High molecular weight kininogen: Its inability to correct the clotting of kininogen-deficient plasma after cleavage of bradykinin by plasma kallikrein, plasmin or trypsin

Human high molecular weight (HMW)-kininogen was cleaved with trypsin, plasmin or plasma kallikrein to release bradykinin. ‡ ‡ ACD, acid citrate dextrose; BAEe, benzoyl arginine ethyl ester; HMW, high molecular weight; LBTI, lima beam trypsin inhibitor; LMW, low molecular weight; PKA, prekallikrein activator; PTT, partial thromboplastin time; QAE, quarternary aminoethyl; SBTI, soy bean trypsin inhibitor; SDS, sodium dodecyl sulfate. When an excess of enzyme was used and all releasable peptide was released, the residual HMW-kininogen could not correct the clotting deficiency of kininogen-deficient plasma. There was an inverse relationship between the amount of bradykinin released and the capacity of the kininogen to correct the abnormal partial thromboplastin time of kininogen-deficient plasma. These findings and earlier ones indicate that the intact HMW-kininogen molecule is required for contact mediated clotting and activation of factor XII.