Interaction of pregnancy-associated plasma protein-A (PAPP-A) with coagulation: a bioassay for PAPP-A.
The observation that pregnancy-associated plasma protein A (PAPP-A) concentrations are higher in plasma compared to serum obtained from the same patient, together with fact that PAPP-A binds to heparin, prompted us to study the interaction between PAPP-A and the clotting system. It was determined that pure PAPP-A inhibits thrombin-induced coagulation of citrated plasma. The presence of antithrombin III (AT III) was necessary since PAPP-A had no inhibitory effect on coagulation of AT III-depleted plasma. The effect of PAPP-A is thus similar to that of heparin. This property of PAPP-A was used to develop a bioassay. Thrombin-induced polymerization of purified fibrinogen was measured in a spectrophotometer. AT III is a weak inhibitor of polymerization, but its effect is magnified in the presence of PAPP-A or heparin. The residual thrombin activity, when plotted against the concentration of PAPP-A, gives a linear relationship. The assay conditions developed allow maximal sensitivity and reproducibility. The kinetics of inhibition due to PAPP-A and heparin was first order. With this bioassay, activities of PAPP-A molecules isolated by the same technique from different fetomaternal compartments were compared.
A
A
Meisser
A
A
Geinoz
P
P
Bischof
D000990:Antithrombin III / Q000378:metabolism; D001681:Biological Assay; D001777:Blood Coagulation / Q000187:drug effects; D004789:Enzyme Activation; D005260:Female; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D010920:Placenta / Q000032:analysis; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000032:analysis*; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis* / Q000378:metabolism; D013917:Thrombin / Q000037:antagonists & inhibitors*
D011257:Pregnancy Proteins; D000990:Antithrombin III; D006493:Heparin; D013917:Thrombin; D011266:Pregnancy-Associated Plasma Protein-A