HEMOLYTIC ANEMIAS
Normal red cell destruction
Normal red cells have a mean life span of about 120 days; removed extravascularly by the macrophages
of the reticuloendothelial (RE) system, especially in the marrow but also in the liver and spleen.
As the cells have no nucleus, red cell metabolism gradually deteriorates as enzymes are degraded and
the cells become non‐viable.
The breakdown of haem from haemoglobin liberates iron for recirculation via plasma transferrin mainly
to marrow erythroblasts, and protoporphyrin, which is broken down to bilirubin.
Bilirubin circulates to the liver where it is conjugated to glucuronides, which are excreted into the gut via
bile and converted to stercobilinogen and stercobilin (excreted in faeces).
Stercobilinogen and stercobilin are partly reabsorbed and excreted in urine as urobilinogen and urobilin.
Globin chains are broken down to amino acids which are reutilized for general protein synthesis in the
body.
Haptoglobins are proteins in normal plasma which bind haemoglobin.
The haemoglobin–haptoglobin complex is removed by the RE system.
Intravascular haemolysis (breakdown of red cells within blood vessels) plays little or no part in normal
red cell destruction.
Introduction to haemolytic anaemias
Haemolytic anaemias are defined as anaemias that result from an increase in the rate of red cell
destruction.
Because of erythropoietic hyperplasia and anatomical extension of bone marrow, red cell destruction
may be increased several‐fold before the patient becomes anaemic – compensated haemolytic disease.
The normal adult marrow, after full expansion, is able to produce red cells at 6–8 times the normal rate
provided this is ‘effective’.
It leads to a marked reticulocytosis.
Therefore, anaemia due to haemolysis may not be seen until the red cell lifespan is less than 30 days.
Classification
Hereditary haemolytic anaemias are the result of ‘intrinsic’ red cell defects, whereas acquired
haemolytic anaemias are usually the result of an ‘extracorpuscular’ or ‘environmental’ change.
, Destruction can stem from either intrinsic (intracorpuscular) red cell defects, which are usually
inherited, or extrinsic (extracorpuscular) factors, which are usually acquired.
Clinical features
Pallor of the mucous membrane
Mild fluctuating jaundice
Splenomegaly
There is no bilirubin in urine but this may turn dark on standing because of excess urobilinogen.
Pigment (bilirubin) gallstones may complicate the condition
Some patients (particularly with sickle cell disease) develop ulcers around the ankle.
Aplastic crises may occur, usually precipitated by infection with parvovirus which ‘switches off’
erythropoiesis, and are characterized by a sudden increase in anaemia and drop in reticulocyte count.
Rarely, folate deficiency may cause an aplastic crisis in which the bone marrow is megaloblastic
Laboratory findings
The laboratory findings are conveniently divided into three groups.
1. Features of increased red cell breakdown:
(a) serum bilirubin raised, unconjugated and bound to albumin;
(b) urine urinobilinogen increased;
(c) serum haptoglobins absent because the haptoglobins become saturated with haemoglobin and the
complex is removed by RE cells.
2. Features of increased red cell production:
(a) reticulocytosis;
(b) bone marrow erythroid hyperplasia; the normal marrow myeloid:erythoid ratio of 2 : 1 to 12 : 1 is
reduced to 1:1 or reversed.
3. Damaged red cells:
(a) morphology (e.g. microspherocytes, elliptocytes, fragments);
(b) osmotic fragility;
(c) specific enzyme, protein or DNA tests (LDH)
Normal red cell destruction
Normal red cells have a mean life span of about 120 days; removed extravascularly by the macrophages
of the reticuloendothelial (RE) system, especially in the marrow but also in the liver and spleen.
As the cells have no nucleus, red cell metabolism gradually deteriorates as enzymes are degraded and
the cells become non‐viable.
The breakdown of haem from haemoglobin liberates iron for recirculation via plasma transferrin mainly
to marrow erythroblasts, and protoporphyrin, which is broken down to bilirubin.
Bilirubin circulates to the liver where it is conjugated to glucuronides, which are excreted into the gut via
bile and converted to stercobilinogen and stercobilin (excreted in faeces).
Stercobilinogen and stercobilin are partly reabsorbed and excreted in urine as urobilinogen and urobilin.
Globin chains are broken down to amino acids which are reutilized for general protein synthesis in the
body.
Haptoglobins are proteins in normal plasma which bind haemoglobin.
The haemoglobin–haptoglobin complex is removed by the RE system.
Intravascular haemolysis (breakdown of red cells within blood vessels) plays little or no part in normal
red cell destruction.
Introduction to haemolytic anaemias
Haemolytic anaemias are defined as anaemias that result from an increase in the rate of red cell
destruction.
Because of erythropoietic hyperplasia and anatomical extension of bone marrow, red cell destruction
may be increased several‐fold before the patient becomes anaemic – compensated haemolytic disease.
The normal adult marrow, after full expansion, is able to produce red cells at 6–8 times the normal rate
provided this is ‘effective’.
It leads to a marked reticulocytosis.
Therefore, anaemia due to haemolysis may not be seen until the red cell lifespan is less than 30 days.
Classification
Hereditary haemolytic anaemias are the result of ‘intrinsic’ red cell defects, whereas acquired
haemolytic anaemias are usually the result of an ‘extracorpuscular’ or ‘environmental’ change.
, Destruction can stem from either intrinsic (intracorpuscular) red cell defects, which are usually
inherited, or extrinsic (extracorpuscular) factors, which are usually acquired.
Clinical features
Pallor of the mucous membrane
Mild fluctuating jaundice
Splenomegaly
There is no bilirubin in urine but this may turn dark on standing because of excess urobilinogen.
Pigment (bilirubin) gallstones may complicate the condition
Some patients (particularly with sickle cell disease) develop ulcers around the ankle.
Aplastic crises may occur, usually precipitated by infection with parvovirus which ‘switches off’
erythropoiesis, and are characterized by a sudden increase in anaemia and drop in reticulocyte count.
Rarely, folate deficiency may cause an aplastic crisis in which the bone marrow is megaloblastic
Laboratory findings
The laboratory findings are conveniently divided into three groups.
1. Features of increased red cell breakdown:
(a) serum bilirubin raised, unconjugated and bound to albumin;
(b) urine urinobilinogen increased;
(c) serum haptoglobins absent because the haptoglobins become saturated with haemoglobin and the
complex is removed by RE cells.
2. Features of increased red cell production:
(a) reticulocytosis;
(b) bone marrow erythroid hyperplasia; the normal marrow myeloid:erythoid ratio of 2 : 1 to 12 : 1 is
reduced to 1:1 or reversed.
3. Damaged red cells:
(a) morphology (e.g. microspherocytes, elliptocytes, fragments);
(b) osmotic fragility;
(c) specific enzyme, protein or DNA tests (LDH)
