Anaemia Flashcards
1
Q
A
C - iron deficiency anaemia
- hypochromic RBCs
- pencil cells
- anisopoikilocytosis
2
Q
What is the definition of anaemia?
How do you clinically check whether someone is anaemic?
A
- anaemia describes a low blood haemoglobin
- check for anaemia by looking for conjunctival pallor
- patients will often also have pale skin, but this can be difficult to identify
3
Q
What is meant by “symptomatic anaemia”?
Why does this develop?
A
- symptomatic anaemia occurs when a patient’s respiratory rate and heart rate are raised
- anaemic patient is not oxygenating their tissues effectively due to less Hb present in the blood
- RR and HR are increased to compensate for the lack of oxygenation
- anaemia can be a cause of acute breathlessness
4
Q
What are the 3 features that help to identify iron-deficiency anaemia on a blood film?
A
- there is anisopoikilocytosis
- RBCs are both hypochromic and microcytic
- a cell is hypochromic when > 1/3 of the cell is pale in colour (central pallor)
- pencil cells are present
5
Q
What is meant by “anisopoikilocytosis”?
A
this is a combination of 2 words:
- poikilocytosis means different shapes are present within the blood film
- anisocytosis means that different sizes are present within the blood film
6
Q
What are the 3 different categories of causes of iron-deficiency anaemia and examples of each?
A
Reduced uptake:
- malnutrition
- coeliac disease
- IBD
Increased loss:
- GI malignancy
- peptic ulcer
- IBD
- menstruation
Increased requirement:
- pregnancy
- breastfeeding
7
Q
What is the biggest concern in older patients (>55) with iron deficiency anaemia?
What other associated symptoms would heighten concern?
A
- in older patients with unexplained IDA, think colon cancer until proven otherwise
- colon cancer presents with a triad of symptoms:
- unexplained iron-deficiency anaemia
- PR bleeding
- change in bowel habit
8
Q
What type of anaemia is anaemia of chronic disease?
What is the main “chemical” that is responsible for this?
A
- it is often normocytic, but can also be microcytic
- the presence of a chronic disease causes increased release of cytokines due to presence of chronic inflammation
- cytokines increase the amount of hepcidin in the body
9
Q
What is involved in removing iron from the gut and what happens to it after this has happened?
A
- iron is loaded via ferroportin in the gut
- iron comes out into the blood via transferrin
- OR it is stored as ferritin
10
Q
How does hepcidin interfere with iron storage and transport?
A
- hepcidin decreases the activity of ferroportin
- this reduces the uptake of iron from the gut
- it also decreases the activity of transferrin
- if some iron manages to come in from the gut, the hepcidin then stops it from getting out of cells and into the blood
- hepcidin causes iron to clump in the interstitial cells and be converted to ferritin
- this makes the iron useless as it is just being stored and can’t be used
11
Q
Why is the production of hepcidin useful in acute inflammation?
How do its actions lead to anaemia of chronic disease?
A
- in acute inflammation, the body wants to ensure bacteria are not provided with iron that they can use for nutrition
- hepcidin prevents iron from being available by storing it as ferritin
- starving an infection of iron will stop it from replicating
- in a chronic state this results in anaemia as there is decreased iron in the blood
12
Q
A
13
Q
How can ferritin be used to distinguish between IDA and ACD?
Why is this not the best marker to use?
A
- ferritin is REDUCED in iron-deficiency anaemia (IDA)
- ferritin is unchanged or INCREASED in anaemia of chronic disease (ACD)
ferritin is upregulated due to hepcidin production
- ferritin is an acute phase protein so can also be raised in acute infections
14
Q
What is the best marker to use for distinguishing between IDA and ACD on blood test?
A
Total Iron Binding Capacity (TIBC)
- this relates to the raw level of transferrin in the blood
- there is HIGH transferrin in IDA as you are trying to get as much iron as possible into the blood from the gut
- there is LOW transferrin in ACD as it is inhibited by hepcidin
15
Q
What is thalassaemia?
What type of anaemia does this produce?
A
- inherited blood disorders characterised by decreased haemoglobin production
- these are autosomal recessive globin chain mutations
- they produce a microcytic anaemia
16
Q
What are the 2 different types of thalassaemia?
