formative

Question 1

A 28 year old woman attending the antenatal clinic has a blood count performed with the results as follows: Haemoglobin 82g/L, MCV 87 fl, white cell count 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.

Answer 1

sickle cell anaemia
The detection of HbS (glutamic acid to valine substitution in the beta chain of haemoglobin) indicates that the patient has sickle cell anaemia (homozygous)

(HbS would also have been detected if the patient had sickle trait (heterozygous), but HbA would also have been present. Also, the patient would not be expected to be anaemic on account of sickle trait.)

Question 2

A 28 year old man has a blood count performed with the results as follows: Haemoglobin 152g/L, MCV 65 fl, white cell count 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.

Answer 2

beta thalassaemia trait

The disproportionate reduction in MCV relative to the haemoglobin reflects a haemoglobinopathy trait (heterozygous state) which accompanied by an increase in HbA2 (α2δ2).

Question 3

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: Haemoglobin 82g/L, MCV 94 fl, white cell count 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 3

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 hereditary spherocytosis the likely diagnosis.

Question 4

mechanisn of action of clopidogrel

Answer 4

it is an ADP antagonist

clopidogrel selectively inhibits the binding of adenosine diphosphate (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

mechanism of action of aspirin

Answer 5

it irreversibly inactivates cyclooxygenase 1

This irreversibly stops production of thromboxane which is an important initiator of platelet aggregation.

Question 6

mechanism of action of rivaroxiban

Answer 6

highly selective direct inhibitor of activated factor X

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

Question 7

A 68 year old woman with fatigue has a blood count performed and the results are as follows: Haemoglobin 87g/L, MCV 110 fl, white cell count 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 7

pernicious anaemia

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

–>Paradoxically some patients can present with neuropathy related to B12 deficiency and have apparently normal blood counts.

Question 8

A 58 year old man with fatigue has a blood count performed and the results are as follows: Haemoglobin 77g/L, MCV 90 fl, white cell count 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 8

acute myeloid leukaemia

Marrow failure (resulting in the low Hb, Neutrophil and Platelet count) in acute myeloid leukaemia 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 9

A 52 year old man with a stroke has a blood count performed and the results are as follows: Haemoglobin 140g/L, MCV 90 fl, white cell count 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 9

essential thrombocythaemia

–>a chronic myeloproliferative disorder characterised by excess production of platelets in the bone marrow and an increased risk of thrombosis.

Question 10

Temperature 37.8C pulse 90 bpm, two hours after starting a blood transfusion. Otherwise well with normal blood pressure.

Answer 10

febrile non-haemolytic transfusion reaction

–>Fever but no hemolysis. It is 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 11

92 year old woman who is breathless after receiving a 4 unit red cell transfusion for chronic anaemia.

Answer 11

transfusion associated circulatory overload

->TACO 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 12

48 year old man becoming breathlessness two hours after an infusion of fresh frozen plasma.

Answer 12

transfusion related acute lung injury

TRALI is caused by anti- leucocyte 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 13

A 77 year old asymptomatic man is found to have a lymphocytosis.

Answer 13

chronic lymphocytic leukaemia

-> that is a clonal (neoplastic) disorder of B cells. Many patients will have asymptomatic disease.

Question 14

causes of hereditary thrombophilia

Answer 14

factor V leiden
antithrombin deficiency
protein C deficienct
protein S deficiency

(antiphospholipid syndrome is ACQUIRED)

Question 15

mechanism of sickle cell disease

Answer 15

point mutation in globin gene

->caused by a point mutation in the beta chain and this predisposes the haemoglobin to polymerisation resulting in sickled cells and reduced red cell survival.

Question 16

mechanism of myelodysplasia

Answer 16

acquired DNA mutations in haematopoietic stem cells

-> Myelodysplasia is a stem cell malignancy that results in ineffective haematopoiesis. It can progress to AML.

Question 17

mechanism of hereditary spherocytosis

Answer 17

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 (resulting in spherocytes) and reduced red cell survival

Question 18

A 28 year old woman attending the antenatal clinic has a blood count performed with the results as follows: Haemoglobin 112g/L, MCV 65 fl, MCH 20 pg, white cell count 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.

what test is likely to be diagnostic?

Answer 18

haemoglobin analysis by high performace liquid chromatography (HPLC)

->The mild anaemia in the presence of a normal serum ferritin reflects the dilutional (physiological) anaemia of pregnancy. The normal serum ferritin makes iron deficiency unlikely. The disproportionate reduction in MCV and MCH compared to the haemoglobin indicates the possibility of a haemoglobinopathy trait (heterozygous) which is best investigated by haemoglobin analysis.

Question 19

A 52 year-old asymptomatic, fit man with no significant medical history has a blood count performed with the results as follows: Haemoglobin 200g/L, MCV 81 fl, white cell count 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.

which test is likely to be diagnostic?

Answer 19

JAK2

A high haemoglobin in someone without a history to suggest a secondary polycythaemia should be investigated by the analysis of the JAK2 gene, which has a somatic mutation in up to 95-97% of patients with myeloproliferative polycythaemia (also called polycythaemia rubra vera or primary polycythaemia).

