重型地贫的诊断和治疗-20140314-广州程重点.ppt

* * Da die physiologischen Eisenverluste nur 1-2 mg pro Tag betragen, mit jedem Erythrozytenkonzentrat jedoch 200-250 mg, also eine Halbjahresration an Eisen zugeführt wird, mu? es auf Dauer zwangsl?ufig zur Eisenüberladung kommen. In patients who are iron-overloaded the capacity of serum transferrin to bind iron may be exceeded, which means that NTBI may circulate in the plasma. This unbound iron, which is carried in the iron storage protein ferritin, can promote the generation of free hydroxyl radicals, which propagate oxygen-related tissue damage. Additionally, insoluble iron complexes called hemosiderins may become deposited in body tissues causing toxicity and death. Cardiac failure is a major, life-threatening complication of iron overload.1 Iron deposition can cause myocarditis and cardiac fibrosis.2 Myocardial fibrosis typically develops after a cumulative dose of approximately 100 units of blood.3 Symptoms of heart failure imply advanced disease and patients with iron-associated congestive heart failure or severe arrhythmias typically survive less than a year.3 There are a number of other possible complications of iron overload: Excess iron deposition in the liver can lead to fibrosis/cirrhosis or cancer, and diabetes mellitus may occur as a result of β-cell destruction secondary to iron overload in the pancreas Excess iron overload in the pituitary may cause growth failure due to hypogonadism and infertility due to reduced gonadotropin levels. References Borgna-Pignatti C et al. Ann NY Acad Sci 1998;850:227–231. Ishizaka N et al. Circulation 2002;106:1840–1846. Hershko C Weatherall DJ. Crit Rev Clin Lab Sci 1988;26:303–345. * Patients were divided into three hemosiderosis groups: (1) mild (2000 ?g/L) 49%, (2) moderate (2000-4000 ?g/L) 28%, and (3) severe (4000 ?g/L) 23%. Statistically significantly different survival probabilities were found between groups with mild, moderate, or severe hemosiderosis (P0.001). Effective management with improved chelat