Hemolytic anaemias Flashcards
What is the normal life span of RBC?
120 days
- if reduced to 15-120 days you rarely see anaemia = due to compensated hemolysis (bone marrow upregaulates RBC production)
<15 = Hemolytic anaemia - excessive destruction of RBCs in blood leading to increase output by the bone marrow
Where is the physiological sites for red cell destruction?
Extravascular - in reticulo-endoethelial system = bone marrow, liver and spleen
Where is the pathological sites for red cell destruction?
intravascular - in the bloodstream - releases free iron which is damaging to cells due to its toxicity
hemoglobin can damage the kidney W
What normally happens to be breakdown products of RBCs?
As it is normally extravascular the iron binds transferrin to prevent it causing toxicity and the bilirubin is conjugated in the liver and excreted in the bowel and kidneys
What are the features of haemolytic anaemia?
Increased red cell production
- increased reticulocyte count = most mature form of RBCs
- erythroid hyperplasia
Increased red cell break down
- increased bilirubin, lactate dehydrogenase (LDH - very sensitive marker of hemolysis), urobilinogen
- reduced haptoglobin level (reduced in intravascular hemolysis)
- pigment gallstones - chronic hemolysis can lead to pigment gallstones due to byproducts such as bilirubin = can lead to cholecystitis
How can hemolysis be classified?
inherited - membrane, enzymes, hb (primarily related to RBCs)
acquired - immune (auto or alloimmune), non-immune
- allo-immune = mismatch RBC transfusion = can be fatal
What is hereditary spherocytosis?
inherited disorder of spectrin (RBC membrane protein - maintains integrity of cell)
Autosomal dominant
Cells lost membrane during circulation - lose a bit of membrane overtime the go through circulation - lose shape and don’t transport O2 well, therefore removed by macrophages before 120 days
What does hereditary spherocytosis look like clinically and histologically?
clinical - variable anaemia and jaundice (acholuric jaundice)
microspherocytes on blood film
increased osmotic fragility
How do you treat hereditary spherocyosis?
splenectomy if required - only required in small number of patients but can help to improve Hb as spleen is a key site of RBC destruction
What is hereditary elliptocytosis?
similar features to hereditary spherocytosis - another membrane defect
milder clinical features
variety of genetic disorders, autosomal recessive - may cause it to develop during childhood
Homozygotes produce severe disease = pyropoikilocytosis
What does NADPH do to RBCs?
protects them from oxidative damage
What is the source of NADPH in RBCs?
Glucose -6 - phosphate dehydrogenase (G6PD)
200 million people are deficient in this enzyme
What are the clinical features of G6PD deficiency?
anaemia after oxidative stress (drugs, fava beans, infection)
neonatal jaundice
non-spherocytic hemolytic anaemia
(blister cells)
Geographically, where is G6DP deficiency more commonly found?
often more common in tropical climates = africa, india, south and north america
Heterozygotes often found to be resistant to malaria - thought to be reason it is more common in tropical areas
How is G6DP deficiency inherited, diagnosed and treated?
inheritance is sex-linked
diagnosis is done by enzyme assay (not in an acute crisis)
treatment - treat symptoms
What type of inheritance is pyruvate kinase deficiency and what does it mean?
autosomal recessive and it means you have a failure to produce ATP
What are the clinical features of pyruvate kinase deficiency?
variable anaemia - 4-10g.dl = well-tolerated
jaundice, gallstones (very pigmented in chronic hemolysis)
How is pyruvate kinase deficiency diagnosed and treated?
diagnosed = enzyme assay treatment= splenectomy if necessary
What are congenital hemoglobin disorders
unstable hemoglobin disease - associated with heinz bodies, also knowns as congenital heinz-body hemolytic anaemia
hemolysis is a feature of many haemoglobinopathies such as sickle cell disease and thalassemia
What are the different forms of acquired (immune) hemolytic anaemias?
1) auto-immune HA- warm or cold (most active at room temp) antibodies
2) allo-immune HA
3) drug induced HA
What test can be done to check for autoimmune hemolytic anaemias?
Direct coombs test
- antibodies on the RBCs don’t do anything (do not clump and agglutinate - only cause them to be removed from circulation early) so you have to add anti-globing leads to clumping of RBCs with antibodies on them
What are the causes of warm hemolytic anaemias?
idiopathic
secondary to: SLE, Lymphoma (CLL), drugs
due to IgG antibodies against red cells which lead to opsonization of red cells in RE system
occur at any age, hemolysis is variable in severity
What investigations are carried out for warm AIHA and what are the treatments?
DCT+ and spherocytosis
treat: remove cause if present
- steroids
- splenectomy if failure
- blood transfusion
What are the causes of cold AIHA?
Primary - cold hemagglutinin disease
Secondary - infection e.g. mycoplasma, EBV
What is the antibody and antigen involved in cold AIHA?
Antibody is IgM = lower affinity and only binds at cooler temperatures e.g. extremities
Red cell antigen is nearly always I or i (specific antigen)
What are the investigations and treatments for cold AIHA?
DCT+ for completment
Treatment = keep warm, occasional cytotoxic (chemo)
Tends to present in elderly with cold fingers and toes
What is hemolytic disease of the newborn?
allo-immune haemolytic anaemia
- maternal immune system recognizes a fetal antigen as foreign and AB crosses the placenta
- usually antigen is RhD, also Kell, c
- Sensitization usually occurs at delivery therefore most problems in the 2nd pregnancy
- Anti-RhD Ab after delivery is effective at reducing sensitization
What happens if the second baby is RhD+ve?
it can trigger an immune reaction - 2nd trimester onwards hemolysis can be fatal
How many deaths are there per year from hemolytic disease of the newborn and what can be done to treat it?
50/year
in affected fetus in utero may need exchange transfusion and post delivery
ABO hemolytic disease of newborns is more common but less severe
Other than hemolytic disease of the newborn what other aloo-immune hemolytic disease is there?
incompatible blood transfusion
- classic example of intravascular haemolysis - due to IgM antibodies
still causes fatalities
What are the mechanisms of drug-induced immune hemolytic anaemia and what are some examples of drugs?
1) antibody to drug-red cell complex
2) complement fixation due to deposition of Ag-Ab complexes
3) Ab to red cell itself (role of the drug?)
- penicillins, quinidine, methyldopa
What are the causes of non-immune acquired hemolytic anaemia?
red cell fragmentation syndrome = microangiopathic HA, march hemoglobinuria, cardiac valve hemolysis (blood going through mechanical heart valve can get damaged)
infection
toxins, drugs, chemical
PNH
What happens in microangiopathic HA and what is it associated with?
due to mechanical intravascular hemolysis following pathological changes in small blood vessels
Associated with:
- hemolytic uraemic syndrome- caused by E.Coli 0157
- thrombotic thrombocytopenia purpura - medical emergency (lead to renal failure, requires emergency plasma exchange treatment)
- pre-eclampsia
- disseminated carcinoma
- collagen vascular diseases
What is march haemoglobinuria caused by?
follows walking or running on hard surfaces
- treat by replacing footwear
What is paroxysmal nocturnal hemoglobinuria?
acquired disorder of red cell membrane due to mutation within PIG-A gene which leads to inability to produce GPI anchor for membrane proteins
- leads to hemolysis due to lack of complement inhibitors on red cell surface
