In this case, anemia may be caused by insufficient red blood cell production in addition to the hemolysis.Historically, the sucrose lysis test, in which a patients red blood cells are placed in low-ionic-strength solution and observed for hemolysis, was used for screening. If this was positive, the Hams acid hemolysis test (after Dr Thomas Ham, who described the test in 1937) was performed for confirmation. The Ham test involves placing red blood cells in mild acid; a positive result (increased RBC fragility) indicates PNH or Congenital dyserythropoietic anemia. This is now an obsolete test for diagnosing PNH due to its low sensitivity and specificity.Today, the gold standard is flow cytometry for CD55 and CD59 on white and red blood cells. Based on the levels of these cell proteins, erythrocytes may be classified as type I, II, or III PNH cells. Type I cells have normal levels of CD55 and CD59; type II have reduced levels; and type III have absent levels. The fluorescein-labeled proaerolysin (FLAER) test is being used more frequently to diagnose PNH. FLAER binds selectively to the glycophosphatidylinositol anchor and is more accurate in demonstrating a deficit than simply for CD59 or CD55. Classification
PNH is classified by the context under which it is diagnosed:
Classic PNH. Evidence of PNH in the absence of another bone marrow disorder. PNH in the setting of another specified bone marrow disorder such as aplastic anemia and myelodysplastic syndrome (MDS). Subclinical PNH. PNH abnormalities on flow cytometry without signs of hemolysis.
Eculizumab
In 2007, the drug eculizumab was approved for the treatment of PNH. Prior to eculizumab, the median life expectancy of an individual with PNH was approximately 10 years. Since that time, short and mid-term studies of patients on eculizumab demonstrate that the drug returns the patient to a normal life expectancy, improves quality of life, and decreases the need for blood transfusions.Eculizumab is controversial due to its high cost, as it is among the most expensive pharmaceuticals in the world, with a price of US$440,000 per person per year. Eculizumab is a humanized monoclonal antibody that acts as a terminal complement inhibitor. The drug interferes with the formation of the membrane attack complex in erythrocytes by binding to C5, compensating for the loss of protective function that results from CD59 deficiency. This alleviates the primary source of intravascular hemolysis, but it does not reduce the opsonization of erythrocytes caused by CD55 deficiency, so patients who receive this medication often still experience mild to moderate hemolysis. The U.S. Food and Drug Administration (FDA) has issued a black-box warning as those who take the medication have a 1,000 to 2,000-fold greater risk of invasive meningococcal disease. People on eculizumab are strongly advised to receive meningococcal vaccination at least two weeks prior to starting therapy and to consider preventative antibiotics for the duration of treatment. Pegcetacoplan
Pegcetacoplan was approved for medical use in the United States in May 2021. Epidemiology
PNH is rare, with an annual rate of 1-2 cases per million. The prognosis without disease-modifying treatment is 10–20 years.