Haematology&

BiochemistryRADIA FAHAMI

RACHEL BURNETT

Groups Group 1

Dr Cox

Dr Lally

Dr Mair

Dr McConnell

Dr Mithani

Dr Tillmanns

Group 2

Dr Dhaliwal

Dr Iqbal

Dr Meagher

Dr Phipps

Dr Quine

Dr Tobiasiewicz

Dr Tripath

Group 3

Dr Maronge

Dr Perry

Dr Pickard

Dr Premasundaram

Dr Thomas

Dr Yeoh

Group 4

Dr Ashida

Dr Burton

Dr Ashby

Dr Dekkar

Dr Aldworth

Dr Davies

Dr Jones

Case 1 A 64 year old woman presented to her general practitioner with fatigue and weight gain. Her past medical history is essential hypertension for which she takes Amlodipine 5mg.

FBC showed haemoglobin 125 g/L (reference range 115-160), MCV 90 fL (80-99; 1fL=1 µm3), platelets 54×109/L (150-400), WCC 6.3×109/L (4-11), and neutrophils 4.8×109/L (2-7.5).

1. What else would you ask for in the history given this blood picture ? Any sx of viral infection e.g. cough/cold Bruising/bleeding - generalised coagulopathy Fevers Night sweats Arthralgia Alcohol Risk factors for HIV / Hep C

2. What investigation(s) would you request next?

Rpt FBC, U+E, CRP, LFTs, Clotting screen, TFTs, B12, Folate, Blood film, Autoimmune screen

If this patient had recently immigrated from Zimbabwe, are there any other tests you would consider?

HIV, Hep C, investigate for TB and malaria (or has she recently been treated for it??)

3. What medications can cause this blood picture?

Quinine, Chloroquine, Sulfonamides, Digoxin, Penicillamine, anticonvulsants, chemotherapy agents, Methyldopa, anti-TB drugs, Aspirin, Heparin….and many more

4. In a pregnant patient, at what point in pregnancy would this blood picture be normal?

In 3rd trimester

A blood film confirmed the low platelet count but was otherwise normal. All other blood tests come back as normal. She comes back on a second visit to discuss her blood results and admits to a 2 month history of troubling dyspepsia.

4. What would you do now? Test for H. pylori 5. What is the likely diagnosis?

ITP (secondary to H. pylori infection) 6. Would you repeat the FBC? If so, when? Yes- in 4-6 weeks but would discuss this case with haem first 7. When would you refer such a patient? When would you need to consider admission? Prepare a 5 minute presentation on thrombocytopenia guidelines which should cover these aspects.

Causes of ThrombocytopeniaCauses ExamplesImmune defects Primary immune thrombocytopenia (ITP) or ITP secondary to conditions such

as systemic lupus erythematosus, lymphoproliferative diseases (such as chronic lymphocytic leukaemia), HIV, or hepatitis C infection

Drugs and some vaccines Alcohol, heparin, quinine, trimethoprim, thiazides, gold, valproate, phenytoin, carbamazepine,

Any acute or chronic infection (bacterial, viral, or protozoan) Streptococcus, tuberculosis, mycoplasma, Helicobacter pylori, malaria, Epstein-Barr virus, varicella zoster virus, rubella, HIV, hepatitis C

Bone marrow dysfunction Myelodysplasia, bone marrow infiltration (including leukaemia, lymphoma, myeloma, and metastases), aplastic anaemia, myelofibrosis

Liver disease Any cause (with or without cirrhosis and hypersplenism)

Hypersplenism Any cause of splenomegalyHaematinic deficiency Vitamin B12 deficiency, folate deficiency

Microangiopathic haemolysis Such as disseminated intravascular coagulopathy, thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome

Pregnancy specific Gestational thrombocytopenia, HELLP (haemolysis, elevated liver enzymes and low platelets) syndrome, disseminated intravascular coagulopathy

Case 2 Mariah, an 18-year-old student who recently immigrated from Cyprus, comes to you complaining of general fatigue and occasional dizziness. Mariah has no significant past medical history and is not on any regular medicines. She does not drink alcohol or smoke. On examination, Mariah has pale skin and conjunctiva, strong peripheral pulses and normal cardiovascular system examination. BP is 115/75 mmHg, pulse 90 / minute, and BMI 19.5. Given her clinical symptoms and the findings on physical examination, you suspect that Mariah may have iron deficiency anaemia.

1. What additional questions would you ask her?

Menstrual history, diet, GI symptoms, occult blood loss, FH, enquire about OTC drugs e.g NSAIDs, blood donation

2. What investigations would you request?

FBC, ferritin, B12, folate, ?coeliac

What is the most reliable marker of early iron deficiency?

