Tirofiban preserves platelet loss during continuous renal replacement therapy in a randomised prospective open-blinded pilot study

Abstract

Introduction: Approximately one third of all patients with cardiogenic shock suffer from acute kidney injury. Percutaneous coronary intervention, intra-aortic balloon pump, and continuous renal replacement therapy (CRRT) require effective antiplatelet therapy and anticoagulation, resulting in a high risk for platelet loss and bleeding events. The reversible platelet glycoprotein IIb/IIIa receptor inhibitor tirofiban was investigated to preserve platelet number and activation in a prospective open-blinded endpoint evaluation study.

Methods: Forty patients with cardiogenic shock and acute kidney injury requiring CRRT were randomly assigned to two groups receiving unfractioned heparin (UFH) (n = 20) or a combined anticoagulation with UFH and tirofiban (n = 20). The primary endpoint was platelet loss during CRRT. Secondary endpoints were urea reduction, haemofilter life span, bleeding events, and necessity for platelet transfusions.

Results: In UFH-treated patients, the percentage of platelet-monocyte aggregates significantly increased (P < 0.001) and consecutively platelet cell count significantly decreased (P < 0.001). In contrast, combined treatment with UFH and tirofiban significantly decreased platelet-monocyte aggregates and platelet numbers (P < 0.001).

Conclusions: This pilot study provides evidence that the use of tirofiban in addition to UFH prevents platelet loss and preserves platelet function in patients with cardiogenic shock and acute kidney injury requiring CRRT. The pathophysiological inhibition of platelet aggregation and platelet-monocyte interaction appears to be causally involved.

Figure 1

Study flowchart. Patients were randomly assigned in different anticoagulation regimens (unfractioned heparin [UFH] versus UFH + tirofiban), separated according to the concomitant therapy with or without intra-aortic balloon pump (IABP). Furthermore, the concomitant antiplatelet therapy and the number of patients included in each subgroup were added. Exclusion criteria include cardiopulmonary resuscitation, suspected concomitant sepsis defined by haemodynamic criteria (reduced systemic vascular resistance), a platelet count of less than 100 × 10⁹/L, or major bleeding signs (one patient retroperitoneal and one patient gastric haemorrhage). aPTT, activated partial thromboplastin time.

Figure 2

Mean platelet counts during the study period in patients treated with unfractioned heparin (UFH) versus UFH + tirofiban and with or without intra-aortic balloon pump (IABP). Data are shown as mean ± standard deviation. n.s., not significant.

Figure 3

Mean platelet counts during the study period in patients treated with unfractioned heparin (UFH) versus UFH + tirofiban and with different antiplatelet therapy regimens. Data are shown as mean ± standard deviation.

Figure 4

Mean platelet-monocyte aggregates during the study period in patients treated with unfractioned heparin (UFH) versus UFH + tirofiban and with or without intra-aortic balloon pump (IABP). Data are shown as mean ± standard deviation. n.s., not significant.