Anaemia

Question 1

Answer 1

Legal issues: ?GMC number

Nil clinical issues

Send to NHS BSA at the end of the month

Nil POM book documentation

Patient counselling:

• Not everyone experiences s.e. however these are some - constipation, diarrhoea, GI disturbances, nausea
• Can colour stool brown
• Do not take NSAID?
• Increase iron levels
• Iron is absorbed in the small intestine (duodenum and first part of the jejunum). This means that enteric-coated iron tablets may not work as well.
• If you take antacids, you should take iron tablets two hours before or four hours after the antacid.
• Vitamin C (ascorbic acid) improves iron absorption, and some doctors recommend that you take 250 mg of vitamin C with iron tablets.

Question 2

A 26-year-old female has been diagnosed with microcytic anaemia.

Which one of the following nutritional deficiencies is most likely to be contributing to this diagnosis?

Select one:
A. Folate deficiency
B. Iron deficiency Correct
C. Vitamin B6 deficiency
D. Vitamin B12 deficiency
E. Vitamin D deficiency

Answer 2

Microcytic Anaemia (low MCV) most commonly due to iron deficiency.

Reference: https://bestpractice.bmj.com/topics/en-gb/93/aetiology

The correct answer is: Iron deficiency

Question 3

When a patient has an overload of this substance, deferasirox should be administered to the patient.

Answer 3

Indicated for the treatment of chronic iron overload when desferrioxamine is contraindicated or inadequate (with non-transfusion-dependent thalassaemia syndromes).

Question 4

How should I treat a person with folate deficiency anaemia?

Answer 4

Prescribe oral folic acid 5 mg daily — in most people, treatment will be required for 4 months. However, folic acid may need to be taken for longer (sometimes for life) if the underlying cause of deficiency is persistent.

Check vitamin B12 levels in all people before starting folic acid — treatment can improve wellbeing, mask an underlying B12 deficiency, and allow the neurological disease to develop.

Give dietary advice about foods that are a good source of folic acid — good sources of folate include:

• Asparagus.
• Broccoli.
• Brown rice.
• Brussels sprouts.
• Chickpeas.
• Peas.

Question 5

Why should iron-deficiency anaemia be managed preoperatively?

Answer 5

• Predictor of postoperative outcome - increased perioperative blood transfusion and postoperative morbidity and mortality
• iron deficiency anaemia: Haemoglobin
• <130 g/L (13 g/dL) in men older than age 15 years,
• <120 g/L (12 g/dL) in nonpregnant women older than age 15 years,
• <110 g/L (11 g/dL) in pregnant women
• Should start 3 weeks before surgery

Question 6

What are the adverse side effects of iron tablets?

Answer 6

Constipation

Nausea Vomiting

Question 7

A 74-year-old man with stage IV chronic kidney disease secondary to type II diabetes mellitus is admitted to the acute medical assessment ward with symptoms of breathlessness and reduced exercise tolerance. He is otherwise systemically well. His blood results are as follows:

• Haemoglobin 80 g/l
• Mean Corpuscular Volume 90 fl
• Mean Corpuscular Haemoglobin 30 pg
• Urea 17 mmol/l
• Creatinine300 µmol/l
• eGFR8 ml/min/1.73m2

Given the likely cause of this patient’s anaemia, which of the following compounds is the patient most likely to be deficient of?

• Vitamin B1
• Ferritin
• Folate
• Erythropoietin
• T3 / T4

Answer 7

In many cases of advanced renal failure, the kidneys’ ability to produce erythropoietin is reduced, leading to anaemia of chronic disease. There are several factors involved in renal anaemia, however a lack of erythropoietin is the most significant contributor.

Typically this deficiency manifests as a normochromic, normocytic anaemia, as seen in this patient’s blood results.

In Vitamin B12/Folate deficiency and some cases of hypo/hyperthyroidism, a macrocytic anaemia is seen. Low ferritin levels will lead to a microcytic anaemia.

Question 8

A 71-year-old male attends renal clinic for a review of his chronic kidney disease (CKD. He has type 2 diabetes and CKD stage 4. His latest eGFR is 21ml/min/1.73m². He explains that over the past 1 month, he has been feeling fatigued and has noticed shortness of breath on exertion. Review of his blood tests show:

• Hb91 g/LMale: (135-180)
• Ferritin16 ng/mL(20 - 230)
• Vitamin B12342 ng/L(200 - 900)
• Folate3.8 nmol/L(> 3.0)

He denies any change in bowel habits, abdominal pain or rectal bleeding.
What is the most appropriate initial action?

• Prescribe an erythropoiesis-stimulating agent (ESA)
• Prescribe ferrous sulphate
• Prescribe folic acid
• Reassurance and monitoring
• Prescribe vitamin B12 injections

Answer 8

The most appropriate initial action, in this case, is to prescribe ferrous sulphate. This patient has an iron deficiency anaemia and therefore should be given iron replacement. Iron deficiency should be corrected before starting erythropoiesis-stimulating agents (ESA).

Prescribe an ESA is not an appropriate first-line management option as this patient has iron deficiency and this should be corrected first.

Prescribe folic acid is inappropriate as this patient has normal folate levels.

Reassurance and monitoring is an incorrect answer as it does not address this patient’s symptomatic anaemia.

Prescribe vitamin B12 injections is inappropriate as his vitamin B12 levels are normal therefore this is not the cause of his anaemia.

Question 9

A 71-year-old male with a background of stage 5 chronic kidney disease presents to the hospital with increasing fatigue and breathlessness. He undergoes haemodialysis regularly, 3 times a week.

Lab results are as follows:

• Hb102g/LMale: (135-180)
• Female: (115 - 160)
• MCV83 fl(82 - 100)
• eGFR14 ml/min/1.73m(>90)
• Ferritin11 ng/mL(20 - 230)
• Transferrin saturation12%(20 - 50)

Which of the following is the most appropriate initial management option?

• Erythropoietin stimulating agent
• Folate supplements
• IM cyanocobalamin
• IV iron infusion
• Venesection

Answer 9

Anaemia is a common complication of chronic kidney disease. It can be due to impaired erythropoietin (EPO) production from the kidneys. EPO stimulates erythropoiesis in the bone marrow. Erythropoietin stimulating agents (ESA) could be given if the patient had a normal iron level, but because iron is required to create new red blood cells, the haemoglobin concentration will not increase by much if the patient is iron deficient. Therefore, correcting the iron deficiency before giving an ESA would be more appropriate in this scenario. IV iron infusion is used instead of oral iron as it has better bioavailability and rapid efficacy.

Folate supplements would treat folate deficiency, which causes a macrocytic anaemia. Folate deficiency is commonly caused by malnutrition, inflammatory bowel disease, coeliac disease and can also be caused by medication such as methotrexate.

Cyanocobalamin supplementation would be the treatment for B12 deficiency, but this patient has a normocytic anaemia, so we would not suspect B12 (or folate) deficiency. B12 deficiency is commonly caused by atrophic gastritis, Crohn’s disease or malnutrition.

Venesection is incorrect as this is the treatment for iron overload disorders such as haemochromatosis.

