The purpose of the study was to evaluate the impact of intravenous metamizole on platelet inhibition by aspirin in patients with coronary artery disease early after on-pump coronary artery bypass grafting (CABG).

Prospective, single-blind, randomized trial.

Tertiary referal hospital.

The study comprised 43 patients with multivessel coronary artery disease undergoing CABG.

Patients were randomized to postoperative intravenous metamizole ± opioids (study group; n = 23) or opioids alone (control group; n = 20). Aspirin was withheld at least 7 days before the surgery and reinitiated (300 mg) immediately after the procedure prior to metamizole use, and continued daily thereafter (150 mg). Platelet function was evaluated using multielectrode impedance aggregometry (acid-induced platelet activation [ASPI] and collagen-induced platelet activation [COL] test), P-selectin expression and urinary 11-dehydro-thromboxane B₂ (11-DTXB₂) level at baseline, postoperative day (POD) 0, POD 1, POD 2, and POD 6. Residual platelet reactivity (RPR) was defined as ASPI test >400 AU*min.

In all study participants, postoperative ASPI test value moderately decreased (1058.2 v 966.6 AU*min, p = 0.047), urinary 11-DTXB₂ level increased (923.4 v 4367.3 pg/mg, p < 0.001), and P-selectin expression and COL test value remained stable postprocedure. The decreases of ASPI (p = 0.146) and COL test (p = 0.642), and P-selectin expression (p = 0.318) did not differ between both groups. Patients in the control group had higher postoperative increase of urinary 11-DTXB₂ level (p = 0.001). The prevalence of RPR was high and comparable between study and control groups (day 1, 95.6% v 100%, p = 0.535; day 6, 100% v 90%, p = 0.21). Multivariate analysis revealed that metamizole use did not predict the fluctuations of ASPI and COL test values and P-selectin expression, yet it independently predicted postoperative change of 11-DTXB₂ level (b = -0.518, p = 0.001).

Intravenous metamizole preceded by a loading dose of aspirin did not modify platelet response to aspirin in the postoperative period after CABG.

The incidence of bleeding and thrombo-embolic complications in patients undergoing mechanical circulatory support therapy remains high and is associated with bad outcomes and increased costs. The need for anticoagulation and anti-platelet therapy varies widely between different pulsatile and non-pulsatile ventricular-assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) systems. Therefore, a unique anticoagulation protocol cannot be recommended. Notably, most thrombo-embolic complications occur despite values of conventional coagulation tests being within the targeted range. This is due to the fact that conventional coagulation tests such as international normalised ratio (INR), activated partial thromboplastin time (aPTT) and platelet count cannot detect hyper- or hypofibrinolysis, hypercoagulability due to tissue factor expression on circulating cells or increased clot firmness, and platelet aggregation as well as response to anti-platelet drugs. By contrast, point-of-care (POC) whole blood viscoelastic tests (thromboelastometry/-graphy) and platelet function tests (impedance or turbidimetric aggregometry) reflect in detail the haemostatic status of patients undergoing mechanical circulatory support therapy and the efficacy of their anticoagulation and antiaggregation therapy. Therefore, monitoring of haemostasis using POC thromboelastometry/-graphy and platelet function analysis is recommended during mechanical circulatory support therapy to reduce the risk of bleeding and thrombo-embolic complications. Notably, these haemostatic tests should be performed repeatedly during mechanical circulatory support therapy since thrombin generation, clot firmness and platelet response may change significantly over time with a high inter- and intra-individual variability. Furthermore, coagulation management can be hampered in non-pulsatile VADs by acquired von Willebrand syndrome, and in general by acquired factor XIII deficiency as well as by heparin-induced thrombocytopenia. In addition, POC testing can be used in bleeding patients to guide calculated goal-directed therapy with allogeneic blood products, haemostatic drugs and coagulation factor concentrates to optimise the haemostasis and to minimise transfusion requirements, transfusion-associated adverse events and to avoid thrombo-embolic complications, as well. However, coagulation management in patients undergoing mechanical circulatory support therapy is somehow like navigating between Scylla and Charybdis, and development of protocols based on POC testing seems to be beneficial.