Published Online
on May 28, 2002

A more recent version of this article appeared on June 18, 2002

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Submitted on February 27, 2002
Revised on April 5, 2002
Accepted on April 8, 2002

Cardiopulmonary Bypass Induces Release of Soluble CD40 Ligand

Lisa Nannizzi-Alaimo BSc, Mark H. Rubenstein MD, Veronica L. Alves BSc, Gil Y. Leong BSc, David R. Phillips PhD^*, and Herman K. Gold MD

From COR Therapeutics, South San Francisco, Calif.

^* To whom correspondence should be addressed. E-mail: dphillips{at}corr.com.

Background—Cardiopulmonary bypass (CPB) is known to induce platelet activation, thrombosis, thrombocytopenia, and a systemic inflammatory response. It is known that CD40 ligand (CD40L) exists in platelets, that a soluble form of this protein (sCD40L) is released on platelet activation, that platelets are the primary source of sCD40L in blood, and that sCD40L is involved in thrombosis and inflammation. The present study was designed to determine whether sCD40L is released during CPB.

Methods and Results—Blood was obtained from patients undergoing CPB-requiring surgery and analyzed for sCD40L, interleukin-6, and platelet factor 4 and ß-thromboglobulin (markers of platelet activation). Platelets were also isolated and analyzed for their levels of CD40L. Plasma levels of sCD40L increased >1.7-fold (from 0.29 to 0.51 ng/mL, P=0.001) within 1 hour on CPB and increased further to 3.7-fold (to 1.08 ng/mL, P=0.03) 2 hours after the procedure. Half of the released sCD40L was cleared in 2 hours, which allowed the sCD40L to return to approximately baseline levels 8 hours after the procedure. The platelet content of CD40L was decreased by 40% (2.675 to 1.64 ng/10⁸ platelets, P=0.001) 1 hour after initiation of CPB and was similar to that observed for platelet factor 4 and ß-thromboglobulin. Interleukin-6, a marker of inflammation, also increased during CPB.

Conclusions—The present study demonstrates that CPB causes an increase in the concentration of plasma sCD40L. The corresponding decrease in platelet CD40L suggests that this prothrombotic and proinflammatory protein was derived primarily from platelets and may contribute to the thrombotic and inflammatory complications associated with CPB.

Key words: platelets • cardiopulmonary bypass • inflammation • thrombosis • platelet-derived factors

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