Question 10

A 71-year-old woman with a background of type II diabetes and chronic kidney disease (CKD) is reviewed by her GP. Her recent blood tests have shown that her haemoglobin level and estimated glomerular filtration rate (eGFR) has fallen gradually over the last year. Her blood tests can be found below.

• Hb94g/LMale: (135-180)
• Female: (115 - 160)
• Platelets268* 109/L(150 - 400)
• WBC5.1* 109/L(4.0 - 11.0)
• MCV76(80-100fL)
• Na+139mmol/L(135 - 145)
• K+3.9mmol/L(3.5 - 5.0)
• Urea5.9mmol/L(2.0 - 7.0)
• Creatinine118µmol/L(55 - 120)
• eGFR31ml/min/1.73m2(>89ml/min/1.73m2)

What would be the next appropriate management in view of her background of CKD?

• Check iron status
• Refer for blood transfusion
• Refer for dialysis
• Refer to commence erythropoietin (EPO)
• Urgently refer to the renal team

Answer 10

In a patient with suspected anaemia of chronic disease secondary to CKD, iron status should be checked prior to commencing EPO

If anaemia is present, arrange tests to exclude other causes of anaemia. Iron deficiency should be done first before considering the need to refer for erythropoietin (EPO). Renal anaemia should only be diagnosed after exclusion of other causes including iron deficiency, folate or B12 deficiency, haemolysis. Renal anaemia is unusual prior to CKD3b but if suspected, nephrology advice would be appropriate.

Referring for a blood transfusion won’t be necessary at this point since we have not excluded other causes for this low Hb. It is also usually not given until the patient’s haemoglobin count falls below 70g/l in a stable scenario where there is no acute haemorrhage or rapid correction of anaemia required.

Referral for dialysis is not appropriate at this point and is not indicated for the treatment of anaemia.

Referral to commence EPO can be considered once other causes are excluded e.g. iron-deficiency anaemia as per NICE guidance.

This scenario can be managed initially in a primary care setting and an urgent referral to the renal team won’t be necessary at this point.

Question 11

A 41-year-old man with a background in polycystic kidney disease is reviewed in the clinic. He has been feeling increasingly fatigued over the past few months and cannot do his usual workout at the gym without becoming very breathless and tired. His blood tests are shown below:

• Hb84 g/LMale: (135-180)
• Female: (115 - 160)
• Platelets214 * 109/L(150 - 400)
• WBC5.6 * 109/L(4.0 - 11.0)
• Urea9.9 mmol/L(2.0 - 7.0)
• Creatinine301 µmol/L(55 - 120)
• Ferritin14 ng/mL(20 - 230)
• Vitamin B12368 ng/L(200 - 900)
• Folate3.2 nmol/L(> 3.0)

What is the most appropriate next step in his management?

• Arrange a packed red cell transfusion
• Start high-dose folate replacement
• Start oral iron replacement
• Start treatment with erythropoietin
• Start hydroxycobalamin replacement

Answer 11

Anaemia in CKD: correct iron deficiency before starting erythropoiesis-stimulating agents

Chronic kidney disease (CKD) is a common cause of anaemia due to several factors but most significantly the loss of the kidney’s production of erythropoietin. Erythropoietin is a cytokine responsible for inducing bone marrow production of erythrocytes (red blood cells). Recombinant erythropoietin can be given to treat CKD-associated anaemia but other factors should be corrected first before giving it. The blood results here indicate low ferritin, suggesting the need for iron supplementation. CKD can cause poor iron absorption and result in a need for supplementation, including regular intravenous infusions for patients receiving dialysis.

A transfusion would be inappropriate at present as his haemoglobin is still above 80 g/L and there is a reversible cause of his anaemia (iron deficiency).

Folate replacement is not required as his folate levels are replete.

Erythropoietin treatment would only be indicated if he remained symptomatically anaemic despite adequate iron replacement.

Hydroxycobalamin is the chemical name for vitamin B12. His vitamin B12 levels are replete so this is not indicated.

Question 12

A 31-year-old gentleman with known epilepsy, depression and type 1 diabetes presents to his GP with a 1-week history of fatigue. He also says his gums have sometimes bled when he brushes his teeth. The GP requests some blood tests, which show the following:

• Haemoglobin92 g/L
• Mean Cell Volume92 fL
• White Cell Count (WCC)1.9 x 10 9 /L
• Platelet count29 x 10 9 /L

Which drug is most likely to explain the patient’s symptoms and blood test results?

• Phenytoin
• Sodium valproate
• Lamotrigine
• Sertraline
• Insulin

Answer 12

Phenytoin is a cause of aplastic anaemia

The blood tests show a normocytic anaemia, leukopenia and thrombocytopenia, which is the definition of aplastic anaemia. This is corroborated by the patient’s symptoms, which are highly suggestive of bone marrow failure.

Of all the medications he is likely to be taking due to his past medical history, only phenytoin is known to cause this. Note: sodium valproate can cause anaemia and thrombocytopenia but does not cause leukopenia.

Doctors at any level of training must be aware of the severe side-effects (like aplastic anaemia) for commonly used drugs, such as phenytoin. This is because not only does the aplastic anaemia need to be treated, but the offending drug must be stopped; this information must also be added to the patient’s medical notes so it is never prescribed again.

Other important drug causes of aplastic anaemia are cytotoxics, chloramphenicol, and sulphonamides.

Question 13

A 62-year-old female presents to her general practitioner with a 2-month history of fatigue and poor concentration. She finds herself getting shortness of breath when walking to the shop, which previously did not cause her any issues. On examination, she is noted to be pale, cardiorespiratory and neurological examination is unremarkable. She has blood tests sent which show:

• Hb102 g/LMale: (135-180)
• Female: (115 - 160)
• Platelets161* 109/L(150 - 400)
• WBC4.0 * 109/L(4.0 - 11.0)
• Blood filmhypersegmented polymorphs
• Vitamin B12120 ng/L(>200)
• Folate1 ng/mL(2-10)

What is the most appropriate management (out of those listed) for this patient?

• Urgent referral to haematology
• Urgent referral to hospital for CT head
• B12 replacement - intramuscular replacement
• B12 replacement - oral replacement
• Folate replacement intramuscularly prior to B12 replacement

Answer 13

This patient has vitamin B12 and folate deficiency.

Symptoms: fatigue, poor concentration, and pallor are common

Bloods: her blood tests confirm this picture (anaemia, low B12, low folate, and hypersegmented polymorphs on blood film). There may also be thrombocytopenia in these patients - this is due to vitamin B12 acting as a co-factor during the synthesis phase of the cells in the bone marrow.

Examination: although her neurological examination is unremarkable, patients may present with peripheral neuropathy and ataxia.

This patient does not warrant urgent referral as she does not have any neurological symptoms and is not pregnant. NICE guidelines advise urgent referral if the patient has loss of cutaneous sensation, muscle weakness, optic neuropathy, psychiatric disturbance, symmetrical neuropathy, or urinary or faecal incontinence.

Referral to haematology should be considered also if the patient has a suspected haematological malignancy or blood disorder, the patient fails to respond to treatment, or mean cell volume is persistently > 105 femtolitres. Referral to gastroenterology should be made if the patient is suspected to have a malabsorption syndrome, gastric cancer, or has pernicious anaemia with GI symptoms.

