During contact activation of plasma, cleavage of surface-bound Hageman

During contact activation of plasma, cleavage of surface-bound Hageman factor (HF) 1 occurs at two closely situated sites, one within a disulfide loop, termed "site 1", and one outside the disulfide loop, termed "site 2" (1). The result of these cleavages is two forms of active HF (2) which we have given the names a-HF a and fi-HFa. Fig. 1 defines these two forms based on their derivation (last column) and molecular characteristics (first four columns). Although it is known that contact activation of plasma will result in coagulation (via the intrinsic pathway), flbrinolysis, and kinin generation, a quantitative comparison of the ability of each form of HF a to initiate these systems has not been made. We therefore undertook the studies reported here to investigate the relative ability of a-HF a and fi-HF a to activate the HF substrates, prekallikrein and factor XI, in plasma during contact activation. The experiments were performed in whole plasma, rather than with purified components, to follow as closely as possible the events as they would occur during contact activation of plasma. It has been shown that the cleavage of prekallikrein is coincident with its activation by HF~ (3). 2 Activation of factor XI has also been shown to be associated with a proteolytic cleavage of its 80,000 mol wt subunit chains (3-5). Thus, by following the cleavage of radiolabeled prekallikrein and factor XI added to plasma, we could measure their rate of activation. It has recently been reported from this laboratory that during contact activation, a large percentage of the factor XI and a small amount of the prekallikrein in plasma become surface bound (6). We have expanded upon these observations by investigating the influence of the surface on the cleavage of factor XI and prekallikrein and have followed the distribution of these