Question 131#

Which one of the following statements regarding heparin-induced thrombocytopaenia (HIT) is correct?

A. A fall in the platelet count of greater than 15% is diagnostic

Correct Answer B: 

Heparin:
There are two main types of heparin - unfractionated, 'standard' heparin or low molecular weight heparin (LMWH). Heparins generally act by activating antithrombin III. Unfractionated heparin forms a complex which inhibits thrombin, factors Xa, IXa, XIa and XIIa. LMWH however only increases the action of antithrombin III on factor Xa.

The table below shows the differences between standard heparin and LMWH:

Heparin-induced thrombocytopaenia (HIT): 

• Immune mediated - antibodies form which cause the activation of platelets
• Usually does not develop until after 5-10 days of treatment
• Despite being associated with low platelets HIT is actually a prothrombotic condition
• Features include a greater than 50% reduction in platelets, thrombosis and skin allergy
• Treatment options include alternative anticoagulants such as lepirudin and danaparoid Both unfractionated and low-molecular weight heparin can cause hyperkalaemia. This is thought to be caused by inhibition of aldosterone secretion

Heparin overdose may be reversed by protamine sulphate, although this only partially reverses the effect of LMWH.

Question 132#

Which one of the following features is least associated with Waldenstrom's macroglobulinaemia?

A. Cryoglobulinaemia

Correct Answer B: 

Waldenstrom's macroglobulinaemia:

Waldenstrom's macroglobulinaemia is an uncommon condition seen in older men. It is a lymphoplasmacytoid malignancy characterized by the secretion of a monoclonal IgM paraprotein.

Features: 

• Monoclonal IgM paraproteinaemia
• Systemic upset: weight loss, lethargy
• Hyperviscosity syndrome e.g. visual disturbance
• Hepatosplenomegaly
• Lymphadenopathy
• Cryoglobulinaemia e.g. Raynaud's

Question 133#

Interferon alpha is a recognized treatment for which one of the following haematological disorders?

A. Acute lymphoblastic leukaemia

Correct Answer D: Interferons (IFN) are cytokines released by the body in response to viral infections and neoplasia. They are classified according to cellular origin and the type of receptor they bind to. IFN-alpha and IFN-beta bind to type 1 receptors whilst IFN-gamma binds only to type 2 receptors. IFN-alpha is produced by leucocytes and has an antiviral action. It has been shown to be useful in the management of hepatitis B & C, Kaposi's sarcoma, metastatic renal cell cancer and hairy cell leukaemia.

Hairy cell leukaemia:

Hairy cell leukaemia is a rare malignant proliferation disorder of B cells. It is more common in males (4:1).

Features:

• Pancytopenia
• Splenomegaly
• Skin vasculitis in 1/3 patients
• 'dry tap' despite bone marrow hypercellularity
• Tartrate resistant acid phosphotase (TRAP) stain positive

Management: 

• Chemotherapy is first-line: cladribine, pentostatin
• Immunotherapy is second-line: rituximab, interferon-alpha

Question 134#

A 17-year-old male is diagnosed with alpha-thalassaemia.

What chromosome is the alpha-globulin genes located on?

A. Chromosome 4

Correct Answer D: 

Alpha-thalassaemia:

Alpha-thalassaemia is due to a deficiency of alpha chains in haemoglobin.

Overview:

• 2 separate alpha-globulin genes are located on each chromosome 16
• Clinical severity depends on the number of alpha chains present
• If 1 or 2 alpha chains are absent then the blood picture would be hypochromic and microcytic, but the Hb level would be typically normal
• Loss of 3 alpha chains results in a hypochromic microcytic anaemia with splenomegaly. This is known as Hb H disease
• If all 4 alpha chains absent (i.e. homozygote) then death in utero (hydrops fetalis, Bart's hydrops)

Question 135#

A woman who is about to commence trastuzumab treatment for breast cancer has an echocardiogram.

Which class of chemotherapeutic agent would predispose her to developing cardiac dysfunction?

A. Vinca alkaloids

Correct Answer C: 

Trastuzumab:

Trastuzumab (Herceptin) is a monoclonal antibody directed against the HER2/neu receptor. It is used mainly in metastatic breast cancer although some patients with early disease are now also given trastuzumab. 

Adverse effects:

• Flu-like symptoms and diarrhoea are common
• Cardiotoxicity: more common when anthracyclines have also been used. An echo is usually performed before starting treatment