Haem I (Anaemia) Flashcards
What is a single test that would reveal a patient is suffering from an autoimmune haemolytic anaemia? [1]
Direct positive coombs test
Describe the lineage of multipotent myeloid stem cells [4]
What is TPO? [1]
Where is it produced? [1]
What does it regulate ? [1]
Thrombopoietin (TPO):
TPO is produced by the liver and essential for the control of platelet production
What is the pathway from Haematopoietic stem cell (HPSCs) - to erythrocyte? [1]
Haematopoietic stem cell (HPSCs)
–>
common myeloid progenitor cell (CMPC)
–>
Proerythroblast
–>
erythroblast
–>
reticulocyte
–>
erythrocyte
The proerythroblast develops into an (early) erythroblast. The erythroblast then undergoes a sequence of changes where its nucleus progressively shrinks and its cytoplasm becomes filled with haemoglobin (not stained). When full of haemoglobin it is called a normoblast. The normoblast then expels its nucleus and becomes a reticulocyte. Most reticulocytes stay in the marrow and mature into erythrocytes but some may be released into the blood, especially after haemorrhage. Reticulocytes can transport oxygen, just not as efficiently as mature erythrocytes. They can mature into adult RBCs in the circulation
Include iron stuff.
Name 5 drugs which cause macrocytic anaemia?
Azathioprine
Methotrexate
Fluorouracil
Phenobarbital
Mercaptopurine
Trimethoprim
What are specific signs associated with anaemia of iron deficiency? [4]
- Koilonychia (spoon shaped nails)
- Angular stomatitis (inflammation of corners of mouth)
- Restless legs syndrome
- Hair loss
- Post-cricoid webs
Name 7 risk factors for IDA
- pregnancy
- vegetarian and vegan diet
- menorrhagia
- hookworm infestation
- chronic kidney disease
- coeliac disease
- gastrectomy/achlorhydria
- non-steroidal anti-inflammatory drug (NSAID) use
- chronic heart failure
Why do PPIs interfere with Fe absorption? [1]
Fe is best absorbed in an acidic environment
Proton pump inhibitors (e.g., omeprazole), can interfere with iron absorption as they reduce stomach acid
Describe what is meant by transferrin saturation [1]
What is the formula for transferrin saturation? [1]
Transferrin saturation refers to the proportion of the transferrin molecules bound to iron, expressed as a percentage.
Transferrin saturation = serum iron / total iron-binding capacity
What do raised ferritin levels indicate? [4]
Inflammation (e.g., infection or cancer)
Liver disease
Iron supplements
Haemochromatosis
A patient presents with IDA without a clear underlying cause. What is the next stage in investigating this patient? [2]
colonoscopy and oesophagogastroduodenoscopy (OGD) for malignancy.
Describe the management of IDA [3]
1ST LINE
- oral iron replacement (ferrous sulfate)
- 200 mg once daily
2ND LINE
- intravenous iron replacement
3rd LINE:
- Blood transfusion
Describe what would describe to a patient about taking oral iron [2]
Oral iron works slowly. A rise in haemoglobin of 20 grams/litre is expected in the first month.
Common side effects are constipation, naseua, **abdominal pain & **black stools.
Describe the pathophysiology of ACD [2]
Hepcidin is acute phase protein that usually works to reduce the availability of iron from infecting microorganisms.
Chronic inflammation mediated by IL-6 can lead to a hepcidin-induced block of iron absorption and iron release from macrophages
This reduction in the availability of iron for the production of erythrocytes as part of erythropoiesis can lead to a microcytic anaemia. However, this is only seen in 25% of cases.
Describe the FBC result for ACD [2]
The FBC may show a normocytic normochromic anaemia (approx. 75%)
or
a microcytic anaemia (approx. 25%).
In ACD, the MCV is rarely below 70 fL.
Describe how Fe tests would help to diagnose ACD [3]
The clinical presentation of ACD is generally that of the underlying disorder
Serum ferritin:
- Normal or raised (due to release during inflammation)
Serum iron:
- Low
TIBC:
- Low
What are specific signs associated with anaemia of vit. B12 deficiency? [7]
- Glossitis
- Positive Rombergs test & neurological impairment - posterior column degeneration
- Decreased vibration sense - posterior column degeneration
- Ataxia - posterior column degeneration
- Hyperpigmentation of nails
- Petechiae: generally a late sign of vitamin B12 deficiency.
