Haematology: Haemolytic Anaemias Flashcards
(54 cards)
1
Q
What is haemolytic anaemia?
A
- Anaemia due to shortened red blood cell survival
2
Q
Briefly describe the red blood cell cycle
A
- Mature red blood cells are produce in the bone marrow
- They then travel from bone marrow into the circulation (lose their nucleus on the way out)
- They stay in circulation for about 120 days
- In circulation they acquire chnages which are recognised by macrophages in liver/spleen that cause them to degrade RBCs after 120 days
3
Q
What proteins/enzymes are required in the production of red blood cells?
A
- Iron
- B12/folate
- Globin chains
- Protoporphyrins
4
Q
What are the main components of a mature red blood cell?
A
- Plasma membrane - biconcave disc
- Haemoglobin
5
Q
What are the 2 main metabolic pathways of a mature red blood cell?
A
- Glycolytic pathway
- Hexose-monophosphate shunt - parallel to glycolytic pathway (produces NADPH, pentoses and ribose-5 phosphate)
6
Q
What is haemolysis?
A
- The rupture or destruction of of red blood cells leading to decreased red cell survival
7
Q
Describe the body’s response to haemolysis?
A
- Bone marrow increases red blood cell production
- This leads to increased levels of reticulocytes in the circulation - this is called reticulocytosis
8
Q
What is compensated haemolysis?
A
- Occurs when red blood cell production is able to compensate for decreased red blood cell lifespan due to haemolysis
- Results in haemoglobin level remaining normal
9
Q
What is incompletely compensated haemolysis?
A
- Occurs when red blood cell production is unable to compensate for decreased red bllod cell lifespan due to haemolysis
- Results in reduced haemoglobin level
10
Q
Name some of the main symptoms of haemolytic anaemias
A
- Jaundice - Yellowing of skin, whites of eyes and mucous membranes
- Pallor/fatigue
- Splenomegaly - enlargement of the spleen
- Dark urine
11
Q
Why do haemolytic anaemias cause jaundice?
A
- Excessive red blood cell break down leads to excessive levels of bilirubin in circulation
- This leads to yellowing of skin etc. seen in jaundice
12
Q
They are 2 types of crises associated with haemolytic anaemia, Explain these 2 crises
A
- Haemolytic crisis - Occurs when there’s an increased level of haemolysis due to an infection leading to increased anaemia and jaundice
- Aplastic crisis - Occurs when person is infected with parvovirus which causes a rapid decrease in Hb levels leading to anaemia. Reticulocytopenia also occurs as parvovirus affects erythroblasts, and therefore eryhtropoiesis, in bone marrow.
13
Q
Name some symptoms of chronic haemolytic anaemias
A
- Pigment gallstones - due to breakdown of excess bilirubin
- Splenomegaly
- Leg ulcers - due to free Hb collects and removes nitric oxide
- Folate deficiency - due to increased use
14
Q
Describe the laboratory findings/results of tests for haemolytic anaemia
A
- Normal/decreased haemoglobin
- Increased reticulocyte count
- Increased unconjugated bilirubin
- Increased LDH (lactate dehydrogenase) - released wehn red cells are broken down
- Low serum haptoglobin - protein that binds free haemoglobin
- Increased urobilinogen
- Increased urinary haemosiderin
- Abnormal blood film
15
Q
What are some of the cahracteristics of the blood film of someone with a haemolytic anaemia?
A
- Presence of reticulocytes
- Polychromasia - high levels of immature red blood cells
- Presence of nucleated red blood cells
- Poikilocytes - abnormally shaped red blood cells
16
Q
What are the different ways that haemolytic anaemias can be classified?
A
- Classification based on inheritance:
- Inherited
- Acquired
- Classification based on site of RBC destruction:
- Intravascular
- Extravascular
- Classification beased on origin of RBC damage:
- Intrinsic
- Extrinsic
17
Q
Name some congenital/acquired disorders that lead to heamolytic anaemia
A
- Membrane disorders:
- Spherocytosis
- Elliptocytosis
- Enzyme disorders:
- Glucose-6-phosphate dehydrogensae (G6PD) deficiency
- Pyruvate Kinase deficiency
- Haemoglobin disorders:
- Sickle Cell Anaemia
- Thalassaemias
18
Q
Name some acquired causes of haemolytic anaemias
A
- Autoimmune causes
- Drugs
- Mechanical - leaky heart valves
- Microangiopathic - severe hypertension
- Infections - malaria
19
Q
A
20
Q
Describe process of intravascular haemolysis
A
- Red blood cell broken down in circulation causing it to release its haemoglobin, iron and bilirubin
21
Q
What conditions does intravascular haemolysis lead to?
