Anaemia Flashcards
Anaemia
1
Q
What are the two causes of raised Hb?
A
True polycythaemia
Pseudopolycythaemia
2
Q
What is the normal pathway for erythrocytosis?
A
Tissue hypoxia
Raised EPO production from kidney
RBC production in bone marrow
3
Q
What are the two types of true polycythaemia?
A
Primary (polycythaemia vera)
Secondary (high EPO)
4
Q
What are some causes of secondary polycythaemia?
A
COPD
Renal cell carcinoma
High altitude
Smoker
5
Q
What is polycythaemia vera?
A
Clonal haematopoietic disorder of bone marrow resulting in erythrocytosis
May be associated with thrombocytosis, leukocytosis, and splenomegaly
6
Q
What is the genetic link with PCV?
A
85% are related to a JAK2 V617F mutation
7
Q
What are the symptoms of PCV?
A
Asymptomatic Headache, dizziness, fatigue Aquagenic pruritus- itching after shower Blurred vision Tinnitus Thrombosis Gangrene
8
Q
What are the signs of PCV?
A
Choreiform movements
Hepatosplenomegaly
Red face, fingers, palms, toes, heels
9
Q
What are the investigations for PCV?
A
FBC- raised Hb, Hct, WCC, platelets
Gene mutation screen for JAK2 V617F
10
Q
What is anaemia?
A
Reduction in Hb, red cell count, and packed cell volume below reference age and sex
11
Q
What are some general features of anaemia?
A
Pale conjunctivae, mucous membranes + skin
Fatigue
Faintness
Dyspnoea, tachycardia (if severe)
Intermittent claudication/angina (severe)
12
Q
What are the three types of anaemia and what are the MCV levels that distinguishes them?
A
Microcytic (<80)
Normocytic (80-96)
Macrocytic (>96)
13
Q
What are the causes of microcytic anaemia?
A
Iron deficiency anaemia (IDA)
Thalassaemia
Anaemia of chronic disease
Sickle cell anaemia
14
Q
What are the 3 broad causes of IDA? Give examples for each
A
Blood loss (GI malignancy, menstruation, peptic ulcer, IBD) Increased demand (pregnancy/growth/breast feeding) Decreased absorption (malnutrition, coeliac, IBD, post-gastrectomy)
15
Q
What are the investigations for IDA?
A
FBC Iron studies Blood film Upper GI endoscopy + colonoscopy (if unexplained) Coeliac serology (IgA TTG antibodies)
16
Q
What is the management for IDA?
A
Treat underlying cause
Animal iron>plant
Oral Fe
IV/IM Fe if poor tolerance/uptake
17
Q
What can cause ACD?
A
Chronic inflammation (RhA)
Chronic infection (TB)
Chronic malignancy
No other obvious cause of anaemia
18
Q
What are the investigations for ACD?
A
Raised ESR/CRP
FBC- low Hb, low/normal MCV
Iron studies:
- low serum iron
- high/normal ferritin (acute phase protein)
- low/normal transferrin
- normal transferrin sat
19
Q
What is normal haemoglobin made of?
A
2 alpha globin chains
2 beta globin chains
20
Q
What are the two main types of thalassaemia?
A
Alpha thalassaemia Beta thalassaemia (most common)
21
Q
How many genes code the alpha Hb chain?
A
4 genes, 2 from each parent
Chr 16
22
Q
How does alpha thalassemia present depending on number of defective genes?
A
- Alpha thalassaemia silent (1 absent gene)
- Alpha thalassaemia trait (2 absent genes)
= these cause very mild anaemias - Haemoglobin H (3 absent genes) = significant, requires transfusions
- Haemoglobin Barts (4 absent genes) = death in utero
23
Q
What are the characteristics of alpha thalassaemia silent?
A
No clinical symptoms
24
Q
What are the characteristics of alpha thalassaemia trait?
A
Low MCV + MCH
Can be confused with IDA
Hb electrophoresis shows low/normal HbA2
25
What are the characteristics of haemoglobin H?
```
Microcytic hypochromic anaemia
Target cells and Heinz bodies
Hepatosplenomegaly
Presents in childhood/early adulthood
Needs lifelong transfusions
```
26
What are the characteristics of haemoglobin Barts?
Often fatal in utero unless intrauterine transfusions
27
What are the types of beta thalassaemia?
Beta thalassaemia minor
Beta thalassaemia trait/intermedia
Beta thalassaemia major
28
What are the characteristics of beta thalassaemia minor?
