haemolytic anaemias Flashcards
what is the reticuloendothelial system?
The Reticuloendothelial System (RES) consists of cells descending from the monocytes (macrophage, histiocytes) which are able to perform phagocytosis of foreign materials and particles. 90% of the RES are located in the liver.
other organs involved include; the spleen, connective tissue, BM, lungs
it is involved in extravascualr haemolysis
What are haemolytic anaemias and what are some of the classifications ?
RBC can be attacked in 3 locations:
- Membrane
- Hereditary spherocytosis
- Elliptocytosis
- Autoimmune:- > A. associated with conditions eg RA
- > B. Cold antiibody haemolytic syndromes- infections
- Haemoglobin
- Sickle cell
- Thalassaemia
- Other unstable haemoglobin variants eg Hb Hammersmith - Enzymes
- G6PD deficiency
- Pyruvate kinase dificiency
Can classify by intravascular and extra vascular.
List some intravascular causes of Haemolytic anaemia?
Haemolysis that occurs inside a BLOOD vessel
Malaria
G6PD deficiency
Mismatched blood transfusion
Drugs
MAHA - HUS+TTP !
DIC, HELLP !
Complement + IgM !
PNH
where does extravascular haemolysis occur?
spleen mainly - reticuloendothelial system
liver + lymph nodes can be implicated
what is the effect of parvovirus B19?
prognosis and ivx findings ?
infect erythroid cells in the bone marrow and arrest their maturation
in individuals with shortened red cell life span (e.g. 5-7 days) this can cause a dangerously low Hb (aplastic crisis)
prognosiis: self-limiting
ivx findings: low reticulocyte count
list some complications of Haemolytic anaemia and associations?
- Gallstones - due to high bilirubin
- > Associated with gilberts syndrome - UGT1A1 7/7 genotype
- Iron overload
- Due to increased intestinal absorption- Also due to transfusion
- Osteoporosis
what is the mechanism of gilberts syndrome?
UGT1A1 7/7 genotype:
there are 7/7 thymine-adenine repeats TA-TA repeats in the TATA promoter instead of 6/6
means there is LESS gene transcription and hence activity of the enzyme:
uridine diphosphate (UDP)-glycuronosyl transferase 1A1 (UGT1A1)
this means liver cant metabolise drugs or bilirubin so well.
how can iron overload be detected/ ivx?
Liver biopsy + Perls prussian blue stain:
may see haemosiderin deposits etc depending on condition
define polychromasia?
macrocytic red cells with bluish tinge - are immature red cells (retiiculocytes) found among normal cells.
list lab and clincial findings in Haemolytic anaemia?
Clinical: Large spleen - particularly extravascular h Pallor Jaundice Pigmenturia Family hx
Lab:
Anaemia
Reticulocytosis
Polychromasia
High bilirubin
High LDH - particularly intravascular (IH) + EH
Haemoglobin and haemosiderin in urine (red or brown urine) - IH
Low haptoglobin - IH + severe EH
what is the role of haptoglobin?
to bind to free circulating haemoglobin and form complexes that are excrreted
when there is too much Hb release, you get haemoglobin and hemosiderin in the urine
How can you tell from ivx results if something is Intravascular haemolyis?
involves molecules that were inside the ceell now coming out so;
haemoglubinuria,increased LDH etc
what is the mechanism responsible for PNH - paroxysmal nocturnal haemoglobinuria?
GPI - glycosylphosphatidylinositol on the red cell membrane is deficient.
this means molecules eg complement cant bind to red cell membrane = red cells prone to destruction
what is the mechanism responsible for hereditary spherocytosis?
defect in vertical interaction* at red cell membrane due to:
Band 3
Protein 4.2
Ankyrin
B Spectrin
- between proteins that link the lipid bilayer to the cytoskeleton
what is the mechanism responsible for hereditary elliptocytosis?
defect in horizontal interaction at red cell membrane due to:
a Spectrin
B Spectrin
Protein 4.1
which is the MOST COMMON genetic defect of the red cell cytoskeleton ?
hereditary spherocytosis
how is hereditary spherocytosis investigated and what would be the findings?
○ Osmotic Fragility Test - the hallmark of red cells in hereditary spherocytosis is that they show increased sensitivity to lysis in hypotonic saline
○ The cells also show reduced binding of the dye, eosin-5-maleimide -> deetermined using flow cytometry
○ Blood film:
§The cells lack the area of central pallor
because they have lost the biconcave shape
§ Microcytic and densely stained
§ FBC will probably show increased MCHC
§Polychromatic cells
what are the genetic types of hereditary elliptocytosis?
Heterozygous - rbc less badly affected
Homozygous - Hereditary Pyropoikilocytosis - rbc very badly affected
how is hereditary elliptocytosis investigated and what would be the findings?
Blood film:
NO polychromasia
Normal FBC
eliptical shaped rbc’s
Hereditary Pyropoikilocytosis:
Red cell fragments - schistocytes
Poikilocytosis
which condition is endemic in west Africa and is thought to be protective against severe malaria - what are the genotypes associated?
G6PD Deficiency - is X linked. more common in males
the notable genotypes are:
Hemizygous males
Females: less affected as it is X-linked. In cases where there is ‘unfavourable Iyonisation’ ( random inactivation of an X-chromosome in certain cells), creates a population of G6PD-deficient red blood cells coexisting with unaffected red blood cells.
in rare cases, including double X-deficiency -> the condition in females can grow in severity similar to males.
what is the role of G6PD enzyme ?
G6PD enzyme catalyses the first step in the pentose phosphate (hexose monophosphate) pathway
This reaction generates NADPH which is required to maintain intracellular glutathione (GSH)
Glutathione is needed to protect the red cell against oxidative stress
what are the effects of haemolysis in G6PD deficiency ?
○ Neonatal jaundice -> kernicterus (brain damage)
○ Acute haemolysis (triggered by oxidants/infection)
○ Chronic haemolytic anaemia (rare)
• Most people with G6PD deficiency are asymptomatic
Can present as diabetic ketoacidosis
If very severe can present with AKI
•Certain triggers can cause acute haemolysis such as: ○ Drugs § Antimalarials (primaquine) § Antibiotics (sulphonamides, ciprofloxacin, nitrofurantoin) § Dapsone - antibiotic § Vitamin K ○ Infections ○ Fava beans/broad beans ○ Naphthalene mothballs
what do Blood Film of G6PD Deficiency during Acute Haemolysis look like?
○ In the steady state, the blood film of someone with G6PD deficiency is usually NORMAL
○ Otherwise there are a lot of :
irregularly contracted cells,
nucleated red cells,
bite cells (cells that look like they’ve had part of their cytoplasm removed)
hemighosts (haemoglobin is retracted to one side of the cell)
Heinz bodies - with methylviolet stain
What is a characteristic feature of oxidative haemolysis on blood film ?
Heinz bodies
