Morrissey and Colleagues Further Unravel Mysteries of Thrombosis

In a new study published in Cell, and rated "exceptional" by the Faculty of 1000 Biology, Professor of Biochemistry Jim Morrissey and colleagues have determined that polyphosphate, an inorganic polymer of phosphate, secreted by human platelets is an important link in thrombotic diseases and inflammation.

In a new study published in Cell, and rated "exceptional" by the Faculty of 1000 Biology, Professor of Biochemistry Jim Morrissey and colleagues have determined that polyphosphate, an inorganic polymer of phosphate secreted by human platelets, is an important link in thrombotic diseases and inflammation.

The three authors of the study from Dr. James Morrissey’s group at the University of Illinois had previously demonstrated, in a paper appearing in The Proceedings of the National Academy of Sciences (PNAS) in 2006, that polyphosphate triggers blood clotting via the contact pathway, one of two known pathways for initiating clotting. The contact pathway is dispensable for hemostasis, the normal clotting process that stops bleeding following injury. On the other hand, the contact pathway was recently shown to play an essential role in thrombosis, the formation of clots inside rather than outside a blood vessel, and also in stroke, in papers published in the Journal of Experimental Medicine in 2005 and 2006 by Dr. Thomas Renné and colleagues.

Said Dr. Morrissey, “I met Dr. Renné over a lobster dinner in a chance meeting at a Gordon conference on hemostasis. We were excited by one another’s research and the connections between our work. His studies in vivo related strongly to our own experiments in vitro. We decided to work together to investigate more closely the relationships between the contact pathway, polyphosphates, and platelets.”

This international collaboration has resulted in new findings appearing in the journal Cell. The paper shows, via a study involving several labs, that polyphosphate is also important in thrombotic diseases—abnormal processes in which unwanted blood clots block arteries or veins, causing often life-threatening tissue damage—and in platelet-driven inflammatory processes.

For many decades, it has been known that the contact pathway of blood clotting can be triggered when blood is mixed with materials such as glass or clay, substances that blood would not normally come into contact with, even in disease states. This is the underlying principle for a widely used diagnostic blood clotting test termed aPTT. The present study indicates that polyphosphate may represent the long-sought "foreign" substance that triggers blood clotting by activated platelets, certain types of tissue damage, and infectious organisms.

“The data obtained in an international collaboration with British, Swedish, Dutch, German and American universities indicate that polyphosphate initiates blood clotting on platelets with critical importance for thrombotic diseases,” said Dr. Renné from the Karolinska Institute, Stockholm.

The new study, suggesting that polyphosphate may represent a new target for interrupting thrombotic and inflammatory processes in multiple diseases, has myriad implications for new medical treatments of major diseases.

Cell
Faculty of 1000 Biology

December 10, 2009 All News