Pregnancy-associated plasma protein-A (PAPP-A) inhibits thrombin-induced coagulation of plasma

Concentrations of immunoreactive PAPP-A have been found significantly lower in the serum as compared to heparin or EDTA plasma from the same patients. After coagulation significant amounts of PAPP-A remain associated with the clot. Purified PAPP-A inhibits thrombin induced coagulation of plasma. This inhibition cannot be attributed to a direct effect of PAPP-A on thrombin. It is exerted via an activation of endogenous antithrombin III since the inhibitory effect of PAPP-A on thrombin induced coagulation in a euglobulin system can be observed only if antithrombin III is added. The fact that protamine sulphate is capable of neutralizing the inhibitory effects of PAPP-A made us postulate that PAPP-A, like heparin, possesses strongly acidic residues which bind to protamine.