The patient does not fulfil criteria for CT head and, as such, this answer is incorrect.

The recommendation of IM over oral replacement of B12 is outlined in the NICE guidelines. Some randomised control trials point to IM replacement being superior to oral and this is still the preferred route of administration as per guidelines.

Vitamin B12 replacement should always occur prior to folate replacement as folate replacement prior to B12 can precipitate subacute combined degeneration of the spinal cord.

Question 14

A 72-year-old woman is brought to surgery with confusion and pallor. Her daughter reports that she has been getting more confused and tired for the past three months. Blood tests are reported as follows:

• Hb8.9 g/dl
• MCV125 fl
• Plt148 * 109/l
• WBC4.4 * 109/l

In light of the macrocytic anaemia some further tests are ordered:

• Intrinsic factor antibodies Negative
• Vitamin B1294 ng/l (200-900 ng/l)
• Folic acid1.1 nmol/l (> 3.0 nmol/l)

What is the most appropriate management?

• Perform an ECG immediately
• Oral folic acid + start Intramuscular vitamin B12 when folic acid levels are normal
• Intramuscular vitamin B12 + start oral folic acid when vitamin B12 levels are normal
• Refer to the local alcohol dependency services
• Admit for blood transfusion

Answer 14

Intramuscular vitamin B12 + start oral folic acid when vitamin B12 levels are normal.

It is important in a patient who is also deficient in both vitamin B12 and folic acid to treat the B12 deficiency first to avoid precipitating subacute combined degeneration of the cord. Consideration in this case should also be given to secondary care referral to identify the underlying cause

Question 15

A 66-year-old man presents with a 3-month history of fatigue. He has hypertension for which he is on lisinopril, amlodipine, and indapamide, which he says he takes every day. There have been no recent changes to his medications or diet and he takes no other prescribed or over the counter medications.

Blood tests are performed and all are within normal ranges apart from full blood count which is as follows:

• Hb91 g/LMale: (135-180) Female: (115 - 160)
• Platelets344 * 109/L(150 - 400)
• WBC7.6 * 109/L(4.0 - 11.0)
• Red cell count2.9 * 109/L(1.0 - 3.5)
• MCV71 fL(82-100)

What is the most appropriate next step?

• Further blood tests for serum ferritin and total iron-binding capacity
• Recommend an iron-rich diet
• Tissue transglutaminase antibody blood test
• Oral ferrous sulfate for 3 months
• Urgent colorectal pathway referral

Answer 15

Patients over the age of 60 who present with iron deficiency anaemia should be investigated for colorectal cancer

The blood results show an iron deficiency anaemia. In patients over the age of 60, iron deficiency anaemia is a criterion for urgent referral (i.e. within 2 weeks) to colorectal services for investigation for colorectal cancer.

In a GP setting, a faecal immunochemical test (FIT) may be performed, but the urgent referral would still be made at the same time.

Colorectal cancer is the third most common type of cancer in the UK and can present with a change in bowel habit or blood in the stool, but can also be asymptomatic as the blood in the stool may not be visible.

• Further blood tests are not the most important next step here, as it is important to first rule out cancer here.
• Recommending an iron-rich diet could be a treatment option if the iron deficiency anaemia is a result of inadequate iron intake, but the cause has not yet been established and this needs to be done first.
• Tissue transglutaminase antibody blood test is the investigation of choice for coeliac disease, which is a potential cause of iron deficiency anaemia. However, the lack of other symptoms makes this less likely, and colorectal cancer is the more important diagnosis to rule out first.
• Oral ferrous sulfate for 3 months is a potential treatment option for iron deficiency anaemia, but it is important to first establish the cause, so this is the wrong answer.

Question 16

A 78-year-old lady presents to general practice complaining of fatigue over several months, during which time she has also lost 7kg of weight.

Her blood tests show:

• Hb 87 g/L Male: (135-180) Female: (115 - 160)
• MCV76 fL(82-100)
• Platelets415 * 109/L(150 - 400)
• WBC5 * 109/L(4.0 - 11.0)

Which of the following investigations is most appropriate for diagnosis?

• B12/Folate
• Bone marrow biopsy
• Colonoscopy
• Iron studies
• Peripheral blood film

Answer 16

Patients over the age of 60 who present with iron deficiency anaemia should be investigated for colorectal cancer

Microcytic anaemia is suggestive of iron deficiency anaemia which needs further investigation via colonoscopy to exclude bowel cancer.

Iron studies/B12/folate may provide further information but would not be diagnostic.

Bone marrow biopsy is an invasive procedure and unlikely to yield diagnostic information in this context.

Peripheral blood film is unlikely to be diagnostic.

Question 17

A 34-year-old woman who presents with heavy menstrual bleeding is found to have a haemoglobin of 102 g/L. Iron studies are organised.

Which of the following results would support a diagnosis of iron deficiency anaemia?

(TIBC = total iron-binding capacity)

• ↓ Ferritin, ↑ total iron-binding capacity, ↓ serum iron, ↓ transferrin saturation
• ↓ Ferritin, ↑ total iron-binding capacity, ↓ serum iron, ↑ transferrin saturation
• ↓ Ferritin, ↓ total iron-binding capacity, ↓ serum iron, ↑ transferrin saturation
• ↓ Ferritin, ↑ total iron-binding capacity, ↑ serum iron, ↓ transferrin saturation
• ↓ Ferritin, ↓ total iron-binding capacity, ↓ serum iron, ↓ transferrin saturation

Answer 17

↓ Ferritin, ↑ total iron-binding capacity, ↓ serum iron, ↓ transferrin saturation

Total iron-binding capacity (TIBC) + transferrin levels are typically raised in iron-deficiency anaemia. A high TIBC reflects low iron stores. . Note that the transferrin saturation will however be low.

Iron-deficiency anaemia:

• Serum iron is going to be low (similarly with the ferritin)
• Not enough iron in the blood and iron binds to transferrin (a binding/transport protein) in the blood, then the ‘transferrin saturation’ is also going to be low - because iron isn’t ‘saturating’ transferrin (note that as per one of the comments above, this q is asking about transferrin SATURATION, not transferrin levels)
• The total iron binding capacity is the capacity of the system to bind iron - the body wants to bind iron, but because iron is lacking (the patient is iron-deficient) - hence the total iron-binding capacity (TIBC) is high. might be helpful to think about it the other way around: if your iron stores were super high, you wouldn’t be able to take on much iron as you’ve got what you need, so your TIBC would be low.

Serum ferritin will likely be low, as serum ferritin correlates with iron stores. However, it is important to recognise that ferritin can be raised during states of inflammation; so a raised ferritin does not necessarily rule out iron deficiency anaemia if the is co-occurring inflammation. For patients with co-occurring inflammatory disease, other iron studies can be performed.

Question 18

A 28-year-old lady who is 9 weeks pregnant comes to see you for review of booking bloods. Her haemoglobin is 105 g/L and the mean cell volume (MCV) is 70 fL (normal range 77-95 fL).

What is the most appropriate management?

• No treatment needed, Hb is within normal range for pregnancy
• Blood transfusion
• Oral iron tablets
• Parenteral iron infusion
• Take a further blood sample for haematinics before deciding management

Answer 18

ANSWER: Oral iron

This question is about the management of anaemia in pregnancy.

