The use of direct thrombin inhibitors is frequently reserved for patients with active or a history of heparin-induced thrombocytopenia. Cost may also prohibit their use in clinical practice. The half-lives of both bivalirudin and argatroban are shorter than heparins, therefore requiring more frequent monitoring. There is also no spe­cic reversal agent for DTIs. Table10.2 shows dosing strategies and pharmacoki­netic considerations [22, 23].

Cangrelor is an intravenous P2Y12 inhibitor with an almost immediate on/off effect. It is primarily used during PCI or when oral P2Y12 therapy is delayed or has to be withheld for various reasons. Dosing consists of a 30mcg/kg bolus followed by a 4mcg/kg/min infusion for a minimum of 2h or the duration of procedure (which­ever is longer). When transitioning to an oral P2Y12 inhibitor, important notice should be taken as to when to initiate [4, 27].

Patients admitted for ACS may and often do receive some form of an oral P2Y12 inhibitor loading dose either at the time of hospitalization prior to or following left heart catheterization. As previously discussed, the platelet inhibitory effects of these medications can range from 5 to 7days depending on the agent used [24–26]. Due to the high risk of bleeding associated with CABG, P2Y12 inhibitors are not recom­mended within 5days in most cases. In patients who did not receive any form of a stent, it is prudent to withhold the P2Y12 inhibitor and consider continuing an anti­coagulant infusion. The P2Y12 inhibitor effect may be evaluated using platelet reactivity testing to demonstrate appropriate medication clearance/platelet activity. Many of these patients may have a new cardiac stent placed during PCI that is high risk for thrombosis requiring some form of antiplatelet agent in conjunction with aspirin. Holding aspirin has been observed to increase the risk for major adverse ischemic events by threefold [4, 27]. If the ASA is held due to surgeon preference, then ASA should be stopped 7days or less prior to the surgery date. In this scenario, IV antiplatelet agents are the drugs of choice. Initiation of IV antiplatelet agents is dependent on the choice of P2Y12 inhibitor but typically should be initiated at approximately 48h from the last dose [28]. IV antiplatelet agents can then be dis­continued within 2–6h prior to surgery depending on the agent’s pharmacokinetic and patient-specic factors. Cangrelor has a shorter half-life than the GP IIb/IIIa inhibitors, and platelet reactivity testing can be used to demonstrate appropriate clearance. However, cangrelor lacks the potency of an antiplatelet effect that may be warranted in high-risk patients.