Hemochromatosis alters the sensitivity of red blood cells to mechanical stress

Abstract

Background: Hemochromatosis (HH) is characterized by chronic iron accumulation, leading to deleterious effects to various organ systems. A common approach to managing iron load involves large-volume venesection. Some countries authorize HH venesections to be used in the development of transfusable blood products, although concerns remain regarding suitability. Due to the high oxidative load associated with hyperferritinemia, it has been proposed that HH blood products may be susceptible to mechanical damage. This is particularly relevant given that typical blood product destinations (eg, transfusion, cardiopulmonary bypass) expose blood to supraphysiologic levels of mechanical stress. We sought to explore the mechanical tolerance of red blood cells (RBC) derived from HH venesections to varied magnitudes and durations of sublethal shear stress. Study Design and Methods: Initially, 110 individuals with HH were recruited; to eliminate the effects of comorbidities, only those who were untreated and uncomplicated were included for comparisons with age-matched healthy controls (Con). RBC were exposed to 25 discrete magnitudes (1-64 Pa) and durations (1-64 seconds) of shear stress. Cellular deformability was assessed before, and immediately after, each shear exposure. Results: In the absence of prior shear exposure, RBC deformability of HH was significantly decreased by 11.5%, compared with Con. For both HH and Con, supraphysiologic shear exposure significantly impaired RBC deformability, although the rate and magnitude of deterioration were elevated for HH. Conclusion: Given that blood products are commonly exposed to high-shear environments (eg, during high-volume transfusion), venesections from asymptomatic and untreated individuals with HH appear suboptimal for the development of therapeutic RBCs.

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

“…In blood units drawn form 19 HC patients, a significantly decreased deformability and increased shear stress were observed compared to controls, but there was no clear evidence that an acute exposure to elevated iron levels was the cause of the observed differences ( 43 ). 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 ).…”

Accelerated Hemocompatibility Testing of Rotary Blood Pumps

“…13 The extensional recovery time for healthy erythrocytes is approximately 100-130 ms 14 ; for blood loops employing a 5 L•min -1 flow rate the test volume would thus approximate 11 ml. Note that the extensional recovery time, recoverability of cell deformability, and cell shear modulus are sensitive to blood quality, 15,16 chemical rigidification, 17 level of shear exposure, 18 and disease states [19][20][21][22] ; thus, this minimum volume threshold represents the best case scenario; however, for pragmatic reasons (e.g., sampling volume requirements or HVAD fill volume of ~15 ml) is unlikely to be of value in the real world. Irrespective, the smallest blood loop in the present study (80 ml) was well above this estimated threshold, and given the agreement in hemolysis with the larger loops, provides encouraging data for those attempting to introduce human blood into preclinical medical device assessment.…”

“…13 The extensional recovery time for healthy erythrocytes is approximately 100–130 ms 14 ; for blood loops employing a 5 L·min -1 flow rate the test volume would thus approximate 11 ml. Note that the extensional recovery time, recoverability of cell deformability, and cell shear modulus are sensitive to blood quality, 15,16 chemical rigidification, 17 level of shear exposure, 18 and disease states 19–22 ; thus, this minimum volume threshold represents the best case scenario; however, for pragmatic reasons ( e.g. , sampling volume requirements or HVAD fill volume of ~15 ml) is unlikely to be of value in the real world.…”