Association among Clopidogrel Cessation, Platelet Function, and Bleeding in Coronary Bypass Surgery: An Observational Trial.

OBJECTIVES: This study sought to determine (1) the association between the length of preoperative clopidogrel discontinuation, blood loss, and transfusion requirements and (2) whether preoperative platelet function testing predicts excessive postoperative bleeding in patients undergoing coronary artery bypass grafting (CABG) surgery. METHODS: In this retrospective analysis, patients undergoing CABG were divided into three groups with regard to the period between preoperative clopidogrel cessation and surgery: group 1 (n = 94, ≤3 days), group 2 (n = 100, 4-5 days), and group 3 (n = 83, 6-7 days), respectively. Impedance aggregometry (Multiplate) with arachidonic acid (ASPI) test assay (used for platelets stimulation) and adenosine diphosphate (ADP) test (used for platelets stimulation) was performed before the surgery. Primary outcome was 24 hours chest tube output (CTO) and transfusion requirements (red blood cell concentrate [RBCC], platelet concentrate [PC], fibrinogen concentrate [FC], and fresh-frozen plasma [FFP]) were considered as secondary outcomes. RESULTS: CTO during 24 hours was significantly higher in group 1 as compared with groups 2 and 3, respectively (p = 0.003). Considering secondary outcomes, RBCC (p = 0.043), PC (p = 0.001), FC (p = 0.003), and FFP (p = 0.010) were more frequently transfused in group 1 as compared with groups 2 and 3, respectively. Multiple electrode aggregometry ASPI and ADP tests were significantly correlated with the 24-hour CTO (ASPI test-rho = -0.258, p < 0.001; ADP test-rho = -0.164, p = 0.007). A significant correlation was observed between clopidogrel-free interval and 24-hour CTO (rho = -0.200, p < 0.001). Receiver-operating characteristics (ROC) curve analysis revealed cutoff values to delineate bleeding tendency (ASPI test ≤ 25 area under the aggregation curve [AUC], ADP test ≤63 AUC, and clopidogrel-free interval ≤3 days). CONCLUSION: Excessive postoperative bleeding occurred less frequently if the period between clopidogrel discontinuation and surgery was longer than 3 days, as compared with shorter waiting time. Inadequate recovery of the platelets function following clopidogrel cessation in preoperative period was associated with increased bleeding risk. Platelet function testing was found to be a useful tool for postoperative bleeding management in our hands.

Intragastric Application of Aspirin, Clopidogrel, Cilostazol, and BPC 157 in Rats: Platelet Aggregation and Blood Clot.

We suggest that the stable gastric pentadecapeptide BPC 157 may rescue thrombocyte function. We focused on the antithrombotic agent aspirin, clopidogrel, and cilostazol application in rats; arachidonic acid, ADP, collagen, and arachidonic acid/PGE1 platelet aggregation (aggregometry) and blood clot viscoelastic properties (thromboelastometry); and the pentadecapeptide BPC 157. Rats received intragastrically for three days once daily treatment with antithrombotic agents-aspirin (10 mg/kg) or clopidogrel (10 mg/kg) or cilostazol (10 mg/kg). Medication (BPC 157 (10 µg/kg) or an equal volume of saline (5 ml/kg)) was given intragastrically, immediately after each antithrombotic agent application. For multiple electrode aggregometry and modified rotational thromboelastometry studies, blood sampling was at 2 h after last application. Adenosine diphosphate (ADP test 6.5 µM), arachidonic acid (ASPI test 0.5 mM), a combination of arachidonic acid and prostaglandin E1 (ASPI test 0.5 mM and PGE1-test 30 nM), and collagen (COL test 3.2 µg/ml) were used as aggregation agonists. Given with aspirin, clopidogrel, or cilostazol in rats, BPC 157 counteracted their inhibitory effects on aggregation activated by arachidonic acid, ADP, collagen, and arachidonic acid/PGE1. Specifically, this includes recovery of the aggregation induced by arachidonic acid (vs. aspirin, vs. clopidogrel, and vs. cilostazol), arachidonic acid/PGE1 (vs. cilostazol), ADP (vs. clopidogrel), or collagen (vs. clopidogrel). Contrarily, there is no effect on the used tests (extrinsic/intrinsic hemostasis system, the fibrin part of the clot) EXTEM, INTEM, and FIBTEM; clotting time; clot formation time; alpha-angle; maximum clot firmness; lysis index after 30 minutes; and maximum lysis. In conclusion, we revealed that BPC 157 largely rescues thrombocyte function.

Bleeding and Thrombotic Events in Patients Undergoing Mechanical Circulatory Support: A Review of Literature.

Bleeding and thrombotic events are among the most common complications detected in patients with mechanical circulatory support (MCS). Herein, we reviewed the available evidence on the prevalence, etiology, and management of bleeding and thrombotic events in patients following MCS procedures, such as implantation of both intra- and paracorporeal devices that generate either pulsatile or nonpulsatile flow. Extracorporeal life support procedures providing support to the failing heart and lungs were also reviewed. Most bleeding and thromboembolic events occur despite appropriate hemostatic and anticoagulation management based on conventional coagulation laboratory parameters. Prevalence of bleeding events in this population ranges between 5 and 81%. Wide range in prevalence of bleeding reported in literature may be explained by different devices with different anticoagulation protocols being used, as well as different definitions of bleeding outcomes. Although bleeding events are more common than thromboembolic events, the consequences of thrombotic events are often detrimental. Management of bleeding events remains challenging and measures to prevent and treat bleeding events are often followed by thromboembolic events. Therefore, a personalized approach based on point-of-care hemostatic tests and adjusted to device type and patient comorbidities is therefore warranted. To provide advanced understanding of hemostatic disturbances during MCS, prospective trials focused on bleeding and thromboembolic events as primary endpoints should be conducted. Better understanding of the underlying pathophysiology and a shift towards a personalized approach based on functional point-of-care hemostatic properties assessment may provide more favorable clinical outcomes. This should, however, be coupled with further technological improvements providing better device surface hemocompatibility as interaction between blood and device surface affects the hemostatic equilibrium.