Anticoagulantes : no son realmente efectivos para prevenir las trombosis en el entorno de la HPN. Natural history of PNH. N Engl J Med. Advances in the diagnosis and therapy of paroxysmal nocturnal hemoglobinuria. Blood Rev. Cell ; 73 4
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This phenomenon mainly occurs in those who have the primary form of PNH, who will notice this at some point in their disease course. The remainder mainly experience the symptoms of anemia, such as tiredness, shortness of breath , and palpitations. This is the main cause of severe complications and death in PNH. These may develop in common sites deep vein thrombosis of the leg and resultant pulmonary embolism when these clots break off and enter the lungs , but in PNH blood clots may also form in more unusual sites: the hepatic vein causing Budd-Chiari syndrome , the portal vein of the liver causing portal vein thrombosis , the superior or inferior mesenteric vein causing mesenteric ischemia and veins of the skin.
Cerebral venous thrombosis , an uncommon form of stroke , is more common in those with PNH. These signaling proteins are physically attached to the cell membrane in various ways, commonly anchored by glycolipids such as glycosyl phosphatidylinositols GPI. PNH occurs as a result of a defect in the assembling of these glycolipid-protein structures on the surface of blood cells.
The gene that codes for PIGA is located on the X chromosome , which means that only one active copy of the gene for PIGA is present in each cell initially, females have two copies, but one is silenced through X-inactivation.
When this mutation occurs in a hematopoietic stem cell in the bone marrow, all of the cells it produces will also have the defect. This theory is supported by the fact that these symptoms improve on administration of nitrates or sildenafil Viagra , which improves the effect of nitric oxide on muscle cells.
This hypothesis has been questioned by researchers who note that not all those with PNH have increased hemolysis during sleep, so it is uncertain how important a role sleep actually plays in this disease. In this case, anemia may be caused by insufficient red blood cell production in addition to the hemolysis. 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.
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. Screening[ edit ] There are several groups where screening for PNH should be undertaken.
These include patients with unexplained thrombosis who are young, have thrombosis in an unusual site e. Transfusion therapy may be needed; in addition to correcting significant anemia , this suppresses the production of PNH cells by the bone marrow, and indirectly the severity of the hemolysis. Iron deficiency develops with time, due to losses in urine, and may have to be treated if present.
Iron therapy can result in more hemolysis as more PNH cells are produced. In patients with only a small clone and few problems, monitoring of the flow cytometry every six months gives information on the severity and risk of potential complications. 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.
The U. Food and Drug Administration FDA has issued a black-box warning as those who take the medication have a 1, to 2,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.
Paroxysmal nocturnal hemoglobinuria
Hemoglobinuria nocturna paroxística
Hemoglobinuria paroxística nocturna
Hemoglobinúria paroxística noturna