Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_104_библиотеки_им_акад_М_И_Перельмана

Unfortunately, worldwide use of these monoclonal com­plement inhibitors is precluded by its high cost. Furthermore, the clinical response is not uniform in all patients. There are several reasons for this variability. First of all, in some cases, the anemia is due not only to hemolysis, but also to BMF with C5inhibitors acting on the former, but not on the latter. Second, in all patients, there is extravascular hemolysis, which occurs because, in the absence of the drug, C3 bound to PNH red blood cell membranes leads to C5 activation and complement- mediated intravascular cell lysis. When C5in blocked iatrogenically, cell lysis does not occur; however, red blood cells become opsonized by C3molecules and are in turn phagocytosed in the reticuloendothelial system. As a result of this iatrogenic opsonization process, the Coombs test becomes positive (typically, it is negative in untreated PNH). Of note, the extent of C3 binding to PNH red blood cells has been shown to correlate with homozygosity for the rare L allele at the complement 1 receptor locus. Thus, the L/L (as opposed to L/H or HH) genotype is associated with lesser response to treatment with eculizumab and higher blood transfusion requirements in patients with PNH. As a result of extravascular hemolysis, approximately 80% of patients do not achieve normal Hb and half of patients still require blood transfusion and, because they no longer lose iron through hemoglobinuria, they are now at risk of iron overload and may require iron chelation. However, it is important to note that these patients still benefit from the abrogation of intravascular hemolysis and the consequent symptoms mentioned above.