A 62-year-old man presents with lethargy. A full blood count is taken and is reported as follows:
What is the most likely diagnosis?
Correct Answer C: Tear-drop poikilocytes = myelofibrosis.
Thrombocytopenia and leucopenia are seen in progressive disease.
Blood films: typical pictures:
Hyposplenism e.g. post-splenectomy:
Iron-deficiency anaemia:
Myelofibrosis:
Intravascular haemolysis:
Megaloblastic anaemia:
A 24-year-old nulliparous female with a history of recurrent deep vein thrombosis presents with shortness of breath. The full blood count and clotting screen reveals the following results:
What is the most likely underlying diagnosis?
Correct Answer D: Antiphospholipid syndrome: (paradoxically) prolonged APTT + low platelets.
The combination of a prolonged APTT and thrombocytopenia make antiphospholipid syndrome the most likely diagnosis.
Antiphospholipid syndrome: Antiphospholipid syndrome is an acquired disorder characterized by a predisposition to both venous and arterial thromboses, recurrent fetal loss and thrombocytopenia. It may occur as a primary disorder or secondary to other conditions, most commonly systemic lupus erythematosus (SLE).
A key point for the exam is to appreciate that antiphospholipid syndrome causes a paradoxical rise in the APTT.
This is due to an ex-vivo reaction of the lupus anticoagulant autoantibodies with phospholipids involved in the coagulation cascade.
Features:
Associations other than SLE:
Management - based on BCSH guidelines:
A 73-year-old man is prescribed cetuximab after being diagnosed with metastatic colorectal cancer.
What target is this monoclonal antibody directed against?
Correct Answer D: Cetuximab - monoclonal antibody against the epidermal growth factor receptor.
Monoclonal antibodies: Monoclonal antibodies have an increasing role in medicine. They are manufactured by a technique called somatic cell hybridization. This involves the fusion of myeloma cells with spleen cells from a mouse that has been immunized with the desired antigen. The resulting fused cells are termed a hybridoma and act as a 'factory' for producing monoclonal antibodies. The main limitation to this is that mouse antibodies are immunogenic leading to the formation of human anti-mouse antibodies (HAMAs). This problem is overcome by combining the variable region from the mouse body with the constant region from an human antibody.
Clinical examples of monoclonal antibodies:
Monoclonal antibodies are also used for:
A 34-year-old female presents due to the development of a purpuric rash on the back of her legs. Her only regular medication is Microgynon 30. She also reports frequent nose bleeds and menorrhagia. A full blood count is requested:
Correct Answer D: The isolated thrombocytopenia in a well patient points to a diagnosis of ITP. The combined oral contraceptive pill does not commonly cause blood dyscrasias.
ITP: Idiopathic thrombocytopenic purpura (ITP) is an immune mediated reduction in the platelet count. Antibodies are directed against the glycoprotein IIb-IIIa or Ib complex. ITP can be divided into acute and chronic forms:
Acute ITP:
Chronic ITP:
Evan's syndrome:
A 26-year-old man with a history of hereditary haemorrhagic telangiectasia is planning to start a family.
What is the mode of inheritance?
Correct Answer D: Hereditary haemorrhagic telangiectasia - autosomal dominant.
Hereditary haemorrhagic telangiectasia: Also known as Osler-Weber-Rendu syndrome, hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant condition characterized by (as the name suggests) multiple telangiectasia over the skin and mucous membranes. Twenty percent of cases occur spontaneously without prior family history.
There are 4 main diagnostic criteria. If the patient has 2 then they are said to have a possible diagnosis of HHT
If they meet 3 or more of the criteria they are said to have a definite diagnosis of HHT:
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