Haemolysis ✅ Flashcards
What is haemolysis?
An increase in breakdown of RBCs
What happens if the bone marrow is unable to compensate for the increased red cell turnover in haemolysis?
Anaemia develops
What can haemolysis be broadly grouped into?
- Inherited causes
- Acquired causes
What are inherited causes of haemolysis usually due to?
Intrinsic red blood cell abnormalities
What are acquired causes of haemolysis usually due to?
Extrinsic abnormalities
Give an example of an acquired mechanism of haemolysis?
Antibody-mediated destruction in immune haemolytic anaemias
What cause of haemolytic anaemias account for the majority of cases in children?
Intrinsic red cell abnormalities
What do blood tests show in haemolytic anaemia?
- Reduced Hb
- Raised reticulocytes
- Raised unconjugated bilirubin
- Raised LDH
- Low haptoglobin
Why is LDH raised in haemolytic anaemia?
The LDH enzyme is present at high levels in RBCs, and so during haemolysis, lysis of RBCs causes large amounts of LDH to be released into the circulation
Where in the body does haemolysis occur?
Can occur in the circulation (intravascular) or in various organs, such as the spleen (extravascular)
What does intravascular haemolysis lead to?
Depletion of haptoglobin, increased LDH, and large numbers of fragmented red blood cells, called schistocytes.
Why does intravascular haemolysis lead to a depletion of haptoglobin?
Haptoglobin binds to free haemoglobin in the plasma to form a haptoglobin-haemoglobin complex, which is then removed from the circulation by the reticuloendothelial system (mostly in the spleen)
What happens after haptoglobin is depleted?
Free haemoglobin is filtered by the kidney
What happens to filtration of free haemoglobin by the kidney in severe cases of intravascular haemolysis?
The reabsorption is overwhelmed
Where in the body is LDH present?
It is present in many tissues, but has high concentrations within RBCs
Where does extravascular haemolysis take place?
Usually in spleen or liver, but can also occur in lung
What is the mechanism of extravascular haemolysis?
Spleen or liver macrophage Fc receptors bind immunoglobulin attached to red blood cells and then either ingest small portions of the cell membrane, creating spherocytes, or phagocytose the whole cells
What happens to the products of extravascular haemolysis?
- Amino acids from globing chains are recycled
- Iron is removed from haem and reused
- Haem is degraded into unconjugated bilirubin
What provides useful clues into the diagnosis and aetiology of haemolysis?
The blood film
What might the blood film show in haemolysis?
- Polychromasia
- Sickle-shaped cells
- Spherocytes
- Fragmented red cells
What is polychromasia?
An increase in immature red blood cells (reticulocytes)
How do reticulocytes appear on most blood film stains?
Lilac
What is the significance of sickle-shaped cells in blood films?
Diagnostic of sickle cell disorders
When might spherocytes be seen on blood film?
- Hereditary spherocytosis
- Immune haemolytic anaemias
What are the types of fragmented red blood cells?
- Degmacytes, or ‘bite’ cells
- Schistocytes
What are bite cells typical of?
Oxidative haemolysis, e.g. G6PD deficiency
When are schistocytes seen?
In intravascular haemolysis, e.g. haemolytic uraemic syndrome
What does the direct antiglobulin test (DAT) detect?
The presence of antibodies coating RBCs
What is DAT essential for?
Diagnosis, or exclusion, of immune-mediated haemolytic anaemia
How is the DAT test performed?
RBCs are incubated with anti-human globulin (AHG), and if antibody is present on the cells, the AHG will cause agglutination
What is counted as a positive DAT?
If agglutination occurs
Give 4 conditions where DAT is positive?
- Haemolytic disease of the newborn
- Autoimmune haemolytic anaemia
- Drug-induced haemolytic anaemia
- Haemolytic transfusion reactions
What are the types of inherited haemolytic disorders?
- Red cell membrane defects
- Red cell enzyme defects
- Haemoglobinopathies
Give 2 red cell membrane defects
- Hereditary spherocytosis
- Hereditary elliptocytosis
Give 2 red cell enzyme defects
- G6PD deficiency
- Pyruvate kinase deficiency
Give 2 haemoglobinopathies
- Sickle cell disorders, e.g. sickle cell anaemia
- Thalassaemias
What are the types of acquired haemolytic disorders?
