Studies of plasmas from individuals with
Hageman trait (
factor XII deficiency),
plasma thromboplastin antecedent (PTA,
factor XI) deficiency, Fletcher trait (plasma
prekallikrein deficiency) and
Fitzgerald trait (
high molecular weight-kininogen deficiency) have revealed the importance of these
proteins in blood coagulation. The interactions among them, however, are not fully elucidated. We have studied these reactions by two different approaches. (1) In a purified system,
high molecular weight kininogen was absolutely required for activation of PTA by HF and
ellagic acid (EA). The yield of activated PTA was proportional to the amount of HF, HMW-K, and PTA in the mixtures, suggesting that these three
proteins may form a complex in the presence of EA. (2) In experiments with whole plasma, we took advantage of the adsorption of EA to
Sephadex gels. When normal plasma or plasma deficient in HF, PK, HMW-K or PTA was exposed to
Sephadex-EA and was separated by centrifugation, each supernatant plasma except that deficient in HF shortened the prolonged partial thromboplastin time (PTT) of HF-deficient plasma. Plasma simultaneously depleted of HMW-K, PK and PTA also shortened the PTT of HF-deficient plasma and of plasma depleted of HF and PK, but had virtually no procoagulant effect upon the PTT of plasma depleted of HF and MHW-K. Thus, exposure of HF in plasma to
Sephadex-EA appeared to generate a clot-promoting form of HF in the absence of other
clotting factors, but its expression required the presence of HMW-K.