Formative

Question 1

A 58 year old lady with a family history of hypothryoidism and atrophic gastritis presents with fatigue, macrocytosis and pancytopenia. What is the likely diagnosis?

Answer 1

• Pernicious anaemia
• B12 deficiency in patients with pernicious anaemia can present with pancytopenia and not just an isolated macrocytic anaemia. It is not uncommon to elicit a personal or family history of other autoimmune disorders

Question 2

A 25 year old male has recurrent admissions to hospital with pain in his legs and chest wall. On one occasion he became extremely breathless and required a red cell exchange transfusion. What is the likely diagnosis?

Answer 2

• Sickle cell anaemia
• Patients with sickle cell disease can have uncomplicated vaso-occlusive crisis in their musculoskeletal system. Sickle cell crisis in the pulmonary vasculature is a life-threatening emergency that requires prompt therapy with exchange transfusion

Question 3

A 21 year old girl has a history of heavy periods and investigations indicate a defect in primary haemostasis. Her blood count is normal. What is the likely diagnosis?

Answer 3

• Von Willebrand’s disease
• Disorder of primary haemostasis due to deficiency of von Willebrand factor which bridges platelets to sub-endothelial collagen following endothelial injury. This affects platelet adhesion at the site of injury

Question 4

Name an example of an ADP antagonist and describe its mechanism of action

Answer 4

Clopidogrel - selectively inhibits the binding of ADP to its platelet receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. This action is irreversible

Question 5

Name an example of a drug that irreversibly inactivates cyclooxygenase 1 and describe how it does this

Answer 5

Aspirin - this irreversibly stops production of thromboxane which is an important initiator of platelet aggregation

Question 6

Name a drug that is a highly selective direct inhibitor of activated factor X and describe how it does this

Answer 6

Riveroxiban - competitively inhibits factor Xa. Factor Xa along with factor Va for the prothrombinase complex which converts prothrombin to thrombin

Question 7

What is the protein target for Rituximab and what is this drug used for?

Answer 7

• CD20
• Rituximab is a monoclonal antibody directed against CD20 expressed on B cells an B cell lymphomas

Question 8

What is the protein target for Imatinib and what is this drug used for?

Answer 8

• BCR-ABL1 tyrosine kinase
• Imatinib is a tyrosine kinase inhibitor that inhibits the BCR-ABL-1 protein unique to CML

Question 9

A 67 year old man with chest pain and STEMI is treated with aspirin in the ambulance on the way to hospital. What is the protein target for aspirin?

Answer 9

• Cyclooxygenase
• Aspirin is an irreversible inactivator of cyclooxygenase that is required for the production of prostaglandins and thromboxanes for platelet aggregation

Question 10

What is the name for an abnormally low platelet count?

Answer 10

Thrombocytopenia

Question 11

What is the name for an abnormally high neutrophil count?

Answer 11

Neutrophilia

Question 12

If a patient has a normal prothrombin time, prologned APTT, normal platelet count and normal fibrinogen,what is the most likely cause?

Answer 12

• Factor VIII deficiency
• Isolated prolonged APTT reflects deficiency of factors involved in the intrinsic pathway of coagulation (factors VIII and IX) or the presence of an anti-phospholipid antibody that is not associated with a bleeding phenotype

Question 13

If a patient has a prolonged PT, normal APTT, normal platelet count and normal fibrinogen, what is the likely cause?

Answer 13

• Factor VII deficiency
• An isolated prolonged PT reflects deficiency of factors involved in the extrinsic pathway of coagulation and the only coagulation factor involved is therefore factor VII.
• Deficiencies of common pathway factors (II, V, X) will cause prolongation of both PT and APTT

Question 14

If a patient has a prolonged PT, prolonged APTT, low platelet count and low fibrinogen, what is the likely cause?

