Potential and Limitations of the New P2Y12 Inhibitor, Cangrelor, in Preventing Heparin-Induced Platelet Aggregation During Cardiac Surgery

BACKGROUND:

Heparin-induced thrombocytopenia (HIT) can put cardiac surgery patients at a high risk of lethal complications. If anti-PF4/heparin antibodies (anti-PF4/Hep Abs) are present, 2 strategies exist to prevent intraoperative aggregation during bypass surgery: first, using an alternative anticoagulant, and second, using heparin combined with an antiaggregant. The new P2Y₁₂ inhibitor, cangrelor, could be an attractive candidate for the latter strategy; several authors have reported its successful use. The present in vitro study evaluated cangrelor’s ability to inhibit heparin-induced platelet aggregation in the presence of anti-PF4/Hep Abs.

METHODS:

Platelet-poor plasma (PPP) from 30 patients with functional anti-PF4/Hep Abs was mixed with platelet-rich plasma (PRP) from 5 healthy donors.

Light transmission aggregometry was used to measure platelet aggregation after adding 0.5 IU·mL⁻¹ of heparin (HIT) to the plasma, and this was compared with samples spiked with normal saline (control) and samples spiked with cangrelor 500 ng·mL⁻¹ and heparin 0.5 IU·mL⁻¹ (treatment). Friedman test with post hoc Dunn-Bonferroni test was used for between-group comparisons.

RESULTS:

Heparin 0.5 IU·mL⁻¹ triggered aggregation in 22 of 44 PPP–PRP mixtures, with a median aggregation of 86% (interquartile range [IQR], 69–91). The median aggregation of these 22 positive samples’ respective control tests was 22% (IQR, 16–30) (P < .001). Median aggregation in the cangrelor-treated samples was 29% (IQR, 19–54) and significantly lower than the HIT samples (P < .001). Cangrelor inhibited heparin-induced aggregation by a median of 91% (IQR, 52–100). Cangrelor only reduced heparin-induced aggregation by >95% in 10 of the 22 positive samples (45%). Cangrelor inhibited heparin-induced aggregation by <50% in 5 of the 22 positive samples (22%) and by <10% in 3 samples (14%).

CONCLUSIONS:

This in vitro study found that cangrelor was an unreliable inhibitor of heparin-induced aggregation in the presence of anti-PF4/Hep Abs. We conclude that cangrelor should not be used as a standard antiaggregant for cardiac patients affected by HIT during surgery. Unless cangrelor’s efficacy in a particular patient has been confirmed in a presurgery aggregation test, other strategies should be chosen.