Alteration of the fibrinogen molecule and its phosphorylation state in myocardial infarction patients undergoing thrombolytic treatment

Fibrinogen was purified by protamine-agarose chromatography from plasma fro m three patients after their submission to hospital due to acute myocardial infarction, The total amount of phosphate bound to fibrinogen and the conc entration of fibrinogen was determined in samples withdrawn immediately aft er submission and after thrombolytic treatment. Streptokinase treatment alm ost totally removed circulating fibrinogen while recombinant tissue plasmin ogen activator spared much of it. In patients treated with streptokinase, t he new circulating fibrinogen was homogenous according to the single alpha- band seen after sodium dodecyl sulphate polyacrylamide gel electrophoresis analysis under reducing conditions, whereas fibrinogen from the recombinant tissue plasminogen activator-treated patient as well as healthy controls e xhibited two alpha-bands in the 66-kDa region. The molar ratios of phosphat e to fibrinogen of healthy controls and commercial fibrinogen were 0.82 (+/ - 0.04) and 0.87 (+/- 0.05), respectively. For two streptokinase-treated pa tients the degree of phosphorylation increased threefold from a normal rang e of 0.97 (+/- 0.11) and 0.67 (+/- 0.09) mol/mol fibrinogen before treatmen t to 3.33 (+/- 0.32) and 1.86 (+/- 0.17) mol/mol in newly formed fibrinogen on day 1. Recombinant tissue plasminogen activator treatment led to a smal ler increase in phosphorylation, from 1.14 (+/- 0.13) pretreatment to 1.65 (+/- 0.11) after treatment on day 1. In conclusion Eye show in this report that after streptokinase treatment of patients with acute myocardial infarc tion, the new Aa-chain of fibrinogen was a homogenous single 66-kDa band on sodium dodecyl sulphate polyacrylamide gel electrophoresis under reducing conditions and that the degree of phosphorylation of plasma fibrinogen was elevated, approaching the theoretical limit of 4 mol phosphate/mol fibrinog en. (C) 2000 Elsevier Science Ltd. All rights reserved.