In which country are both these types relatively common?
A
- alpha thalassaemia is more rare than beta thalassaemia
- in alpha - there is a defect affecting chromosome 16
- in beta - there is a defect affecting chromosome 11
- Cyprus has one of the highest levels of thalassaemia in the world
17
Q
What are the different subtypes of alpha thalassaemia?
How does the severity differ?
A
- alpha+
- alphao
- Hb H
- Hb Barts
- there are 4 alpha genes, 2 from your father and 2 from your mother
- different subtypes arise depending on how many genes are knocked out
- the more genes that are knocked out, the increased severity of disease
(someone with Hb H has only 1 alpha gene and needs blood transfusions for life
in Hb Barts there are no alpha genes at all and it produces death in utero)
18
Q
A
19
Q
What are the different types of beta-thalassaemia?
How does their severity vary?
A
- beta minor
- beta intermedia
- beta major
- beta minor involves only one allele bearing a mutation, and sufferers have microcytic anaemia
- beta intermedia involves the need for occasional transfusions e.g. in pregnancy
- beta major occurs when both alleles have mutations and requires blood transfusions for life
20
Q
What are the investigations involved in thalassaemia?
A
- diagnosis involves identification of microcytic anaemia but with normal iron studies
- normal levels of iron show it is not IDA or ACD
-
gel electrophoresis is performed to confirm the diagnosis
- different sized proteins depend on the number of genes present
21
Q
What is a benefit of having thalassaemia minor?
A
- it is associated with resistance to falciparum Malaria
22
Q
Around what age do alpha and beta thalassaemia present?
A
- at birth the child has foetal Hb (blue line) which decreases with age
- B-Hb compensates for foetal Hb and increases in the first 3 months of life
- if you are lacking a B-globin chain in B-thalassaemia, it will present here
- A-thalassaemia will present from birth
23
Q
What causes sickle cell disease?
In what population is it common and why?
A
- caused by a point mutation on the B globin gene on chromosome 11
- it is an autosomal recessive condition
- 20% of tropical Africa population have sickle cell trait as it has resistance to Falciparum Malaria
24
Q
What factors predispose to sickling of RBCs?
A
- hypoxia
- dehydration
- acidosis
- infection (particularly encapsulated bacteria)
- these all upset the membrane potential of the cell and make it more predisposed to sickling
- sickle cells can then go on to cause occlusion of blood vessels
25
How is sickle cell anaemia identified on blood film?
* **_sickled cells_** are present
* **_Howell-Jolly bodies_** are present, which are nuclear remnants
* they would usually be taken up and removed by the spleen
26
What are the 4 different types of sickle cell crises?
What causes these?
* **acute painful crisis**
* **stroke**
* **sequestration crisis**
* **chronic cholecystitis**
* these all occur due to sickle cells entering small, narrow vessels and causing **_vessel occlusion_**
27
What happens during a sequestration crisis?
* sickle cells can become lodged in the spleen
* the spleen decides whether RBCs are functional or not, so attempts to **remove the sickle cells**
* there are so many sickle cells, that as the spleen tries to remove them it becomes **_massively enlarged_**
* the sequestration crisis occurs due to all the RBCs **getting stuck inside the spleen**
28
Are Howell-Jolly bodies typically seen in older or younger patients and why is this the case?
* in **younger patients**, the spleen is still functioning so they will get **_sequestration crisis_** (and splenomegaly)
* the presence of Howell-Jolly bodies tells you that the spleen is **_no longer functioning_** as it would've removed these if it could
* **older patients** will have **_Howell-Jolly bodies_** and **_hyposplenism_** as their spleen is no longer functioning
29
30
How is sickle cell anaemia diagnosed and treated?
* it is diagnosed by **_Hb electrophoresis + blood film_**
* management involves preventing problems related to sickling from happening before they occur
***_Conservative:_***
* avoid triggers
***_Medical:_***
* hydroxyurea
* prophylactic antibiotics - as patients are susceptible to certain infections
* vaccination - to prevent infection, which can cause sickling
***_Surgical:_***
* bone marrow transplant
31
What are the 5 most severe consequences of sickle cell anaemia?
