Natural molecule that indirectly prevents stable clot formation discovered

A scientist from The Scripps Research Institute has identified a new role for a natural signaling molecule in preventing blood clot formation. The molecule could become a target for the development of novel and cost-effective treatments for blood clotting diseases such as Hemophilia A.

The findings, from a study by Scripps Research Assistant Professor Laurent O. Mosnier, were published in a recent edition of Journal of Biological Chemistry.

The study focused on Platelet Factor 4 – a small cytokine (intracellular signaling molecule) released during platelet aggregation.

Based on Platelet Factor 4 effects on another coagulation protein, it was thought that Platelet Factor 4 could potentially stimulate activation of thrombin-activatable fibrinolysis inhibitor (TAFI) – an enzyme (soluble protein) that protects clot longevity, making clots last longer and preventing excess bleeding; TAFI is like a hardener that is added to the mortar used between the bricks in a brick wall, without which the mortar would never completely solidify, and the wall would never be solid.
The new study, however, found exactly the opposite role for Platelet Factor 4-inhibition of TAFI activation.

For Mosnier, this finding led to a radical idea - sequestering Platelet Factor 4 using such molecules as heparin derivatives could improve clot stability.

Heparin - a highly sulfated or negatively charged glucoseaminoglycan (polysaccharide or sugar derivative) – is a commonly used anticoagulant. Mosnier, however, was able to modify the compound to have the reverse effect and aid in blood clotting in laboratory tests.