Anaemia in pregnancy is defined using different cut off values than in non-pregnant women and varies according to trimester. British Committee for Standards in Haematology (BCSH) guidance gives the following values:

• first trimester Hb less than 110 g/l
• second/third trimester Hb less than 105 g/l
• postpartum Hb less than 100 g/l

In this question, the Hb is checked at booking and is less than 110 g/L therefore this is first-trimester anaemia.

The correct answer is - oral iron tablets. (RCOG) guidelines advise for normocytic or microcytic anaemia a trial of oral iron should be considered as the first step, and further investigations only required if no rise in haemaglobin after 2 weeks.

Parenteral iron is only indicated if oral iron is not tolerated, absorbed, patient is not compliant or they are near term and there is insufficient time for oral iron to be effective. Blood transfusion is inappropriate at this level of haemoglobin without active bleeding.

Pregnant women are screened for anaemia at:

• the booking visit (often done at 8-10 weeks), and at
• 28 weeks

NICE use the following cut-offs to determine whether a woman should receive oral iron therapy:

• Gestation Cut-off
• Booking visit < 11 g/dl
• 28 weeks < 10.5 g/dl

Question 19

A 45-year-old obese woman with a background of fibroids and menorrhagia is in pre-op assessment prior to having a left total knee replacement. She is due to have surgery in 10 days. She weighs 105kg.

• Hb79 g/l
• MCV68.1 fL
• Platelets196 * 109/l
• WBC4.9 * 109/l
• Iron low
• Ferritinlow
• TIBChigh

Based on the above findings, you offer her a pre-operative blood transfusion 72 hours before the procedure however she declines. She was previously prescribed oral iron by her GP but stopped taking it due to gastrointestinal side effects. What is the most appropriate next intervention to offer her?

• Ferrous sulphate 200mg BD for 10 days prior to her procedure
• IV iron (ferric carboxymaltose) 1g, repeated 1 week later
• IM iron (iron dextran) 2ml (50mg/ml), repeated 1 week later
• No intervention necessary
• Tranexamic acid 1g 3 times a day during menstruation

Answer 19

IV iron (ferric carboxymaltose) 1g, repeated 1 week later

IV iron should be used in patients who are found to have iron deficiency anaemia prior to surgery where oral iron either can’t be tolerated or the time interval is too short

The rate-limiting step with oral iron is the amount which can be absorbed from the GI tract. As such the shortest time interval for oral iron to work is 2-4 weeks, however usually patients are treated for 2-3 months before a decent treatment response is demonstrated in the blood tests.

Additionally, in the above scenario, the patient has previously taken oral iron and has been unable to tolerate it due to side effects. As she has declined transfusion, IV iron is the most appropriate and timely way to replace her iron stores, with a view to improving her anaemia prior to surgery. Her anaemia is sufficiently severe that her postoperative morbidity and mortality are increased, and hence it needs to be addressed prior to surgery. Tranexamic acid would help reduce blood loss during menstruation however it would not help raise her haemoglobin.

See the below guidelines:
https://www.nice.org.uk/guidance/ng24/chapter/Recommendations#alternatives-to-blood-transfusion-for-patients-having-surgery-2

Question 20

A 52-year-old female presents to her general practitioner with a two-week history of lethargy and paraesthesia in her hands. She denies any recent changes in her weight, has not had a change in her bowel habits and denies low mood or muscle cramps.

She takes no regular medications.

A full blood count reveals the following:

• Hb102 g/L Male: (135-180) Female: (115 - 160)
• MCV 114 fL(77-95)
• Platelets392 * 109/L(150 - 400)
• WBC7.52 * 109/L(4.0 - 11.0)

Haematinics reveal the following:

• Folate1.2 ug/L(3-20)
• Vitamin B1282 ng/L(197-771)

How might you manage this patient initially?

• Folate replacement 4mg/day lifelong
• Folate replacement 5mg/day for 4 months
• Folate replacement 400mcg/day for 4 months
• 10mg IM vitamin B12 followed by 3 monthly doses of 1mg IM
• Vitamin B12 1mg IM three times/week then 1mg IM every 3 months

Answer 20

Vitamin B12 deficiency is managed with a loading and maintenance regime. To begin with, 1mg of hydroxocobalamin is administered IM 3 times a week for two weeks. Maintenance involves hydroxocobalamin 1mg IM every 3 months. If the deficiency is not thought to be diet-related, then this maintenance treatment continues lifelong.

Folate replacement is an appropriate therapy for this patient. However, folate should never be replaced before vitamin B12 due to the risk of precipitating subacute combined degeneration of the cord. (Think BeFore: B before F to help you remember).

4mg of folate is not an appropriate dose.

5mg of folate for 4 months is an appropriate dose, however should not come before replacement of vitamin B12.

400mcg is a prophylactic dose, not a treatment dose of folate.

A one-off dose of IM vitamin B12 is not adequate therapy.

Question 21

A 25-year-old woman presents with a history of fatigue, dyspnoea upon exertion and restless legs. Her symptoms are keeping her up at night. She has two young children.

Examination reveals conjunctival pallor and spooning of her nails. There is no lymphadenopathy or hepatosplenomegaly. Lab results are displayed below.

• Hb98 g/L Male: (135-180) Female: (115 - 160)
• Platelets212 * 109/L(150 - 400)
• WBC5.2 * 109/L(4.0 - 11.0)
• MCV76 fL(80-100)

Iron studies reveal low serum iron and ferritin, with a raised total iron-binding capacity.

What should be performed as a first-line investigation in this patient?

• CT colonography
• Faecal occult blood test (FOBT)
• Haemoglobin electrophoresis
• Tissue transglutaminase IgA
• Urea breath testing

Answer 21

Tissue transglutaminase IgA

This patient has iron-deficiency anaemia. This is evident from her iron studies and low MCV, indicating microcytic anaemia. Tissue transglutaminase IgA is recommended as screening for coeliac disease, this is suggested as a first-line investigation in people with iron deficiency anaemia.

CT colonography is not considered a first-line investigation for all people with iron deficiency anaemia. In certain patient groups such as men >50 years of age and post-menopausal women, the investigation into upper and lower gastrointestinal lesions must be performed in all patients with iron deficiency anaemia if there is no history of overt non-gastrointestinal bleeding. These patients usually undergo a colonoscopy and oesophagogastroduodenoscopy. CT colonography may be an appropriate option for an older male or post-menopausal female patient who is not suitable for a colonoscopy as it is minimally invasive and does not require sedation. As this patient is a young female, she does not require a colonoscopy or CT colonography as a first-line investigation in the work-up of her iron deficiency anaemia.

FOBT is a test that detects the presence of blood in a stool sample. Typically, it is used as a screening test for suspected colon cancer in asymptomatic patients. However, there is no indication that this patient is at risk of cancer, so this is not the most appropriate first-line investigation in this patient.

Haemoglobin electrophoresis utilises an electric current to separate and assess haemoglobin. This enables the identification of anomalous haemoglobin types, such as sickle cell and thalassaemias, as well as quantifying the amount of haemoglobin present. However, as the iron study results in this patient are not within normal ranges, this investigation would not be the first-line investigation.