```
Asymptomatic heterozygous carrier
Mild/absent anaemia
Low MCV
Normal ferritin
Electrophoresis shows increased HbA2
```
29
What are the characteristics of beta thalassaemia trait?
Combination of homozygous beta and alpha thalassaemias
Moderate anaemia that doesn't require transfusions
Splenomegaly, gallstones, bone deformities, recurrent leg ulcers
30
What are the characteristics of beta thalassaemia major?
Presents first 2-3 months of life
Severe anaemia, failure to thrive, recurrent infections
Bony abnormalities due to bone marrow hypertrophy
Extramedullary haematopoiesis
Electrophoresis shows HbF and reduced/absent HbA
31
What are the investigations for thalassaemia trait? What would they show?
FBC- low Hb, low MCV
Iron studies would be NORMAL
Gel electrophoresis
32
What is the management for severe thalassaemia?
```
Blood transfusions
Iron chelators
Bone marrow transplant:
-only curative treatment
-causes infertility
```
33
What are the types of macrocytic anaemia?
Megaloblastic
| Normoblastic
34
What is a megaloblast?
developing RBCs in the bone marrow with a delayed nuclear maturation relative to their cytoplasm
35
What are the causes of megaloblastic macrocytic anaemia?
Vit B12 deficiency
| Folate deficiency
36
What are the causes of normoblastic macrocytic anaemia?
```
Pregnancy
Alcohol excess
Reticulocytosis
Liver disease
Hypothyroidism
Haematological disorders (eg. aplastic anaemia)
Drugs (eg. hydroxycarbamide)
```
37
What are the causes of Vit B12 deficiency?
Low intake (eg. vegans)
Impaired absorption:
Stomach: pernicious anaemia, gastrectomy
Small bowel: Crohn's, coeliac, tropical sprue
38
What is pernicious anaemia?
Autoimmune condition of atrophic gastritis and the destruction of parietal cells
Lack of intrinsic factor, which is needed for B12 absorption
39
What are the symptoms of B12 deficiency?
```
Progressive anaemia
Weight loss
Change in bowel habits
Muscle weakness
Symmetrical paraesthesia
Visual impairment
Memory disturbance
```
40
What are the signs of B12 deficiency?
```
Progressive anaemia
Jaundice (ineffective erythropoiesis- RBC precursor breakdown)
Glossitis
Angular stomatitis
Polyneuropathy
```
41
What are the investigations for B12 deficiency?
FBC and film:
-low Hb, high MCV, low reticulocytes, hypersegmented neutrophils
Serum vit B12- low
Serum autoantibodies: 90% parietal cells, 50% IF
42
What is the management for B12 deficiency?
IM hydroxycobalamin or oral cyanocobalamin
43
What are the causes of folate deficiency?
```
Poor intake
-elderly, poverty, alcohol XS, eating disorders
Malabsorption
-Coeliac, Crohn's, tropical sprue
XS utilisation
-pregnancy, adolescence, prematurity, haemolytic anaemia, malignancy, inflammatory diseases
Drugs
-methotrexate, phenytoin
```
44
What are the investigations for folate deficiency?
```
FBC and film
-low HB, high MCV, low reticulocyte, hypersegmented neutrophils
Serum folate
-low
Red cell folate (diagnostic)
-low
```
45
What is the management for folate deficiency?
Treat underlying cause
| Folic acid replacement
46
What are the causes of normocytic anaemia?
```
Acute blood loss
Anaemia of chronic disease
Combined microcytic and macrocytic e.g. iron and folate deficiency
Marrow infiltration/fibrosis
Endocrine disease
Haemolytic anaemia
```
47
What is myelofibrosis?
A disorder of haematopoietic stem cells and progressive marrow fibrosis
48
What are the clinical features of myelofibrosis?
Insidious onset
-FLAWS
Splenomegaly
Hepatomegaly (extramedullary haematopoiesis)
49
What are the investigations for myelofibrosis?
FBC- anaemia
Peripheral blood smear:
- leukoerythroblastic change
- characteristic “tear drop” poikilocyte red cells
Bone marrow aspiration- dry tap
Bone marrow biopsy- hypocellular marrow fibrosis
50% primary MF have JAK2
50
What are the hereditary causes of haemolytic anaemia?
Membrane defects
- hereditary spherocytosis
- hereditary elliptocytosis
Metabolic defects
- G6PD deficiency
- pyruvate kinase deficiency
Haemoglobinopathies
- thalassaemia
- sickle cell disease
51
What are the acquired causes of haemolytic anaemia?
