54. Aplastic anemia and anemias of complex etiology in disease states

From greek.doctor

Aplastic anaemia

Aplastic anaemia is any anaemia associated with severe decrease or death of haematopoietic stem cells in the bone marrow. It results in fewer RBCs being produced. It can be caused by:

  • Drugs
    • Drugs against hyperthyroidism
    • Antihypertensive drugs
    • Antipsychotics
  • Irradiation
    • Cancer treatment
  • Chemicals
    • Benzene
    • Organic solvents
    • Insecticides
  • Viruses
    • Hepatitis
    • HIV
    • Epstein-Barr virus
  • Hereditary
    • Fanconi anaemia
    • Diamond-Blackfan syndrome
  • Other
    • Pregnancy
    • Graft-versus-host disease

Fanconi anaemia is a genetic disease where the normal repair response to DNA damage is impaired. It especially affects the bone marrow. It’s a very rare disease associated with acute myeloid leukaemia and aplastic anaemia.

Disease-associated forms of anaemia

Chronic renal failure

Chronic renal failure is a progressive loss of glomerular function caused by long-standing renal parenchymal disease. The destruction of the renal parenchyme also limits the ability to produce EPO. Chronic renal failure also causes uraemia. Urea in the blood causes formation of uraemic toxins. These toxins suppress the bone marrow and decrease the survival time of RBCs in the peripheral circulation, which worsens the anaemia. Renal failure is also associated with protein and iron deficiency, making it even worse.

Anaemia of chronic disease

Chronic inflammation also causes anaemia. Neutrophils produce a protein called lactoferrin. This protein binds to Fe atoms, forming complexes that are phagocytosed by macrophages. This is a good defence against bacteria, because bacteria need iron and this mechanism depletes serum iron. However, this iron can’t be reclaimed later; it’s permanently lost (like iron in haemosiderin). Chronic inflammation will therefore lead to chronic suppression of the serum iron level, which leads to microcytic hypochromic anaemia.

Anaemia of inflammation

During inflammation is serum iron level decreased by another mechanism as well. Hepcidin is an acute phase protein, produced by the liver during inflammation. It’s a hormone that suppresses the bone marrow and decreases EPO release from the kidney. It also decreases iron absorption from the gut.

Sideroblastic anaemia

Sideroblastic anaemia is a condition where the bone marrow produces cells called ringed sideroblasts rather than producing healthy red blood cells. It’s associated with genetic problems with enzymes of the heme synthesis, like δ-aminolevulinic acid synthase (DALA). Deficient Hb production causes microcytic hypochromic anaemia.