Drospirenone enhances GPIb‐IX‐V‐mediated platelet activation

Publisher: John Wiley & Sons Inc

E-ISSN: 1538-7836|1538-7933|10|1918-1924

ISSN: 1538-7933

Source: JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol.1538-7933, Iss.10, 2015-10, pp. : 1918-1924

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Abstract

SummaryBackgroundEpidemiologic studies recently revealed that using drospirenone (DRSP)‐containing contraceptives is associated with an increased risk of thrombosis in women. However, the underlying causality is unclear.ObjectiveTo study the effects of DRSP on coagulation in vitro and the probable mechanisms involved.MethodsFirst, the effects of DRSP on the activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen (FIB) were measured. Then, the effects of DRSP on platelet activation were investigated in response to low levels of collagen, adenosine 5′‐diphosphate (ADP), thrombin, U46619, adrenaline and botrocetin/von Willebrand factor (VWF).ResultsDRSP has no direct effect on APTT, PT, TT, FIB and platelet aggregation induced by low levels of collagen, ADP, thrombin, U46619 or adrenaline. However, DRSP enhances botrocetin/VWF‐induced platelet aggregation and VWF receptor glycoprotein Ib‐IX‐V (GPIb‐IX‐V)‐mediated signaling. This enhancement can be blocked by the progesterone receptor membrane component 1 (PGRMC1) inhibitor AG205, or by the ADP scavenger apyrase and the cyclooxygenase inhibitor indomethacin.ConclusionsAlthough DRSP did not directly induce platelet activation, it obviously facilitated VWF receptor GPIb‐IX‐V‐mediated platelet activation. The potential DRSP‐binding protein PGRMC1 may play a role in this process. Our study also suggested that the inhibition of thromboxane A2 production and the activation of ADP receptors might prevent the side‐effects of DRSP.