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Research Article Free access | 10.1172/JCI106145

Studies on a complex mechanism for the activation of plasminogen by kaolin and by chloroform: the participation of Hageman factor and additional cofactors

Derek Ogston, C. Marie Ogston, Oscar D. Ratnoff, and Charles D. Forbes

1Department of Medicine, Case Western Reserve University School of Medicine, and University Hospitals of Cleveland, Cleveland, Ohio 44106

Find articles by Ogston, D. in: PubMed | Google Scholar

1Department of Medicine, Case Western Reserve University School of Medicine, and University Hospitals of Cleveland, Cleveland, Ohio 44106

Find articles by Ogston, C. in: PubMed | Google Scholar

1Department of Medicine, Case Western Reserve University School of Medicine, and University Hospitals of Cleveland, Cleveland, Ohio 44106

Find articles by Ratnoff, O. in: PubMed | Google Scholar

1Department of Medicine, Case Western Reserve University School of Medicine, and University Hospitals of Cleveland, Cleveland, Ohio 44106

Find articles by Forbes, C. in: PubMed | Google Scholar

Published October 1, 1969 - More info

Published in Volume 48, Issue 10 on October 1, 1969
J Clin Invest. 1969;48(10):1786–1801. https://doi.org/10.1172/JCI106145.
© 1969 The American Society for Clinical Investigation
Published October 1, 1969 - Version history
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Abstract

As demonstrated by others, fibrinolytic activity was generated in diluted, acidified normal plasma exposed to kaolin, a process requiring Hageman factor (Factor XII). Generation was impaired by adsorbing plasma with glass or similar agents under conditions which did not deplete its content of Hageman factor or plasminogen. The defect could be repaired by addition of a noneuglobulin fraction of plasma or an agent or agents eluted from diatomaceous earth which had been exposed to normal plasma. The restorative agent, tentatively called Hageman factor-cofactor, was partially purified by chromatography and had an apparent molecular weight of approximately 165,000. It could be distinguished from plasma thromboplastin antecedent (Factor XI) and plasma kallikrein, other substrates of Hageman factor, and from the streptokinase-activated pro-activator of plasminogen. Evidence is presented that an additional component may be needed for the generation of fibrinolytic activity in mixtures containing Hageman factor, HF-cofactor, and plasminogen.

The long-recognized generation of plasmin activity in chloroform-treated euglobulin fractions of plasma was found to be dependent upon the presence of Hageman factor. Whether chloroform activation of plasminogen requires Hageman factor-cofactor was not determined, but glass-adsorbed plasma, containing Hageman factor and plasminogen, did not generate appreciable fibrinolytic or caseinolytic activity.

These studies emphasize the complex nature of the mechanisms which lead to the generation of plasmin in human plasma.

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