The absence of gastrointestinal symptoms suggests this is unlikely to be a H. pylori infection. Testing for Helicobacter pylori may be recommended in patients with iron deficiency anaemia, but would usually be screened with serology which has an excellent negative predictive value, before being confirmed with urea breath testing.

Question 22

A 40-year-old man with a past medical history of lymphoma has been seeing his haematologist about his painful hands associated with colour change to dark red and blue, which only occurs when he goes out in cold weather. He has a routine set of bloods which shows some new findings:

• Hb82 g/l
• Mean cell volume (MCV)101 fL

Which of the following investigations is most likely to confirm the diagnosis?

• Vitamin B12 level
• Ferritin
• Direct antiglobulin test (Coombs’ test)
• Blood film
• Thyroid stimulating hormone (TSH)

Answer 22

Direct antiglobulin test (Coombs’ test)

Cold autoimmune haemolytic anaemia causes IgM-mediated haemolysis at cold temperatures (4 degrees)

Important for meLess important

The history points towards cold autoimmune haemolytic anaemia (AIHA) for the following reasons:

• 1) Background a lymphoma (risk factor for cold AIHA)
• 2) Raynaud’s phenomenon
• 3) Symptoms worse in the cold
• 4) New macrocytic anaemia, the macrocytosis here is occurring due to reticulocytosis (new immature RBCs which are larger) to compensate for the haemolysis.

In cold AIHA, IgM-mediated haemolysis occurs at cold temperatures (<4 degrees) which leads to anaemia made worse by the cold and symptoms such as Raynaud’s phenomenon and acrocyanosis. It causes mainly intravascular haemolysis. The direct antiglobulin test (Coombs’ test) would be positive specifically for cell-surface complement (as cold AIHA is complement-mediated).

For (1) and (2) haematinics would be checked routinely but are unlikely to yield the diagnosis with this history. (4) a blood film would be useful and show reticulocytes but wouldn’t be diagnostic and (5) TSH should be measured for a macrocytic anaemia but there is another obvious cause in this question.

Question 23

A 45-year-old man complains of feeling tired all the time to his GP. He has no other symptoms and his examination is normal. Blood tests are arranged which show:

• Hb104 g/l
• MCV 69.7 fL
• Platelets304 * 109/l
• WBC8.7 * 109/l
• Ironlow
• Ferritinlow
• TIBChigh

Based on the above findings, what would be the most appropriate next step?

• Routine referral for upper and lower GI endoscopy
• Routine referral for CT chest, abdomen and pelvis
• Further bloods including TFTs, bone profile and haemoglobinopathy screen
• Urgent referral for CT chest, abdomen and pelvis
• Urgent referral for upper and lower GI endoscopy - under the 2ww pathway

Answer 23

Urgent referral for upper and lower GI endoscopy - under the 2ww pathway

Men of any age with a Hb below 110g/L should be referred for upper and lower GI endoscopy as a 2ww

In accordance with NICE guidelines, men of any age with a Hb below 110g/L should be referred for upper and lower GI endoscopy as a 2ww. These are separate guidelines to the cancer referral guidelines. It is important to note that the cancer referral guidelines are not mutually exclusive and if there are red flag symptoms in people of any age then a pragmatic approach is needed as to the urgency of investigation. A haemoglobin this low is not normal and should ring alarm bells, and needs to be investigated urgently. GI malignancy is the most pressing thing to exclude in this gentleman and as such an OGD and colonoscopy are the most appropriate next tests, given that he has no other symptoms.

Question 24

A 6-year-old child is brought to the emergency department by his mother. A couple of hours ago, he started crying uncontrollably and shaking his hands, complaining about how painful they are. He has recently come off with a flu-like illness, but a COVID swab is negative. He is otherwise well and up-to-date with all of his vaccinations. His family history is unknown as he is adopted, but he is of Afro-Caribbean descent.

Which one of the following is the gold standard investigation to confirm the likely underlying diagnosis?

• Blood film
• Bone marrow biopsy
• Haemoglobin electrophoresis
• Serum-free light chain assay
• JAK2 mutation panel

Answer 24

The definitive diagnosis of sickle cell disease is by haemoglobin electrophoresis.

During these crises, the sickle-shaped red blood cells occlude the vessels causing momentary ischemia. The treatment is supportive, with analgesia and abundant fluids. These crises are usually triggered by infection, dehydration or deoxygenation. In this case, the child has come off with a flu-like illness, probably exacerbating the crisis. A formal diagnosis of sickle cell disease is executed by haemoglobin electrophoresis, which will show the presence of two HbSS.

• A blood film is used to visualise the shape of red blood cells. This can be helpful in the diagnosis of sickle cell disease, as the cells will have a classical ‘target’ appearance. But the definitive diagnosis of sickle cell disease can only be done by haemoglobin electrophoresis.
• Bone marrow biopsy is diagnostic for multiple conditions affecting the bone marrow such as myelofibrosis. Usually, these conditions cause bone marrow failure, resulting in leukopenia, thrombocytopenia and anaemia. This patient does not complain of any of these features.
• Serum-free light chain assay is used to diagnose multiple myeloma. This condition is characteristic of the 6th decade of life and presents with bone disease, infection, hypercalcaemia and renal failure, making the diagnosis unlikely.
• A JAK2 mutation panel is used to diagnose polycythaemia vera, a myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume. This causes hyperviscosity that can cause pruritus and arterial occlusion. But this condition is usually seen in older patients and does not usually have such acute crisis, making this diagnosis unlikely.

Question 25

A 40-year-old female patient diagnosed with sickle cell anaemia had complicated recurrent hospital admissions with a recent episode where she suffered from acute severe pain affecting both her arms, pain when breathing in and out as well as extreme tiredness. She was seen in the haematology clinic as an outpatient to optimise the management of her underlying condition to reduce the incidence of such complications. Which of the following medications should this patient be commenced on? * Deferoxamine * Folic acid * Hydroxycarbamide * Penicillin V * Vitamin D

Answer 25

Sickle cell patients should be started on long term hydroxycarbamide to reduce the incidence of complications and acute crises. Hydroxycarbamide reduces the frequency of painful episodes and the risk of life-threatening illness or death. However, it can also increase your risk of infections. It is advised not to be taken in pregnancy. Hydroxycarbamide essentially makes your red blood cells bigger, stay rounder and more flexible. Therefore, less likely to turn into a sickle shape. This is achieved by increasing a special kind of haemoglobin called haemoglobin F. Folic acid taken regularly in anaemia raises haemoglobin levels and helps provide a healthy reticulocyte response. However, the use of folic acid in patients with sickle cell disease is not well supported by primary literature. Deferoxamine is an iron chelation therapy used in sickle cell disease to enhance iron excretion and removes excessive tissue iron in regularly transfused patients with sickle cell disease. Vitamin D deficiency has been shown in 98 per cent of patients with sickle cell disease. As a result of low bone density, patients may develop osteonecrosis, chronic inflammation and related pain. Therefore whilst vitamin D supplementation is important, hydroxycarbamide has a more crucial role in reducing the incidence of complications and acute crises. Penicillin V helps prevent life-threatening infections, particularly in patients who have undergone a splenectomy, which is not the case here.

