Lipoprotein-Associated Coagulation Inhibitor (LACI) Is a Cofactor for Heparin: Synergistic Anticoagulant Action Between LACI and Sulfated Polysaccharides

Lipoprotein-associated coagulation inhibitor (LACI) is a plasma-derived protein that inhibits tissue factor (TF)/factor Vlla-induced coagulation in a factor Xa-dependent manner. The roles of endogenous plasma LAC1 and exogenously added LAC1 and heparin, in the regulation of coagulation, initiated via the intrinsic and extrinsic pathways, were studied using the activated partial thromboplastin time (APTT) and the modified prothrombin time (PT) assays, respectively. Both LACI-depleted plasma and normal plasma have identical APTTs and similar prolongations of the APlT in response to heparin; both are fully anticoagulated (arbitrarily defined as clotting times of > 1 hour) at similar concentrations of heparin. These results indicate that heparin is an effective anticoagulant when coagulation is initiated by the intrinsic pathway and that endogenous LAC1 is not significantly involved in the regulation of this pathway. The PT of normal plasma is only marginally longer than that of LACI-depleted plasma in the absence of heparin, suggesting that endogenous plasma LAC1 has a very limited capacity to inhibit TF-induced clotting. However, in the presence of heparin, the PTs of LACI-depleted plasma and normal plasma are different. Prolongation of the PT occurred only moderately and