Paroxysmal nocturnal hemoglobinuria
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Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease characterised by aplastic anemia, thrombosis and red urine in the morning due to breakdown of red blood cells.
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Signs and symptoms
As the name implies, the hemoglobin appears in urine in attacks (paroxysms). The symptom in itself is harmless, although excessive hemolysis could cause renal failure.
More importantly, PNH can cause aplastic anemia (decreased production of blood cells) and thrombosis. Aplastic anemia may warrant blood transfusion (transfused blood is not hemolysed), and thrombosis can occur in the vein tree and less commonly in arteries. A very characteristic form of venous thrombosis is Budd-Chiari syndrome, thrombosis of the hepatic vein, and cerebral venous thrombosis.
Many patients with aplastic anemia develop PNH (10-33%), possibly signifying an escape mechanism.
Diagnosis
Traditionally, this was done with Ham's test. Modern methods include flow cytometry for CD55, CD16 and CD59 on white and red blood cells. Dependent on the presence of these molecules on the cell surface, they are classified as Type I, II or III PNH cells.
Pathophysiology
PNH is caused by a mutation in PIG-A, the gene that regulates the productions of the GPI anchor. This molecule links many proteins to the cell membrane, but in blood cells the main GPI-linked molecules are CD16, CD55 and CD59 (CD is an acronym of cluster of differentiation). These molecules protect blood cells from destruction by the complement system.
The exact mechanism of PIG-A mutations is not known. Some studies suggest that these mutations occur frequently in healthy people (Hu et al 2005), although the authors aknowledge that the mutations were not observed in stem cells.
Treatment
Treatment is symptomatic (blood transfusion). Recent research has suggested that prophylactic use of anticoagulants (warfarin) might be warranted.
A new agent, eculizumab, might protect blood cells against immune destruction by inhibiting the complement system (Hillmen et al 2004).
In severe aplasia, bone marrow transplants are occasionally undertaken.
References
- Hillmen P, Hall C, Marsh JC, Elebute M, Bombara MP, Petro BE, Cullen MJ, Richards SJ, Rollins SA, Mojcik CF, Rother RP.Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med 2004;350:552-9. PMID 14762182.
- Hu R, Mukhina GL, Piantadosi S, Barber JP, Jones RJ, Brodsky RA. PIG-A mutations in normal hematopoiesis. Blood 2005;105:3848-54. PMID 15687243.