible disease occurred during 5,000 donations. As of September 2007, hemochromatosis donors were contributing 800 units of red cell yearly, or 11% of the units collected for allogeneic use in the NIH Clinical Center, and another 200 units per year were made available for research use from donors who did not meet standard donor eligibility criteria. Family member screening and counseling were facilitated by concentrating the care within the Blood Center. During the 6 years that this study has been active, and the results disseminated at meetings and in the medical literature, the number of Blood Centers nationwide that have instituted hemochromatosis donor programs has grown from 26 to 76. Our data demonstrate that hemochromatosis subjects can safely and significantly augment the allogeneic blood supply. Provision of phlebotomy therapy in the Blood Center, unrestricted by considerations of insurance reimbursement or suitability for donation, can improve access to care and remove incentives for incomplete risk disclosure. Evaluations performed to date in this cohort indicate that there is a higher than expected incidence of thyroid abnormalities in hemochromatosis subjects, most commonly subclinical hypothyroidism. Thyroid function abnormalities were found in 30% of female subjects with homozygosity for the C282Y HFE mutation. A recent series of cardiology studies in these patients indicate that C282Y homozygotes have a statistically increased incidence of mild, subclinical abnormalities in atrial contractility and exercise-associated arrhythmias when compared to normal subjects, and these changes may be associated with elevated serum markers of oxidative stress. Left ventricular contractility and response to stress were found to be normal in C282Y homozygotes compared with control subjects. A comprehensive analysis of arthritis in these subjects revealed that 8% (19 of 224) C282Y-homozygous versus 2.2% (2 of 91) non-homozygous subjects underwent a total of 24 total hip, 6 total knee, and 4 total ankle replacements. The frequency of total joint replacement was significantly greater in C282Y-homozygotes than in the control group. The cumulative risk of total joint replacement hemochromatosis subjects was 31% by age 75. Among C282Y homozygotes, the risk of total joint replacement was markedly greater in subjects with initial ferritin levels greater than the median value of 640 ng/mL. Among the estimated 23,966 Caucasian U.S. males age 40-79 undergoing total hip replacement each year, the data suggest that 3-4% are C282Y-homozygous. Current efforts are focused on overcoming community and Red Cross Blood Center resistance to use of hemochromatosis subjects as allogeneic blood donors, on dissemination of best phlebotomy practices as exhibited in this study, on critical examination of the role of double red cell donation by apheresis in the management of HH subjects, and on assessing changes in serum non-transferrin bound iron levels during therapy