Ferritin

A full blood count showed haemoglobin 86 g/L (reference range 115-160 g/L), mean cell volume 68 fL (76-96 fL), mean cell haemoglobin 22 pg (27-32 pg), white cell count 8×109/L (4-11×109/L), and platelet count 460×109/L (150-400×109/L). Ferritin is 5mcg/L (6-81 mcg/L) and peripheral blood film done by the lab showed normal reticulocytes.

3. Would you want any further investigations or would you start treatment? If so, what would you give?

Request repeat FBC, iron studies, coeliac screen (if not already done) and HB electrophoresis as ferritin only borderline low so need to confirm true cause of anaemia. Can start Ferrous Sulphate 200mg TDS after bloods done.

4. Regardless of your answer in Q3, if Mariah were to be prescribed oral iron, list 2 tips you would recommend to maximise iron absorption.

Take on empty stomach or with orange juice. Avoid milk/tea/coffee around the time of taking it.

5. What might explain the platelet count?

Possibly due to increased production of endogenous erythropoietin

Laboratory investigations to help differentiate causes of microcytic anaemia

InvestigationIron deficiency anaemia Thalassaemia trait Sideroblastic anaemia

Anaemia of chronic disease

Serum ferritin level Decreased Normal, unless iron overload is present

Increased Normal or increased

Serum iron level Decreased Normal Increased Decreased

Total iron binding capacity

Increased Increased Normal Decreased

Transferrin saturation Decreased Normal Normal Decreased

Haemoglobin electrophoresis and quantitation of haemoglobin A2

Normal Increased haemoglobin A2 in β thalassaemia trait. Normal in α thalassaemia trait

Normal Normal

6. How would you follow up a patient with confirmed iron deficiency anaemia?

7. How would your management change if Mariah had been a 75 year old?

Enquire about bowel habit, do PR, consider OGD/colonoscopy and referral for 2ww

8. When would you consider referring a patient?

Refer patients to a haematology service when the type of anaemia is in doubt, laboratory findings suggest iron deficiency anaemia but there has been a poor response to oral iron supplements, or when further haematological investigations, such as bone marrow examination or an investigation of bleeding state is required.

Refer women to a gynaecologist if there is a structural abnormality on pelvic ultrasonography, menorrhagia unresponsive to medical management, or postmenopausal bleeding

Back to Mariah Haemoglobin electrophoresis was requested and showed the presence of haemoglobin A and haemoglobin A2; haemoglobin A2 concentration was 3.4% (normal <3.5%).

This patient was started on oral iron supplements but her increase in haemoglobin level was less than expected after a month. She denied non-compliance with her treatment. Haemoglobin A2 quantitation was repeated and her haemoglobin A2concentration increased to 3.7%, consistent with the unmasking of β thalassaemia trait by iron therapy. DNA sequencing to confirm diagnosis is not necessary and is only available in specialised laboratories.

She was diagnosed as having both iron deficiency anaemia and β thalassaemia trait. Most patients with β thalassaemia trait are asymptomatic and do not have any abnormal physical findings apart from mild pallor. Although antenatal screening for sickle cell disease and thalassaemia has been carried out routinely in the UK since 2005, it is not performed in some parts of the world.

Case 3 A 76 year old gentleman with a background of mild COPD, ANCA positive vasculitis with chronic glomerulonephritis (diagnosed April 2013) had some bloods requested by the practice nurse which come back showing a FBC with haemoglobin 113 g/L (reference range 135-165), MCV 107 fL (80-99; 1fL=1 µm3), platelets 369×109/L (150-400), WCC 7.3×109/L (4-11), and neutrophils 5.02×109/L (2-7.5). U+Es show a stable CKD picture.

His FBC just over a year ago had shown haemoglobin 129 g/L (reference range 135-165), MCV 91.1 fL (80-99; 1fL=1 µm3), platelets 488×109/L (150-400), WCC 10.9×109/L (4-11), and neutrophils 7.32 ×109/L (2-7.5).

He has come to see you to discuss the blood results :

1. What would you ask him in the history?

Worsening SOB/ other sx of anaemia, neurological sx, diet, alcohol intake, weight loss, risk factors for HIV/hepatitis, sx of hypothyroidism, ensure you confirm drug hx as it might not be updated on the system if he has been having outpatient treatment!

2. What further investigations would you want?

Vit B12, folate, LFTs, TFTs, blood film

3. List the causes of megaloblastic and non-megaloblastic macrocytosis

Megaloblastic:

Vitamin B12 deficiency due to:◦ After surgery such as gastrectomy or ileal resection.◦ Bacterial or parasitic infestation.◦ HIV infection◦ Dietary deficiency, which may occur in strict vegans but, even in them, it is rare.◦ Pernicious anaemia, which tends to be a disease of the elderly

Folate deficiency due to:◦ Dietary deficiency.◦ Malabsorption.◦ Increased demands including haemolysis, leukaemia and rapid cell turnover. Macrocytosis

but without anaemia will develop in 30% of women in late pregnancy unless they take folic acid supplements.