***_Dactylitis:_***
* RBCs enter vessels of the hands and cause **swelling of the fingers**, which is very painful
***_Acute chest syndrome_***
***_Priapism:_***
* sickle cells clog up vessels in the penis and cause an **erection that lasts for 4-5 hours** and is painful
***_Haemolytic anaemia:_***
* the cells break apart and haemolysis occurs
* this leads to **jaundice** due to the build-up of bilirubin
***_Aplastic crisis:_***
* this occurs due to infection by **parvovirus B19**
32
What type of anaemia is produced from folate or B12 deficiency?
How can this be identified on blood film?
* it is a **_megaloblastic anaemia_** (macrocytic)
* folate helps the nucleus to develop, so in megaloblastic anaemia there is a **problem with nuclear development**
* this produces **_hypersegmented neutrophils_**
* the cells become **_very large_** as the cytoplasm carries on growing, whilst the nucleus cannot
33
What are the different causes of megaloblastic anaemia caused by vitamin B12 and folate deficiency?
***_Vitamin B12 deficiency:_***
* alcohol
* IBD and coeliac disease
* **malnutrition**
* **pernicious anaemia**
* this is the autoimmune cause of B12 deficiency
***_Folate deficiency:_***
* alcohol
* IBD and coeliac disease
* **anti-folate drugs**
* **pregnancy**
* folic acid supplements are given to women who are planning on getting pregnant
34
Why does B12 deficiency produce neurological signs?
What are these signs?
* B12 is important for **_preserving the myelin sheath_** in the nervous system, so deficiency produces neurological symptoms
* these symptoms are referred to as ***"subacute combined degeneration of the cord"*** and include:
* glove and stocking parasthesiae
* hyporeflexia
* Romberg's positive
35
What is glove and stocking paraesthesia?
* numbness or tingling sensations
* the distal portions of the nerves are affected, meaning that this affects the hands and feet
36
When do the symptoms of B12 deficiency typically arise?
B12 reserves last for **_3-4 years_**
symptoms of deficiency do not arise until after this time
37
What is meant by a positive Romberg's sign?
* the patient **stands upright** and is asked to **close their eyes**
* a **_loss of balance_** is interpreted as a **_positive Romberg's test_**
* this is a test of **proprioception** (body's sense of positioning), which requires healthy functioning of the **dorsal columns** of the spinal cord
38
What is meant by the phrase "subacute combined degeneration of the cord"?
* this is **_progressive degeneration_** of the spinal cord due to **_vitamin B12 deficiency_**
* there is damage to nerve fibres that control movement and sensation
* there is tingling / numbness in the hands / feet, stiff limbs and confusion / irritability
39
What is pernicious anaemia?
* **autoimmune** condition which produces **_autoantibodies_** against **_intrinsic factor_** or cells in the stomach (**_parietal cells_**) that produce intrinsic factor
* intrinsic factor **binds vitamin B12** so that it can be absorbed
* the body cannot produce enough RBCs due to **_lack of vitamin B12_**
40
What are the 4 main causes of non-megaloblastic macrocytic anaemia?
remember **_A_**lcoholics **_M_**ay **_H_**ave **_L_**iver failure
* A - Alcohol
* M - Myelodysplasia
* H - Hypothyroidism
* L - Liver disease
41
What is haemolytic anaemia?
What are the 2 different mechanisms by which this can occur?
* anaemia resulting from RBCs being ***destroyed faster than they can be reproduced***
***_Intravascular haemolysis:_***
* RBCs lyse / rupture **_within the blood vessels_**
* this occurs due to rupture of the RBC membrane
***_Extravascular haemolysis:_***
* this is haemolysis occurring in the **_liver, spleen, bone marrow and lymph nodes_**
* the spleen removes RBCs that are not functioning properly
42
What are the clinical features of haemolytic anaemia?
* scleral icterus (jaundice)
* pale conjunctivae & skin
43
What will blood tests show in haemolytic anaemia and why?
* **low haemoglobin**
* **_low haptoglobin_**
* this is the molecule that **mops up Hb** in the blood
* you would expect Hb levels to be high as it leaks out of RBCs, but it is not as haptoglobin mops it up
* eventually **levels drop as haptoglobin is exhausted**
* this is a sign of **_intravascular haemolysis_**
* **raised unconjugated bilirubin**
* **_raised LDH_**
* this leaks out of RBCs
44
What are the 4 different hereditary haemolytic anaemias?
