Haemolytic anaemias Flashcards
Autoimmune Haemolytic anaemia RBC membrane defects (G6PD, spherocytosis, eliptocytosis) MAHAs (HUS +TTP)
What are the different causes for congenital haemolytic anaemias?
- Inherited (most)
- Haemolytic disease of the newborn (ABO/Rh) due to trans placental passage of antibodies
Which “sites” of the RBC can abnormalities occur in inherited haemolytic anaemias?
- RBC membrane
- Haemoglobin moleculse
- RBC enzymes: glycolytic pathway and pentose shunt
- Other rare conditions
What are typical features of haemolytic anaemias on Blood tests?
- FBC
- anaemia
- increased production: reticulocytes - Evidence of breakdown
- jaundice, bilirubin, LDH? - Are there abnormal cells?
What are common Red cell membrane defects?
- Hereditary spherocytosis
- hereditary elpitocytosis
Explain the pathophysiology of hereditary spherocytosis
Genetic mutation impact the connection of the cell membrane to the lipid layer –> makes RBC more round and more stiff as they age
- Splenomegaly –> causes splenic infarction
- Extravascular haemolytic –> destruction via splenic macrophages
What are clinical features of hereditary spherocytosis?
Often asymptomatic
- anaemia
- jaundice
- Pigment gallstones
How is a diagnosis of Hereditary Spherocytosis made?
What are the expected results for each of the investigations?
- FBC&LFT
- may/may not anaemia
- MCHC often increased
- Increased reticulocytes
- Bilirubin + LDH increased
Film
- spherocytosis + polychromasia + increased reticulocytes
Important differential for Spherocytes: autoimmune haemolytic anaemia (perform a negative direct anti globulin test - negative in hereditary spherocytosis)
What is the epidemiology of hereditary spherocytosis?
1 in 1.000 - 1 in 3.000 in caucasians
75% autosomal dominant
25% spontaneous or autosomal recessive
What is the epidemiology of hereditary spherocytosis?
1 in 1.000 - 1 in 3.000 in caucasians
75% autosomal dominant
25% spontaneous or autosomal recessive
What is the epidemiology + clinical significance of hereditary eliptocytosis?
2% of west Africans, rare in caucasians
Usually no clinical significance (asymptomatic + incidental diagnosis)
Might cause symptomatic anaemia
What disorder is a RBC disorder in the Glycolytic pathway?
How common is it?
All Glycolytic pathway defect are rare
Most common of the rare conditions
1. Pyruvate kinase deficiency - chronic haemolytic anaemia but usually asymptomatic/ little clinical significance
What is the pathophysiology of G6PD deficiency?
Defect in pentose shunt
Reduced levels of glutathione lead to increases susceptibility of RBC to oxidative stress+ free radicals
–> increased RBC membrane damage
–> increased intravascular and extravascular haemolytic
What is the epidemiology of G6PD deficiency?
x-linked recessive disease (male)
Usually Mediterranean + Afro-carribeans and other African descent
What is usually the first clinical presentation of G6PD deficiency?
Can present as
- neonatal jaundice
- acute intermittent haemolytic in times of oxidative stress
What are common triggers for an haemolytic episode in patients with G6PD deficiency?
- Infections (reactive oxygen generated by neutrophils)
- Food: Fava beans
- Drugs: antimalarials, nitrofurantoin, isoniazid, etc.
Other chemicals: moth balls ( naphthalene)
What does the blood film of a patient with G6PD deficiency show?
Can be normal if no oxidative stress
In oxidative stress
- Anaemia
- irregular contracted cells
- hemighost, ghost cell (empty membrane)
- Heinz bodies
- increased reticulocytes
How is the diagnosis of G6PD deficiency made?
G6PD assay
but can be normal in acute haemolytic with high reticulocytes, as reticulocytes have higher levels of the enzyme
How is G6PD deficiency managed?
- Prevention: avoid foods, certain drugs
- in crisis: transfusion might be ecessary
What is autoimmune haemolytic anaemia?
Antibodies are produced against erythrocyte antigens leding to haemolytic anaemia due to intravascular and extravascular haemolysis
How is autoimmune haemolytic anaemia diagnosed?