Autoimmune
Non-autoimmune:
- drugs
- infx
- hypersplenism
- paroxysmal nocturnal haemoglobinuria
- MAHA
- HUS
- thrombocytopenic purpura
- DIC
52
What are the clinical features of haemolytic anaemia?
Splenomegaly
Increased RBC production and reticulocytes
Bone marrow erythroid hyperplasia
Polychromatic cells on blood film
Low serum folate
Increased serum bilirubin
Increased risk of iron overload and osteoporosis
53
What is an aplastic crisis?
```
Temporary suspense of RBC production
Parvovirus B19 susceptibility
Virus arrests the maturation of erythroid cells in bone marrow for ~10 days
Sudden drop in Hb
Low/absent reticulocyte count
```
54
What is hereditary spherocytosis?
Autosomal dominant condition
Commonest inherited haemolytic condition in Northern Europe
Defect in membrane causes cell to become spherical, hence gets destroyed in the spleen
55
What are the clinical features of hereditary spherocytosis?
Can be asymptomatic
| Anaemia, jaundice, splenomegaly
56
What are the investigations for hereditary spherocytosis?
FBC- anaemia, reticulocytosis
Blood film- spherocytes
Coomb's test- negative
57
What is Coomb's test assessing?
If your blood contains auto-antibodies for RBCs
58
What are the triggers for G6PD deficiency?
```
Fava beans
Moth balls
Infections
Drugs eg. quinine, sulphonamide, nitrofurantoin
-anti-malaria drugs
```
59
What are the investigations for G6PD deficiency?
Peripheral blood smear- Heinz bodies
| Direct measure of enzyme levels in red cells
60
What is sickle cell anaemia?
Autosomal recessive condition where both alleles create HbS
| Deoxygenated HbS is insoluble and polymerises
61
What may trigger sickling in sickle cell anaemia?
```
Hypoxia
Dehydration
Infection
Cold
Acidosis
```
62
What are the consequences of sickling?
- increased RBC fragility --> haemolysis (plasma Hb also triggers occlusion)
- increased RBC adhesion --> microvascular occlusion + ischaemia
63
What are the 3 crises that may present in sickle cell anaemia?
Splenic Sequestration Crisis
- pooling of blood in spleen
Vaso-occlusive Crisis (AKA painful crisis)
- sickle shaped blood cells clogging capillaries and causing distal ischaemia
Aplastic crisis
- temporary loss haematopoesis
- triggered by infection with parvovirus B19
64
What is acute chest syndrome?
Due to sickle cell sequestration crisis or infection:
- SOB
- Cough
- Fever
- New infiltrates on CXR
MEDICAL EMERGENCY- supportive/underlying cause
65
What are the investigations for sickle cell anaemia?
Diagnosed at birth with heel prick test
| FBC- low Hb, high reticulocyte
66
What is the management for sickle cell anaemia?
Avoid precipitating factors
Folic acid
Pneumococcal/influenza vaccination
Acute painful crisis- analgesics, oxygen, fluid, ABx
Blood transfusions if severe symptoms occur
Recurrent painful crisis- hydroxycarbamide
Splenectomy/cholecystectomy if severe
Bone marrow transplant is curative
67
What are the complications of sickle cell anaemia?
```
Swollen joints
Sickle chest syndrome/pneumonia
Bowel ischaemia
Splenic/hepatic sequestration
Cholecystitis
Arrhythmia
Priapism
```
68
What is autoimmune haemolytic anaemia?
Autoimmune destruction of RBCs
| Diagnosed via Coomb's test/direct antiglobulin test (DAT)
69
What are warm antibodies?
IgG that attaches to RBC at 37 degrees
| Idiopathic/associated with autoimmune conditions, lymphomas, CLL, carcinomas
70
What are cold antibodies?
IgM that attaches to RBC below 37 degrees
| Idiopathic/associated with infections (e.g. mycoplasma spp, EBV etc), lymphomas, paroxysmal cold
71
What is microangiopathic haemolytic anaemia?
Damage to endothelial surface results in fibrin strand deposition and platelet aggregation in small vessels
Red cells are fragmented as they pass causing intravascular haemolysis
72
What are the investigations for microangiopathic haemolytic anaemia?
Blood count and film: reticulocytosis, schistocytes
73
What is haemolytic uraemic syndrome?
Triad of:
- MAHA
- AKI
- thrombocytopenia
74
What are the causes of HUS?