Which parts of the RBC are affected in each type?
* **_hereditary spherocytosis_** affects the RBC **membrane**
* **_G-6-PD deficiency_** affects **enzymes** within the RBC
* **_sickle cell anaemia_** and **_thalassaemia_** result from **haemoglobin defects**
45
Why do broad beans (fava beans) predispose to glucose-6-phosphate deficiency?
* G6P is an enzyme that is involved in making **_glutathione_**, which helps the body to deal with **_oxidative stress_**
* if there is a G6P deficiency, the person may **run out of glutathione**
* they cannot respond to oxidative stress and the **_cell becomes damaged_**
* things that are oxidative stressors, such as fava beans, are more likely to cause problems
46
How is glucose-6-phosphate deficiency contracted?
it is an **_X-linked recessive_** condition
47
What 2 signs on blood film will be present in G6PD?
What do these result from?
***_Heinz bodies:_***
* these are small bits of **oxidative damage** from the nucleus
* they are detected by the spleen which attempts to remove them
* the spleen literally **"takes a bite"** out of the cell producing...
***_Bite cells:_***
* these indicate **_previous haemolysis_** as the spleen takes time to respond
48
How can hereditary spherocytosis be identified on blood film?
What causes it?
* this is an **_autosomal dominant_** inherited condition
* the blood film shows **_spherocytes_**
* these cells are shaped like a sphere so have **no central pallor**
49
What is involved in the pathogenesis of hereditary spherocytosis?
* it is caused by a **_beta spectrin_** or **_ankyrin deficiency_**
* these proteins usually anchor the centre of the cell to make it a **biconcave shape**
* when these proteins are defected, the cell loses its shape and becomes **_spherical_**
50
What is the investigation for hereditary spherocytosis?
How does it work?
**_osmotic fragility test_**
* **_hypotonic fluid_** is given, which puts stress on the RBC
* a normal RBC can expand in response to the extra fluid
* when fluid enters a spherocyte, they are more prone to breaking apart, so **_lysis_** occurs
* this test identifies whether there are **_spherocytes_**
51
How does an aplastic crisis occur in hereditary spherocytosis and sickle cell anaemia?
* **_parvovirus B19_** infects children (usually) and enters the **bone marrow**
* it prevents the bone marrow from making RBCs, so you need to rely on the **current store** of RBCs circulating in the body
* if someone has HS or SCD, RBCs in the body are **_prone to lysis_**
* this leads to **very few RBCs** in the periphery as they are breaking apart and **none are being made** in the bone marrow
* this is an aplastic crisis
52
What type of "sheared cell" is associated with haemolytic-uraemic syndrome?
How are they formed?
* **_schitsocytes_** are seen in HUS
* they occur as a result of **mechanical destruction** of a normal RBC
* RBCs get trapped in **fibrin strands**
* the sheer force of the blood flow produces a **"cheese grater" effect** that causes the RBC to break
53
What type of anaemia is seen in haemolytic uraemic syndrome?
What is the triad of symptoms associated with this condition?
* this is a disease of early childhood that is characterised by **microangiopathic haemolytic anaemia** (MAHA)
* the triad of HUS includes:
* **thrombocytopenia**
* **AKI**
* **MAHA**
* it presents with **_jaundice_** and **_conjunctival pallor_**
54
What type of infection is the main cause of HUS in children aged 4-5?
**EHEC O157:H7**
* this is a nasty **_haemorrhagic E. coli infection_** that can be acquired through eating **dodgy food**
* it is a gastric infection so also causes **_abdominal pain_** and **_bloody diarrhoea_**
55
What is disseminated intravascular coagulation?
DIC involves **_concurrent clotting and bleeding_**
* there is an underlying problem that **activates the clotting cascade**
* no proper clots are formed as there is no specific problem/injury
* the **supply of clotting factors** is eventually **exhausted**
* there are lots of **small ineffective clots** that are not doing anything, and now clots can not be formed when needed
* bleeding occurs very easily as **_clotting factors have been depleted_**
56
What are the 6 most common causes of DIC?