Question 26

A 13-year-old boy is brought to the emergency department by his fathers. The boy complains of chest pain. On examination, he is short of breath and has a blue tinge on his lips. He was adopted from sub-Saharan Africa and little is known about his family history other than a 'blood condition' in his maternal grandmother. His vital signs show that he is hypoxic, tachypnoeic, and has a fever. A chest x-ray shows bilateral full-field opacification. A subsequent blood smear shows Howell-Jolly bodies and he is treated with an exchange transfusion. Given the likely underlying diagnosis leading to this presentation, what is the method for definitive diagnosis? * Autoantibody screen * Flow cytometry * Full blood count and reticulocyte count * Haemoglobin electrophoresis * Repeat blood smear

Answer 26

Definitive diagnosis of sickle cell disease is by haemoglobin electrophoresis --- This boy has presented with a worrying picture of desaturation. His vague family history, and presence of abnormal cells on a blood smear point towards an underlying haematological problem. Howell-Jolly cells are characteristic of sickle cell disease. In this context, his current presentation may be due to acute chest syndrome - which is a vaso-occlusive crisis of pulmonary vasculature. This leads to pain, shortness of breath, fever, and hypoxia. It is an indication for exchange transfusion in those with sickle cell disease. Whilst presentation with a known complication of sickle cell, and the findings on his blood smear point towards sickle cell disease, he still requires definitive diagnosis. Haemoglobin electrophoresis is the test of choice. This is where a gel medium and electricity are used to separate out different types of haemoglobin. The presence of haemoglobin S will be indicative of the diagnosis. Autoantibodies are not useful in the diagnosis of sickle cell disease, as it is not an autoimmune disorder. Flow cytometry is a technique used to quantify the number of cells, but it is not useful in the diagnosis of sickle cell disease. A full blood count and reticulocyte count can give clues to the diagnosis. However, it is not specific enough to be a definitive diagnosis. A repeated blood smear may be carried out, but there is always a margin of error, and therefore a more reliable method is required for definitive diagnosis.

Question 27

A 32-year-old man has recently registered to your practice. He attended to the surgery for a pre-employment medical examination. He is fit and well. He has a past medical history of sickle cell disease. His immunisation record shows that he was last given the pneumococcal polysaccharide vaccine five years ago. How often should he be given the vaccine? * Every 12 months * Every 2 years * Every 3 years * Every 5 years * Every 10 years

Answer 27

Sickle cell patients should receive the pneumococcal polysaccharide vaccine every 5 years The correct answer is 4. For adults with sickle cell disease, they should receive the pneumococcal polysaccharide vaccine every 5 years. For children, they should have the first pneumococcal polysaccharide vaccine at 2 years, then every 5 years. Patients with sickle cell anaemia suffer from hypofunction of the spleen due to recurrent splenic infarction. As a result, they are at high risk of pneumococcus infections.

Question 28

A 14-year-old boy is seen in clinic for his homozygous sickle cell disease status. He has managed with his condition well, and has not had any acute crises for the last three years. However, he has been feeling more tired than usual over the last 6 months, and the doctor decides to organise some routine blood tests. Which of the following combinations of blood results are most likely to be seen in sickle cell patients? * Raised haemoglobin; normal MCV; and normal reticulocytes * Raised haemoglobin; raised MCV; and raised reticulocytes * Normal haemoglobin; raised MCV; and raised reticulocytes * Low haemoglobin; normal MCV; and raised reticulocytes * Low haemoglobin; reduced MCV; and reduced reticulocytes

Answer 28

Low haemoglobin; normal MCV; and raised reticulocytes Sickle cell disease causes a normocytic anaemia with raised reticulocyte count – due to haemolysis Sickle cell disease causes intravascular haemolysis - resulting in a normocytic anaemia. The haemolysis results in a greater drive from the bone marrow to compensate for this loss, causing a rise in reticulocytes (the precursor to mature red blood cells). Therefore option 4 is the correct answer.

Question 29

A 37-year-old female presents to her general practitioner with a 2-month history of progressive fatigue. She has a background medical history of type-1 diabetes mellitus. Her doctor orders a full blood count, which is reported as follows: * Hb78 g/L(115 - 160) * Mean cell volume136 fl(82-100) * Platelets156 \* 109/L(150 - 400) * WBC4.2 \* 109/L(4.0 - 11.0) Based on the above information, testing for which of the following antibodies is most appropriate to aid diagnosis? * Anti-histone antibodies * Anti-tissue transglutaminase (TTG) antibodies * Gastric parietal cell antibodies * Intrinsic-factor antibodies * Lupus anticoagulant

Answer 29

Intrinsic factor antibodies are more useful than gastric parietal cell antibodies when investigating vitamin B12 deficiency, given low specificity of gastric parietal cell antibodies Megaloblastic anaemia (low haemoglobin, raised mean cell volume) can be caused by B12 or folate deficiency and should raise the suspicion of pernicious anaemia. This is an autoimmune condition that causes B12 deficiency resulting in anaemia. Normally, intrinsic factor released from parietal cells of the stomach bind to dietary B12, forming a complex which can be absorbed in the distal ileum. Autoantibodies directed against either intrinsic factor or these gastric parietal cells will impair B12 uptake and result in this megaloblastic anaemia. A firm diagnosis here would require a blood test confirming low B12 levels and the presence of either of these autoantibodies. However, the intrinsic factor antibodies are much more specific for pernicious anaemia, and so this test is more commonly used in practice. Anti-histone antibodies are involved in drug-induced lupus. This can be caused by several drugs, including infliximab, isoniazid, carbamazepine and procainamide. Anti-TTG antibodies are used as a screening test for coeliac disease. Coeliac disease can cause anaemia. However, it tends to be a microcytic (low mean cell volume) anaemia caused by iron deficiency due to malabsorption. Gastric parietal cell antibodies are linked to pernicious anaemia, as mentioned above. However, they have low specificity, meaning that it has a high false-positive rate. Therefore, it is not as reliable for confirming a diagnosis of pernicious anaemia. In clinical practice, intrinsic factor antibodies are preferred over gastric parietal cell antibodies, for this reason. Lupus anticoagulant is part of the spectrum of anti-phospholipid antibodies that are used in the diagnosis of systemic lupus erythematosus (SLE) and anti-phospholipid syndrome.

