Question 11#

Which one of the following is not a feature of paroxysmal nocturnal haemoglobinuria?

A. Haemolytic anaemia

Correct Answer E: Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired disorder leading to haemolysis (mainly intravascular) of haematological cells. It is thought to be caused by increased sensitivity of cell membranes to complement (see below) due to a lack of glycoprotein glycosyl-phosphatidylinositol (GPI). Patients are more prone to venous thrombosis.

Pathophysiology:

• GPI can be thought of as an anchor which attaches surface proteins to the cell membrane
• Complement-regulating surface proteins, e.g. decay-accelerating factor (DAF), are not properly bound to the cell membrane due a lack of GPI
• Thrombosis is thought to be caused by a lack of CD59 on platelet membranes predisposing to platelet aggregation

Features:

• Haemolytic anaemia
• Red blood cells, white blood cells, platelets or stem cells may be affected therefore pancytopaenia may be present
• Haemoglobinuria: classically dark-coloured urine in the morning (although has been shown to occur throughout the day)
• Thrombosis e.g. Budd-Chiari syndrome
• Aplastic anaemia may develop in some patients 

Diagnosis:

• Flow cytometry of blood to detect low levels of CD59 and CD55 has now replaced Ham's test as the gold standard investigation in PNH
• Ham's test: acid-induced haemolysis (normal red cells would not)

Management:

• Blood product replacement
• Anticoagulation
• Eculizumab, a monoclonal antibody directed against terminal protein C5, is currently being trialled and is showing promise in reducing intravascular haemolysis
• Stem cell transplantation

Question 12#

A 21-year-old man comes for review. He recently had an abdominal ultrasound for episodic right upper quadrant pain which demonstrated gallstones. A full blood count was also ordered which was reported as follows:

• Hb 9.8 g/dl
• MCV 91 fl
• Plt 177 * 10⁹/l
• WBC 5.3 * 10⁹/l

The patient also mentions that his father had a splenectomy at the age of 30 years.

Which one of the following tests is most likely to be diagnostic?

A. Ham's test

Correct Answer D: This patient has hereditary spherocytosis as evidenced by the normocytic anaemia, gallstones and family history.

Hereditary spherocytosis:

Basics:

• Most common hereditary haemolytic anaemia in people of northern European descent
• Autosomal dominant defect of red blood cell cytoskeleton
• The normal biconcave disc shape is replaced by a sphere-shaped red blood cell
• Red blood cell survival reduced as destroyed by the spleen

Presentation:

• Failure to thrive
• Jaundice, gallstones
• Splenomegaly
• Aplastic crisis precipitated by parvovirus infection
• Degree of haemolysis variable

Diagnosis:

• Osmotic fragility test 

Management:

• Folate replacement
• Splenectomy

Question 13#

A 42-year-old female is noted to have a Hb of 17.8 g/dL.

Which one of the following is least likely to be the cause?

A. Polycythaemia rubra vera

Correct Answer D: Haemochromatosis is not associated with polycythaemia. Blood tests typically reveal a raised ferritin and iron, associated with a transferrin saturation of greater than 60% and a low total iron binding capacity.

Polycythaemia:
Polycythaemia may be relative, primary (polycythaemia rubra vera) or secondary.

Relative causes:

• Dehydration
• Stress: Gaisbock syndrome

Primary:

• Polycythaemia rubra vera

Secondary causes:

• COPD
• High Altitude
• Obstructive sleep apnoea
• Excessive erythropoietin: cerebellar haemangioma, hypernephroma, hepatoma, uterine fibroids* To differentiate between true (primary or secondary) polycythaemia and relative polycythaemia red cell mass studies are sometimes used. In true polycythaemia the total red cell mass in males > 35 ml/kg and in women > 32 ml/kg

*Uterine fibroids may cause menorrhagia which in turn leads to blood loss - polycythaemia is rarely a clinical problem

 

Question 14#

Which one of the following is a marker of a bad prognosis in acute lymphoblastic leukaemia?

A. Pre-B phenotype

Correct Answer E: Philadelphia translocation, t(9;22) - good prognosis in CML, poor prognosis in AML + ALL.

Acute lymphoblastic leukaemia: prognostic features:

Good prognostic factors:

• French-American-British (FAB) L1 type
• Common ALL
• Pre-B phenotype
• Low initial WBC

Poor prognostic factors:

• FAB L3 type
• T or B cell surface markers
• Philadelphia translocation, t(9;22)
• Age < 2 years or > 10 years
• Male sex
• CNS involvement
• High initial WBC (e.g. > 100 * 10⁹/l)
• Non-Caucasian

 

Question 15#

A 34-year-old man who is HIV positive is starting treatment for Burkitt's lymphoma. His chemotherapy regime includes cyclophosphamide, vincristine, methotrexate and prednisolone. Around 24 hours after starting chemotherapy he becomes confused and complains of muscle cramps in his legs.

Which one of the following is most likely to have occurred?

A. Prednisolone-induced psychosis

Correct Answer E: Burkitt's lymphoma is a common cause of tumour lysis syndrome.

Tumour lysis syndrome occurs as a result of cell breakdown following chemotherapy. This releases a large quantity of intracellular components such as potassium, phosphate and uric acid. 

Burkitt's lymphoma:

Burkitt's lymphoma is a high-grade B-cell neoplasm. There are two major forms:

• Endemic (African) form: typically involves maxilla or mandible
• Sporadic form: abdominal (e.g. ileo-caecal) tumours are the most common form. More common in patients with HIV

Burkitt's lymphoma is associated with the c-myc gene translocation, usually t(8:14). The Epstein-Barr virus (EBV) is strongly implicated in the development of the African form of Burkitt's lymphoma and to a lesser extent the sporadic form.

Management is with chemotherapy.

This tends to produce a rapid response which may cause 'tumour lysis syndrome'. Complications of tumour lysis syndrome include:

• Hyperkalaemia
• Hyperphosphataemia
• Hypocalcaemia
• Hyperuricaemia
• Acute renal failure