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A48 year old man presented with intermittent central chest pain and tingling in the left arm of two days’ duration. He had no past medical history of ischaemic heart disease but had been diagnosed with sleep apnoea syndrome 18 months previously and was being treated with continuous positive airway pressure. He was on no medication. General and systemic examination were unremarkable. Resting 12 lead ECG showed sinus rhythm with a normal axis and 1 mm ST segment depression with T wave inversion in the inferolateral leads. He was diagnosed as having acute coronary syndrome and treated with aspirin (300 mg dose immediately followed by 75 mg daily), clopidogrel (300 mg dose immediately followed by 75 mg daily), low molecular weight heparin (1 mg/ kg body weight twice daily), atenolol 50 mg daily, and nitrate infusion. His ECG reverted to normal and he was pain-free. The troponin I measured 12 and 24 hours after admission were found to be 3.9 μg/l and 4.9 μg/l, respectively (normal < 0.1 μg/l) confirming the diagnosis. Thirty six hours after admission the patient complained of frontal headache and blurring of vision followed by bilateral ptosis with complete right ophthalmoplegia. He had a left third cranial nerve palsy with a partial fourth and a partial sixth cranial nerve palsy. Magnetic resonance imaging scan of the head revealed an extensive pituitary tumour extending into the cavernous sinuses with areas of haemorrhage and infarction (below left and right).
Pituitary function tests at that time revealed high prolactin concentrations of 10 072 mu/l, thyroid stimulating hormone 2 mu/l, Free T4 9.8 pmol/l, cortisol 212 nmol/l, luteinising hormone 1.2 iu/l, follicle stimulating hormone 1.1 iu/l, and growth hormone 1.2 mu/l. Aspirin, low molecular weight heparin, and clopidogrel were discontinued. The patient underwent transsphenoidal decompression of the infarcted pituitary; neurosurgery was uncomplicated. Immunocytochemistry was strongly positive for prolactin. An echocardiogram two weeks following neurosurgery revealed normal left ventricular function confirmed by ventriculogram. Selective coronary angiography showed mild generalised diffuse disease with a moderate/severe stenosis in the circumflex proximal to the origin of a large obtuse marginal branch. Four weeks following neurosurgery the patient had a 30% recovery of third and sixth cranial nerve function in the left eye and complete ophthalmoplegia in the right eye.
While the combinations of aspirin/low molecular weight heparin and aspirin/clopidogrel have been shown to be beneficial in acute coronary syndrome, there is no evidence that the use of these three agents in combination have an added beneficial effect without an increase in the risk of major bleeding. The above case serves as a reminder of the possibility of increased bleeding tendency with the use of the above three drugs in combination.
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