Haem I Flashcards
What is essential thrombocytosis and what investigations / results help to differ it from secondary thrombocytosis? [2]
Essential:
- Dysregulated megakaryocyte proliferation
- Platelet count consistently high
Secondary:
- Triggered by infection, trauma, bleeding, hyposplenism
- Transiently raised platelet count
Describe how you manage essential thrombocytosis (depending if they are low or high risk)
Low risk = > 40 OR platelet count < 1500, no hx of thrombosis or haemorrhage. no CV risk
- Aspirin alone
High risk: > 60 OR DM/HTN; platelet count > 1500; Hx of thrombosis or haemorrhage, CV risk
- Hydroxycarbamide and aspirin
How do you differentiate between an aplastic and sequestration crisis in SCA? [1]
Aplastic: reduced reticulocytes
Seq. crisis: increased reticulocytes
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
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
What do raised ferritin levels indicate? [4]
Inflammation (e.g., infection or cancer)
Liver disease
Iron supplements
Haemochromatosis
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 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
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
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
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.
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
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.
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
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
Mycoplasma pneumoniae
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 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
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
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
What is the inheritance patten of thalassaemias? [1]
Both alpha and beta conditions are autosomal recessive
Describe the different types of alpha thalassaemias [4]
Alpha thalassemia minima:
- 1 defective alpha subunit
- Silent carriers: slightly reduced / normal MCV but no clinical symptoms
- Hypochromic and microcytic anaemia
Alpha thalassemia minor:
- 2 defective alpha subunits
- Hypochromic and microcyticnaemia
- The remaining two alpha genes produce nearly normal levels of RBCs
HbH disease:
- 3 defective alpha subunits
- Excess beta chains causes RBC membrane damage and intramedullary haemolysis AND does not release oxygen to tissues, causing increased RBC production
Hydrops fetalis, Bart’s hydrops (γ4):
- 4 defective alpha subunits
- Extreme affinity to O2: incompatible with life
What is the management of thallassemia major? [4]
Management involves;
- regular transfusions
- iron chelation
- splenectomy
- A bone marrow transplant can be curative.
Write down the genotype of Beta thalassaemia minor, intermedia and major [3]
Minor: (b+/b OR b0/b)
Intermedia: (b+/b+)
Major: (b+/b0 OR b0/b0)
Mutation leading to absent production (0)
Mutation leading to reduced production (+)
Describe the bone deformities that can occur in B.T major [4]
Unusual bone formation:
* Facial deformities: frontal bossing, maxilla overgrowth, prominence of upper incisors, ‘chipmunk’ facies, dental malocculsion.
* Body habitus changes: typically short limbs due to early fusion of epiphyses. Skull, pelvis, ribs and spinal changes may be seen
* Osteopaenia/osteoporosis
* Bone pain
Describe how beta thalassaemia interacts with Fe levels in the body [2]
Ineffective erythropoiesis leads to an increase in iron absorption from the gastrointestinal tract that is compounded by regular blood transfusions.
Describe the diagnostic testing used to confirm the presence of beta thalassaemia [2]
Haemoglobin analysis:
- completed using haemoglobin electrophoresis or high-performance liquid chromatography (HPLC). Electrophoresis causes different types of haemoglobin to separate into bands. HPLC is an alternative method of determining the types of haemoglobin in blood.
- Patients with beta thalassaemia will have an increased proportion of HbA2 and HbF due to the absence of beta globin chains. Even in beta thalassaemia minor, there will be an elevation in HbA2.
Genetic testing:
- DNA testing provides a definite and precise diagnosis of beta thalassaemia. It is able to determine the type of mutation present.
Compared to alpha thal: just genetic testing
When does screening for beta thalassaemia occur? [1]
What result would indicate B.T? [1]
Antenatal screening is offered to all pregnant women within the UK. It involves concurrent assessment of different haemoglobinopathies (i.e. thalassaemia and haemoglobin variants) at 10 weeks gestation.
In beta thalassaemia, the level of HbA2 is quantified. Levels of HbA2 >3.5% is suggestive of being a beta thalassaemia carrier and further analysis of the father is required to determine the risk of beta thalassaemia in the fetus.
Describe the managment of beta-thalassaemia intermedia: non-transfusion-dependent [3]
1ST LINE:
- Transfusions at times of symptomatic anaemia
Patients with beta-thalassaemia intermedia do not usually require regular transfusions (non-transfusion-dependent thalassaemia). They are able to grow and develop at a nearly normal rate despite the moderate anaemia.
Occasionally, patients become severely anaemic and develop symptoms as a result. This usually occurs at times of major stress to the body, such as perioperatively, or during a serious illness or infection.
CONSIDER
- iron monitoring + chelation with desferrioxamine or deferasirox
PLUS
- genetic counselling
Describe the managment of beta-thalassaemia intermedia: transfusion-dependent AND beta-thalassaemia major [4]
1ST LINE:
- Regular transfusions
PLUS
- iron monitoring + chelation with desferrioxamine or deferasirox
PLUS
- genetic counselling
CONSIDER
- Splenectomy
CONSIDER
- Assessment for stem cell transplantation
Vaccinations agaisnt with pathogens are recommended in splenectomy patients? [4]
Vaccinations against S. pneumoniae, N. meningitidis, H. influenzae type b and influenza virus are strongly recommended.
Name some pathologies that cause hyposplenism [5]
sickle cell anaemia (chronic damage to the spleen results in atrophy)
coeliac disease
dermatitis herpetiformis
essential thrombocythaemia
ulcerative colitis.
What are 4 blood film findings of hyposplenism [4]
Blood film: features of hyposplenism include Howell-Jolly bodies, Pappenheimer bodies, target cells and irregular contracted red blood cells.
