Immunology Of The Platelet Surface

Platelet-bound IgG, measured by quantitative anti globulin consumption, may be due to: 1. Heteroimmune reactions - the antibody binds to foreign antigen which binds to platelet surface either specifically (quinidine) or (possibly) not. 2. Alloimmune reactions - platelet- specific antigens (PI^A1) are located on glycoproteins IIb- III; HLA antigens are located on two-peptide units similar but not identical to HLA units on lymphocytes. 3. Autoimmune reactions - the antigens have not been identified chemically or serologically but some are present on glycoproteins Ilb-III, others are on other (minor) proteins. 4. Immune complexes - these are presumably bound through the Fc receptor of platelets, the chemical identity of which is not known. 5. “Non-immune” adherence IgG is normally bound to four proteins of the platelet surface, including the major glycoproteins Ilb-III. The binding of supranormal amounts of IgG to normal platelets initiates the release reaction if sufficient is bound; this occurs regardless of which type of reaction outlined above leads to its binding. This results in the release of PF3 and serotonin and the aggregation of the platelets. Complement (C) is bound by some but not all IgG antibodies; immune complexes and fluid-phase activation may also bind it. The site of C3 binding is not known. The fixation of C3 can cause a release reaction similar to that seen with IgG binding. Sufficient bound C3 to mediate this is difficult to attain with normal platelets. Since the platelets of patients with paroxysmal nocturnal hemoglobinuria fix much more C3 for a given level of complement activation, they are much more likely to undergo these reactions than normal cells. This may account for the thrombotic tendency in these patients. Complement may lyse platelets by insertion of the terminal complex through the membrane surface; this is more easily accomplished on PNH than normal platelets.