Vasospasm – Hemoglobin release can cause vasospasm by depleting circulating nitric oxide (NO), leading to smooth muscle dystonia, abdominal or muscle pain, pulmonary hypertension, or renal insufficiency.Iron repletion in an iron-deficient patient can increase hemolysis by facilitating production of a large population of PNH RBCs that are highly susceptible to complement lysis. Some individuals have paroxysms of hemolysis that are triggered by infections, inflammatory stimuli, surgery, strenuous physical activity, blood transfusion, or alcohol use. Hemolysis typically occurs at a low level throughout the day and increases at night, as the name of the disease implies. Anemia-related symptoms – Many patients present with persistent or episodic fatigue (which may seem out of proportion to the degree of anemia), weakness, jaundice, or hemoglobinuria (ie, red, pink, or "cola-colored" urine).Hemolysis - The degree of hemolysis and associated manifestations generally correlate with the size (ie, percentage) of the RBC PNH population. Hematologic - PNH is typically associated with anemia-related findings caused by hemolysis of red blood cells (RBCs) bone marrow hypoplasia or dysplasia and folate or iron deficiency may also contribute. Nearly all (>93 percent) were symptomatic and many experienced a poor quality of life, had been hospitalized (23 percent), or were unable to work (17 percent):Ī retrospective review of 220 patients with PNH reported that half had neutropenia and/or thrombocytopenia, with a cumulative incidence of pancytopenia in 15 percent at eight years. Some patients present with venous thrombosis (especially at atypical sites) or have only nonspecific symptoms associated with smooth muscle dystonia, which can cause abdominal pain, erectile dysfunction, renal insufficiency, or pulmonary hypertension.Īn international registry reported clinical findings in 1610 patients with PNH. Many patients present with unexplained hemolytic anemia, fatigue, jaundice, or red/pink/dark urine, while others experience headache, dysphagia, scleral icterus, or confusion. PNH is also associated with aplastic anemia (AA) and, less commonly, with myelodysplastic syndromes (MDS) and can have manifestations of thrombocytopenia and/or neutropenia. PNH-associated hemolysis is associated with a range of symptoms, clinical findings, and complications, including anemia-related findings (eg, dyspnea, fatigue), pain, organ dysfunction, and increased risk for thrombosis. (See "Pathogenesis of paroxysmal nocturnal hemoglobinuria", section on 'PIGA gene mutation'.)Ĭlinical presentation - The clinical presentation of PNH varies between individuals. The equal sex distribution of PNH reflects the fact that somatic cells use only one X chromosome in females, the other X chromosome is inactivated ("lyonized"). The vast majority of cases of PNH are caused by an acquired mutation in hematopoietic stem cells (ie, not a germline mutation) of PIGA, a gene on the X chromosome that is involved with glycosylphosphatidylinositol (GPI) synthesis. There is no known racial or ethnic association, and PNH has been reported worldwide. PNH is mostly a disease of adults, with a median age of onset in the 30s, but childhood cases have been reported. The incidence of clinically significant PNH is estimated to be at least 1 to 10 cases per million population, but this may be an underestimate as some individuals remain undiagnosed. (See "Pathogenesis of paroxysmal nocturnal hemoglobinuria" and "Treatment and prognosis of paroxysmal nocturnal hemoglobinuria".)ĮPIDEMIOLOGY - PNH primarily affects adults, with no clear predilections for geography, race, ethnicity, or sex. Pathogenesis, management, and prognosis of PNH are presented separately.
This topic discusses the clinical manifestations and diagnosis of PNH. Prompt and accurate diagnosis is particularly important since effective complement inhibitors have become available. A subset of patients with PNH have clinically significant aplastic anemia or myelodysplastic syndrome.ĭiagnosis of PNH may be delayed because of its nonspecific clinical features, variable clinical presentation, and rarity. Loss of the GPI-linked complement inhibitors, CD55 and CD59, on red blood cells (RBCs) leads to chronic and/or paroxysmal intravascular hemolysis and a propensity for thrombosis, organ dysfunction, and hypocellular or dysplastic bone marrow. INTRODUCTION - Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disorder in which hematopoietic stem cells and their cellular progeny have reduced or absent glycosylphosphatidylinositol (GPI)-anchored proteins on the cell surface.
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