A
- Haemoglobinaemia - Excess free haemoglobin in blood
- Methaemalbuminaemia - Breakdown of haemoglobin forms haem and methaem which binds to albumin to form methemalbumin
- Haemoglobinuria - Excess haemoglobin in urine
- Haemosiderinuria - Haemosiderin in urine
22
Q
There are two main types of red cell membrane disorder that can cause haemolytic anaemias. Name these 2 types of red cell membrane disorder and give examples of proteins that can be affected by them.
A
- Defects in proteins involved vertical interaction:
- Spectrin
- Band 3
- Protein 4.2
- Ankyrin
- Defects in proteins involved in horizontal interaction:
- Protein 4.1
- Glycophorin C
- Spectrin – Can cause hereditary pyropoikilocytosis (HPP)
23
Q
What condition is usually caused by disorders affecting vertical interaction?
A
- Hereditary spherocytosis
24
Q
What condition is usually caused by disorders affecting horizontal interaction?
A
- Hereditary elliptocytosis
25
What are some of the main characteristics of hereditary spherocytosis?
* Most common hereditary haemolytic anemia
* Shows autosomal dominant inheritance
* Bone marrow makes biconcaves RBCs but they lose membrane as they go around circulation causing them to become spherical
26
What are some of the clinical feautures of hereditary spherocytosis?
* **Can be asymptomatic to severe haemolysis** - shows no symptoms of haemolysis
* **Neonatal jaundice** - Bilirubin in babies can cross blood-brain barrier and cause brain damage
* **Jaundice**
* **Splenomegaly**
* **Pigment gallstones**
* **Reduced eosin-5-maleimide (EMA) binding** – binds to band 3, a membrane protein.
27
How can you manage/treat hereditary spherocytosis?
* Monitor condition
* Folic acid supplemements
* Blood transfusion
* Splenectomy - removal of spleen
28
Glucose-6-phosphate dehydrogenase is involved in the hexose monophpsphate pthway/shunt. What is the function of this pathway?
* Produces NADPH as well as reduced glutathione (GSH)
* Reduced glutathione is an anti-oxidant and so one of the functions of the pathway is to protect cell from effects of oxidative stress
29
Glucose-6-phosphate dehydrogenase deficiency means cells are less able to protect against effects of oxidative stress. What are some of the effects of oxidative stress on a red blood cell?
* If oxidant radicals come into contact with RBCs they will cause oxidation of Haemoglobin
* This causes haemoglobin to denature and aggregate
* This forms Heinz bodies which bind to the RBC membrane
* This causes membrane proteins to also become oxidised – leads to reduced RBC deformability
30
What are some characterisitics of glucose-6-phosphate deficiency?
* Hereditary, X-linked disorder
* Common in African, Asian, Mediterranean and Middle Eastern populations
* Two types: Type A (mild) and Type B (severe)
* Clinical features range from asymptomatic to acute episodes to chronic haemolysis (rare)
31
Name some things that can cause oxidation leading to oxidative haemolysis in patients with glucose-6-phosphate deficiency
* **Infections**
* **Fava/ broad beans**
* **Drugs** - e.g. Dapsone, Nitrofurantoin and Ciprofloxacin
32
What characetristics would a blood film of somebody with glucose-6-phosphate deficiency have?
* Bite cells
* Blister cells & ghost cells
* Heinz bodies - RBCs with oxidised haemoglobin (identified using methylene blue stain)
33
What is the function of pyruvate kinase?
* Catalyses transfer of phosphate group from phosphoenolpyruvate (PEP) to adenosine diphosphate (ADP) to form pyruvate and ATP.
34
What are some characteristics of pyruvate kinase deficiency?
* Autosomal recessive
* Causes chronic haemolytic anaemia
* Condition can be improved via splenectomy
35
What characteristics would a blood film of somebody with pyruvate kinase deficiency have?
