Paroxysmal hemoglobinuria

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood characterized by the destruction of red blood cells (Hemolysis), blood clots (Thrombosis), and impaired bone marrow function (not making enough of the different types of blood cells). This condition is caused by mutations in the PIGA gene, which is necessary for the synthesis of GPI anchors that attach certain proteins to the cell membrane. In PNH, the absence of these proteins makes red blood cells more susceptible to being destroyed by the complement system, a part of the body’s immune system.

Symptoms and Signs

The most notable symptom of PNH is dark-colored urine, especially in the morning, due to the presence of hemoglobin released from destroyed red blood cells. Other symptoms may include fatigue, difficulty breathing (Dyspnea), anemia, acute and chronic kidney failure, jaundice, and an increased risk for developing blood clots.

Diagnosis

Diagnosis of PNH is typically made through flow cytometry testing of blood samples, which can identify the absence of GPI-anchored proteins on the surface of blood cells. Other tests may include complete blood count (CBC), lactate dehydrogenase (LDH) levels, and a bone marrow exam.

Treatment

Treatment for PNH has significantly improved with the introduction of eculizumab (Soliris), a monoclonal antibody that inhibits the complement system, thereby reducing hemolysis, improving quality of life, and decreasing the risk of thrombosis. Bone marrow transplantation may be considered in severe cases.

Epidemiology

PNH is a rare condition, with an estimated incidence of 1-2 cases per million people per year. It can occur at any age but is most commonly diagnosed in adults in their 30s and 40s.

Prognosis

The prognosis for individuals with PNH varies. Before the advent of treatments like eculizumab, the median survival was approximately 10 years from diagnosis. However, with current treatments, individuals with PNH can have a normal life expectancy, although they must continue treatment indefinitely and remain under medical supervision.