- Autoimmune
- Microangiopathic
- Infection
- Other
Give 5 causes of autoimmune haemolytic anaemia?
- Idiopathic
- Rheumatological conditions
- Infection-associated
- Paroxysmal nocturnal haemoglobinuria
- Lymphoproliferative disease
Give 2 rheumatological conditions that can cause autoimmune haemolytic anaemia?
- SLE
- JIA
Give 2 infections that can cause autoimmune haemolytic anaemia?
- Varicella zoster
- EBV
Give a lymphoproliferative disease that can cause autoimmune haemolytic anaemia?
Hodgkin’s lymphoma
Give 3 microangiopathic causes of haemolytic anaemia?
- HUS
- Thrombotic thrombocytopenia purpura
- Haemangiomas
Give an example of a haemangioma that can cause haemolytic anaemia?
Kasabach-Merritt syndrome
Give 2 examples of infections that can cause haemolytic anaemia?
- Malaria
- Sepsis
Give 3 other causes of haemolytic anaemia
- Hypersplenism
- Burns
- Poisoning
Give 3 poisons that can cause haemolytic anaemia
- Lead
- Arsenic
- Napthalene
What is the most common inherited disorder of the red cell membrane?
Hereditary spherocytosis (HS)
What are most cases of HS due to?
A mutation in spectrin or ankyrin genes
What do spectrin and ankyrin genes do?
Encode key red cell membrane structural proteins
What do the proteins encoded for my spectrin and ankyrin do?
Anchor the lipid membrane of the red cell to the protein skeleton
What is the result of loss of the anchoring effect in HS?
Allows small membrane fragments to be lost during red cell passage through the spleen
What happens as membrane loss progresses in HS?
The red cell gradually becomes spherical
What happens to the spherocytic red cells in HS?
They are destroyed by the spleen, resulting in haemolytic anaemia
What is the inheritance of HS?
Usually autosomal dominant, but up to 25% of cases are autosomal recessive, or the result of de novo mutations
What are the clinical features of HS in most patients?
- Mild anaemia (Hb 80-100)
- Variable splenomegaly (typically 1-2 cm)
- Fluctuating jaundice
When in particular is there likely to be jaundice in mild HS?
At times of infection
What can HS lead to in more severe cases?
Profound, chronic haemolytic anaemia
When does HS usually present?
Early childhood or neonatal period
Do neonates with HS require treatment?
Most will not, apart from phototherapy for jaundice
What will around 25% of neonates with HS require?
1-3 transfusions due to moderately severe haemolytic anaemia during the first 1-2 months of life
How common is transfusion dependence beyond neonatal life in HS?
Extremely uncommon
How can a diagnosis of HS be made in most cases?
Positive family history and presence of spherocytes on the blood film
What will blood tests show in HS?
Usually show mild anaemia with raised reticulocytes and bilirubin
What is the most important differential for HS in neonates?
Haemolytic disease of the newborn
How can HS be differentiated from haemolytic disease of the newborn?
In alloimmune haemolysis, DAT is almost always positive. In HS, it is negative
What is usually enough for diagnosis of HS in those without family history?
Typical blood film findings and exclusion of other conditions
What treatment is required for most patients with HS?
None, other than prophylactic oral folic acid to prevent megaloblastic anaemia
What treatment can improve the anaemia in HS?
Splenectomy
What is the problem with splenectomy in HS?
Side effects mean it is restricted to children who are failing to thrive or develop transfusion dependence
What are the side effects of splenectomy?
- Increased susceptibility to infection
- Risk of thrombosis
What is common in older children and adults with HS?
Pigment gallstones due to chronic haemolysis
What can complicate chronic haemolytic disorders?
Parvovirus B19 infection
What can parvovirus B19 cause in chronic haemolytic disorders?
Severe reduction in red cell production (red cell aplasia)
In what conditions can parvovirus B19 precipitate an aplastic crisis?
Any chronic haemolytic disorder
What might support a diagnosis of parvovirus B19 as a cause of deterioration in children with chronic haemolytic disorders?
A preceding coryzal illness
How can a diagnosis of aplastic crisis caused by parvovirus B19 be made in chronic haemolytic disorders?
- Low Hb
- Markedly reduced reticulocytes
- IgM antibodies against parvovirus B19
How low can the Hb be in aplastic crisis caused by parvovirus B19 infection?
Often 20-30g/L
