Cold Promoted Activation and Factor XII, Prekallikrein and C₁-Inhibitor

Summary

During incubation of plasma in the cold an amidolytic activity due to the kallikrein-α₂-macroglobulin complex appears in the plasma of about 40% of the women under hormonal contraception. The factor XII and prekallikrein activity are significantly increased 151.9% and 112.4% respectively in the cold promoted activation positive plasmas (CPA pos) whereas the activity of C₁-inhibitor is decreased, 76%. The quotient of the product of the C₁-inhibitor and α₂-macroglobulin values divided by the product of the FXII and prekallikrein values is significantly lower in the CPA pos plasma 0.49 than in CPA neg plasma 0.96 (p <0.05). These results alone do not explain the cold promoted activation, since a patient with a C₁-inhibitor as low as 9% showed no increase of the amidolytic activity after a 24 hr incubation at 4° C. However, the addition of purified C₁-inhibitor to a CPA pos. plasma inhibits the cold activation. Heparin at a concentration of 0.5 IU/ml delays the appearance of the amidolytic activity.

Keywords

Cold activation - Prekallikrein - C₁-inhibitor - Factor XII - α₂-macroglobulin

• References

• 1 Schrogie JJ, Solomon HM, Zieve PD. Effect of oral contraceptives on vitamin K dependent clotting activity. Clin Pharmacol Ther 1967; 8: 670-675
• 2 Gjønnaess H. Cold promoted activation of F VII. Occurrence and relation to sex hormones and antifertility compounds. Gynecol Invest 1973; 4: 61-72
• 3 Gjønnaess H. Cold promoted activation of F VII. II Identification of the activator. Thrombos Diathes Haemorrh 1972; 28: 169-181
• 4 Gjønnaess H. Cold promoted activation of F VII. III Relation to the kallikrein system. Thrombos Diathes Haemorrh 1972; 28: 182-193
• 5 Gjønnaess H. Cold promoted activation of F VII. IV Relation to the coagulation system. Thrombos Diathes Haemorrh 1972; 28: 194-205
• 6 Seligsohn U, Østerud B, Brown SF, Griffin JH, Rappaport SI. Activation of human F VII in plasma and in purified systems: Roles of activated F IX, Kallikrein and activated F XII. Clin Invest 1979; 64: 1056-1065
• 7 Østerud B, Laake K, Prydz H. The activation of human factor IX. Thrombos Diathes Haemorrh 1975; 33: 553-563
• 8 Laake K, Østerud B. Activation of purified plasma F VII by human plasmin, plasma kallikrein and activated components of the human intrinsic coagulation system. Thromb Res 1974; 5: 759-772
• 9 Lämmle B, Eichlisberger R, Marbet GA, Duckert F. Amidolytic activity in normal human plasma assessed with chromogenic substrates. Thromb Res 1979; 16: 245-254
• 10 Gallimore MJ, Friberger P. Simple chromogenic peptide substrate assays for determining prekallikrein, kallikrein inhibition and kalli-krein “like”activity in human plasma. Thromb Res 1982; 25: 293-298
• 11 Lämmle B, Tran TH, Duckert F. Assay of F XII clotting activity in heparinized plasma. Am J Clin Pathol 1983; 80: 474-477
• 12 Laurell CB. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal Biochem 1966; 15: 45-52
• 13 Gordon EM, Ratnoff OD, Saito H, Donaldson VH, Pensky J, Jones PK. Rapid fibrinolysis, augmented Hageman factor (F XII), and decreased C₁-esterase inhibitor titers in women taking oral contraceptives. J Lab Clin Med 1980; 96: 762-769
• 14 Van der Graaf S, Koedam JA, Bouma BN. Inactivation of Kallikrein in human plasma. J Clin Invest 1983; 71: 149-158
• 15 Gigli I, Ruddy S, Austen KF. The stoichiometric measurement of serum inhibitor of the first component of complement by the inhibition of immune hemolysis. J Immunol 1968; 100: 1154-1164
• 16 Schreiber AD, Kaplan AP, Austen KF. Plasma inhibitors of the components of the fibrinolytic pathway in man. J Clin Invest 1973; 52: 1394-1401