NUMBERS AND FUNCTION OF PLATELETS ARE NOT REDUCED DURING CARDIOPULMONARY BYPASS, BUT BOTH ARE REDUCED AFTER ADMINISTRATION OF PROTAMINE

Abstract

<h3>Objective</h3> To assess changes in numbers and function of platelets during cardiopulmonary bypass (CPB) in CABG surgery. <h3>Methods</h3> Platelet concentration and numbers corrected for hemodilution using hemoglobin as a marker were measured before anesthesia induction (Baseline), at the end of CPB (End CPB), after administration of protamine (After protamine), at arrival at the ICU (ICU) and after 3 hours in the ICU (ICU 3h). Platelet function was assessed after activation with thrombin PAR1-receptor activating peptide (TRAP) and adenosine diphosphate (ADP), with both flow cytometry for fibrinogen receptor activation and impedance aggregometry. Flow cytometry data are presented as median fluorescence intensity (MFI), impedance aggregometry data as area under the curve in units (U). Mean ± SD and repeated measures mixed effects model together with Šídák's multiple comparisons test was used. Subsequent time points were compared to baseline. In addition, "After protamine" was compared to "End CPB". <h3>Results</h3> Thirty-nine CABG patients with mean CPB time 85.1 ± 21.3 mins were studied. During CPB platelet concentration decreased from 227 ± 48 *109/L at baseline to 179 ± 38*109/L at end of CPB (p<0.001), remained at 171 ± 41*109/L after protamine, but increased to 204 ± 48*109/L at ICU 3h (p<0.001 vs baseline). Corrected for hemodilution the number of platelets increased during CPB from 1.73 ± 0.41*109/g to 1.91 ± 0.49 *109/g (p<0.001) but decreased to 1.74 ± 0.51*109/g after protamine (p<0.01 vs End CPB), and then increased to 1.82 ± 0.48*109/g at ICU 3h (p<0.01 vs Baseline). Activation of the fibrinogen receptor, after stimulation using TRAP, did not change during CPB, but was reduced after protamine administration and lower than baseline at ICU arrival (see figure). With ADP as agonist the fibrinogen receptor activation increased from baseline 2.15 ± 1.6 to end of CPB 2.55 ± 1.6 (p<0.001) but decreased to 2.01 ± 1.3 after protamine (p<0.001 vs End CPB), returning to baseline levels at ICU 2.17 ± 1.2 and ICU 3h 2.26 ± 1.2. Platelet function measured with impedance aggregometry using TRAP as activator showed a similar pattern from baseline 114 ± 29 U, maintained levels at end of CPB 118 ± 40 U, but decreased after protamine 103 ± 34 U (p<0.05 vs End CPB), and returned to baseline levels at ICU 118 ± 32 U and finally increased at ICU 3h 126 ± 30 (p<0.05 vs Baseline). With ADP as activator the changes were similar; baseline 77.1 ± 26 U, maintained at end of CPB 68.6 ± 28 U, reduced after protamine 58.9 ± 29 U (p<0.001 vs Baseline), with return to baseline levels at ICU 66.5 ± 28 U, and ICU 3h 86.7 ± 26 U. <h3>Conclusions</h3> The number of circulating platelets increased during CPB when corrected for hemodilution. CPB did not impair platelet function. Administration of protamine reduced the function and numbers of platelets with a return to normal values at the arrival or after 3 hours in the ICU.