Haemochromatosis: Pathophysiology and the red blood cell1.

Abstract

Haemochromatosis remains the most prevalent genetic disorder of Caucasian populations in Australia and the United States, occurring in ∼1 of 200 individuals and having a carrier frequency of 10-14%. Hereditary haemochromatosis is an autosomal recessive condition, that is phenotypically characterised by a gradual accumulation of iron, above and beyond that required for biological function. Once the binding capacity of iron carriers reaches saturation, the highly reactive free iron generates radicals that may lead to widespread cellular dysfunction. Thus, the compounding effects of systemic iron overload and the associated oxidative stress in untreated haemochromatosis patients results in tissue damage precipitating severe complications, including: liver cirrhosis, hepatocellular cancer, cardiomyopathy, and diabetes. The primary treatment indicated for individuals with haemochromatosis is venesection therapy (i.e., regular bloodletting of ∼450 mL). Given the frequency of venesection required to decrease and normalise the elevated iron levels, this population may serve as a valuable source of blood products which are in short supply. While the complications associated with elevated iron deposits are frequently reported, the influence of haemochromatosis on the rheological properties of blood and red blood cells (RBC) - major determinants of microvascular blood flow and tissue perfusion - are poorly understood. Limited studies investigating haemorheology in patients with haemochromatosis have reported altered physical properties of blood, which may partly explain the comorbidities associated with the disorder. The current review will explore the aetiology, pathology, and clinical implications of haemochromatosis disease and the associated oxidative stress, with particular emphasis on RBC.