◦ Increased urinary excretion occurs in heart failure, acute hepatitis and dialysis.◦ Drug-induced deficiency includes alcohol, anticonvulsants, Methotrexate, Sulfasalazine and

Trimethoprim but they last only if high-dose and prolonged course.

Non-megaloblastic:

Alcohol abuse is a common cause.

Liver disease.

Severe hypothyroidism.

Reticulocytosis.

Other blood disorders including aplastic anaemia, red-cell aplasia, myelodysplastic syndromes, myeloid leukaemia.

Drugs that affect DNA synthesis, such as Azathioprine.

The patient is asymptomatic and all his blood tests come back normal. You write a letter to his renal consultant for advice about his anaemia. You receive a reply stating that the patient has been on Azathioprine 100mg OD for the past 5 months.

4. How is Azathioprine treatment monitored?

FBC- weekly for first 6 weeks and if stable monthly thereafter for first 6 months, when dose and blood monitoring stable, reduce to 3 monthly. Repeat 2 weeks after a dose change then monthly (as above)

U+Es- every 6 months

LFTs- monthly until dose stable then reduce to 3 monthly

5. When would you want to refer a patient with a macrocytic anaemia?

6. If a patient with macrocytic anaemia had both vitamin b12 and folate deficiency, which would you treat first and why? What is the regime of Vit B12 administration?

Start treating the B12 deficiency before starting folate or the latter may aggravate the B12 deficiency and precipitate subacute combined degeneration of the cord.

Hydroxocobalamin is usually given by parenteral injection in the form of 1 mg in 1 mL. In severe anaemia it may need to be given every week at first but this is changed to once every 3 months and continued for life.

Case 4 You have been called by the lab to inform you that a patient’s routine blood count has shown a neutrophil count of 0.44. The patient is a 52 year old with severe learning disability and retinitis pigmentosa who lives in a care home. He does not take any regular medications. The rest of the FBC shows a haemoglobin 145 g/L (reference range 135-165), MCV 87.5 fL (80-99; 1fL=1 µm3), platelets 193×109/L (150-400), WCC 2.73×109/L (4-11). U+Es and LFTs were all normal.

1. What would you do next?

Call patient’s home and enquire- fevers? Feeling unwell in anyway? Full systems enquiry i.e. cough/cold/dysuria/wounds etc. Plan a home visit and examine all systems including urine dip. Discuss with duty haematologist.

Patient was found to have bilateral conjunctivitis and athletes foot and treated appropriately.

2. When would you repeat the FBC? What other investigations would you request? Repeat same day and then a week later. Also check ANA, LDH, Vit B12, folate, TFTs, serum electrophoresis

All other investigations are normal. The FBC is repeated a week later and shows haemoglobin 156 g/L (reference range 135-165), MCV 87.6 fL (80-99; 1fL=1 µm3), platelets 219×109/L (150-400), WCC 3.3×109/L (4-11) and neutrophils 0.88.

3. What would you do now? Rpt FBC in 4 weeks to monitor, ask carer to call asap if any signs of infection

4. Apart from medications, list other causes of acquired neutropenia Bone marrow infiltration with malignancy, aplastic anaemia, Vitamin B12 / folate/ iron deficiency, Chemotherapy, Radiotherapy, Autoimmune neutropenia, Infections - eg, infectious mononucleosis/ Hepatitis B or C/ HIV/ CMV/ typhoid/malaria, thyroid dysfunction

5. What are the different categories of neutropenia? When would you refer or admit a neutropenic patient? Prepare a 5 minute presentation on neutropenia guidelines which should cover these aspects.

Mild Neutropenia 1.0 – 2.5 x 109/L, Moderate Neutropenia 0.5 – 1.0 x 109/L, Severe Neutropenia <0.5 x 109/L

Biochemistry case 1 50 year old lady attends surgery c/o nausea, thirst, constipation, tatt and generalised muscle aches.

She is previously fit and well other than mild hypertension for which she takes bendroflumethiazide 2.5mg mane and a recent history of a colle’s fracture sustained and treated while on holiday in Greece.

Her current BP is 145/84.

Examination is otherwise unremarkable.

1. Differential diagnosis?

•Hypothyroidism

•Diabetes

•Vitamin D deficiency

•Hypercalaemia

•Heart failure

•Anything else?

What would you do next? Bloods.

