Haemolytic Anaemia Flashcards
1
Q
Define a Haemolytic Disorder
A
Any condition that leads to a reduction of the mean lifespan of a red cell
2
Q
Define Haemolytic Anaemia
A
- increased red cell destruction
- bone marrow can compensate for initial losses so may not be obvious till red cell lifespan is reduced to 30 days
3
Q
What are some hereditary causes of haemolytic anaemia ?
A
- elliptocytosis
- G-6-PD deficiency
-pyruvate kinase deficiency
4
Q
What are some acquired causes of haemolytic anaemia ?
A
- drug associated
- secondary liver & kindey disease
- aulloimmune - transfusion reactions
5
Q
Wher does destruction of RBCs occur in intravascular haemolysis?
A
within blood vessels
6
Q
What can cause intravascular haemolysis?
A
- transfusion mismatch
-drugs - infections (malaria)
- G-6-PD deficiency with oxidant stress
- autoimmune haemolytic anaemias
7
Q
What does a haptoglobin do?
A
Binds dimers of haemoglobin in the circulation
7
Q
What are some lab diagnoses for intravascular haemolysis?
A
- absent haptoglobins
- haemoglobinemia
- haemoglobinuria
8
Q
Define haemoglobinemia
A
- condition where there is too much haemoglobin in the blood
9
Q
Where does extravascular haemolysis occur?
A
In the spleen, liver or bone marrow
10
Q
Describe the process of Extravascular haemolysis
A
- Damaged RBCs are recognised by macrophages & engulfed
- inside macrophages haemoglobin s broken down into its components
- haem –> unconjugated bilirubin
- globin chains -> amino acids
11
Q
What are some clinical features of extravascular haemolysis?
A
- jaundice due to build up of unconjugated bilirubin
- splenomegaly
- anaemia
- dark urine (excess bilirubin excretion)
12
Q
What are some lab findings for intravascular haemolysis?
A
- increased RBC breakdown
- serum bilirubin is raised, its unconjugated & bound to albumin
- haptoglobins absent
13
Q
Why are haptoglobins absent in intravascular haemolysis ?
A
- free haemoglobin binds to haptoglobins & this complex is removed by the reticulo-endothelial system
14
Q
What do microspherocytes indicate?
A
- indicated the binding of an antibody to RBCs which is removed by macrophages
- this removal takes some of the membrane - creating microspherocytes
15
Q
What is detected by the Schumms test
A
- Methaemalbuminaemia
16
Q
What is haemosiderin?
A
- A complex of iron and protein which is stored in tissues
- haemosiderin in the blood can indicate intravascular haemolysis
17
Q
How can you test for haemosiderin ?
A
- kindeys release haemosiderin into the urine
- urine is centrifuged & deposit is stained with Perls stain
18
Q
What can Methaemalbuminaemia indicate ?
A
- severe intravascular haemolysis
- methaemalbumin is elevated in blood
19
Q
Describe Hereditary Spherocytosis
A
- bioconcase RCs are produced in bone marow
- defects in named proteins (ankyrin/spectrin) mean that parts of membrane are lost and the cell adopts a spherical shape
- may be due to areas of the lipid bilayer not supported by the cytoskeleton
20
Q
What causes hereditary spherocytosis?
A
- Ankyrin deficiency/abnormalities
- Spectrin deficiency/abnormalities
- Band 3 abnormalities
- Palladin abnormalities
21
Q
Why does hereditary sphereocytosis generate a haemolytic state?
A
- spherocytes arent able to pass through the microcirculation of the spleen
- they remain & die prematurely
22
Q
What are some clinical features of hereditary spheroctytosis ?
A
- mostly presents as autosomal dominant (can be autosomal recessive)
- anaemia present at any age (infancy-old age)
- fluctuating jaundiced state
23
Q
What are the lab findings for Hereditary Spherocytosis?
A
- spherocytes visible on blood smear - smaller, darker red cells
24
How can hereditary spherocytosis be treated?
- some cases splenectomy - cause rise in haemoglobin
- risks post-operative sepsis, especially in young people
25
What causes Hereditary Elliptocytosis?
- a & b spectrin mutants lead to defective spectrin dimer formation
- a & b spectrin mutants leading to defective spectrin-ankyrin associations
- protein 4.1 deficiency/abnormality
25
How does hereditary elliptocytosis present in humans?
- camel red cells are elliptial in shape
- mild disorder - may be no evidence of haemolysis
- homozygotes for disease, elliptocytosis can present with severe haemolytic anaemia
26
Describe G-6-PD Deficiecny (glucose-6-phosphate-dehydrogenase)
- 1st stage of the pentose phosphate pathway
- red cells have no nucleus so it uses glutathione pathway to generate NADP+
27
What can be used to treat the oxidants generated by G-6-PD?
- Dapsone
- side effects = oxidation of red cell membrane, oxidation of haemoglobin & formation of heinz bodies
28
Who does G-6-PD deficiency affect ?
- sex lined - affecting males & carried by women
- offers heterozygous females some protection against P.Falciparum (worst kind of malaria)
- 400 varients of the deficiency
29
What are some clinical features of G-6-PD Deficiency ?
- usuaully asymptomatic
- acute haemolytic anaemia in response to an oxidant stress drug (fava beans&infection)
- intravascular haemolysis with haemoglobinuria
30
What are some agents than may cause haemolytic aneamia in G-6-PD deficiency?
- infections & other acute illnesses
- antimalarials (primaquine)
- sulphonamides (dapsone)
- fava beans & possible other vegetables
31
How is G-6-PD deficiency diagnosed?
- between crises blood count is normal
- during crisies the blood may show - bite & blister cells --> results from heinz bodies beign removed from cells in liver & spleen
32
What is Favism ?
- associated with G-6-PD deficiency
- V.faba contain high conc. of 2 B-glucosides = vicine & convicine
- upon digestion 2 compounds are formed = divicine (2,6-diamino-4,5-dihydroxypyrimidine) and isouramil (6-amino-2,4,5-trihydroxypyrimidine --> these cause oxidative stress of red cells
- if you have G-6-PD, Favism will cause haemolysis
33
How can G-6-PD deficiency be treated ?
- stop drug treatment - maintain a high urinary output & give transfusion if necessary
- babies may be prone to jaundice-phototherpay & exchange transfusion in some cases
34
What are warm type antibodies?
- active at 37 degrees
- examples of diseases which generate warm type antibodies;
- ulcerative colitis
- systemic lupus erthematosus
- malignant lymphoma
35
What are cold type antibodies?
- antibodies which bind best to RBCs at temps below body temp
- examples of diseases that generate cold type = infectious mononucleosis (mono), mycoplasma pneumonia
36
Describe March Haemoglobinuria
-RBC abnormalities due to microcirculation
- mechanical damage to red cells between small bones of feet during prolonged running/marching
- intravascular
37
Describe Paroxysmal Nocturnal Haemoglobinuria (PNH)
- clonal disorder - increased risk of leukaemia
- rare, acquired disorder of bone marrow stem cells
- defect in synthesis of GPI anchor - attached several proteins to the surface of the red cell
- defect means CD55 & CD59 are missing from RC surface
- CD59 = membrane inhibitor of reactive lysis
38
What are some common complications of PNH?
- Thrombosis
- chronic kidney disease
- anaemia
- pulmonary hypertension
39
How is PNH detected ?
- flow cytometry
- replaced older Ham's test
40
How can PNH be treated ?
- Eculizmab = inhibits complement & reduces haemolysis
- iron therapy maybe be needed,
- as well as warfarin to prevent thrombosis
