Effects of Heparin and α₁-Acid Glycoprotein on Thrombin or Activated Thrombofax Reagent-Induced Platelet Aggregation and Clot Formation

Abstract

α₁-Acid glycoprotein (AAG) obtained from ascites and/or pleural fluids exhibited anti-heparin effects in platelet-poor plasma when evaluated by activated partial thromboplastin (Activated Thrombofax Reagent) and heparin-thrombin clotting time assays. An anti-heparin effect for AAG was also demonstrable in platelet-rich plasma (PRP) challenged with thrombin, but only over a limited range of heparin concentrations; at elevated heparin concentrations, and only in the presence of AAG, both platelet aggregation and clot formation were substantially inhibited. However, no detectable anti-heparin effect was observed following challenge of PRP with Activated Thrombofax Reagent; indeed, the anti-coagulant effect of heparin appeared synergistically amplified in these systems containing AAG, and AAG exhibited platelet pro-aggregate and pro-coagulant properties in the absence of heparin. The platelet pro-aggregating activity of AAG, though independent of heparin, appeared to require the onset of the coagulation cascade prior to the generation of thrombin; in the absence of such initiation, AAG remained a potent inhibitor of platelet activation.

Different glycoforms of alpha-1-acid glycoprotein contribute to its functional alterations in platelets and neutrophils

“…These results, then, suggest that sAGP‐1 inhibits platelet aggregation by weaker agonists via cAMP–PKA‐mediated signaling (Fig. 8), supporting the claim that AGP‐1 demonstrates antithrombotic effects 28–30 …”

“…8), supporting the claim that AGP-1 demonstrates antithrombotic effects. [28][29][30] Previously, AGP-1 is shown to act via, a family of receptors called Sialic acid binding immunoglobulin like lectins (Siglec), Siglec-5.…”

“…26,27 Contradicting to this, AGP-1 is shown to be a potent inhibitor of platelet aggregation, shown to have antithrombotic activity and offers protection against ischemia/reperfusion injury by preventing apoptosis and inflammation. 20,[28][29][30] Earlier studies have shown that activated TLR-4 triggers prothrombotic effects and that TLR-4 signaling is a potential therapeutic target. [31][32][33][34] In accordance to this, we previously observed that sAGP-1 preferentially inhibits the TLR-4 agonist bacterial LPS, but not TLR-2…”

“…AGP‐1 is shown to interact with plasminogen activator inhibitor type I and stabilizes its activity and is shown to induce platelet shape change and activation, with an impact on thrombosis 26,27 . Contradicting to this, AGP‐1 is shown to be a potent inhibitor of platelet aggregation, shown to have antithrombotic activity and offers protection against ischemia/reperfusion injury by preventing apoptosis and inflammation 20,28–30 …”

Proteomic Characterization of Plasma in Lemierre's Syndrome

“… 37 This is in line with the common finding of thrombocytopenia as a part of Lemierre's syndrome 2 and could potentially be one of the mechanisms through which it develops. Several proteins (e.g., Apolipoprotein A-I, 38 Alpha-1-acid glycoprotein 1 and 2 39 ) identified as differentially expressed in Lemierre's syndrome have been shown to be involved in platelet activation, aggregation, and degranulation. CD44 antigen 40 has been described to upregulate tissue factor, which activates both the extrinsic pathway and platelets, 26 and has been hypothesized to be of importance in adhesion of activated platelets to endothelial cells.…”