Blood results:

Hb 12.5 Na 140 bili 23 Ca 2.89

Wcc5.7 K 5.2 ALP 125 Acca 2.89

Plt 168 Ur 8.2 ALT 38 TSH 2.5

MCV 86 Cr 118 Alb 40 HBA1C 4.7

eGFR 56 Glob 51

What further blood tests would you need?

PTH - 35

Vitamin D -30

What is the cause of hypercalcaemia based on results?

Hyperparathyroidism

Differential diagnosis◦ Primary hyperparathyroidism◦ Familiam (MEN/ FHH)◦ Tertiary hyperparathyroidism (renal disease)◦ Medications (Lithium)

What further Ix?

Calcium excretion index (serum calcium and urinary calcium to be sent at the same time).

Treatment.

Stop bfz

Check and correct dietry calcium excess.

If young and primary hyperparathyroidism likely to have corrective surgery.

Biochemistry case study 2

A 33 year old lady of Pakistani origin comes to see you. She has 2 small children with her,the youngest of which she is still breast feeding.

She c/o feeling tatt, of aching all over her body and of numbness in her hands.

You notice a very slight twitching of her hand when you take her BP.

What is your differential diagnosis?

Anaemia

Diabetes

Hypothyroidism

Hypocalcaemia

Which blood tests would you request?

Tatt screen, haematinics

FBC normal ACCA 1.93 (2.2-2.6)

TFTs normal LFTs normal

U&E normal B12 220 Folate 5.2

What further blood tests would you like from the lab?

PTH 84 Phos 0.75

Vit D 15

What is this lady’s diagnosis?

Hypocalcaemia secondary tovitamin D deficiency.

Predisposing factors?

Breast feeding

Lack of sunlight due to modest dress

Other possible causes - malabsorption

Treatment:

See Vit D deficiency guidelines

Vitamin D 20,000 units orally daily for 14-30 days

Vitamin D 800 units orally daily maintenance.

Check calcium intake is sufficient – may need supplementation.

Biochemistry case study 3 33 year old man attends surgery c/o palpitations, weight loss and sweating. He is previously fit and well. He is a smoker and his current BMI is 19. He has no cough, his palpitations are at rest not on exertion and there is no chest pain or breathlessness associated with the palpitations.

Examination reveals he is afebrile, p105 regular BP110/62, he has no clubbing, is not icteric. His heart sounds are normal and there are no signs of heart failure. Abdominal examination reveals no hepatosplenomegaly

What is your differential diagnosis?

What investigations would you organise?

Results FBC normal ECG sinus tachycardia, no signs LVH

Inflammatory markers normal

TSH <0.5

Free T4 65pmol/L

Free T3 12pmol/L

LFTs normal

eGFR 55

Causes of hyperthyroidism Excess prescribed levothyroxine

Grave’s Disease

Multinodular goitre

Toxic adenoma

Thyroiditis

Medication.

Further investigation Examine for exophthalmos and goitre.

Discuss FHxk drug Hx.

Check thyroid peroxisomal antibodies

Chec

Treatment and referral Prepare a 5 minute presentation on management of hyperthyroidism in primary care.

B-blocker if symptomatic tachycardia.

Start carbimazole if symptomatic: 20mg if T4 >30 &/or T3>10

: 10mgif T422-30 &/or T3 6.9-9.9

If asymptomatic then recheck TFTs 8 weeks

If start treatment recheck TFTs in 8 weeks

Refer all new cases hyperthyroidism to endocrinology

Admit if thyroid storm – hyperthyroid, pyrexia and lowBP

end organ failure (renal, liver or cardiac

fast AF

Biochemistry case 4 58 year old gentleman has routine bloods done prior to his NHS health check at the surgery. He is clinically well, but his eGFR is reduced at 54 with urea 8.9 and creatinine 122.

You look back at last year’s results and see that his renal function had been entirely normal then.

What medication may be contributing?

Diuretics, ace inhibitors, nsaids,

On examination : check BP, examine abdomen to check for palp kidneys, dip urine. Check for rashes.

Next steps?

Recheck U&Es non fasting sample, no red meat for 12 hours prior to repeat test.

Urine sample for ACR.

Frequency of monitoring – repeat after 3 months to confirm diagnosis of CKD3 and check no progression.

Thereafter check yearly or during intercurrent illness.

Management of CKD If ACR >30 start ace inhibitor,

Check CVD risk with correction for CKD3. Start statin if indicated.

Aim for BP 140/85

If deteriorates to CKD 3B or lower need to monitor FBC and bone profile.

Prepare a 5 min presentation on CKD guidelines in particular covering when to consider referral and renal USS

Indications for referral Progressive deterioration in eGFR (>5m/min in 1 year or >10ml/min in 5 years)

Proteinuria

CKD 4 and 5

Suspected renal artery stenosis

Urology referral if suspect renal outflow obstruction