Eculizumab produces an immediate and sustained improvement in all symptoms, reducing hemolysis, decreasing risk of thrombosis, and increasing quality of life. Newer therapeutic options, such as stem cell transplantation and the anticomplement antibody eculizumab (Soliris), have radically changed the outlook for patients with PNH. The course of PNH is variable, with the median survival time for an untreated patient being around 10 years. Thrombosis can occur at common sites (e.g., deep veins of lower limb) as well as uncommon sites (e.g., hepatic vein, dermal veins, cerebral veins). Arterial or venous thrombosis is seen in 25% to 40% of patients and is the leading cause of death. Erectile dysfunction is seen in the majority of men with PNH. Upper abdominal pain due to esophageal spasms is a characteristic finding. The most common are fatigue (typically out of proportion to the degree of anemia), shortness of breath, and hemoglobinuria (red urine), especially in the first morning sample ( Figure 1). The clinical features of PNH are shown in Table 1.
In patients with PNH, the absence of CD55 and CD59 results in complement-mediated hemolysis, thrombosis, and pancytopenia. GPI is a bridge protein that binds many proteins on the outside of the cell, including complement-inactivating proteins CD55 and CD59. Patients with PNH lack a protein called glycosylphosphatidylinositol (GPI), normally present on the membrane of blood cells. PNH is seen equally in both sexes, in all races and ages, and at a rate of approximately 5 to 10 cases per million people. Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare, acquired blood disorder that is characterized by hemolysis, thrombosis, and pancytopenia (anemia, leukopenia, and thrombocytopenia) due to bone marrow failure. Family physicians should be aware of indications for paroxysmal nocturnal hemoglobinuria so that they can include this disease in a differential diagnosis and test for it when appropriate. We recommend that all patients with proven aplastic anemia or unexplained hemolysis, thrombosis, or persistent pancytopenia be tested for paroxysmal nocturnal hemoglobinuria, but that patients with cytopenia involving only one or two cell lines not be tested. Given that testing costs several hundred dollars per patient and is a significant expense for the BC health care system, we recommend changes be made to the list of indications for testing. A review of testing at the laboratory found that tests for certain indications, especially cytopenia involving only one or two cell lines (approximately one-third of all tests conducted), did not yield positive results. In British Columbia the vast majority of diagnostic tests for this disorder are conducted at the flow cytometry laboratory at Vancouver General Hospital, where the number of tests per year has increased thirtyfold since 2001. Now that a highly effective treatment is available (eculizumab, a complement inhibitor), the outlook for patients has changed dramatically and it has become more important to include paroxysmal nocturnal hemoglobinuria in a differential diagnosis and to test for it. It is seen equally in both sexes, in all races and ages, and at a rate of approximately 5 to 10 cases per million people.
ABSTRACT: Paroxysmal nocturnal hemoglobinuria is an ultra-rare disorder characterized by hemolysis, thrombosis, and pancytopenia.
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