Infanti Laura, Leitner Gerda, Moe Morten, Pehlic Vildana, Cattaneo Marco, Benkert Pascal, Holbro Andreas, Passweg Jakob, Worel Nina, Buser Andreas
Regional Blood Transfusion Centre Swiss Red Cross Basel, Basel, Switzerland.
Division of Hematology, University Hospital, University of Basel, Basel, Switzerland.
Front Med (Lausanne). 2024 Mar 19;11:1362941. doi: 10.3389/fmed.2024.1362941. eCollection 2024.
Elevated serum ferritin with/without HFE variants in asymptomatic persons leads frequently to referral for blood donation. Hemochromatosis (p.C282Y/p.C282Y) only requires treatment. We evaluated safety and feasibility of iron removal in healthy persons with elevated ferritin and HFE variants using blood donation procedures.
Thirty subjects with ferritin >200 ng/mL (women) or >300 ng/mL (men) with p.C282Y/p.C282Y, p.C282Y/p.H63D or p.H63D/p.H63D were randomized to weekly phlebotomy (removal of 450 mL whole blood) or erythrapheresis (removal of 360 mL red blood cells) every 14 days. The ferritin target was <100 ng/mL. A full blood count and ferritin were measured at each visit. Hemoglobin (Hb) ≥140 g/L was required at inclusion. If Hb dropped to <120 g/L (women) or <130 g/L (men), procedures were postponed (7 or 14 days). Primary endpoint was the number of procedures needed to the ferritin target; secondary objectives were duration of treatment and compliance. The treatment effect was tested with Poisson regression; number of procedures and treatment duration were compared between study arms with the Kruskal-Wallis test.
Twenty-five of 30 participants were men (83%); mean age was 47 years (SD 10.5), mean BMI 26.6 kg/m (SD 3.6); 17 had p.C282Y/p.C282Y, nine p.C282Y/p.H63D, four p.H63D/p.H63D. Median baseline Hb was 150 g/L (IQR 144, 1,559), median ferritin 504 ng/mL (IQR 406,620). Twenty-seven subjects completed the study. Treatment arm ( < 0.001) and HFE variant ( = 0.007) influenced the primary endpoint significantly. To ferritin levels <100 ng/mL, a median number of 7.5 (IQR 6.2, 9.8) phlebotomies and 4.0 (IQR 3.0, 5.8) erythraphereses ( = 0.001) was needed during a median of 66.5 days (IQR 49,103) and 78.5 days (IQR 46139), respectively ( = 0.448). Low Hb was the principal reason for protocol violation; anemia occurred in 13 participants (48%). Immediate complications were infrequent; fatigue was reported after 25% of phlebotomies and 45% of erythraphereses. Thirty-five procedures were postponed because of low Hb and 15 for non-medical reasons. The median interval was 7.0 (IQR 7.7) and 14.0 (IQR 14, 20) days between phlebotomies and erythraphereses, respectively.
Blood donation procedures remove iron effectively in HC, but frequent treatments cause Hb decrease and fatigue that can impair feasibility.
无症状人群中血清铁蛋白升高伴或不伴有HFE变异体常导致被转介去献血。纯合子血色素沉着症（p.C282Y/p.C282Y）才需要治疗。我们评估了使用献血程序在铁蛋白升高且有HFE变异体的健康人群中去除铁的安全性和可行性。
30名铁蛋白>200 ng/mL（女性）或>300 ng/mL（男性）且携带p.C282Y/p.C282Y、p.C282Y/p.H63D或p.H63D/p.H63D的受试者被随机分为每周进行一次静脉放血（去除450 mL全血）或每14天进行一次治疗性红细胞单采术（去除360 mL红细胞）。铁蛋白目标值为<100 ng/mL。每次就诊时均检测全血细胞计数和铁蛋白。纳入时要求血红蛋白（Hb）≥140 g/L。如果Hb降至<120 g/L（女性）或<130 g/L（男性），则推迟操作（7天或14天）。主要终点是达到铁蛋白目标所需的操作次数；次要目标是治疗持续时间和依从性。采用泊松回归检验治疗效果；使用Kruskal-Wallis检验比较研究组之间的操作次数和治疗持续时间。
30名参与者中有25名男性（83%）；平均年龄为47岁（标准差10.5），平均体重指数为26.6 kg/m²（标准差3.6）；17名携带p.C282Y/p.C282Y，9名携带p.C282Y/p.H63D，4名携带p.H63D/p.H63D。基线Hb中位数为150 g/L（四分位间距144，155.9），铁蛋白中位数为504 ng/mL（四分位间距406，620）。27名受试者完成了研究。治疗组（P<0.001）和HFE变异体（P = 0.007）对主要终点有显著影响。要使铁蛋白水平降至<100 ng/mL，静脉放血组在中位数66.5天（四分位间距49，103）内需要进行中位数7.5次（四分位间距6.2，9.8）操作，治疗性红细胞单采术组在中位数78.5天（四分位间距46，139）内需要进行中位数4.0次（四分位间距3.0，5.8）操作（P = 0.001）。Hb水平低是违反方案的主要原因；13名参与者（48%）发生贫血。即刻并发症不常见；25%的静脉放血和45%的治疗性红细胞单采术后报告有疲劳感。因Hb水平低推迟了35次操作，因非医学原因推迟了15次。静脉放血和治疗性红细胞单采术之间的间隔中位数分别为7.0天（四分位间距7，7）和14.0天（四分位间距14，20）。
献血程序能有效去除遗传性血色素沉着症患者体内的铁，但频繁治疗会导致Hb降低和疲劳，可能影响可行性。