Answer 14

Disseminated intravascular coagulation is a consumptive coagulopathy due to abnormal activation of the coagulation system with deposition of thrombi in micro and macro vasculature. The consumptive nature of the process is reflected by an acquired reduction in coagulation factors causing the prolonged clotting times and thrombocytopenia

Question 15

Uncontrolled production of essentially normally functioning blood cells. What is this?

Answer 15

Polycythaemia rubra vera

Question 16

Uncontrolled production of immature blood cells in the bone marrow. What is this?

Answer 16

• Acute myeloid leukaemia
• Bone marrow based malignancy where there is a block in differentiation and an excess of primitive cells accumulate rapidly

Question 17

Clonal B cell disorder usually resulting in a large number of circulating malignant cells. What is this?

Answer 17

• Chronic lymphocytic leukaemia
• Unlike AML there is not a block on early differentiation but failure of cell death and so a steady accumulation of cells over time.
• They are produced in bone marrow and seen circulating as an excess of small mature lymphocytes in the blood.
• Diagnosis is confirmed by peripheral blood immunophenotying

Question 18

A 28 year old woman attending the antenatal clinic has a blood count performed with the results as follows: Hb 82g/L, MCV 87 fl, WCC 6.4 x 109/l, neutrophil count 3.8 x 109/l and platelet count 270 x 109/l. Haemoglobin analysis identifies a high level of Hb S without detectable HbA. What is the likely diagnosis?

Answer 18

• Sickle cell anaemia
• The detection of HbS indicates that the patient has sickle cell anaemia. HbS would also have been detected if the patient had sickle cell trait but HbA would also have been present. Also the patient would not be expected to be anaemic on account of sickle trait

Question 19

A 28 year old man has a blood count performed with the results as follows: Hb 152g/L, MCV 65 fl, WCC 6.4 x 109/l, neutrophil count 3.8 x 109/l and platelet count 270 x 109/l. Haemoglobin analysis identifies the presence of raised Hb A2. What is the likely diagnosis?

Answer 19

• Beta-thalassaemia trait
• The disproportionate reduction in MCV relative to the Hb reflects a haemoglobinopathy trait, accompanied by an increase in HbA2 suggests Beta-thal

Question 20

An 18 year old man with fatigue and a family history of a haemolytic disorder has a blood count performed with the results as follows: Hb 82g/L, MCV 94 fl, WCC 5.9 x 109/l, neutrophil count 3.2 x 109/l and platelet count 170 x 109/l. Blood film shows polychromasia and red cells with loss of central pallor.

Answer 20

• Hereditary spherocytosis
• Red cells that have lost central pallor are called spherocytes and an excess of these in a patient with family history of haemolytic anaemia makes HS the likely diagnosis

Question 21

Temperature 37.8C pulse 90 bpm, two hours after starting a blood transfusion. Otherwise well with normal blood pressure. What is the likely cause?

Answer 21

• Febrile non-haemolytic transfusion reaction
• Fever but no haemolysis
• Most commonly caused by antibodies directed against donor leukocytes and HLA antigens present in the patient or donor cytokines present in the transfusion that were released by white cells in the blood that have broken down during storage

Question 22

92 year old woman who is breathless after receiving a 4 unit red cell transfusion for chronic anaemia. What is the likely cause?

Answer 22

• Transfusion associated circulatory overload
• Can occur when patients with chronic anaemia and a compensatory high cardiac output are given a large volume load.
• The result is often pulmonary oedema

Question 23

48 year old man becoming breathlessness two hours after an infusion of fresh frozen plasma. What is the likely cause?

Answer 23

• Transfusion related acute lung injury
• TRALI is caused by anti-leukocyte antibodies present in the donation that bind to the patients white cells and cause acute lung injury by degranulation of the affected neutrophils in the lungs
• Pulmonary infiltrates are seen on CXR

Question 24

A 68 year old woman with fatigue has a blood count performed and the results are as follows: Hb 87g/L, MCV 110 fl, WCC 2.4 x 109/l, neutrophil count 1 x 109/l and platelet count 100 x 109/l. The blood film shows macroovalocytes and hypersegmented neutrophils.