Infection- shiga toxin of E. coli 0157 (Pt has diarrhoea), non E. coli related (no diarrhoea)
Drug- OCP, cyclosporin
Other- pregnancy, SLE
75
What are the clinical features of HUS?
```
Pallor (anaemia)
Jaundice (haemolysis)
Bruising (thrombocytopenia)
Oligo/anuria (AKI)
Haematuria (AKI)
Oedema
Hypertension
Fever
Fatique
Abdo pain
```
76
What are the investigations for HUS?
FBC and film: normocytic anaemia, thrombocytopenia, reticulocytosis, schistocytes
U+E: raised creatinine
PT + APTT: normal
Renal biopsy
77
What is thrombotic thrombocytopenic purpura?
Pentad of:
- MAHA
- AKI
- thrombocytopenic purpura
- fever
- neurological dysfunction
78
What are the causes of TTP?
Deficiency of ADAMTS-13:
| -secondary to AI process (eg. SLE), drugs, pregnancy, infection
79
What are the clinical features of TTP?
Same as HUS
Fever
Florid purpura
Fluctuating cerebral dysfunction (headaches, confusion, seizures, coma)
80
What are the investigations for TTP?
```
Same as HUS
FBC and film: normocytic anaemia, thrombocytopenia, reticulocytosis, schistocytes
U+E: raised creatinine
PT + APTT: normal
Renal biopsy
```
81
A 60 year old man presents with lethargy to the GP. A full blood count and smear is requested. The following is found:
Hb: 10 g/dl (13.5-18.0)
Platelets: 310 (150-400)
WBC: 14 (4-11)
Film: Leucoerythroblastic picture with tear-drop poikilocytes seen
What is the most likely diagnosis:
```
A. Iron deficiency anaemia
B. Myelofibrosis
C. Chronic myeloid leukaemia
D. Haemolytic anaemia
E. Myelodysplasia
```
B. Myelofibrosis
82
A 55 year old lady presents to the GP with long standing pain in her hands. On examination there are gross deformities of her fingers and joint swelling.
FBC reveals
Hb: 7.3 (11.5-16.0)
MCV: 94 (82-100)
WCC: 7 (4-11)
What is the most likely cause of the blood results?
```
A. Thalassaemia
B. Iron deficiency anaemia
C. Vitamin B12 deficiency
D. Anaemia of chronic disease
E. Sideroblastic anaemia
```
D. Anaemia of chronic disease
83
A 21 year old female presents with chronic fatigue and tiredness. On further questioning she reveals a longstanding history of heavy periods. On examination you notice pale conjunctivae.
What is the most likely cause of her symptoms:
```
A. Alcohol excess
B. Iron deficiency anaemia
C. Folate deficiency
D. Thalassaemia
E. Vitamin B12 deficiency
```
B. Iron deficiency anaemia
84
A 35 year old man presents to his GP with worsening fatigue over the past few months. He mentions that his stools have been darkening recently and he’s been having recurrent pins and needles in his hands. His has a history of Crohn’s disease which is managed with azathioprine but has had several flares this year which required hospital admission. A full blood count shows the following:
Hb: 10 (13.5-18.0)
MCV: 124 (84-100)
Platelet: 240 (150-400)
What is the most likely diagnosis:
```
A. Vitamin B12 deficiency
B. Anaemia of chronic disease
C. Alcohol excess
D. Iron deficiency anaemia
E. Haemolytic anaemia
```
A. Vitamin B12 deficiency
85
A 7 year old male with known sickle cell disease present to A+E with a cough and mild pain in his back for the last 2 days. He has already tried paracetamol and ibuprofen. On examination he has a blood pressure of 94/62 mmHg, heart rate of 110 bpm, respiratory rate of 30/min and a temperature of 38.4 degrees. There is no obvious source of infection.
What is the most appropriate next step?
A. Prescribe oramorph and review tomorrow
B. Prescribe daily codeine and ask GP to review in a week
C. Chest x-ray and dipstick urine (give antibiotics if +ve)
D. Admit urgently
E. Full blood count and review tomorrow
D. Admit urgently
| Acute chest syndrome
SOB, fever, cough
86
A 22 year old female presents with lethargy. The following blood results are obtained:
```
Hb: 10.6 (11.5-16)
Platelets: 300 (150-400)
WCC: 5.5 (4-11)
MCV: 65 (84-100)
HbA2: 4.5% (<3%)
```
What is the most likely diagnosis?