In alpha thalassemia, the Hemoglobin H (HbH) disease results from the deletion of three alpha-globin genes. What is the recommended treatment for patients with HbH disease, according to NICE?
a) Blood transfusion
b) Hydroxyurea
c) Folic Acid supplementation
d) Hematopoietic stem cell transplantation
c) Folic Acid supplementation
NICE recommends screening for alpha thalassemia in newborns. What is the primary screening test used for this purpose?
a) Hemoglobin electrophoresis
b) Complete Blood Count (CBC)
c) DNA analysis
d) Serum Ferritin
NICE recommends screening for alpha thalassemia in newborns. What is the primary screening test used for this purpose?
a) Hemoglobin electrophoresis
b) Complete Blood Count (CBC)
c) DNA analysis
d) Serum Ferritin
According to NICE guidelines, which diagnostic test is recommended for confirming the diagnosis of beta thalassemia major?
a) Complete Blood Count (CBC)
b) Hemoglobin electrophoresis
c) Serum Ferritin
d) Molecular genetic testing
d) Molecular genetic testing
subtertian malaria (fever < every 48hrs) is caused by
Plasmodium falciparum
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
Plasmodium knowlesi
Plasmodium falciparum
quartan malaria (fever spikes every 72 hours is caused by
Plasmodium falciparum
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
Plasmodium knowlesi
Plasmodium malariae
State 3 signs of malaria [3]
Pallor (anaemia)
Splenomegaly
Jaundice (due to haemolysis)
TOM TIP: The most characteristic symptom of malaria is the fever, which spikes very high every 48 hours. In someone with an unexplained fever, consider whether they have travelled somewhere with malaria present. Even exposure several years ago may be relevant, as P. vivax and P. ovale can lie dormant for up to 4 years.
What determines if malaria is uncomplicated or complicated? [3]
Criteria for uncomplicated malaria includes:
* Parasitaemia < 2%
* No schizonts on film
* No clinical complications
Describe the management plan of uncomplicated P. falciparum malaria [2]
First-line options:
* Riamet (Artemether + lumefantrine): four tablets orally at 0, 8, 24, 36, 48 and 60 hours,
OR
* Malarone (atorvaquone + progunail): 4 tablets daily for 3 days
Second-line options:
* Quinine sulphate (600 mg TDS) + Doxycycline (200 mg OD): 7 days, OR
* Quinine sulphate (600 mg TDS) + Clindamycin (450 mg TDS): 7 days
Describe the management plan of complicated P. falciparum malaria [3]
First-line options:
* Artesunate: 2.4 mg/kg intravenous at 0, 12, 24 hours then once daily. Always follow local guidelines on prescribing.
* If unavailable, may require quinine initially until artesunate is acquired.
Second-line options:
* Quinine dihydrochloride: Requires dose adjustment in renal and hepatic impairment and cardiac monitoring duration administration. Follow local guidelines.
Follow-on therapy (once improved and able to tolerate oral tablets):
* Riamet (Artemether + lumefantrine): four tablets orally at 0, 8, 24, 36, 48 and 60 hours, OR
* Doxcycline: 200 mg once daily for 7 days, OR
* Clindamycin: 450 mg three times a day for 7 days (preferred in pregnancy)
TOM TIP: Remember artesunate and quinine as treatment options for your exams, as these are the most likely to be relevant. Remember that Plasmodium falciparum is the most common and severe cause, and these patients should be admitted for artesunate treatment and monitoring for complications.
Describe the treatment of of non-falciparum malaria or mixed [1]
Non-falciparum malaria should be discussed with microbiology and local guidelines followed.
Patients are usually able to be managed as outpatients.
Treatment is usually with chloroquine, but this depends on resistance patterns.
Follow-on treatment is typically required for P. vivax and P. ovale.
Explain which genetic disorder you need to consider when treating malaria?
Glucose-6-phosphate deficiency (G6PD) (red cell lysis when erythrocytes are put under oxidative stress) because antimalarials, can induce red cell haemolysis.
Specifically:
* Primaquine (definite risk of haemolysis, G6PD needs to be excluded before use)
* Chloroquine (possible risk of haemolysis, acceptable in acute malaria)
* Quinine (possible risk of haemolysis, acceptable in acute malaria)
Describe the complications of malaria
Severe malaria is invariably fatal if left untreated. Also:
Cerebral malaria (mortality of 50%)
ARDS
DIC
AKI
Severe anaemia
Septic shock
Splenic rupture
Multi-organ failure
Death
Which medications can be used as prophylaxis for malaria [4]
Proguanil with atovaquone (Malarone)
Doxycycline
Mefloquine (risk of psychiatric side effects)
Chloroquine with proguanil (less often used due to high resistance)
Name 3 side effects of doxycyline treatment [3]
diarrhoea
thrush
skin sensitivity to sunlight
Which of the following is the most effective form of malaria prophylaxis
Doxycycline
Proguanil with atovaquone (Malarone)
Mefloquine
Chloroquine with proguanil
Which of the following is the most effective form of malaria prophylaxis
Doxycycline
Proguanil with atovaquone (Malarone)
Mefloquine
Chloroquine with proguanil
Which of the following has a risk of pysc side effects
Doxycycline
Proguanil with atovaquone (Malarone)
Mefloquine
Chloroquine with proguanil
Mefloquine: causes anxiety, depression and abnormal dreams.
Vaccinations against S. pneumoniae, N. meningitidis, H. influenzae type b and influenza virus are strongly recommended for asplenic patients.
Which of the above is the most likely infection for asplenia? [1]
S. pneumoniae
