activator of the coagulation cascade; (iii) acute anemia may lead to demand ischemia; (iv) blood transfusion, sometimes necessary, leads to untoward proinflammatory and prothrombotic effects. One-half to two-thirds of major bleeding events are femoral access site bleeds, while the remaining events are gastrointestinal or genitourinary bleeds, a drop in hemoglobin without an overt source, or, rarely but fatally, an intracranial bleed.
Radial access drastically reduces bleeding and is associated with improved outcomes when performed by experienced operators. Appropriate antithrombotic therapy, with a limited use of GPI, reduces access and non-access bleeding and improve short- but also long-term outcomes.
B. Transfusion in ACS
Anemia may exacerbate myocardial ischemia in patients with CAD or ACS. Yet transfusion, by itself, does not necessarily reverse this ischemia and may be associated with worse clinical outcomes. This is linked to potential prothrombotic (ADP release) and proinflammatory effects of transfusion and to the impaired oxygen-carrying capacity of the transfused red blood cells.141 In addition, while normal red blood cells transport and dispense nitric oxide to the microvasculature, this function is disrupted in transfused red blood cells, which leads to impaired regional vasodilatation. Two analyses have found that transfusion is associated with increased mortality in ACS patients with a hematocrit > 25–27%.143,144 A randomized trial, REALITY, showed that a restrictive transfusion strategy (transfusion for Hb ≤8 g/dl) is as safe as a more liberal strategy (transfusion for Hb ≤10 g/dl) in patients with MI, most of whom underwent an invasive strategy.145 Other studies have found a strong association between transfusion and adverse outcomes after PCI, performed for ACS or stable CAD, and after CABG.143 Thus, unless the patient is hemodynamically unstable from bleeding, severely tachycardic, or has refractory angina, transfusion should be withheld when hemoglobin is >8 g/dl or hematocrit is >25% (grade I recommendation, ESC).4,146 For patients who continue to exhibit episodes of angina at rest or mild exertion, a higher transfusion cutoff may be used (9 g/dl). Also, in patients about to undergo PCI, a higher cutoff has generally been used in real-world registries (9 g/dl).147
C. Patients on chronic anticoagulation who present with ACS
Warfarin, per se, is protective against coronary events.148,149 If a conservative strategy is selected and the patient is appropriately anticoagulated, it may be reasonable to continue warfarin along with other therapies and withhold from adding any other anticoagulant. There is no reason to believe that combining two anticoagulants reduces ischemic events. In fact, overlapping two anticoagulants worsened the bleeding risk in the SYNERGY trial.
Warfarin management in transfemoral catheterization- Warfarin may be held for a few days before the coronary angiogram and a short-acting anticoagulant used instead of warfarin before and during the procedure. This way, the anticoagulation can be stopped after the procedure, reducing the bleeding complications and allowing for the removal of the arterial sheath. Heparin is started as soon as INR<2. The angiogram may be performed transfemorally when the INR is ≤ 1.6. Warfarin is restarted the evening of the procedure, and heparin may be restarted along with warfarin until INR is ≥ 2, because an early procoagulant effect occurs upon warfarin re-initiation and may not be tolerated post ACS. Anticoagulation with heparin at a low PTT target (~1.5× normal) may generally be resumed 12 hours after sheath removal. Avoid LMWH in those patients with a recent femoral access: LMWH is associated with a higher bleeding risk than controlled-dose heparin (SYNERGY trial), and should a bleeding occur, the prolonged effect of LMWH makes it difficult to control.
Warfarin management in transradial catheterization- Warfarin therapy is not interrupted (class IIa ESC), or only one dose is withheld. If PCI is performed, UFH is administered and adjusted according to ACT (UFH is mainly required if INR<2.5, per ESC).
NOAC management- NOAC may be continued around a transradial procedure without any interruption (class IIa ESC), and UFH is administered during PCI. For transfemoral procedures, hold NOAC for 1-2 days.
D. Gastrointestinal (GI) bleed in patients receiving aspirin and clopidogrel after stent placement
In case of chronic blood loss and a recently placed stent, dual antiplatelet therapy should probably be continued as mandated, and, if indicated, endoscopic intervention performed while the patient is on dual antiplatelet therapy. PPI is administered and testing for H. pylori performed.150
In case of a major GI bleed, the cessation of one antiplatelet agent may be judged necessary, mainly when DES is >1 month old. Following successful endoscopic therapy of upper GI bleed combined with high-dose PPI therapy, it may be reasonable to reintroduce antiplatelet therapy 3–7 days later in those who remain free of recurrent bleeding. In case of lower GI bleed, one may delay antiplatelet therapy for 7–10 days, depending on the colonic lesion size and the adequacy of endoscopic treatment.111
E. Management of elevated troponin in a patient with GI bleed
The elevated troponin often results from the combination of stable CAD and demand ischemia from anemia and tachycardia. Therefore, the treatment of anemia is the first and most important line of therapy. The patients should receive fluid resuscitation ± blood transfusion (particularly in hemodynamic instability, severe tachycardia, persistent angina, or Hb <8 g/dl). PPI therapy is initiated, and endoscopy is performed if appropriate, usually before any coronary procedure. A coronary procedure, with the possible ensuing need for anticoagulation and antiplatelet therapy, should only be performed after stabilization and etiologic diagnosis of the GI bleed, typically several days later or, if possible, in an angina-free patient, weeks later.
Similarly, a patient with stable angina who has chronic anemia should undergo anemia workup before any potential coronary procedure.
A coronary procedure is performed more urgently and potentially before the GI procedure in rare cases: (i) STEMI, (ii) ACS with ongoing angina despite transfusion, or (iii) major ST changes or severe troponin rise occurring with a rather mild or chronic anemia.
Appendix 4. Antiplatelet and anticoagulant therapy
A. Antiplatelet therapy (Table 1.7)
1 Aspirin is given as a 325 mg dose the first day (chewed for rapid absorption and effect), then 81 mg daily. On the second day and beyond, 81 mg is as effective as 325 mg with less bleeding risk, including in patients receiving coronary stents (CURRENT-OASIS trial).151 In the case of aspirin allergy that consists of asthma or urticaria without anaphylaxis, perform aspirin desensitization, which may be performed urgently over less than 24 hours.
2 Clopidogrel is started as a 300 mg load, followed by 75 mg daily. In the CURE trial of NSTE-ACS patients managed invasively or conservatively, high or low risk, this clopidogrel regimen reduced the combined risk of death/MI by 2% at the cost of an increase in major bleeding risk by 1%; the life-threatening bleeding was not increased, and bleeding was overall attenuated when aspirin 81 mg, rather than 325 mg, was used.71 The benefit was more marked in patients who were eventually managed invasively (~3% risk reduction) (PCI CURE).152 The benefit was already significant by 24 hours of therapy and maximal within a few days.Patients who undergo PCI should be loaded with 600 mg of clopidogrel, which has a more potent and faster onset of antiplatelet effect than 300 mg (2 h for 600 mg vs. 6–24 h for 300 mg). If the patient has already received 300 mg, an additional 300 mg is administered during PCI. If the patient requires CABG, clopidogrel is preferably withheld for 5 days to prevent an increase in bleeding risk (absolute risk increase = 4%).71,153 Yet, in the highest-risk patients with critical CAD or ongoing ischemia, CABG may be performed sooner, as clopidogrel cessation for 3 days is often enough.154,155 In addition, the peri-CABG use of clopidogrel does not adversely affect mortality.153
3 Prasugrel and ticagrelor are