Answer 24

• Pernicious anaemia
• Causes B12 deficiency that will result in impaired nuclear maturation affecting the development of all 3 haemopoietic lineages, so pancytopenia with macrocytic red cell development can occur in deficiency states

Question 25

A 58 year old man with fatigue has a blood count performed and the results are as follows: Hb 77g/L, MCV 90 fl, WCC 22.4 x 109/l, neutrophil count 0.1 x 109/l and platelet count 30 x 109/l. The blood film shows an excess of blasts with Auer rods.

Answer 25

* Acute myeloid leukaemia * Marrow failure in AML is caused due to the **excessive proliferation of primitive cells** (myeloblasts). * **Abnormalities of granulation** in these blasts can be visualised in the form of **Auer rods**

Question 26

A 52 year old man with a stroke has a blood count performed and the results are as follows: Hb 140g/L, MCV 90 fl, WCC 10.4 x 109/l, neutrophil count 6.8 x 109/l and platelet count 930 x 109/l. The blood film shows an excess of platelets with some giant forms

Answer 26

* Essential thrombocythaemia * Chronic myeloproliferative disorder characterised by **excess production of platelets in the bone marrow and an increased risk of thrombosis**

Question 27

A 28 year old woman attending the antenatal clinic has a blood count performed with the results as follows: Hb 112g/L, MCV 65 fl, MCH 20 pg, WCC 6.4 x 109/l, neutrophil count 3.8 x 109/l and platelet count 170 x 109/l. The serum ferritin is within the normal range. How would you investigate this?

Answer 27

* Haemoglobin analysis by high performance liquid chromatography (HPLC) * The mild anaemia in the presence of a normal serum ferritin reflects the dilutional anaemia of pregnancy. The normal serum ferritin makes iron deficiency anaemia unlikely. * The **disproportionate reduction in MCV and MCH compared to the Hb** indicates the possibility of a **haemoglobinoathy trait** which is best investigated by Hb analysis

Question 28

A 52 year-old asymptomatic, fit man with no significant medical history has a blood count performed with the results as follows: Hb 200g/L, MCV 81 fl, WCC 11 x 109/l, neutrophil count 7.2 x 109/l and platelet count 402 x 109/l. Blood film confirms the blood count abnormalities. How would you investigate this?

Answer 28

* **JAK2 gene** mutational analysis * A high Hb in someone without a history to suggest a secondary polycythaemia should be invsestigated by the analysis of the JAK2 gene, which has a somatic mutation in up to 95-97% of patients with myeloproliferative polycythaemia (aka **polycythaemia rubra vera**)

Question 29

A 21 year-old man with fatigue and easy bruising has a blood count performed with the results as follows: Hb 8.0g/L, MCV 92 fl, WCC 50 x 109/l, neutrophil count 0.2 x 109/l and platelet count 40 x 109/l. The blood film shows an excess of blasts. How would you investigate this?

Answer 29

* Immunophenotyping by flow-cytometry * The **cytopenias and excess blasts are highly suggestive of an acute leukaemia**. * **Immunophenotyping will clarify the lineage involved** which is important therapeutically

Question 30

An 18 year old woman with heavy periods has a blood count performed and the results are as follows: Hb 67g/L, MCV 69 fl, WCC 6.4 x 109/l, neutrophil count 4.2 x 109/l and platelet count 495 x 109/l. Serum ferritin is low. She is relatively asymptomatic from her anaemia. How is this best managed?

Answer 30

* Oral iron replacement * Asymptomatic iron deficiency anaemia should be treated with oral iron replacement. * Based on the history and likely cause of iron deficiency anaemia, treatment should also include management of her menorrhagia

Question 31

A 52 year old man has a blood count performed for investigation of mild fatigue: Hb 100g/L, MCV 94 fl, WCC 6.4 x 109/l, neutrophil count 4.2 x 109/l and platelet count 295 x 109/l. There is a reticulocytosis and serum lactate dehydrogenase is raised. Direct antiglobulin test (Coombs’ test) is strongly positive. How is this best managed?

