Haemoglobinopathies and haemolytic anaemia Flashcards
What is haemolytic anaemia?
- increased peripheral destruction of RBCs
- shortened RBC lifespan (normal = 120days)
- bone marrow continues to produce cells
- pathology is in the red cell itself or its environment
- increased consumption means BM has to work harder to compensate
- as BM tries to keep up, the pt becomes anaemic
- RBC destroyed > RBC produced
What is the categorisation of haemolysis?
- inherited vs acquired
- immune vs non-immune
- extravascular vs intravascular
What are examples of inherited and acquired haemolytic pathologies?
Which investigations are important to do in a haemolysis screen?
if there is increased haemolysis, there will be…
- FBC - normocytic anaemia
- blood film - spherocytes or red cell fragments
- reticulocytes - increased
- LDH - increased (due to cell turnover)
- bilirubin - increased (unconjugated)
- haptoglobin - decreased
- DAT - positive in some immune cases
Intravascular haemolysis refers to site of destruction being within the vascular space whereas extravascular refers to site of destruction being in the spleen and other RES organs.
What biochemical findings would there be on investigation for intravascular vs extravascular haemolysis? Ie. What haemolytic findings would be the same and what would be different?
What are the two types of acquired immune haemolytic anaemias?
-
auto-immune
- warm AIHA
- cold AIHA (eg. CHAD, PCH)
- drug-induced
-
allo-immune
- transfusion rxns
- haemolytic disease of fetus + newborn (HDFN)
What are autoimmune haemolytic anaemias (AIHA)? What is meant by the cold and warm subtype of this?
- autoantibodies directed against a pt’s own RBCs
- usually IgG (generally warm AIHA) mediated
- or IgM (generally cold AIHA) mediated
warm and cold classifications due to the behaviour of the antibodies involved and whether they react more strongly with RBCs at 37oC or 4oC - may have a mixed picture in reality
What is meant by the ‘direct antiglobulin/Coombs test’ (DAT)?
Describe warm AIHAs
- usually IgG mediated: DAT +ve
- autoAb binds to RBCs at 37o
- removed by RE macrophages
- part of RBC membrane lost: spherocyte
- destroyed in spleen prematurely
- extravascular
- 50% idiopathic
- other associations - CLL, LPD, SLE, RA
Cold AIHAs are mediated usually by IgM. There are two types you need to know: primary CHAD and paroxysmal cold haemoglobinuria (PCH).
What is primary CHAD - what is it associated with and what triggers it?
- primary cold haemagglutinin disease
- Ab binds to RBCs at 4oC
- cases red cell agglutination on blood film, worse in the cold so transport sample in warm
- associated w/ acrocyanosis, Raynaud’s, intravascular haemolysis
- often triggered by mycoplasma pneumonia, EBV (secondary CHAD)
- may be associated w underlying LPDs
What is PCH?
- paroxysmal cold haemoglobinura (PCH)
- Donath-Landsteiner antibody - biphasic
- binds to RBCs at 37o and lyses them at 20o
- often triggered by viral infections
- in exams, tends to be child playing outside, who comes into a warm house
What is the management of warm AIHAs?
- look for associated/underlying conditions + treat
- steroids
- blood as needed
- rituximab (anti-CD20)
- splenectomy
What is the management for cold AIHAs?
- look for associated/underlying conditions + treat
- keep warm
- blood warmers
- occasionally chemotherapy if LPD
We have touched on auto-immune acquired haemolytic anaemias.
What is meant by allo-immune (acquired) haemolytic anaemia? What are the 2 examples?
- there is antibody against ‘foreign’ red blood cells
-
transfusion rxns - immediate or delayed
- donor blood antigen to already formed antibodies
-
haemolytic disease fetus + newborn (HDFN)
- fetus Ag positive (from father) and mother Ab positive (Ag negative). Ab in mother developed from exposure to fetal blood and then Ab crosses placenta to affect fetal RBCs
What is microangiopathic haemolytic anaemia (MAHA)?
- a type of acquired non-immune haemolytic anaemia
- characterised by mechanical destruction (due to env) of RBCs
- therefore fragments (schistocytes) on the blood film
- often associated w/ thrombocytopenia
- predominantly an acquired intravascular haemolysis
- examples include TTP, DIC, HELLP
An example of MAHA is thrombotic thrombocytopenic purpura (TTP).
For TTP, what are the:
- clinical features (pentad)
- biochemical findings
- aetiology
- rare
- fever, renal failure, confusion, thrombocytopenia, MAHA on blood film
- low plts, low Hb, high bili, high LDH, high creat, +/- positive troponin
- microthrombi
- often idiopathic, but also due to HIV, preg, drugs + congenital
What is the diagnosis + management of TTP?
- endothelial cell damage releases ultra large vWF multimers
- into bloodstream which bind to vWF on platelets -> aggregation
- reduction of ADAMTS 13 (normally proteolysis vWF multimers)
- with associated IgG antibody against ADAMTS 13
- ADAMTS 13 is vWF cleaving protease
- reduction leads to platelet aggregation
- no antibody in congenital forms - V RARE
-
treatment:
- plasma exchange, high-dose steroids, blood, folic acid, rituximab, RRT?
- aspirin + prophylactic LMWH when platelets recover
What happens in disseminated intravascular coagulopathy (DIC)?
- systemic activation of coagulation pathways
- generation of fibrin clots that may cause organ failure
- concomitant consumption of platelets + coag factors may result in clinical bleeding
- MAHA picture due to microthrombi in vessels + mild haemolysis
- diagnosis - inc PT, APTT, raised d-dimer, reduced fibrinogen + platelet count
- look for underlying cause + treat - severe sepsis, trauma, cancer, burns, toxins, obstetrics
The one type of acquired non-immune HA you need to know is PNH. What is PNH?
- paroxysmal nocturnal haemoglobinuria
- v rare
- PIG-A defect leading to a lack of GPI proteins (CD55 + CD59)
- CD59 normally protects against the MAC so these cells undergo complement mediated lysis
When does homozygous sickle cell anaemia (HbSS) first present?
- usually in early childhood with anaemia + jaundice due to chronic haemolytic anaemia
- painful hands + feet w/ inflammation of fingers due to dactylitis
What are the 3 clinical features of a chest crisis in homozygous sickle cell anaemia?
- pleuritic chest pain
- SoB
- hypoxia
ddx: pneumonia, pneumothorax, PE
What are precipitants of having a chest crisis?
- dehydration
- infection (eg. sore throat)
- cold or damp conditions
- unaccustomed exercise
- stress
- pregnancy, operations
What is the management of a chest crisis?
- hosp admission
- IV fluids, oxygen, adequate analgesia
- infection should be treated w/ antibiotics
- definitive investigation is haemoglobin electrophoresis which will demonstrate HbS, absent HbA, and variable HbF level
- exchange transfusion may be needed to reduce level of his sickle cells to less than 30%
- may benefit from long-term hydroxyurea which raises the HbF level + reduces number of crises
What is the normal structure of Hb?
- iron containing, oxygen carrying protein in RBC
- fetus, neonates + adults have diff structures
- most adults have:
- 2 alpha chains
- 2 beta chains
- producing HbA (>90%)
- and some HbA2 (<5%)
