Clinical History
A young man was being studied with a history of episodes of jaundice and dark urine for 12 months. He also reported progressive pallor, weakness and dyspnoea on moderate exertion. His medical history disclosed no abnormal findings.
Imaging Findings
Laboratory tests showed: haemoglobin = 7, 4 g / dl, haematocrit = 21, 3%; myelogram: hypoplastic marrow aspirate with the deposit of iron present. Ham test positive. Flow cytometry: no expression of CD55 and CD59 in 60% of granulocytes and 40% of erythrocytes.
MRI was performed to exclude any hepato-biliary abnormalities. Renal cortex showed high signal on a short TE out-of-phase sequence, compared to the longer TE in-phase sequence consistent with the presence of iron. Iron deposition in liver, spleen, adrenals and medulla results in significantly low signal intensity seen in these organs on MRI, best shown on T2 or T2-weighted images and is related to administration of blood transfusions.
A diagnosis of paroxysmal nocturnal haemoglobinuria was performed. The patient is being treated with serial blood transfusions and corticoids and is referred for allogeneic bone marrow.
Discussion
Paroxysmal nocturnal haemoglobinuria (PNH) is a rare acquired disorder of nonmalignant haematopoietic stem cells, which occurs particularly in young adults with no gender prevalence [1, 2].
It is a chronic disorder caused by a somatic mutation of the X-linked gene PIG-A, which is required for formation of the glycosylphosphatidylinositols - anchor structure of the blood cells walls. Its deficiency results in an inability of erythrocytes to inactivate the surface complement which originates intravascular haemolysis.
The clinical course of PNH is very variable. The classic description is the presence of dark urine during the night, more frequently in episodes lasting 3-10 days.
Bone marrow failure is present in all patients with PNH. Weakness, dyspnoea and pallor are common in chronic haemolysis. Granulocytopenia increases sensitivity to infections. Thrombocytopenia may lead to haemorrhagic complications [2].
Venous thrombosis might occur. Headaches or pulmonary hypertension have been attributed to thrombosis of cerebral and pulmonary microvasculature. About 12% of cases of hepatic vein thrombosis or Budd-Chiari syndrome occur in patients with PNH [2].
Factors reported as precipitating haemolysis include infections, exercise, transfusions, surgery, or iodinated endovenous contrast, but the cause often remains unknown [2, 3].
Progressive chronic renal failure can occur after several years of haemoglobinuria caused by haemosiderin deposition in the proximal convoluted tubules, decreased renal perfusion due to microvascular thrombosis or direct nephrotoxic effect of iron [1]. Other known complications include aplastic anaemia, and leukaemia [3].
The low signal intensity of the renal cortex on MRI T1 sequences is characteristic, giving a typically reversed renal cortex-medulla differentiation. Renal cortex becomes higher in signal on a short TE out-of-phase, comparing to the longer TE in-phase sequence. The liver and spleen are usually of normal signal intensity, unless patients receive repeated transfusions which results in decreased signal intensity on T2 sequences [1, 3].
The diagnosis is mostly clinical and laboratorial and bases on the sensitivity of circulating blood cells to complement mediated lysis. The positivity of the Ham test remains important, however, it must be confirmed by flow cytometry which is considered the more accurate method to quantify the proportion of abnormal cell population (absence or reduced expression of CD59 and CD55 on red blood cells is diagnostic) [2].
Treatment with glucocorticoids and/or androgen is sometimes helpful. Allogeneic bone marrow transplantation is the only curative treatment available, although it is itself associated with high rates of morbidity and mortality [2].
The disease process of PNH is insidious and has a chronic course, with a median survival of about 10.3 years.
Differential Diagnosis List
Paroxysmal nocturnal haemoglobinuria
Sickle-cell disease
Haemolysis due to malfunctioning prosthetic cardiac valve
Paroxysmal cold haemoglobinuria
Aplastic anaemia
Final Diagnosis
Paroxysmal nocturnal haemoglobinuria
