What is PNH?

PNH (Paroxysmal Nocturnal Hemoglobinuria), is a clonal disease of the stem cell that manifests with acquired, non-immune findings of intravascular hemolysis, bone marrow failure and thrombosis. As PNH is caused by the somatic mutation of the hematopoietic stem cell, it affects all 3 cell lines of the hematopoietic system. PNH is a rare disease. Because PNH is rare and its clinical features may easily be confused with that of other disorders, its real incidence is yet to be known. Although its name implies a benign disorder, a 5-year mortality rate of 35% suggests that the disease should in fact, be considered a malignant condition. In addition to its high rate of mortality, the disease also has a quite high morbidity rate.

The somatic mutation in the PIG-A gene results in a deficiency in certain erythrocyte membrane proteins. These proteins protect the erythrocytes from hemolysis and membrane attack complex generated by complement activation. Hemolysis is intravascular and leads to NO deficiency through capturing of NO by the free hemoglobin released during intravascular, and the release of erythrocyte arginase. The clinical course of PNH largely based on this picture. For this reason, the presence of hemolysis, whether small or extensive, indicates that the underlying destruction is continuing even in patients with no clinical findings, and that it may lead to morbidity or mortality of the patient at a point in the future. Clinical findings caused by intravascular hemolysis are extremely variable and include: general findings pertaining to iron deficiency and anemia, muscular weakness, asthenia, fatigue, decline in quality of life, clinical findings that vary according to thrombosis and the location of thrombosis, renal failure, smooth muscle contractions and dysphagia due to NO depletion, abdominal pain, erectile dysfunction, bone marrow deficiency and clinical findings caused by cytopenia. Thrombosis is the primary cause of mortality. Studies have revealed that hemoglobinuria, dyspnea, chest pain and abdominal pain are complaints and findings that may be indicative of the risk of thrombosis. Studies also indicate that the mean time between the PNH diagnosis and the occurrence of a thromboembolic event is 2,1-2,3 years. The first item in the diagnostic algorithm of PNH is for the physician to consider the possibility of PNH. Presence or history of hemolysis, cytopenia or thrombosis should all be a sign of warning for the physician.


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