Mechanical sensitivity of red blood cells improves in individuals with hemochromatosis following venesection therapy

Abstract

Background: Individuals with hereditary hemochromatosis (HH) receive frequent blood withdrawals (ie, venesections) as part of their primary treatment to assist in normalizing blood iron levels. It remains unclear whether this source of blood is suitable for use in blood product development, as current data indicate that red blood cell (RBC) deformability, both before and after shear stress exposure, is impaired in individuals with HH, relative to healthy controls. Given that venesection therapy is known to significantly reduce circulating iron levels in individuals with HH, the current study examined whether venesection therapy is effective at improving RBC mechanical properties, both before and after shear stress exposure, in individuals with HH. Study Design and Methods: Blood samples were initially collected from untreated HH patients (age, 61 ± 9 years; 14% female) undergoing their first venesection, and then again during their second (approx. 9 weeks later) and third (approx. 16 weeks later) venesections. RBC deformability was measured at each time point with a commercial ektacytometer. Moreover, to determine cell responses to mechanical stimuli, the mechanical sensitivity of blood samples was determined at each time point. Results: The salient findings indicate that venesection therapy used for managing plasma ferritin concentration significantly improves the cellular deformability of RBC in individuals with HH. Further, the sensitivity of RBC to supraphysiological mechanical stress is decreased (ie, improved) in a doseresponse fashion with routine venesection. Conclusion: While cellular mechanics of RBC from individuals with HH are impaired when untreated, venesection therapy significantly improves cellular properties of RBC, supporting the use of venesections in blood product development from individuals with well-managed HH. K E Y W O R D S hemorheology, iron overload, mechanical damage, RBC deformability, sublethal trauma Abbreviations: EI, elongation index; EI max , maximal theoretical elongation index at an infinite shear stress; HH, hereditary hemochromatosis; NO, nitric oxide; RBC-NOS, shear-sensitive nitric oxide synthase isoform; SS 1/2 , shear stress required to obtain half the EI max value.

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

“…An Australian study on 15 volunteers with HC and 11 controls confirmed these data, suggesting that blood products from HC individuals can be more prone to damage and that this can be exacerbated in situations of elevated shear stress (e.g., transfusion during surgery) ( 44 ). However, the same authors also reported on an improvement of the mechanical properties of red blood cells of HC individuals following iron removal treatment, indicating a possibly crucial role of elevated ferritin in plasma in determining the previously observed cellular changes ( 45 ). Currently, a study ongoing in Switzerland aims to compare standard quality and biologic characteristics of red blood cell products of individuals with HC and of persons with reactively elevated ferritin on a larger number of blood units (registered as NCT05742035 at https://clinicaltrials.gov ).…”

Making a virtue out of an evil: Are red blood cells from chronic mountain sickness patients eligible for transfusions?

“…This is in line with a similar proposal, where venesections of wellmanaged hereditary hemochromatocytosis patients are suggested for blood product development. 9 Considering the scarcity of blood supply, particularly in low and medium-income countries in the Andes region such as Ecuador, Peru, or Bolivia, 10…”

“…Emeric Stauffer 1,2 , Aurélien P. Pichon 3 , Benoit Champigneulle 4 , Michaël Furian 5 , Ivan Hancco 6 , Alexis Darras 7 , Paul Robach 4,8 , Julien V. Brugniaux 4 , Elie Nader 1 , Philippe Connes 1 , Samuel Verges 4 , Lars Kaestner 7,9…”