- Optic neuropathy
Define what is meant by pernicious anaemia [2]
Pernicious anaemia is an autoimmune condition involving antibodies against the parietal cells or intrinsic factor. Intrinsic factor is essential for B12 absoprtion
Specifically have:
- Antibodies to intrinsic factor: block vitamin B12 binding site
- Antibodies to gastric parietal cells: reduced acid production and atrophic gastritis. Therefore less B12 absorption
Describe the clinical features of pernicious anaemia
Peripheral neuropathy, with numbness or paraesthesia (pins and needles)
mild jaundice: combined with pallor results in a ‘lemon tinge’
Loss of vibration sense
Loss of proprioception
Visual changes
Mood and cognitive changes
TOM TIP: For your exams, remember to test for vitamin B12 deficiency and pernicious anaemia in patients presenting with []
TOM TIP: For your exams, remember to test for vitamin B12 deficiency and pernicious anaemia in patients presenting with peripheral neuropathy, particularly with pins and needles.
Describe the treatment regime for pernicious anaemia
Intramuscular hydroxocobalamin is initially given to all patients with B12 deficiency, depending on symptoms:
No neurological symptoms
- 3 times weekly for two weeks
Neurological symptoms
- alternate days until there is no further improvement in symptoms
MAINTENANCE:
Pernicious anaemia
– 2-3 monthly injections for life of intramuscular hydroxocobalamin
Diet-related:
- oral cyanocobalamin or twice-yearly injections
Describe the presentation of subacute combined degeneration of the spinal cord [3]
progressive weakness
ataxia
paresthesias that may progress to spasticity and paraplegia
Which vitamin is folate? [1]
B9
Describe causes of folate deficiency [6]
- Inadequate dietary intake
- Alcohol excess
- Malabsorption (e.g. coeliac disease, Crohn’s disease)
- Increased requirements (e.g. pregnancy, malignancy)
- Increased loss (e.g. Chronic liver disease)
- Other (e.g. anti-convulsants, ETOH abuse)
Which investigations are used to diagnose folate deficiency? [1]
Red cell folate is a better measure of levels than serum folate, since levels are affected even with a short period of deficiency.
How do you treat folate deficiency? [1]
Folic acid is usually given as a once daily oral dose of 5 mg for up to four months.
[] is the most common cause of a non-megaloblastic anaemia
Explain your answer [1]
Chronic alcohol use is the most common cause of a non-megaloblastic anaemia.
It is thought to be due to the toxic effects of acetaldehyde on erythrocyte progenitors.
What advice should you give pregnant women regarding folic acid intake? [1]
Folate deficiency causes an increased risk of which pathology? [1]
all women should take 400mcg of folic acid until the 12th week of pregnancy
Risk of neural tube defects
Which heridatory diseases fall under umbrella of haemolytic anaemia? [5]
- Hereditary spherocytosis
- Hereditary elliptocytosis
- Thalassaemia
- Sickle cell anaemia
- G6PD deficiency
What are the subdivisions of hereditary haemolytic anaemias? [3]
Hereditary causes:
membrane:
* hereditary spherocytosis/elliptocytosis
metabolism:
- G6PD deficiency
haemoglobinopathies:
- sickle cell
- thalassaemia
What are the subdivisions of acquired haemolytic anaemias? [2]
Acquired: immune causes
autoimmune
-: warm/cold antibody type
alloimmune:
- transfusion reaction
- haemolytic disease newborn
drugs:
- methyldopa
- penicillin
Acquired: non-immune causes
microangiopathic haemolytic anaemia (MAHA):
- TTP/HUS
- DIC,
- malignanc
- pre-eclampsia
prosthetic cardiac valves
paroxysmal nocturnal haemoglobinuria
infections:
- malaria
drug:
- dapsone
What are the key investigation results for haemolytic anaemia? [3]
Full blood count shows a normocytic anaemia
Blood film shows
schistocytes (fragments of red blood cells)
Direct Coombs test is positive in autoimmune haemolytic anaemia (not in other types)
Define what is meant by: [3]
- Hereditary spherocytosis
- Hereditary elliptocytosis
Hereditary spherocytosis
- Autosomal dominant familial condition; autoantibodies produced against proteins in RBC membrane mean it causes a spherical shape when they pass through the spleen
- Can still perform adequately despite reduced SA
- Fragile and easily lysed
Hereditary elliptocytosis:
- Autosomal dominant familial condition; autoantibodies produced against proteins in RBC membrane mean it causes an ellipse shape
- Can still perform adequately despite reduced SA
- Fragile and easily lysed
Describe a patient with hereditary spherocytosis may present [4]
- Jaundice at birth
- However the onset of jaundice can be delayed for many years and some
patients may go through life with no symptoms and are detected only during
family studies - May eventually develop anaemia
- Splenomegaly
- Ulcers on the leg
- Chronic haemolysis leads to the formation of gall stones
What investigations would indicate either hereditary spherocytosis or hereditary elliptocytosis? [3]
- Raised mean corpuscular haemoglobin concentration (MCHC) on a full blood count
- Raised reticulocyte count due to rapid turnover of red blood cells
- Spherocytes / elpitocytes on a blood film
- EMA testing and cryohaemolysis test if results unequivocal from blood film
What is the treatment of hereditary spherocytosis or hereditary elliptocytosis? [5]
- Folate supplementation- indicated in moderate to severely affected individuals or those who are pregnant to avoid megaloblastic anaemia due to the relative folate deficiency that occurs when the rate of RBC production increases to compensate for the increased rate of haemolysis.