Question 30

A 56-year-old woman presents to the GP for investigations of 3 weeks history of dyspnea. She is also complaining of a recent history of paraesthesia in her hands. Her past medical history includes type 1 diabetes and hypothyroidism. She is found to be anaemic and has intrinsic factors antibodies. For her most likely diagnosis, which of the following cancers does she predispose to? * Breast carcinoma * Gastric carcinoma * Lung carcinoma * Lymphoma * Ovarian carcinoma

Answer 30

Pernicious anaemia predisposes to gastric carcinoma Gastric carcinoma is the correct answer. Pernicious anaemia (PA) is a disease in which **not enough red blood cells are produced due to a deficiency of vitamin B12.** The most common initial symptom is feeling tired. Other symptoms may include shortness of breath and paraesthesia. Individuals with pernicious anaemia have been suggested to have an excess risk of gastric cancer. Such an association is plausible, as hypochlorhydria, as well as chronic inflammation, are among the mechanisms by which H. pylori is thought to cause gastric cancer. Breast carcinoma is incorrect. The patient does not have any symptoms or signs of breast cancer for example a lump in the breast, dimpling of the skin, nipple discharge It is not associated with pernicious anaemia as presented in this scenario. The patient also does not have any risk factors associated with breast cancer mentioned include hormone replacement therapy during menopause, ionizing radiation, early age at first menstruation, having children late in life or not at all, older age, having a prior history of breast cancer. Lung carcinoma is incorrect. It is not associated with pernicious anaemia as presented in this scenario. The patient does not have common symptoms such as coughing, haemoptysis, weight loss, shortness of breath, and chest pain. She also does not present with risk factors include smoking, family history, radiation exposure and asbestos. Lymphoma is incorrect. It is not associated with pernicious anaemia as presented in this scenario. The history is not consistent with the signs and the symptoms including include enlarged lymph nodes, fever, drenching sweats, unintended weight loss, itching, and constantly feeling tired. There is no risk factor mentioned including Epstein–Barr virus, HIV/AIDS, tobacco smoking and family history. Ovarian carcinoma is incorrect. Symptoms become more noticeable as the cancer progresses. This patient presents 3 weeks from the onset of symptoms which is early for ovarian cancer to be presented. These symptoms may include bloating, pelvic pain, abdominal swelling, and loss of appetite which are not indicated in this case. Risk factors include nulliparity, hormone therapy after menopause, family history. It is usually associated with tumour marker CA125.

Question 31

A 56-year-old woman presents to the GP surgery with a three-month history of fatigue. Her past medical history includes asthma and vitiligo. On examination **she is pale and she has a red, swollen tongue.** Her blood results are as follows. * Hb 98 g/L Male: (135-180) Female: (115 - 160) * MCV110 \* 1015/L(80 - 100) * Platelets160 \* 109/L(150 - 400) * WBC8.6 \* 109/L(4.0 - 11.0) * Reticulocytes0.95%(0.5 - 1.5) Which additional blood test would be most useful in confirming the likely diagnosis? * Anti-endomysial cell antibodies * Anti-mitochondrial antibodies * Anti-tissue transglutaminase antibodies * Gastric parietal cell antibodies * Intrinsic factor antibodies

Answer 31

**Intrinsic factor antibodies** are more useful than gastric parietal cell antibodies when investigating vitamin B12 deficiency, given low specificity of gastric parietal cell antibodies This woman has symptomatic **megaloblastic anaemia associated with glossitis.** This is likely due to **pernicious anaemia** (common in middle aged/older women and **more common** in people with other autoimmune disorders e.g. vitiligo). **Anti-tissue transglutaminase antibodies and anti-endomysial antibodies** are used in the diagnosis of **coeliac disease**. Whilst coeliac disease can cause anaemia including due to low B12 and/or low ferritin, there are no specific symptoms in the question that point towards a diagnosis of coeliac disease. Therefore, the most likely diagnosis remains pernicious anaemia, and intrinsic factor antibodies are more useful as a first-line investigation. **Anti-mitochondrial antibodies** are associated with primary biliary cholangitis and autoimmune hepatitis, and hence not useful as a first line test for investigating B12 deficiency.

Question 32

A 65-year-old woman presents with symptoms of fatigue. Routine blood tests reveal the following: * Hb105 g/L Male: (135-180) Female: (115 - 160) * MCV 104 fL (80-96 fL) * Platelets305 \* 109/L(150 - 400) * WBC9.3 \* 109/L(4.0 - 11.0) Subsequent blood tests reveal positive intrinsic factor antibodies. The diagnosis is discussed with the patient and the question of serious complications is raised. What is a serious potential complication of this condition? * Chronic lymphocytic leukaemia * Gastric cancer * Gastritis * Non-Hodgkin's lymphoma * Oesophageal cancer

Answer 32

Pernicious anaemia predisposes to gastric carcinoma This patient has pernicious anaemia given the macrocytic anaemia and positive intrinsic factor antibodies. Pernicious anaemia is an autoimmune disease that inactivates intrinsic factor and prevents further production. It leads to low vitamin B12 levels and anaemia. The most serious complication that can occur secondary to this condition is gastric carcinoma. Chronic lymphocytic leukaemia is not strongly associated with pernicious anaemia. It would be more likely due to ageing and subsequent genetic mutations. Gastritis is not necessarily a serious complication and would be more likely with other conditions such as Helicobacter pylori infection. Non-Hodgkin's lymphoma is not strongly associated with pernicious anaemia. Like leukaemia, it is more likely related to genetic mutations acquired over time. Oesophageal cancer is not strongly associated with pernicious anaemia. It has been associated with gastro-oesophageal reflux disease and premalignant changes in the transition zone known as Barret's oesophagus.

Question 33

A 71-year-old male attends his general practice with a 3-month history of lethargy. He has also noticed painful cracks in the corners of his mouth. He has a background of psoriasis and has a healthy balanced diet, including meat. Blood tests are taken which show: * Hb105 g/L(135-180) * MCV115 fl(82-100) * Ferritin210 ng/mL(20 - 230) * Vitamin B12130 ng/L(200 - 900) * Folate7.7 nmol/L(\> 3.0) Considering the most likely underlying diagnosis, which type of cancer is he at increased risk of developing? * Colorectal cancer * Gastric cancer * Prostate cancer * Small-cell lung cancer * Thyroid cancer

Answer 33

Pernicious anaemia predisposes to gastric carcinoma This patient has vitamin B12 deficiency and angular cheilitis- these are two common symptoms of pernicious anaemia. A long-term complication of pernicious anaemia is the development of gastric cancer. Studies have reported a two to threefold increased risk of gastric cancer in patients with pernicious anaemia than in healthy controls. Although vitamin B 12 therapy resolves the anaemia, atrophic gastritis remains, which can progress to the development of gastric cancer. * Colorectal cancer is not known to be linked to pernicious anaemia in current literature. * Prostate cancer has not been linked to pernicious anaemia in current literature. * Small-cell lung cancer is not known to be linked to pernicious anaemia. * Thyroid cancer is not known to be more prevalent in patients with pernicious anaemia.

Question 34

A 43-year-old woman on a general medical ward presents with lethargy, memory impairment, poor concentration, and paraesthesia of her arms, hands, and feet. A blood film reveals hypersegmented polymorphs. Her other blood results are included below. She has no significant past medical history and lives with her husband. She eats a varied diet including meat and fish. * Hb111 g/LMale: (135-180) Female: (115 - 160) * MCV110 \* 1015/L(80 -100) * Platelets157 \* 109/L(150 - 400) * WBC3.4 \* 109/L(4.0 - 11.0) * Na+136 mmol/L(135 - 145) * K+3.7 mmol/L(3.5 - 5.0) * Urea3.4 mmol/L(2.0 - 7.0) * Creatinine96 µmol/L(55 - 120) * CRP\<5 mg/L(\< 5) Given the likely diagnosis, what single test would be most specific for investigation? * Anti-Ro antibodies * Anti-TSH antibodies * Gastric parietal cell antibodies * Intrinsic factor antibodies * Thyroid peroxidase antibodies

