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Activation of factor XII-dependent pathways in human plasma by hematin and protoporphyrin.

Abstract
Intravenous administration of hematin is effective in the treatment of acute exacerbations of the inducible porphyrias. In the course of such treatment, coagulopathies have occurred that are characterized by prolongation of prothrombin time, partial thromboplastin time, and formation of fibrin split products. In experiments in vitro with normal human plasma, we observed that hematin and protoporphyrin activated Factor XII-dependent pathways of coagulation and fibrinolysis, and that they generated kallikrein activity. Incubation of protoporphyrin with purified Factor XII resulted in activation as measured by amidolysis of a chromogenic substrate. Neither coproporphyrin, uroporphyrin, delta-aminolevulinic acid, porphobilinogen, or bilirubin activated Factor XII-dependent pathways. Exposure of serum containing added uroporphyrin, coproporphyrin, and protoporphyrin, but not hematin, to ultraviolet light (405 nm) resulted in activation of the classical pathway of the complement system. On the other hand, exposure of plasma containing uroporphyrin or coproporphyrin to ultraviolet light did not result in activation of Factor XII-dependent pathways.
AuthorsC G Becker, M Wagner, A P Kaplan, M Silverberg, R W Grady, H Liem, U Muller-Eberhard
JournalThe Journal of clinical investigation (J Clin Invest) Vol. 76 Issue 2 Pg. 413-9 (Aug 1985) ISSN: 0021-9738 [Print] United States
PMID4031058 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Lipopolysaccharides
  • Porphyrins
  • Protease Inhibitors
  • Protoporphyrins
  • Heme
  • Hemin
  • Factor XII
Topics
  • Animals
  • Factor XII (blood, radiation effects)
  • Fibrinolysis
  • Heme (analogs & derivatives)
  • Hemin (pharmacology)
  • Hot Temperature
  • Humans
  • In Vitro Techniques
  • Lipopolysaccharides (pharmacology)
  • Partial Thromboplastin Time
  • Porphyrins (pharmacology)
  • Protease Inhibitors (pharmacology)
  • Prothrombin Time
  • Protoporphyrins (pharmacology)
  • Rabbits
  • Ultraviolet Rays

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