By a Direct antiglobulin test ( Coombs test)
–> Test to identify immunoglobulins and complements on the RBC membrane
What is the cause of autoimmune haemolytic anaemia?
Most commonly idiopathic
Are associated with several other diseases, such as
- SLE
(can also be associated with lymphoma, other malignancies)
What is the difference between Warm and cold autoimmune haemolytic anaemias?
Features and Causes
Causes
The temperature at which the agglutination is most pronounced
How is warm AIHA usually managed?
- Steroids
- Splenectomy
- Immunosuppressionn (Rituximab)
How is cold AIHA usually managed?
- Treat underlying condition
- Avoid the cold
- If lymphoma: chemotherapy
How is cold AIHA usually managed?
- Treat underlying condition
- Avoid the cold
- If lymphoma: chemotherapy
What is Microangiopathic haemolytic anaemias?
What are common causes?
Pathological processes in capillaries cause fragmentation of red cells
There are many causes
Some causes include
1. HUS
2. TTP
3. Metastatic tumours
4. DIC
What is HUS? Explain the pathophysiology
Infection with E.coli O157:H7
–> production of toxins that lead to endothelial cell damage (particularly in kidneys)
–> Vasoconstriction and thrombus formation
What is the common clinical presentation of HUS?
Usually infant - child
Haematology is proceeded by 5-10 days of bloody diarrhoea
with
1. Jaundice + clinical features of anaemia + oliguria
What is the clinical triad of Presentation of HUS?
- Thrombocytopenia
- Petechiae, purpura
- Mucosal bleeding
- Prolonged bleeding after minor cuts - Microangiopathic hemolytic anemia
- Fatigue, dyspnea, and pallor
- Jaundice - Impaired renal function
- Hematuria, proteinuria
- Oliguria, anuria
What is the difference between HUS and TTP?
Both cause thrombotic MAHA (microangiopathic haemolytic anaemias) with the same pathophysiology.
- HUS: is caused by an external trigger (e.coli infection)
- TTP is autoimmune
Clinically similar presentation but TTP has neurological involvement, HUS not
What does the blood film of MAHA show?
- schistocytes (fragmented RBC)
- thrombopenia
What are expected blood results of MAHA?
FBC + LFTs
- anaemia
- reticulocytosis
- increased bilirubin + LDH
(in HUS: increased creatinine?)
What is the confirmatory test for a diagnosis of hereditary spherocytosis?
Reduced red cell binding to eosin-5-maleimide
What is Thrombotic thrombocytopenic purpura?
thrombotic Microangiopathic haemolytic anaemia, caused by (usually) autoimmune destruction of the ADAMTS13 (VWBf -cleaving protease)
Explain the pathophysiology of TTP
- Autoantibodies or gene mutations → deficiency of ADAMTS13 (a metalloprotease that cleaves von Willebrand factor)
- ↓ Breakdown of vWF multimers → vWF multimers accumulate on endothelial cell surfaces
- Platelet adhesion and microthrombosis
- Microthrombi → fragmentation of RBCs with schistocyte formation → hemolytic anemia
- Arteriolar and capillary microthrombosis → end-organ ischemia and damage, especially in the brain and kidneys (potentially resulting in acute kidney injury or stroke)
What is the clinical presentation of TTP?
Pentad of clinical symptoms in ADULTS (usually)
- Fever
- Neurological signs + symptoms
+ Triad of HUS
1. Thrombocytopenia
2. Haemolytic anaemia
3. Renal impairment
What are biochemical + blood film presentations of TTP?
Thrombocytopenia
Red cell fragments
Polychromasia
+ increase creatinine (renal impairment) + signs of haemolytic
What is your confirmatory test for the diagnosis of TTP?
Clinical diagnosis + reduced ADAMTS13 and the presence of ADAMTS13 inhibitors
How is TTP managed?
Medical emergency - usually start treatment before confirmed diagnosis to reduce mortality
- Plasmapheresis (remove autoantibodies and replace ADAMTS13)
- immunosuppression
? Caplacizumab (WVF antibody)
NO platelet transfusion –> might make microangiopathy worse
What happens to haptoglobin in haemolytic anaemias?
Why?
Would be low
Because Haptoglobin binds free Hb
Haemolysis –> High free Hb –> Low Haptoglobin