Answer 34

Intrinsic factor antibodies Intrinsic factor antibodies are more useful than gastric parietal cell antibodies when investigating vitamin B12 deficiency, given low specificity of gastric parietal cell antibodies Intrinsic factor antibodies are far more specific for the investigation of vitamin B12 deficiency. Note here although macrocytic anaemia is present, hypersegmented polymorphs are an early sign of megaloblastic anaemia. Of the tests listed only gastric parietal cell and intrinsic factor antibodies test for a cause of megaloblastic anaemia eg. Vitamin B12 deficiency. Anti-Ro antibodies are associated with systemic lupus erythematosus (SLE), Sjogren's and other rheumatological conditions. They are not associated with vitamin B12 deficiency. Anti-TSH antibodies are associated with Graves' disease whilst thyroid peroxidase (TPO) antibodies are associated with both Graves' and Hashimoto's disease. Although the symptoms of this patient could represent a thyroid pathology, the blood film results point away from this. Thyroid disease would likely result in macrocytic anaemia, but would not account for the hypersegmented polymorphs seen. Gastric parietal cell antibodies are non-specific for investigating vitamin B12 deficiency, the likely diagnosis here. Gastric parietal cell antibodies are therefore incorrect as they are not most specific. Thyroid peroxidase antibodies are associated with both Graves and Hashimoto's disease, and would not account for the hypersegmented polymorphs seen on the blood film. Vitamin B12 is found in meat and fish products, but not found in plants. Dietary B12 deficiency may be seen in vegans or those with gastrointestinal malabsorption.

Question 35

A 64-year-old woman books an appointment to discuss her recent blood results. These were done as part of routine monitoring for her hypertension, she has no symptoms of note. * Hb107 g/LFemale: (115 - 160) * Platelets320 \* 109/L(150 - 400) * WBC4.0\* 109/L(4.0 - 11.0) * MCV107 fl(80-100) * Ferritin50 ng/mL(20 - 230) * Vitamin B12142 ng/L(200 - 900) * Folate9.5 nmol/L(\> 3.0) Based upon these results, which is the most important test to now request? * Faecal calprotectin * Schilling test * Tissue Transglutaminase Antibodies (TTG) * Serum gastric parietal cell antibodies * Serum intrinsic factor antibodies

Answer 35

Intrinsic factor antibodies are more useful than gastric parietal cell antibodies when investigating vitamin B12 deficiency, given low specificity of gastric parietal cell antibodies Pernicious anaemia (PA) is a disease of the stomach that results in vitamin B12 deficiency and macrocytic anaemia. Intrinsic factor antibodies are highly specific but only present in 50-60% of cases. A positive result is diagnostic of PA but is not necessary for a diagnosis. Gastric parietal cell antibodies, whilst highly sensitive for PA, have a low specificity and are not generally tested for. A faecal calprotectin would be an appropriate first line investigation for inflammatory bowel disease. A schilling test involves administering radiolabeled B12. Given that artificial B12 replacement is now widely available it is generally no longer needed. TTG is a first line blood test to investigate coeliac disease, it would be particularly important if there was an iron-deficiency anaemia.

Question 36

A 67-year-old man with a background of stage 5 chronic kidney disease attends an appointment in the nephrology clinic. Over the past year, he has become increasingly short of breath. Blood tests indicated anaemia and low erythropoietin levels. The patient was subsequently commenced on darbepoetin alfa four months ago. The patient describes still feeling very short of breath despite this treatment. He states he has not had any other new symptoms. On examination, the patient has a red inflamed tongue, red dry patches at the corners of his lips, brittle hair and thin flattened nails. A blood film shows hypochromic pencil red cells. What is the most likely reason the patient has not responded to erythropoietin therapy? * Iron deficiency * B12 deficiency * Concurrent haemolytic anemia * Myeloma * Insufficient treatment time with darbepoetin alfa

Answer 36

Iron deficiency. Iron deficiency can cause patients to fail to respond to erythropoietin therapy. Anaemia usually occurs in CKD (chronic kidney disease) when the GFR (glomerular filtration rate) is less than 35ml/min. In advanced chronic kidney disease, stages 4-6 and in the dialysis population, the prevalence of anaemia can be as high as 90%. Anaemia may occur more commonly at earlier stages in patients with co-existent diabetes. There are several different reasons for not responding to erythropoietin therapy, including iron deficiency anaemia, concurrent infection/ inflammation, hyperparathyoid bone disease and aluminium toxicity. Iron deficiency anaemia is the correct answer. This matches with the clinical features, the red sore tongue is known as glossitis, the red dry patches at the corner of the mouth are known as angular stomatitis, the flattened thin nails are known as koilonychia. These signs including the brittle hair are features of iron deficiency anaemia. Additionally, the blood film showing hypochromic pencil red cells is characteristic of iron deficiency anaemia. B12 deficiency can present clinically with glossitis and angular stomatitis also. In more progressive forms it can present with gait abnormalities and paraesthesia due to subacute degeneration of the spinal cord. The blood film here would show a megaloblastic picture with hypersegmented neutrophils. Concurrent haemolytic anaemia is incorrect as this would not account for the clinical features and a blood film here may have schistocytes (red blood cell fragments) and bite cells (red blood cells missing small pieces). Myeloma is incorrect as there are no other features suggestive of this in the clinical scenario. Features of this can be remembered by the acronym CRAB: C: raised calcium, R: renal complications, A: anaemia, B: bone disease. This also would not explain the blood film. Darbepoetin alfa has not been taken for a sufficient length of time' is incorrect, as this would not explain the other clinical features and blood film, as discussed above.

Question 37

A 72-year-old female patient, with a past history of chronic kidney disease (CKD) and type 2 diabetes mellitus, presents to her general practitioner for the results of her annual urinary albumin:creatinine ratio (ACR) test. Her previous results have all been below 3mn/mmol, but on this occasion, it is reported as 4.7mg/mmol. The patient also has the following blood results: * Hb116 g/L115 – 165 g/L * Na+143 mmol/L133–146 mmol/L * K+4.8 mmol/L3.5–5.3 mmol/L * Ca2+(adjusted)2.5 mmol/L2.2-2.6 mmol/L * Mg2+0.9 mmol/L0.7–1.0 mmol/L * Chloride102 mmol/L98-106 mmol/L * Urea5..8 mmol/L2.5 – 7.8 mmol/L * Creatinine96 μmol/ L45–84 μmol/ L * Phosphate1.41 mmol/L1.12 to 1.45 mmol/L What is the most important change which should be made in her management plan, in response to this finding? * Commence an ACE inhibitor * Commence darbepoetin * Commence phosphate binders * Increase the frequency of ACR monitoring to twice yearly * Refer to nephrology

Answer 37

Commence an ACE inhibitor Commence an ACE inhibitor is correct as this should be done In all patients with a clinically raised ACR (\>3mg/mmol) and co-existent diabetes mellitus. Commence darbepoetin is incorrect, for this should only be done if the patient had developed anaemia secondary to her CKD. Commence phosphate binders is incorrect as this should only be done if the patient had developed hyperphosphatemia secondary to her CKD. Increase the frequency of ACR monitoring to twice yearly is incorrect, while it may be agreed with the patient to increase the frequency of ACR monitoring, commencing an ACE inhibitor is of greater importance in her management. Refer to nephrology is incorrect as there is nothing in the question to suggest she needs specialist input.