Question 20

A 21 year-old man with fatigue and easy bruising has a blood count performed with the results as follows: Haemoglobin 8.0g/L, MCV 92 fl, white cell count 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.

which test is likely diagnostic?

Answer 20

immunophenotyping by flow-cytometry

The cytopenias and excess of blasts are highly suggestive of an acute leukaemia. Immunophenotyping will clarify the lineage involved (ie myeloid or lymphoid) which is important therapeutically.

Question 21

Uncontrolled production of essentially normally functioning blood cells

Answer 21

polycythaemia rubra vera

-> The red cells production is uncontrolled (unlike secondary polychythaemia where it is controlled by high epo driven by the secondary cause eg hypoxia). The result is an excess of normally functioning red cells. In CLL cells have no useful function.

Question 22

Uncontrolled production of immature blood cells in the bone marrow

Answer 22

acute myeloid leukaemia

-> AML is a bone marrow based malignancy where there is a block in differentiation and an excess of primitive cells accumulate rapidly.

Question 23

Clonal B cell disorder usually resulting in a large number of circulating malignant cells

Answer 23

chronic lymphocytic leukaemia

->CLL is a chronic leukaemia so unlike acute leukaemia 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 (often with smear cells seen on a blood film). Diagnosis is confirmed by peripheral blood immunophenotyping.

Question 24

thrombophilia

Answer 24

an increased thrombotic tendency

Question 25

vitamin K

Answer 25

• absorbed in upper intestine
• responsible for bile salt absorption
• carboxylates specific preformed clotting factors
• is antagonised by warfarin

(is NOT water soluble)

Question 26

A 58 year old lady with a family history of hypothyroidism and atrophic gastritis presents with fatigue, macrocytosis and pancytopenia.

Answer 26

pernicious anaemia

B12 deficiency in patients with pernicious anaemia (autoimmune destruction of gastric parietal cells) 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 27

A 25 year old male has recurrent admissions to hospitals with pain in his legs and chest wall. On one occasion, he became extremely breathless and required a red cell exchange transfusion.

Answer 27

sickle cell anaemia

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

Question 28

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

Answer 28

Von willebrands disease

-> disorder of primary platelet haemostasis due to deficient of von willebrand factor which bridges platelets to sub endothelial collagen following endothelial injury. this affects platelet adhesion at the site of injury

Question 29

A 52 year old lady with non-Hodgkin’s lymphoma is treated with Rituximab. what is the protein target for this drug?

Answer 29

CD20

Rituximab is a humanised monoclonal antibody directed against CD20, expressed on B cells and B cell lymphomas.

Question 30

A 77 year old man with chronic myeloid leukaemia is treated with Imatinib, what is the protein target for this drug?

Answer 30

BCR -ABL 1 tyrosine kinase

Imatinib is a tyrosine kinase inhibitor that is inhibits BCR-ABL-1 protein unique to chronic myeloid leukaemia.

Question 31

A 67 year old man with chest pain and ST-elevated myocardial infarction is treated with aspirin in the ambulance on the way to hospital. what is the protein target for this drug?

Answer 31

cyclooxygenase

spirin is an irreversible inactivator of cyclooxygenase that is required for the production of prostaglandins and thromboxanes for platelet aggregation.

Question 32

Normal prothrombin time, prolonged partial thromboplastin time, normal platelet count, normal fibrinogen.

Answer 32

factor VIII deficiency

An isolated prolonged partial thromboplastin time reflects
- deficiency of factors involved in the ‘intrinsic’ pathway of coagulation
- the presence of an anti-phospholipid antibody (lupus anticoagulant) that is not associated with a bleeding phenotype wasnt an option

Question 33

Prolonged prothrombin time, normal partial thromboplastin time, normal platelet count, normal fibrinogen.

Answer 33

factor VII deficiency

An isolated prolonged prothrombin time reflects deficiency of factors involved in the ‘extrinsic’ (but not ‘common’) pathway of coagulation and the only coagulation factor involved is therefore Factor VII. Deficiencies of common pathway factors (II,V and X) will cause prolongation of both the prothrombin and activated partial thromboplastin time.

Question 34

Prolonged prothrombin time, prolonged partial thromboplastin time, low platelet count, low fibrinogen.

Answer 34

disseminated intravascular coagulation

-> 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 if reflected by an acquired reduction in coagulation factors (including fibrinogen) causing the prolonged clotting times and thrombocytopenia.

Question 35

A 52 year old man has a blood count performed for investigation of mild fatigue: Haemoglobin 100g/L, MCV 94 fl, white cell count 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. management?

Answer 35

steroid therapy
–> The results suggest an autoimmune haemolytic anaemia, front-line treatment of which consists of steroid (1mg/kg of prednisolone per day) and folic acid
- Steroids suppress the autoimmune process and folic acid supplements prevent deficiency which can occur when the red cell turnover is high (evidenced by the reticulocytosis).

Question 36

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

Answer 36

red cell transfusion
-> This lady has pancytopenia due to drug-induced marrow failure (as part of her therapy). Therefore, in the absence of intrinsic haemopoietic cell activity, she requires a red cell transfusion, in the presence of symptoms.