Anaemia

Anaemia is defined as the reduction in circulating red blood cell-mass below normal levels. It reduces the oxygen-carrying capacity of the blood, leading to tissue hypoxia. It is diagnosed by haemoglobin concentration. The WHO defines anaemia as a haemoglobin concentration < 13 g/dL for men and < 12 g/dL for women, but the normal ranges vary a bit from laboratory to laboratory.

People with chronic anaemia develop compensatory mechanisms, which is why they can function with lower Hb.

Classification of anaemias according to morphology

Anaemias can be classified according to the morphology of the RBCs or according to the etiology.

	Microcytic anaemia	Normocytic anaemia	Macrocytic anaemia
MCV (fL)	< 80	80 – 100	> 100
Pathomechanism	Insufficient haemoglobin production	Increased RBC loss and/or decreased erythropoiesis	Insufficient RBC production and/or maturation, possibly due to defective DNA synthesis or DNA repair
Possible causes	Iron deficiency anaemia	Haemolytic anaemias:	Vitamin B12 deficiency
	Anaemia of chronic disease (late phase)	Sickle cell anaemia	Folate deficiency
	Thalassaemia	G6PD deficiency	Certain drugs (phenytoin, sulfa drugs)
	Lead poisoning	Paroxysmal nocturnal haemoglobinuria	Fanconi anaemia
	Chronic blood loss	Hereditary spherocytosis	Liver disease
		Autoimmune haemolytic anaemia	Alcohol abuse
		Microangiopathic haemolytic anaemia (TTP/HUS)
		Macroangiopathic haemolytic anaemia
		Non-haemolytic anaemias:
		Acute blood loss
		Aplastic anaemia
		Anaemia of chronic disease (early phase)

Classification of anaemia according to reticulocytes

In response to anaemia, a healthy bone marrow will increase production of RBCs. This is evidenced on labs as an elevated reticulocyte count. If reticulocytes are not elevated or are decreased, it points to a primary problem with the bone marrow causing the anaemia.

Increased reticulocytes – bone marrow works hard
- Bleeding
- Haemolysis
Decreased reticulocytes – bone marrow doesn’t work
- Aplastic anaemia
- Leukaemia
- Myelodysplasia
- Myelofibrosis
- Chronic kidney disease (EPO deficiency)

Haemolytic anaemia

Haemolytic anaemias are a form of anaemia characterized by the pathologically increased breakdown of RBCs (haemolysis), reducing their to less than the normal 120 days. To compensate for increased turnover of RBCs the bone marrow can increase the output of RBCs 6 – 8-fold. Anaemia only manifests if the rate of destruction exceeds this increased production rate.

There exist many types of haemolytic anaemia, both congenital and acquired.

Diagnosis and evaluation

A protein called haptoglobin is important in the diagnosis of haemolysis. Haptoglobin is a plasma protein which binds to free haemoglobin in the plasma. When there is haemolysis, more haemoglobin is released into the plasma. Haptoglobin in the plasma will bind to the released haemoglobin. This decreases the amount of free circulating haptoglobin, which is what’s measured in the lab.

Laboratory tests
- In both types of haemolysis
  - Haptoglobin ↓
  - Lactate dehydrogenase ↑
  - Indirect bilirubin ↑
  - Reticulocytes ↑ – due to increased erythropoiesis
  - Urinary urobilinogen ↑
- Only in intravascular haemolysis
  - Free haemoglobin in plasma ↑ (only in severe cases)
  - Brown-coloured urine – due to haemoglobinuria or haemosiderinuria
Peripheral blood smear
- Spherocytes – Small, spherical RBCs with no central pallor

It can be difficult to differentiate intravascular and extravascular haemolysis on a lab test as no one parameter is different in the two. In extravascular haptoglobin can be normal, and there is rarely free haemoglobin in the plasma.

The Coombs test is essential in the diagnosis of antibody-mediated anaemias. There are two types of Coombs test, the direct type and the indirect type. The direct Coombs test is positive if there are autoantibodies against the patient’s own RBCs bound to the RBCs in the patient’s blood. The direct Coombs test is positive in immune-mediated haemolytic anaemias.

The indirect Coombs test is positive if there are autoantibodies against foreign (not the patient’s) RBCs in the patient’s blood. The indirect Coombs is used to check if the patient’s blood contains anti-D antibodies, which would cause haemolytic disease of the newborn due to ABO or Rh incompatibility.