- Blood transfusions when required
- Splenectomy.
- Erythropoietin may reduce the need for transfusions in young infants until they can mount an adequate hematopoietic response to the haemolysis.
- Gallbladder removal (cholecystectomy) may be required if gallstones are a problem.
Which drugs can trigger acute bouts of haemolytic anaemia in G6PD deficiency? [5]
Acute drug-induced haemolysis (dose-related):
- Aspirin
- Antimalarials such as; Primaquine, Quinine & Chloroquine
-
Antibacterials such as; Most Sulphonamides, Nitrofurantoin and
Chloramphenicol - Dapsone
- Quinidine
- Sulfonylureas; sulfasalazine
Fava beans.
What is the inheritance of G6PD deficiency? [1]
It is an X-linked recessive genetic condition
Describe the presentation of G6PD deficiency [4]
How can you diagnose this pathology? [1]
G6PD deficiency presents with:
- jaundice (often in the neonatal period)
- gallstones
- anaemia
- splenomegaly
- Heinz bodies on a blood film.
Diagnosis can be made by doing a G6PD enzyme assay.
Describe how you would treat a patient with hereditary spherocytosis in:
- neonates [2]
- infants (>28 days old), children, and adults [5]
Neonates:
- 1st line: supportive care +/- red blood cell transfusions
- 2nd line: folic acid supplementation
infants (>28 days old), children, and adults
- 1st line: supportive care +/- red blood cell transfusions
- 2nd line: folic acid supplementation
- 3rd line: splenectomy with pre-op vaccination regimen
- Consider: cholecystectomy or cholecystostomy
- Plus: post-splenectomy antibiotic pneumococcal prophylaxis
According to NICE guidelines, what hemoglobin level is indicative of anemia in adult males?
A. < 12 g/dL
B. < 13 g/dL
C. < 14 g/dL
D. < 15 g/dL
According to NICE guidelines, what hemoglobin level is indicative of anemia in adult males?
A. < 12 g/dL
B. < 13 g/dL
C. < 14 g/dL
D. < 15 g/dL
In the context of macrocytic anemias, which laboratory test is crucial for differentiating between vitamin B12 deficiency and folate deficiency?
A. Methylmalonic acid (MMA)
B. Homocysteine levels
C. Serum vitamin B12
D. Reticulocyte count
In the context of macrocytic anemias, which laboratory test is crucial for differentiating between vitamin B12 deficiency and folate deficiency?
A. Methylmalonic acid (MMA)
B. Homocysteine levels
C. Serum vitamin B12
D. Reticulocyte count
Methylmalonic acid (MMA) is a metabolite that accumulates when there is a deficiency of vitamin B12. Elevated levels of MMA are specific to vitamin B12 deficiency.
Which type of anemia is characterized by a low serum iron, low total iron-binding capacity (TIBC), and a high transferrin saturation?
A. Iron deficiency anemia
B. Anemia of chronic disease
C. Sideroblastic anemia
D. Thalassemia
Which type of anemia is characterized by a low serum iron, low total iron-binding capacity (TIBC), and a high transferrin saturation?
A. Iron deficiency anemia
B. Anemia of chronic disease
C. Sideroblastic anemia
D. Thalassemia
According to NICE guidelines, what is the primary confirmatory test for hereditary hemochromatosis?
A. Liver biopsy
B. Serum ferritin
C. Genetic testing (HFE mutations)
D. Iron studies
According to NICE guidelines, what is the primary confirmatory test for hereditary hemochromatosis?
A. Liver biopsy
B. Serum ferritin
C. Genetic testing (HFE mutations)
D. Iron studies
Which form of thalassemia is characterized by a microcytic hypochromic anemia with target cells on peripheral blood smear?
