A 31-year-old woman, who had previously been well, presented to her General Practitioner after ‘passing blood in her urine’. It was assumed that she had passed a renal stone and had now recovered. She had a similar episode 5 months later where she passed blood for 2 days. She was then referred to a urologist who performed a variety of investigations but found no abnormality to explain her haematuria. She had no further problems until she presented again 12 months later with a prolonged episode of haematuria, symptoms of anaemia, abdominal pain and difficulty in swallowing. At this time her full blood count was abnormal: white blood cells 5.4 × 109/l; neutrophils 2.2 × 109/l; haemoglobin 6.8 g/dl; mean cell volume 69 fl; platelets 123 × 109/l.
What diagnosis would explain all of her features ?
What tests would you perform to establish the diagnosis?
What other tests would you perform?
What is the most feared complication of this disorder?
The diagnosis that explains all of the symptoms and abnormalities is paroxysmal nocturnal haemoglobinuria (PNH).1 The red urine is actually haemoglobinuria not haematuria (there are no intact red cells in the urine – a simple test is to allow the urine to stand for approximately 30 minutes and haematuria will settle whereas haemoglobinuria will not). Patients with PNH have chronic intravascular haemolysis due to the uncontrolled effect of complement on the abnormal red blood cells and this results in intermittent episodes of haemoglobinuria (particularly in the mornings), anaemia due to haemolysis and to iron loss in the urine, and symptoms associated with free haemoglobin in the plasma (dysphagia, abdominal pain and severe lethargy out of keeping with the degree of anaemia).
The diagnostic test for PNH is flow cytometry to assess the expression of glycosyl phosphatidyl inositol (GPI)-linked antigens on the surface of the blood cells (Figure 9.1).2 Flow cytometry was performed using samples from our patient and this confirmed the diagnosis of PNH: 99.5% of her neutrophils were GPI deficient (CD59–, CD16low = PNH phenotype) and 37% of her red cells were GPI deficient (CD59– and CD55–).
(A) Urine passed through the day, showing initially intense haemoglobinuria which clears through the day. (B) Hepatic vein thrombosis. (C) Red cell flow cytometry demonstrating deficiency of CD59 (a GPI-linked antigen) diagnostic of PNH. This case has 28.0% red cells with complete deficiency of CD59 and 3.5% with a partial deficiency. (D) Neutrophil flow cytometry demonstrating 51.7% neutrophils with deficiency of two GPI-linked antigens (CD16 and CD24).
The other tests that should be performed are on markers of haemolysis (reticulocyte count, lactate dehydrogenase, haptoglobins) and haematinics (including folic acid and ferritin). The patient may also require an abdominal ultrasound scan to ...