The Relation of 'Fletcher Factor' to Factors XI and XII

S ummary . Further evidence is presented for the existence of a new coagulation factor which is closely related to Hageman factor (XII) and plasma thromboplastin antecedent, PTA (XI). This factor has been tentatively designated 'Fletcher factor'. Coagulant activity of Fletcher factor was separated from the clotting activity of factors XI and XII by C-M Sephadex column chromatography of intact normal plasma. Other studies showed that the prolonged partial thromboplastin time or plasma recalcification time of Fletcher-deficient plasma could be 'corrected' by prolonged contact with celite, glass, kaolin, or ellagic acid; all are known activators of factor XII. Cytochrome c, known to inhibit the contact activation of factor XII, completely abolished this contact 'correction' of Fletcher-deficient plasma. Thus, the clotting times of plasmas deficient in Fletcher factor (presently found in seven individuals from four unrelated families) are readily corrected by activated factors XII and XI. None of these individuals has any bleeding tendencies.
Fletcher factor activity is deficient in the plasma of newborn infants; the factor is probably produced in the liver and not dependent on vitamin K for its synthesis.