Mildly elevated unconjugated bilirubin is associated with reduced platelet activation-related thrombogenesis and inflammation in Gilbert's syndrome.
Kundur AR , et al.
«Gilbert's syndrome (GS) is associated with a mild unconjugated hyperbilirubinemia, increased circulating antioxidant capacity, and reducedcardiovascular disease (CVD) risk. The current study investigated whether mildly elevated circulating unconjugated bilirubin (UCB) is negatively associated with multiple thrombotic risk factors including platelet activity, hemostatic function, and inflammation in individuals with GS. Blood samples were collected from matched GS and control subjects (14 per group). Activation-dependent platelet surface marker expression of PAC-1 (binds to GPIIb/IIIa surface receptors on activatedplatelet) and CD62P (marker for P-selectinreleased from activated degranulated platelet) was assessed in adenosine diphosphate (ADP)-stimulatedplatelet using flow cytometry. Exogenous agonists, ADP, collagen, and arachidonic acid (AA), were used to stimulateplatelet aggregation. A statistically significantdecrease in the expression of P-selectin (P = 0.030) on activatedplatelet was observed in GS subjects. Collagen and AA-inducedplatelet aggregation were significantly (P = 0.018; P = 0.032 for respective agonists) reduced in GS versus control group. Elevated UCB (P = 0.001) and high density lipoprotein (P = 0.033) in addition to reducedlow density lipoprotein (P = 0.024) and high sensitive C-reactive protein (P = 0.043) were also observed in GS when compared to the control group. ReducedP-selectin expression suggests decreasedplatelet activation-dependent degranulation, while reducedplatelet aggregation by AA and collagen indicates a quantitative decrease in platelet aggregation consequently targeting the cyclooxygenase-1 and GP VI pathways, respectively. These findings are the first to demonstrate that the activation of platelet is mildly inhibited in individuals with GS, an effect that might contribute to protection from platelet hyperactivation-inducedthrombosis and thus cardiovascular mortality in individuals with benign hyperbilirubinemia.»