Indices of iron homeostasis in asymptomatic subjects with HFE mutations and moderate ferritin elevation during iron removal treatment

Infanti, Laura; Leitner, Gerda; Moe, Morten K.; Pehlic, Vildana; Benkert, Pascal; Cattaneo, M.; Holbro, Andreas; Passweg, Jakob; Worel, Nina; Buser, Andreas

doi:10.1016/j.bcmd.2022.102689

Cited by 2 publications

(8 citation statements)

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“…Because one objective of the study was evaluating iron indices in different HFE genotypes during treatment, enrolled were not only subjects with HC but also individuals with p.C282Y/p.H63D and p.H63D/p.H63D. In the publication describing these results, non-transferrin bound iron, the cytotoxic iron form, was detected in all subjects with p.C282Y/p.C282Y and in only few of those with p.C282Y/p.H63D, corroborating current guidelines that recommend treatment in all persons with HC having increased ferritin but not in all individuals with the p.C282Y/p.H63D genotype ( 19 ). It is a common experience, however, that clinicians often prescribe iron removal also for patient with elevated ferritin for whom treatment is not actually indicated, such as in those with the homozygous p.H63D HFE variant.…”

Section: Discussionmentioning

confidence: 99%

“…At each study visit, laboratory assessment included a complete blood count (Sysmex K-4500, Sysmex Digitana AG, Horgen, Switzerland) on a venous blood sample and ferritin determination. Beside ferritin, several other iron indices were analyzed for a separate evaluation of some secondary outcomes (as reported in ( 19 )). Infectious disease markers were tested as for routine blood donation (HBsAg, HIV p24/antibodies, HCV, and syphilis antibodies; Architect ci8200, Abbott Diagnostics, Abbott Park, IL, United States) including NAT for HBV, HCV and HIV when the blood drown from the study participants could be used for transfusion, as explained below.…”

Section: Methodsmentioning

confidence: 99%

“…Secondary objectives included the number of days needed to reach the ferritin target and the evaluation of safety and feasibility: immediate and delayed AEs, occurrence of anemia; number of procedures postponed or not performed for any reason. Outcomes of iron biomarkers are described in Infanti et al ( 19 ). In addition, and limited to the site of Basel, the number of blood components used for transfusion was evaluated.…”

Section: Methodsmentioning

confidence: 99%

“…An impaired quality of red blood cells of HC blood donors is a potential consequence of the exposition to reactive iron forms. Even in preclinical HC, the enhanced iron absorption frequently exceeds the binding capacity of transferrin, the physiologic iron transporter, resulting in elevated transferrin saturation and in the appearance of redox-active non-transferrin bound iron in the circulation ( 19 ). An oxidative damage on cells due to free iron has been observed in vitro ( 40 ), but the amount of free iron in blood collections from donors with HC has actually been shown to be minimal ( 41 ).…”

Section: Short Review On Hc and Blood Donationmentioning

confidence: 99%

“…A first evaluation of our experience with 86 carriers of HFE variants donating whole blood or RBC units with erythrapheresis ( 18 ) prompted the initiation of a randomized study on iron removal in persons with HC using routine blood donation procedures. The study was conducted at the centers of Basel and Vienna and aimed to explore the feasibility of frequent procedures as well as patterns and changes of iron indices in otherwise healthy persons with different HFE genotypes (reported in ( 19 )). In designing the study, an intensive treatment frequency was intentionally defined.…”

Section: Introductionmentioning

confidence: 99%

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Blood donation for iron removal in individuals with HFE mutations: study of efficacy and safety and short review on hemochromatosis and blood donation

Infanti,

Leitner,

Moe

et al. 2024

Front. Med.

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BackgroundElevated 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.Materials and methodsThirty 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.ResultsTwenty-five of 30 participants were men (83%); mean age was 47 years (SD 10.5), mean BMI 26.6 kg/m2 (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 (p < 0.001) and HFE variant (p = 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 (p = 0.001) was needed during a median of 66.5 days (IQR 49,103) and 78.5 days (IQR 46139), respectively (p = 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.ConclusionBlood donation procedures remove iron effectively in HC, but frequent treatments cause Hb decrease and fatigue that can impair feasibility.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Short Review On Hc and Blood Donationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Blood donation for iron removal in individuals with HFE mutations: study of efficacy and safety and short review on hemochromatosis and blood donation

Infanti,

Leitner,

Moe

et al. 2024

Front. Med.

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Eicosanoids and Oxylipin Signature in Hereditary Hemochromatosis Patients Are Similar to Dysmetabolic Iron Overload Syndrome Patients but Are Impacted by Dietary Iron Absorption

Lobbes,

Dalle,

Pereira

et al. 2024

Ann Nutr Metab

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Introduction: Oxylipins are mediators of oxidative stress. To characterize the underlying inflammatory processes and phenotype the effect of iron metabolism disorders, we investigated the oxylipin profile in hereditary hemochromatosis (HH) and dysmetabolic iron overload syndrome (DIOS) patients. Methods: LC-MS/MS based method to quantify plasma oxylipins in 20 HH and 20 DIOS patients in fasting conditions and 3 hours after an iron-rich meal in HH patients. Results: Principal component analysis showed no separation between HH and DIOS, suggesting that the clinical phenotype has no direct impact on oxylipin metabolism. 20-HETE was higher in DIOS and correlated with hypertension (p = 0.03). Different oxylipin signatures were observed in HH before and after the iron-rich meal. Discriminant oxylipins include epoxy fatty acids derived from docosahexaenoic acid and arachidonic acid as well as 13-HODE and 9-HODE. Mediation analysis found no major contribution of dietary iron absorption for 16/22 oxylipins significantly affected by the meal. Discussion: The oxylipin profiles of HH and DIOS seemed similar except for 20-HETE, possibly reflecting different hypertension prevalence between the two groups. Oxylipins were significantly affected by the iron-rich meal but the specific contribution of iron was not clear. Although iron may contribute to oxidative stress and inflammation in HH and DIOS, this does not seem to directly affect oxylipin metabolism.

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Indices of iron homeostasis in asymptomatic subjects with HFE mutations and moderate ferritin elevation during iron removal treatment

Cited by 2 publications

References 30 publications

Blood donation for iron removal in individuals with HFE mutations: study of efficacy and safety and short review on hemochromatosis and blood donation

Blood donation for iron removal in individuals with HFE mutations: study of efficacy and safety and short review on hemochromatosis and blood donation

Eicosanoids and Oxylipin Signature in Hereditary Hemochromatosis Patients Are Similar to Dysmetabolic Iron Overload Syndrome Patients but Are Impacted by Dietary Iron Absorption

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