Blood Journal
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In vivo roles of factor XII

  1. Thomas Renné1,2,
  2. Alvin H. Schmaier3,4,
  3. Katrin F. Nickel1,2,
  4. Margareta Blombäck1, and
  5. Coen Maas1,5
  1. 1Division of Clinical Chemistry, Department of Molecular Medicine and Surgery and
  2. 2Center of Molecular Medicine, Karolinska Institutet and University Hospital, Stockholm, Sweden;
  3. Departments of 3Medicine and
  4. 4Pathology, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, OH; and
  5. 5Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands

Abstract

Coagulation factor XII (FXII, Hageman factor, EC = 3.4.21.38) is the zymogen of the serine protease, factor XIIa (FXIIa). FXII is converted to FXIIa through autoactivation induced by “contact” to charged surfaces. FXIIa is of crucial importance for fibrin formation in vitro, but deficiency in the protease is not associated with excessive bleeding. For decades, FXII was considered to have no function for coagulation in vivo. Our laboratory developed the first murine knockout model of FXII. Consistent with their human counterparts, FXII−/− mice have a normal hemostatic capacity. However, thrombus formation in FXII−/− mice is largely defective, and the animals are protected from experimental cerebral ischemia and pulmonary embolism. This murine model has created new interest in FXII because it raises the possibility for safe anticoagulation, which targets thrombosis without influence on hemostasis. We recently have identified platelet polyphosphate (an inorganic polymer) and mast cell heparin as in vivo FXII activators with implications on the initiation of thrombosis and edema during hypersensitivity reactions. Independent of its protease activity, FXII exerts mitogenic activity with implications for angiogenesis. The goal of this review is to summarize the in vivo functions of FXII, with special focus to its functions in thrombosis and vascular biology.

  • Submitted July 17, 2012.
  • Accepted September 11, 2012.
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