title: Creatine kinase inhibits ADP-induced platelet aggregation.
abstract: Bleeding risk with antiplatelet therapy is an increasing clinical challenge. However, the inter-individual variation in this risk is poorly understood. We assessed whether the level of plasma creatine kinase, the enzyme that utilizes ADP and phosphocreatine to rapidly regenerate ATP, may modulate bleeding risk through a dose-dependent inhibition of ADP-induced platelet activation. Exogenous creatine kinase (500 to 4000 IU/L, phosphocreatine 5 mM) added to human plasma induced a dose-dependent reduction to complete inhibition of ADP-induced platelet aggregation. Accordingly, endogenous plasma creatine kinase, studied in 9 healthy men (mean age 27.9 y, SE 3.3; creatine kinase 115 to 859 IU/L, median 358), was associated with reduced ADP-induced platelet aggregation (Spearman's rank correlation coefficient, -0.6; p < 0.05). After exercise, at an endogenous creatine kinase level of 4664, ADP-induced platelet aggregation was undetectable, normalizing after rest, with a concomitant reduction of creatine kinase to normal values. Thus, creatine kinase reduces ADP-induced platelet activation. This may promote bleeding, in particular when patients use platelet P2Y12 ADP receptor inhibitors.
authors.affiliation: Dept. of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: D L
authors.initials: DL
authors.lastname: Horjus
authors.affiliation: Dept. of Laboratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Nieuwland
authors.affiliation: Dept. of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: K B
authors.initials: KB
authors.lastname: Boateng
authors.affiliation: Dept. of Laboratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: M C L
authors.initials: MC
authors.lastname: Schaap
authors.affiliation: 1] Dept. of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands [2] Dept. of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: G A
authors.initials: GA
authors.lastname: van Montfrans
authors.affiliation: Dept. of Neurology, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Clark
authors.affiliation: Dept. of Laboratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Sturk
authors.affiliation: 1] Dept. of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands [2] Dept. of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands [3] Dept. of Social Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: L M
authors.initials: LM
authors.lastname: Brewster
mesh_terms: D000244:Adenosine Diphosphate / Q000008:administration & dosage*; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects; D003402:Creatine Kinase / Q000097:blood*; D006470:Hemorrhage / Q000097:blood* / Q000473:pathology; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058925:Receptors, Purinergic P2Y12 / Q000187:drug effects
chemical_list: C548576:P2RY12 protein, human; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12; D000244:Adenosine Diphosphate; D003402:Creatine Kinase