The new P2Y12 inhibitor cangrelor unreliably inhibits heparin-induced platelet aggregation in the presence of hit antibodies, an in vitro study

Abstract

Introduction Cardiac surgery in patients with HIT puts the patient at high risk of lethal thrombotic complications if heparin is used during surgery. Two strategies exist to prevent intraoperative platelet aggregation during cardio-pulmonary bypass if anti-PF4/heparin antibodies (HIT-Abs) are present. The first is to use an alternative anticoagulant, the second is to use heparin combined with an antiaggregant agent, iloprost or tirofiban. The new P2Y12 inhibitor cangrelor could be an attractive candidate in this setting and several authors report its successful use. In this in vitro study we evaluated the capacity of cangrelor to inhibit platelet aggregation induced by heparin in the presence of HIT-Abs. Methods Platelet poor plasma (PPP) from 30 patients with functional HIT-Abs was mixed with platelet rich plasma (PRP) from healthy donors. Heparin-induced platelet aggregation (HIPA) was measured by light transmission aggregometry (LTA) after adding heparin to achieve a final concentration of 0.5 IU ml-1 and compared to samples with normal saline only (negative control) or cangrelor (final concentration 500 ng ml-1) added prior to heparin (treatment). Results Heparin 0.5 IU ml-1 triggered platelet aggregation in 22 out of 44 PPP-PRP mixtures, with a median aggregation of 85.9 % (IQR 69.2 to 90.9). For these 22 HIPA positive samples, the median aggregation in the corresponding negative control was 22.1% (IQR 15.9 - 29.7) (p Discussion In this in vitro study we found that cangrelor unreliably inhibits heparin-induced platelet aggregation in the presence of HIT-Abs. We conclude that cangrelor cannot be used as a standard antiaggregant agent in combination with heparin for cardiac surgery in HIT patients, unless its efficacy has been confirmed in a functional test prior to surgery.