Protective effect of calcium in the plasmin degradation of fibrinogen and fibrin fragments D

Abstract

Prolonged degradation of fibrinogen by plasmin at calcium chloride concentrations of about 2 mM yields one major fragment D, designated as D(cate) ∗ ∗ cate (= calcium terminal) refers to the final product of plasmin digestion with Ca 2+ present. . This fragment has a MW of 93,000 as derived from the MW of its subunits of 12,000, 38,000 and 43,000. Calcium ions protect D(cate) against further attack by plasmin. After sequestration of calcium ions with EGTA, fragment D(cate) is further degraded to a final fragment D, designated as D(EGTA), with a MW of 80,000 by breakdown of the γ-chain subunit ∗∗ ∗∗ subunits = products obtained after reduction of fragments D. 38,000 MW to 25,000 MW. The varying degrees of degradation of D(cate) in a medium containing no calcium or only traces may account for most of the in vitro heterogeneity of fibrinogen fragment D described in the literature. Similarly, degradation of non-crosslinked fibrin by plasmin depends on the calcium concentration. Prolonged incubation of crosslinked fibrin with plasmin at 2 mM calcium chloride concentration resulted in the formation of a fragment D-dimer, with subunits of MW of 12,000, 43,000 and 75,000, indicating that it is comprised of two molecules of D(cate) which are crosslinked by the γ-subunit of 38,000 MW. The D-dimer also appeared to be plasmin-resistant by virtue of the presence of calcium ions. Both D(cate) and the D-dimer formed at calcium concentrations normally occurring in blood can be expected to represent physiologically important fragments D.