* pancreatitis
* sepsis
* obstetric complications
* cancer
* trauma
* ABO reaction
57
What are the bleeding features, clotting features and haemolytic features associated with DIC?
***_Bleeding features:_***
* petechiae
* ecchymoses (bruising)
* haematuria
***_Clotting features:_***
* prolonged APTT
* prolonged PT
***_Haemolytic features:_***
* jaundice
* conjunctival pallor
58
What blood test results would you expect to see in DIC?
* **decreased platelets**
* **decreased fibrinogen**
* this has all been exhausted as it is part of the clotting cascade
* increased FDPs
* **_increased D-dimer_**
* this indicates that excess thrombolysis is occurring
59
Why does thrombotic thrombocytopaenic purpura occur?
* there is a defect of the **_ADAMTS-13 enzyme_**
* ADAMSTS-13 enzyme **cleaves vWF,** decreasing the activity of vWF multimers
* without this enzyme, **platelets bind vWF** as they **_spontaneously aggregate_** in small blood vessels
* this is a form of microangiopathic haemolytic anaemia (MAHA)
* the platelet-vWF complexes form **small blood clots** that **shear RBCS**, leading to their rupture and formation of **_schistocytes_**
60
61
What are the features of the clinical pentad associated with thrombotic thrombocytopenic purpura?
How can this be remembered?
remember there is a defunct **_ADAMSTS-13_** enzyme:
* **A** - Antiglobulin negative
* **D** - Decreased platelets
* **A** - AKI
* **M** - MAHA
* **T** - Temperature
* **S** - Swinging CNS signs
* decreased platelets, AKI and MAHA are all signs of HUS
* temperature and swinging CNS signs are not present in other MAHAs
62
What test is negative in all 3 MAHAs?
**_DAT / Coombs test_** is negative
63
How does the Direct Antiglobulin Test (DAT) / Coombs test work?
In what type of condition will it be positive?
* it is used to detect the presence of **_autoimmune_ haemolytic anaemias** by detecting the presence of antibody bound to the red cell surface
* if it is autoimmune, there will be **antibodies bound to the RBC antigen**
* DAT test uses **_antibodies to human globin_**
* these will **bind to the autoantibodie**s anchored to the RBC and cause **_RBC agglutination_**
64
What is meant by warm and cold types of autoimmune haemolytic anaemias?
What can cause these?
***_Warm:_***
* agglutination occurs at **_\> 37oC_**
* associated with **_IgG antibodies_** attacking the RBC
* idiopathic
* SLE
* CLL
***_Cold:_***
* agglutination occurs at **_\< 37oC_**
* associated with **_IgM antibodies_** attacking the RBC
* idiopathic
* **_M_**ycoplasma
* **_M_**ononucleosis
both of these will be **_DAT / Coombs positive_** as there are **anti-RBC antigen antibodies**
65
myelofibrosis
66
What is primary myelofibrosis?
What causes it?
***fibrosis in response to a _bone marrow malignancy_***
* myelofibrosis means fibrosis of the bone marrow
* **fibroblasts** are very **overactive**
* the interior of the bone marrow is **destroyed by fibroblast tissue**, leading to formation of **_scar tissue_**
* the scar tissue crowds the bone marrow so it cannot work properly, leading to **_anaemia_** and **_low WCC_**
67
What are the risk factors for primary myelofibrosis?
What would you expect to see on blood film?
* increased risk with **_radiation exposure_** and **_\>65 years old_**
* **_tear drop cells_ (dacrocytes)** are seen on blood film
these occur when there is fibrosis as the RBCs have to **squeeze out of the bone marrow**, which distorts their shape
68
What would you expect to see on bone marrow aspirate in primary myelofibrosis?
**_"dry tap" fibrosis_**
* bone marrow is usually **highly vascularised** and will **bleed**
* when there is **_scarring and fibrosis_**, it has all **_dried up_** so you won't be able to extract anything out of it
69
What might be found on examination in someone with primary myelofibrosis?
**_massive splenomegaly_**
* this is due to **_extramedullary haematopoiesis_**
* the bone marrow is ruined so the rest of the body tries to compensate and form new blood cells
* as the spleen **tries to compensate for the BM**, it increases in size