* Ecchinocytes
* May also see polychromasia
36
Briefly describe structure of haemoglobin
* Ferrous iron (Fe2+) and Protoporphyrin IX (which binds iron) form haem complex
* Also contains Globin proteins
37
What are the 3 types of haemoglobin?
* HbA - α2β2
* HbA2 - α2δ2 (makes up 2-3.5% of adult Hb)
* HbF - α2γ2
38
What are the different types of Haemoglobinopathies (inherited genetic conditions affecting the haemoglobin)?
* Thalassaemias - Increased/ decreased production of a globin chain (structurally normal)
* Variant haemoglobins - Production of a structurally abnormal globin chain e.g. sickle cell anaemia
39
What is Thalassaemia and what problems does it cause?
* Disorder in which there's imbalanced alpha and beta chain production
* Excess unpaired globin chains are unstable which causes a number of problems:
* They precipitate and damage RBC and their precursors
* They lead to Ineffective erythropoiesis in bone marrow
* They cause Haemolytic anaemia
40
What is Beta thalassaemia?
* Form of thalassaemia caused by caused by reduced or absent synthesis of the betachains of hemoglobin
* Autsomal recessive disorder so a person can have the beta thalassaemia trait or can have the disease (beta thalassaemia major).
41
What are some characteristics of the beta thalassaemia trait?
* Asymptomatic
* Causes microcytic hypochromic anaemia
* Low Hb, MCV, MCH
* Increased RBC
* HbA2 increased
42
Children with beta thalassaemia are transfusion dependent within 1st year of life. What problems occur if they don't have a blood transfusion?
* **Failure to thrive**
* **Progressive hepatosplenomegaly** - swelling of liver and spleen
* **Bone marrow expansion** – skeletal abnormalities
* **Death in 1st 5 years of life from anaemia**
43
What are some of the side effects of a blood transfusion for children with beta thalassaemia?
* Iron overload - this can lead to:
* Endocrinopathies
* Heart failure
* Liver cirrhosis
44
What is the mutation that causes sickle cell disease and how does it lead to sickle cell diease?
* Point mutation in beta globin gene that causes glutamate to be converted into valine at position 7
* This causes production of insoluble haemoglobin which polymerises when deoxygenated
* This leads to sickle shaped RBCs
45
What are some of the acute complications associated with sickle cell disease?
* **Stroke: ischaemic & haemorrhagic**
* **Splenic sequestration** - sickled red blood cells become trapped in the spleen acusing it to enlarge
* **Aplastic crisis**
* **Chest syndrome**
* **Leg ulcers**
46
What are some of the chronic complications associated with sickle cell disease?
* Chronic lung disease (bronchiectasis)
* Chronic renal failure
* Pulmonary hypertension
* Delayed puberty
47
What are some clinical feautures of sickle cell disease?
* Painful crises
* Aplastic crises
* Infections
48
What laboratory results would you expect someone with sickle cell disease to have?
* Anaemia (Hb often 65-85)
* Reticulocytosis
* Increased no. of nucleated red blood cells (NRBC)
* Raised bilirubin
* Low creatinine
49
What diagnostic tests can be used to confirm diagnosis of sickle cell anaemia?
* **Solubility test** - Expose blood to reducing agent and if haemoglobin precipitates then person has HbS
* **Electrophoresis**
50
What are the 2 types of acquired haemolytic anaemia?
* Anaemia due to immune haemolysis
* Anaemia due to non-immune haemolysis
51
What are the 2 types of immune haemolysis?
* Autoimmune
* Alloimmune
52
What are some causes of autoimmune haemolysis?
* **Idiopathic**
* **Drug-mediated**
* **Cancer associated** - e.g. some lymphoproliferative disorders such as chronic lymphocytic anaemia
53
What are some causes of alloimmune haemolysis?
* **Transplacental transfer** - Haemolytic disease of the newborn:
* **Transfusion related** - Acute or delayed haemolytic transfusion reaction
54
What are some causes of non-immune acquired haemolysis?
* **Paroxysmal nocturnal haemoglobinuria**
* **Fragmentation haemolysis** - Can be mechanical or microangiopathic
* **Severe burns**
* **Some infections** - e.g. malaria
