Lipolysis generates platelet dysfunction after in vivo heparin administration

Area of Science:

• Biochemistry
• Hematology
• Cardiovascular Surgery

Background:

• Heparin administration during cardiopulmonary bypass (CPB) is known to impair platelet macroaggregation.
• This effect is observed in vivo but not with in vitro heparinization, suggesting plasma-derived factors are involved.
• Heparin releases endothelial proteins, including lipases, which may mediate the observed platelet dysfunction.

Purpose of the Study:

• To investigate the role of heparin-released endothelial proteins, specifically lipases, in impairing platelet macroaggregation.
• To determine if specific enzymes like lipoprotein lipase and hepatic lipase are responsible for reduced platelet function after in vivo heparinization.

Main Methods:

• Proteins were added in vitro to hirudin-anticoagulated blood from healthy volunteers.
• Platelet macroaggregatory responses were assessed using whole-blood impedance aggregometry after stimulation with collagen.
• Plasma concentrations of non-esterified fatty acids were correlated with platelet macroaggregation.

Main Results:

• Human lipoprotein lipase and hepatic lipase significantly reduced platelet macroaggregatory response over a 4-hour period.
• Other lipoprotein lipases also impaired platelet aggregation, while platelet factor-4 and superoxide dismutase did not.
• Platelet macroaggregation showed a strong inverse correlation with plasma non-esterified fatty acids, indicating heparin-induced lipolysis inhibits platelet function.

Conclusions:

• Heparin-induced lipolysis, mediated by enzymes like lipoprotein lipase, is a key mechanism for inhibiting platelet macroaggregation during CPB.
• The findings suggest that degradation products of lipids interfere with platelet metabolism, potentially affecting eicosanoid pathways.
• Understanding this mechanism is crucial for managing hemostasis and preventing bleeding complications in patients undergoing CPB.