A. Beta-thalassemia major
B. Alpha-thalassemia minor
C. Beta-thalassemia minor
D. Alpha-thalassemia major
Which form of thalassemia is characterized by a microcytic hypochromic anemia with target cells on peripheral blood smear?
A. Beta-thalassemia major
B. Alpha-thalassemia minor
C. Beta-thalassemia minor
D. Alpha-thalassemia major
In the diagnosis of aplastic anemia, which parameter is typically reduced in the peripheral blood count?
A. Reticulocyte count
B. White blood cell count
C. Platelet count
D. Hematocrit
In the diagnosis of aplastic anemia, which parameter is typically reduced in the peripheral blood count?
A. Reticulocyte count
B. White blood cell count
C. Platelet count
D. Hematocrit
What is the primary screening test for sickle cell anemia in newborns, as recommended by NICE guidelines?
A. Hemoglobin electrophoresis
B. High-performance liquid chromatography (HPLC)
C. Sickle solubility test
D. Complete blood count (CBC)
What is the primary screening test for sickle cell anemia in newborns, as recommended by NICE guidelines?
A. Hemoglobin electrophoresis
B. High-performance liquid chromatography (HPLC)
C. Sickle solubility test
D. Complete blood count (CBC)
Which one would be the most likely diagnostic for for spherocytosis haemolytic anaemia?
Ham’s test
PAS staining of RBC
G6P levels
EMA binding test
Direct Coombs test
Which one would be the most likely diagnostic for for spherocytosis haemolytic anaemia?
Ham’s test
PAS staining of RBC
G6P levels
EMA binding test
Direct Coombs test
Mycoplasma pneumoniae
specific features of autoimmune haemolytic anaemia: positive direct antiglobulin test (Coombs’ test).
SCA
Hyposplenism
Hyposplenism
Hyposplenism
Hyposplenism
Autoimmune haemolytic anaemia is which type of hypersensitivity reaction?
Type I
Type II
Type III
Type IV
Type II
State 4 acute clinical presentations of SCA [6]
- Vaso-occlusive crises
- Acute chest syndrome
- Pulmonary hypertension
- Anaemia
- Priapism
- Splenic sequestration crisis
Describe the clinical presentation of a vaso-occlusive crisis in SCA [3]
(Which bones are more commonly impacted?)
Vaso-occlusive crises:
- Acute pain in the hand and feet (dactylitis) owing to vasoocclusion of the small vessels and avascular necrosis of the bone
marrow in children
- Possible to have CNS infarction in children leading to stroke,
seizures and cognitive defects
- In adults there is pain in the long bones such as the femur, spine, ribs and pelvis due to avascular necrosis of the bone marrow
A vaso-occlusive crisis is typically associated with what other clinical presentation? [1]
fever
Describe the clinical presentation of acute chest syndrome in SCA [5]
What can cause this? [3]
A vaso-occlusive crisis of the pulmonary vasculature: presents with
- Fever
- SOB
- Chest pain
- Cough
- Hypoxia
Caused by infection (due to Chlamydia, mycoplasma and
Streptococcus pneumoniae), fat embolism from necrotic bone
marrow or pulmonary infarction due to sequestration of sickle
cells (where sickle cells get trapped in the pulmonary vasculature)
How does an acute chest syndrome present on CXR? [1]
Pulmonary infiltrates
Describe the management for an acute chest syndrome presentation [6]
1st line:
- Oxygen & Incentive spirometry using a machine that encourages effective and deep breathing, prevents atelectasis
Plus:
- Analgesia
Plus:
- broad-spectrum antibiotics (because bacterial pneumonia cannot always be ruled out)
Consider:
- Antihistamine (many opioids cause pruritus, which should be managed with an oral antihistamine)
Consider:
- Blood transfusion
Consider:
- Hydration
BMJ BP
Describe the management for an vaso-occlusive crisis presentation [6]
1st line:
- Analgesia
Plus:
- Supportive care
Plus:
- broad-spectrum antibiotics
Consider:
- Antihistamine
Consider:
- Blood transfusion
Consider:
- Hydration
Define what is meant by pulmonary hypertension [1]
Why does SCA lead to PH? [1]
Defines as a mean pulmonary artery pressure greater then
25mmHg by right heart catheterisation
caused by damage from repeated chest crises and
repeated thromboembolism and intravascular haemolysis
Describe what is meant by a splenic sequestration crisis in SCA [1]
Splenic sequestration crisis:
- The rapid pooling of blood in the spleen due to sickled cells block the blood vessels leading out of the spleen - splenomegaly, hypovolemic shock, and potentially death if not promptly treated.
- This event is more common in paediatric patients.
