Haematopoiesis and ageing

There is an age-associated decline in haematopoietic stem cells and haematopoietic cell function. The reasons for this are unclear and much of our knowledge is derived from studies of mouse models rather than humans. It is probable that this decline arises from a combination of accumulated genetic and epigenetic changes, alterations in the marrow microenvironment and systemic effects such as inflammation. Practical consequences of these biological changes include reduced immune function, an increased incidence of cancer, and a lesser tolerance of haematopoietic stress (e.g. chemotherapy). Stem cells from older donors are less efficient at reconstituting haematopoiesis in transplant recipients.

Anaemia

Anaemia is a common clinical problem in the elderly. The prevalence rises rapidly after 50 years and approaches 20% in people aged over 80 years. In general, one third of cases will have an identifiable nutritional deficiency (iron, vitamin B₁₂ or folate) (Fig 46.1). Where iron deficiency is the cause of anaemia it is often secondary to gastrointestinal blood loss, and underlying bowel pathology (e.g. colonic carcinoma) should be excluded. Another third of cases have the anaemia of chronic disease. These patients have an obvious chronic inflammatory condition (see p. 36) and will often have a measurable acute phase response (e.g. elevated C-reactive protein). In the final third of elderly patents, there is no clear cause for the anaemia (sometimes termed ‘anaemia unexplained’). This entity is a diagnosis of exclusion and has been the focus of much recent interest. A few cases may be explained by myelodysplastic syndrome or other rarer causes of anaemia but it is probably mainly due to a combination of age-related suppression of erythroid colony formation, insensitivity to erythropoietin and impaired iron utilisation.

Whatever its aetiology, anaemia in the elderly is a relevant finding. It is associated with reduced physical and cognitive functioning, an increased chance of falls, an aggravation of comorbidity such as cardiac and neurological disease, and reduced survival. A low haemoglobin level should not be readily dismissed as part of ‘normal ageing’.

Where the anaemia has an explained cause (e.g. iron deficiency), treatment is specific for that disorder. Erythropoeitin may be used in chronic renal failure. Blood transfusion is needed in only a minority of cases (e.g. for the symptomatic anaemia of myelodysplastic syndrome), and in the very elderly and frail must be undertaken cautiously to avoid fluid overload and the exacerbation of cardiac failure. The treatment of unexplained anaemia in the elderly remains controversial with no clear guidelines.

Thrombosis and anticoagulation