Pathology
Haematology
Which of the following is NOT mainly characterised by intravascular haemolysis:
Answer:
Causes of intravascular haemolysis:- Haemolytic transfusion reactions
- G6PD deficiency
- Red cell fragmentation syndromes
- Some severe autoimmune haemolytic anaemias (including TTP)
- Some drug-and infection-induced haemolytic anaemias
- Paroxysmal nocturnal haemoglobinuria
Haemolytic Anaemia
Pathology / Haematology / Anaemia
Last Updated: 12th August 2019
Haemolytic anaemias are caused by a shortened red cell lifespan. Because of erythropoietic hyperplasia and anatomical extension of bone marrow, red cell destruction may be increased several-fold before the patient becomes anaemic.
Causes
Hereditary causes:
- Red cell membrane e.g. hereditary spherocytosis, hereditary elliptocytosis
- Red cell metabolism e.g. glucose-6-phosphate dehydrogenase (G6PD) deficiency, pyruvate kinase deficiency
- Haemoglobin synthesis e.g. thalassaemia, sickle cell disease
Acquired causes:
- Autoimmune e.g. warm or cold antibody type (characterised by a positive direct Coombs test and divided into 'warm' and 'cold' types according to whether the antibody reacts more strongly with red cells at 37 degrees Celsius or 4 degrees Celsius)
- Alloimmune e.g. haemolytic disease of the newborn or haemolytic transfusion reactions
- Red cell fragmentation syndromes e.g. DIC, TTP, HUS
- Infections e.g. malaria
- Drug or chemical-associated
- Secondary to liver or renal disease
- Paroxysmal nocturnal haemoglobinuria
Pathophysiology
Physiological red cell destruction is normally extravascular in the macrophages of the reticuloendothelial system. Globin is degraded to amino acids, haem to protoporphyrin, carbon monoxide and iron. Protoporphyrin is metabolised to biliverdin, and then bilirubin, conjugated to a glucuronide in the liver, excreted in faeces (as stercobilinogen) and, after reabsorption, in urine as urobilinogen.
Pathological red cell destruction is also usually extravascular. However it may also be intravascular. Some haemoglobin may then appear in plasma, where it is toxic and may cause fever, rigors and tissue damage. It is excreted unchanged in the urine and may cause renal damage. It is also partly reabsorbed by the renal tubules and broken down in the tubular cells to haemosiderin which appears in the urine.
Causes of intravascular haemolysis:
- Haemolytic transfusion reactions
- G6PD deficiency
- Red cell fragmentation syndromes
- Some severe autoimmune haemolytic anaemias
- Some drug-and infection-induced haemolytic anaemias
- Paroxysmal nocturnal haemoglobinuria
Clinical Features
- Anaemia
- Jaundice (caused by unconjugated bilirubin in plasma, bilirubin is absent from urine)
- Pigment gallstones
- Splenomegaly
- Ankle ulcers
- Expansion of marrow with, in children, bone expansion e.g. frontal bossing in beta-thalassaemia major
- Aplastic crisis caused by parvovirus
- Megaloblastic anaemia caused by folate deficiency
Laboratory Features
- Haemoglobin may be normal or reduced
- Reticulocyte count is raised
- Blood film shows polychromasia and altered red cell shape
- Bone marrow shows increased erythropoiesis
- Serum indirect (unconjugated) bilirubin is raised
- Urine urobilinogen is raised
- Serum haptoglobin is absent
- Lactate dehydrogenase is raised
- +/- Features of intravascular haemolysis
- Haemoglobinaemia
- Methaemalbuminaemia
- Haemoglobinuria (dark urine)
- Haemosiderinuria
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