Describe the following chronic complications of SCA [4]
- Anaemia
- Infections
- Leg ulcers
- Growth retardation and delayed puberty
Anaemia:
- chronic haemolytic anaemia is a constant feature in sickle-cell patients, characterized by pallor, fatigue, and exertional dyspnoea.
Infections:
- Functional asplenia due to recurrent splenic infarctions increases susceptibility to encapsulated bacterial infections, such as Streptococcus pneumoniae and Haemophilus influenzae.
Leg ulcers:
- Chronic venous insufficiency resulting from vaso-occlusion can lead to non-healing leg ulcers, predominantly around the medial malleoli.
Growth retardation and delayed puberty:
- due to chronic hypoxia and undernutrition related to increased metabolic demands from their condition.
Describe the following chronic complications of SCA [4]
- Ocular complications
- Skeletal complications
- Renal complications
- Cardiopulmonary complications
- Neurological complications
Ocular complications:
- Retinal vessel occlusions may cause proliferative retinopathy, vitreous haemorrhage or retinal detachment leading to vision loss.
Skeletal complications:
- Chronic bone infarcts can result in avascular necrosis of the femoral and humeral heads.
- Marrow hyperplasia may cause osteopenia and pathologic fractures.
Renal complications:
- Repeated renal medullary ischemia predisposes patients to papillary necrosis and renal tubular dysfunction
- can manifest as nocturia, polyuria, proteinuria or even chronic kidney disease.
Cardiopulmonary complications:
- pulmonary hypertension and eventually right-sided heart failure (cor pulmonale).
Neurological complications:
- ischemic or hemorrhagic strokes
- Silent cerebral infarcts are also common findings on neuroimaging studies.
Describe the long-term managment of SCA [7]
1ST LINE:
- supportive care + prevention of complications: e.g. pneumococcal immunisation, antibiotic prophylaxis with penicillin in children under 5 years of age, nutritional counselling
CONSIDER
* hydroxycarbamide: works by stimulating the production of fetal haemoglobin (HbF).
CONSIDER
* L-glutamine:
CONSIDER
* crizanlizumab: is a monoclonal antibody that targets P-selectin. P-selectin is an adhesion molecule found on endothelial cells on the inside walls of blood vessels and platelets. Prevents red blood cells from sticking to the blood vessel wall and reduces the frequency of vaso-occlusive crises.
CONSIDER
* voxelotor
CONSIDER
* repeated blood transfusions
2ND LINE
- haematopoietic stem cell transplantation
NICE CKS suggest that sickle cell patients should receive which vaccine every 5 year? [1]
NICE CKS suggest that sickle cell patients should receive the pneumococcal polysaccharide vaccine every 5 years
Which drug used in SCA management increases HbF concentrations?
- L-glutamine
- hydroxycarbamide
- crizanlizumab
- voxelotor
Which drug used in SCA management increases HbF concentrations?
- L-glutamine
- hydroxycarbamide
- crizanlizumab
- voxelotor
Which drug used in SCA management targets P-selectin, preventing sticking of RBC to vessel walls
- L-glutamine
- hydroxycarbamide
- crizanlizumab
- voxelotor
Which drug used in SCA management targets P-selectin, preventing sticking of RBC to vessel walls
- L-glutamine
- hydroxycarbamide
- crizanlizumab
- voxelotor
According to NICE guidelines, which laboratory test is considered the gold standard for confirming the diagnosis of sickle cell anemia?
a) Complete Blood Count (CBC)
b) Hemoglobin Electrophoresis
c) Serum Ferritin
d) Coagulation Profile
According to NICE guidelines, which laboratory test is considered the gold standard for confirming the diagnosis of sickle cell anemia?
a) Complete Blood Count (CBC)
b) Hemoglobin Electrophoresis
c) Serum Ferritin
d) Coagulation Profile
How often does NICE recommend monitoring renal function in adults with sickle cell anemia who are receiving long-term hydroxyurea therapy?
a) Every 3 months
b) Every 6 months
c) Annually
d) Biennially
How often does NICE recommend monitoring renal function in adults with sickle cell anemia who are receiving long-term hydroxyurea therapy?
a) Every 3 months
b) Every 6 months
c) Annually
d) Biennially
According to NICE, what is the recommended daily fluid intake for adults with sickle cell anemia to maintain adequate hydration?
a) 1 liter
b) 2 liters
c) 3 liters
d) 4 liters
According to NICE, what is the recommended daily fluid intake for adults with sickle cell anemia to maintain adequate hydration?
a) 1 liter
b) 2 liters
c) 3 liters
d) 4 liters
