Interactions of the platelets in paroxysmal nocturnal hemoglobinuria with complement. Relationship to defects in the regulation of complement and to platelet survival in vivo.
The blood cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) have abnormal interactions with complement. The activity of the alternative pathway C3 convertase on the platelets of 9 out of 19 patients with PNH was elevated. 10 patients had C3 convertase activity within the normal range even though 80-95% of their platelets lacked the complement regulatory protein decay accelerating factor (DAF) that is absent from the affected blood cells in PNH. PNH and normal platelets released factor H when C3 was bound to their surfaces. This may account for the apparent regulation of C3 convertase activity on platelets that lack DAF. The abnormal uptake of the membrane attack complex of complement by PNH III erythrocytes was not seen in PNH platelets. 111Indium-labeled platelet survival times were normal in five of eight patients, which suggests that the lack of the membrane attack complex defect results in normal platelet survival in PNH.
D001779:Blood Coagulation Factors / Q000378:metabolism; D001792:Blood Platelets / Q000502:physiology*; D001798:Blood Proteins / Q000378:metabolism; D018958:CD55 Antigens; D002470:Cell Survival; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism; D050577:Complement C3-C5 Convertases / Q000378:metabolism; D003180:Complement C3b Inactivator Proteins / Q000378:metabolism; D017242:Complement Factor H; D003169:Complement Inactivator Proteins / Q000378:metabolism; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000378:metabolism*; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism
D001779:Blood Coagulation Factors; D001798:Blood Proteins; D018958:CD55 Antigens; C493495:CFH protein, human; D003176:Complement C3; D003180:Complement C3b Inactivator Proteins; D003169:Complement Inactivator Proteins; D015938:Complement Membrane Attack Complex; D008565:Membrane Proteins; D017242:Complement Factor H; D003165:Complement System Proteins; D050577:Complement C3-C5 Convertases