```
A. Beta-thalassaemia major
B. Sickle cell anaemia
C. Hereditary spherocytosis
D. Beta-thalassaemia trait
E. Iron deficiency anaemia
```
D. Beta-thalassaemia trait
Signs similar to IDA with raised HbA2
87
State some diseases that can cause a normocytic anaemia
```
Myelofibrosis
Acute blood loss
Aplastic anaemia
Haemolytic anaemias (acquired/congenital)
ACD (may be microcytic)
```
88
State some diseases that can cause a macrocytic anaemia
```
Liver disease
Alcohol
B12/folate deficiency
Hypothyroid
Myelodisplasia
```
89
Krusty is a 54 year old Clown and fast food franchise owner. He reports 6 kg of weight loss over the last 3 months alongside ‘stomach issues’. On examination, he has angular cheilitis, koilonychia and appears pale.
A blood film shows hypochromic red blood cells with evident anisopoikilocytosis and multiple pencil cells.
```
What is the diagnosis?
Anaemia of Chronic Disease
Thalassaemia Major
Iron Deficiency Anaemia
Chronic Lymphocytic Leukaemia
Hyperthyroidism
```
IDA
a) ACD: does not explain angular cheilitis, koilonychia or the pencil cells
b) Thalassaemia major tends to present in childhood due to its severity: does not explain angular cheilitis, koilonychia or the pencil cells
c) Correct
d) CLL would have abnormal and abundant white cells present on the blood film (as well as some possible anaemic features).
e) Hyperthyroidism is not particularly associated with microcytic anaemia: does not explain angular cheilitis, koilonychia or the pencil cells
90
give 2 signs of IDA
On examination:
- angular cheilitis
- koilonychia
91
What are the 4 classic features of IDA on blood film?
- Anisopoikilocytosis (unequal size (poikilo) + shape (aniso))
- Pencil cells- cigar shaped elliptocytes
- Hypochromic cells (reduced Hb)
- Cells may show increased red cell distribution width (reticulocytes + microcytic anaemia due to increased RBC production with the same amount of Hb)
92
A patient presents with unexplained IDA. what is the key differential that you need to rule out?
COLON CANCER- triad of:
- IDA
- PR bleeding
- change in bowel habit
93
globally the most common cause of IDA is....?
parasitic infection: Ascariasis & Schistosomiasis.
94
What would you see on iron study of IDA?
- low serum iron
- low ferritin (stored iron in cells)
- high transferrin (iron transport protein, attempt to increase iron in blood)
- low transferrin saturation
95
How can iron studies differentiate IDA from ACD?
IDA:
- Ferritin = low
- TIBC(transferrin) = high
ACD:
- Ferritin = high
- TIBC(transferrin) = low
96
Explain the cause of ACD
Chronic disease causes cytokine release
Cytokines increase levels of hepcidin which:
- blocks GI uptake (ferroportin)
- blocks TIBC (transferrin)
- increases levels of ferritin- lock iron in cells
- blocks EPO production
This prevents the infection exploiting the body and starves it of iron.
97
Ferritin is an example of what?
an acute phase protein
98
How can alpha and beta thalassemia traits be distinguished?
Hb electophoresis
- alpha trait: low/normal HbA2
- beta trait: high HbA2 (compensatory mechanism)
99
Epidemiology of thalassemia?
- Very common in Cyprus
| - Increased prevalence in malaria belt- thalassaemia Minor provides resistance to falciparum Malaria
100
State the 3 possible combinations of Hb molecule and when they present
```
HbA1 = 2 Alphas + 2 Beta chains
HbA2= 2 Alphas + 2 Delta chains
HbF = 2 Alphas + 2 Gamma chains
```
Alpha is often present from birth
Beta typically presents between first 3 & 6 months
Gamma declines after birth to zero at 3-6 months
Delta is always pretty low
101
Complication of splenic sequestration crisis
- rapid splenomegaly with fall in Hb
- causes severe haemolytic anaemia + shock
- increased risk of infection
102
Complications of vaso-occlusive crisis
- Dactilyitis
- Priapism
- Acute chest Syndrome- infarcts in lungs (can be a solitary event)
103
Complications of aplastic crisis
sudden severe anaemia
| bone pain --> bone marrow ischaemia and necrosis
104
Which virus causes aplastic crisis in SCD?
parvovirus B-19
105
What would you see on blood film of a patient with sickle cell anaemia?
- Sickle cells
| - Howell-Jolly bodies- nuclear remnants from RBCs. Normally they are filtered out via the spleen (occur in hyposplenism)
106
What would you see on Hb electropheresis of a patient with sickle cell anaemia?
HbS, no HbA
| beta globin gene mutation, makes abnormal variant