Answer 31

* Steroid therapy * Case suggests an **autoimmune haemolytic anaemia, first-line treatment of which consists of steroid and folic acid.** * Steroids suppress the autoimmune process and folic acid supplements prevent deficiency which can occur when the red cell turnover is high

Question 32

A 67 year old lady has recently completed intensive chemotherapy for acute myeloid leukaemia. She is fatigued and short of breath on minimal exertion. Hb 78g/L, MCV 94 fl, WCC 0.2 x 109/l, neutrophil count 0.1 x 109/l and platelet count 25 x 109/l. How is this best managed?

Answer 32

* Red cell transfusion * This lady has **pancytopenia due to drug-induced marrow failure**. Therefore in the absence of intrinsic haemopoietic cell activity, she requires a red cell transfusion, in the presence of symptoms

Question 33

What is the mechanism behind sickle cell disease?

Answer 33

* Point mutation in globin gene * Caused by a **point mutation in the beta chain** and this predisposes Hb to polymerisation resulting in **sickled cells and reduced red cell survival**

Question 34

What is the mechanism behind myelodysplasia?

Answer 34

* Acquired DNA mutations in haemopoietic stem cells * Myelodysplasia is a stem cell malignancy that results in **ineffective haematopoiesis** * It **can progress to AML**

Question 35

What is the mechanism behind hereditary spherocytosis?

Answer 35

* Congenital mutation in structural red cell proteins * A mutation in one of the structural red cell membrane proteins resulting in reduced red cell deformability and so **membrane is removed in spleen and reduced red cell survival**

Question 36

Vitamin K is water soluble, absorbed in the upper intestine, responsible for bile salt absorption, carboxylates specific preformed clotting factors and is antagonised by warfarin. True or false?

Answer 36

* False * Vitamin K is absorbed in the upper intestine, responsible for bile salt absorption, carboxylates specific preformed clotting factors, is antagonised by warfarin but is **NOT water soluble**

Question 37

A 22 year old lady presenting with fatigue, menorrhagia and a microcytic anaemia. What is the likely diagnosis?

Answer 37

* Iron deficiency anaemia * Most common anaemia and causes a **microcytosis due to a lack of iron delivery to the haem group**

Question 38

A 77 year old asymptomatic man is found to have a lymphocytosis. What is the likely diagnosis?

Answer 38

* Chronic Lymphocytic Leukaemia * Associated with a **lymphocytosis.** * CLL is a **clonal disorder of B cells**. * Many patients will have **asymptomatic disease**

Question 39

A 67 year old man admitted to hospital with back pain, hypercalcemia and renal failure is found to have significant Bence Jones proteinuria. What is the likely diagnosis?

Answer 39

* Multiple myeloma * **Bence-Jones proteins** are found in up to 75% of patients with myeloma and in the urine, reflect the **excretion of immunoglobulin light chains**

Question 40

What does this blood film image show?

Answer 40

Neutrophil - polymorphonuclear leukocyte **(segmented nucleus**)

Question 41

What does this blood film image show?

Answer 41

Eosinophil - **bi-lobed spectacle shaped nuclei** and cytoplasmic granules that typically **stain red**

Question 42

What does this blood film image show?

Answer 42

Monocyte - **horse shaped nucleus** and steel-grey cytoplasm with vacuoles

Question 43

Factor V Leiden, antiphospholipid syndrome, antithrombin deficiency, protein C deficiency, protein S deficiency are causes of hereditary thrombophilia. True or false?

Answer 43

* False * Factor V Leiden, antithrombin deficiency, protein C deficiency, protein S deficiency are causes of hereditary thrombophilia * **Antiphospholipid syndrome is an acquired cause of thrombophilia**