Lessons from an incidental diagnosis of paroxysmal nocturnal haemoglobinuria

Abstract

Dear Editor, The diagnosis of paroxysmal nocturnal haemoglobinuria (PNH) is usually suspected in patients who develop unexplained haemolytic anaemia, thrombotic episodes or pancytopenia. The report describes an incidental finding of this rare condition during the workup of a young adult with stroke and discusses the clinical implications of such a diagnosis. A 29-year-old male presented with sudden onset of right-sided weakness and speech difficulties. Clinical findings were consistent with a left partial anterior circulation stroke. There were no obvious vascular risk factors or family history of cardiovascular disease although there was history of cocaine abuse 3 years earlier and heavy alcohol intake. He had had an admission 3 years earlier with abdominal pain and was noted to have abnormal liver function tests. This was attributed to excessive alcohol consumption following unremarkable clinical assessment and liver ultrasound. Although he had been unwell with non-specific symptoms, an episode of transient limb weakness, 3 months preceding the admission, could have been related to a transient ischaemic attack. On this admission, full blood count revealed a haemoglobin of 11.4 g/dl, white cell count of 4.8×10/l and platelet count of 95×10/l. Renal screen was normal although the liver function tests showed some abnormalities [gamma glutamyl transferase of 183 U/l (normal range less than 40 U/l) and alanine transaminase of 47U/l (normal range less than 35U/l), normal serum bilirubin]. Computerised tomography (CT) and magnetic resonance imaging confirmed a cerebral infarct. CT angiogram identified a left middle cerebral artery (MCA) primary bifurcation stenosis. There was visible thrombus in the left carotid artery and left MCA. Initially it was thought there was a carotid artery dissection but it was difficult to prove on imaging. A follow-up scan revealed normal blood vessels. The patient was appropriately anticoagulated. This would also be consistent with previous dissection. Other investigations into the potential aetiology of the stroke excluded antiphospholipid syndrome (IgG and IgM anticardiolipin antibodies within normal limits and lupus anticoagulant tests negative) and inherited thrombophilic factors (normal antithrombin, protein C and S levels and negative for prothrombin gene and factor V Leiden mutations). Liver ultrasound to identify the cause of his persistent abnormal liver function tests showed an unexpected finding of large portal venous thrombus, later confirmed with a dual-phase CT abdomen. The finding of non-cirrhotic portal vein thrombosis prompted tests for paroxysmal nocturnal haemoglobinuria and myeloproliferative disorder, two under-recognised causes for this unusual site thrombosis [1]. PNH screen revealed 55% clonal population in the red cells and 80% in the granulocytes by flow cytometry confirming the diagnosis of the acquired haemolytic condition. Janus kinase-2V617F mutation was however not detected. Further laboratory workup for PNH revealed normal lactate dehydrogenase (LDH), reticulocyte count J. Thachil (*) :V. Martlew Department of Haematology, Roald Dahl Haemostasis and Thrombosis Centre, Royal Liverpool University Hospital, L7 8XP, Liverpool, UK e-mail: jeckothachil@yahoo.co.uk