Haemolytic Anaemias Flashcards
What is haemolysis?
The premature red cell destruction ie shortened red cell survival
What is haemolytic anaemia?
Anaemia caused by premature breakdown of RBCs, before their normal life span of approximately 120 days.
How is haemolytic anaemia defined based on where it is occuring?
- Intravascular - destroyed within circulation
- Extravascular - taken up by reticuloendothelial system
Causes of haemolytic anaemia (intravscular vs extravascular)
- Intravascular
- ABO incompatible blood transfusion
- G6PD deficiency
- Severe falciparum malaria
- Extravascular
- Essentiall all other causes
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Why are red cells particularly susceptible to damage?
- They NEED to have a biconcave shape to transit the circulation successfully
- They have limited metabolic reserve and rely on anaerobic glucose metabolism for energy (since they have no mitochondria)
- Can’t generate new proteins once in the circulation (no nucleus)
What system falls under the term extravascular when describing the location that haemolysis is occuring?
Reticuloendothelial system - e.g macrophages in the liver, spleen and bone marrow
What are the groups causes of haemolytic anaemia?
- Acquired - immune, non-immune and other causes
- Hereditary - enzyme or membrane defects, or haemoglobinopathy
What are immune mediated causes of acquired haemolytic anaemia?
- Autoantibodies - Warm, Cold, CHAD, PCH
- Drug-induced
- Alloantibodies
What are non-immune causes of of acquired haemolytic anaemia?
- Acquired membrane defects - paroxysmal nocturnal haemoglobinuria
- Mechanical factors - prosthetic heart valves, or microangiopathic haemolytic anaemia
- Secondary to systemic disease - renal and liver disease
What are causes of acquired haemolytic anaemia that fall neither under immune or non-immune mediated acquired haemolytic anaemias?
- Toxins
- Infections
- Hypersplenism
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Drugs - oxidative haemolysis
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What is a Coomb’s Test?
DIRECT ANTIGLOBULIN TEST (DAGT)
Aim of this test is to determine if haemolysis is immune moderated or not
A test used to detect the antibodies or complement proteins that are bound to the surface of red blood cells.
A blood sample is taken and the RBCs are washed. These are then incubated with anti-human globulin (“Coombs reagent”). If this produces agglutination of RBCs, the direct Coombs test is positive, a visual indication that antibodies (+/- complement proteins) are bound to the surface of red blood cells.
What are the main types of autoimmune mediated haemolysis?
- Warm Autoantibody
- Cold Autoantibody
Type is determined depending on whether the antibody attaches better to the red cells at body temperature (37°C) or at lower temperatures
What are causes of Cold autoantibody autoimmune haemolysis?
IgM
- Infections - CMV, EBV, chickenpox, measles, mumps, mycoplasma pneumoniae
- Lymphomas
- Paroxysmal cold haemoglobinura
What antibody type predominates in Cold autoantibody AIHA?
IgM
What are causes of Warm Auto-antibody AIHA?
IgG
- Autoimmune rheumatic disorders e.g. SLE
- CLL
- Lymphoma’s (CLL)
- Carcinoma’s
- Drugs - metyldopa, penicillins, cephalosporins
What is the predominant type of antibody in warm type AIHA?
IgG
If its not autoimmune but its immune… what is it?
Alloimune - eg from haemolytic transfusion reaction OR passive transport to a newborn
Eg RhD, ABO incompatability
If you performed a DAGT and it was positive, what would this indicate?
Haemolysis is immune mediated
When performing a DAGT, what would a negative result indicate?
Non-immune mediated cause of haemolytic anaemia
If immune haemolysis was present on DAGT, how would you determine what type of autoantibodies are present?
Look at temperature at which they bind - Warm/Cold
When taking a history from someone with suspected haemolytic anaemia, what are you looking out for?
- Jaundice
- Dark urine
- Previous anaemia
- Travel
- Family history
- Drugs
What might you see on examination in someone with haemolytic anaemia (extravascular)?
- Jaundice (unconjugated bilirubinaemia)
- Hepatosplenomegaly
- Gallstones
- Leg ulcers
If you suspected haemolytic anaemia, what investigations might you do?
- FBC
- LDH
- Reticulocyte count
- Haptoglobin
- Urinary urobilinogen
- Bilirubin
- Thick and thin blood film
What is G6PD deficiency?
Glucose-6-phosphate dehydrogenase deficiency
The enzyme G6PD holds a vital position in the hexose monophosphate shunt, oxidizing glucose-6-phosphate to 6-phosphoglycerate with the reduction of NADP to NADPH. The reaction is necessary in red cells where it is the only source of NADPH, which is used via glutathione to protect the red cell from oxidative damage.
Deficiency in this enzyme means that cells are more vulnerable to oxidant damage. After an oxidant shock the Hb level may fall precipitously; death may follow unless the condition is recognized and the patient is transfused urgently.
What is pyruvate kinase deficiency?
This is the most common defect of red cell metabolism after G6PD deficiency. There is reduced production of ATP, causing rigid red cells.
What is hereditary spherocytosis?
HS is a membrane defect which results in the cells losing part of the cell membrane as they pass through the spleen. The best-characterized defect is a deficiency in the structural protein spectrin. The abnormal membrane in HS is associated functionally with an increased permeability to sodium, and this requires an increased rate of active transport of sodium out of the cells which is dependent on ATP produced by glycolysis.
The surface-to-volume ratio decreases, and the cells become spherocytic. Spherocytes are more rigid and less deformable than normal red cells. They are unable to pass through the splenic microcirculation so they have a shortened lifespan.
So in english - sphere shaped erythrocytes that mean there is an inability to travel from the arteries to smaller capillaries, they are more prone to rupture and symptoms of extravascular hamolysis as the spleen attempts to destroy them.
