Platelet dysfunction after normothermic cardiopulmonary bypass in children: Effect of high-dose aprotinin

Abstract

Platelet dysfunction after cardiopulmonary bypass (CPB) can contribute to excessive post-operative bleeding. Most trials of the protective effect of aprotinin in this setting have involved hypothermic CPB, which is more deleterious for platelets than normothermic CPB. Here we investigated the effect of aprotinin on platelet function during normothermic CPB in pediatric patients. Twenty patients (9 newborns [<1 month old] and 11 infants [<36 month old]), weighting less than 15 kg and undergoing normothermic CPB (35-36 degrees C) were randomly assigned to two equal groups, one of which received high-dose aprotinin. Platelet function was assessed by flow cytometry just before CPB and 5 minutes after heparin neutralization. F1 + 2 fragments were measured by ELISA before and 5 minutes after CPB. Platelet activation marker expression (CD62P and activated alphaIIbbeta3) induced by ADP or TRAP was lower after CPB than before CPB, suggesting a deleterious effect of normothermic CPB on platelet function. Prothrombin fragment F1 + 2 levels increased after CPB. Aprotinin administration did not influence the level of prothrombin fragments or platelet marker expression measured in basal condition. However, after CPB, the capacity for platelet activation was higher in the aprotinin group, as shown by measuring CD62P expression after TRAP activation (p = 0.05). This study suggests that pediatric normothermic CPB causes platelet dysfunction, and that high-dose aprotinin has a protective effect.

Platelet Functions During Extracorporeal Membrane Oxygenation. Platelet–Leukocyte Aggregates Analyzed by Flow Cytometry as a Promising Tool to Monitor Platelet Activation

“…The authors suggested that this could actually be consecutive to the vast activation of platelets in the ECMO circuit, related to the high shear stress, consistent with the increased surface expression of the activated fibrinogen receptor at rest, and a decreased expression of P-selectin, probably due to its shedding [15]. This was in agreement with previous data from our group in the setting of cardiopulmonary bypass in children [16].…”

Platelet-dependent thrombography gives a distinct pattern of in vitro thrombin generation after surgery with cardio-pulmonary bypass: potential implications

“…Many alterations have been reported, including α granule depletion and membrane glycoprotein decreases such as GPIIbIIIa [2,11,12]. No major alteration of procoagulant properties of platelets has been reported however, which is consistent with the slight decrease in ETP we observed with patients’ PRP.…”

“…Although we have not studied platelet function in the PRP of our patients, many other studies have described that platelet dysfunction is thought to result from many factors, such as contact with the synthetic surfaces of the extracorporeal circuit and hypothermia associated with bypass [2,11,12]. Many alterations have been reported, including α granule depletion and membrane glycoprotein decreases such as GPIIbIIIa [2,11,12].…”

“…In addition, we have shown that this decrease in ETP values occurs also with PRP after CPB. Several mechanisms have been implicated in the haemostatic defects observed after CPB: consumption of coagulation factors and platelets, dilution, activation of fibrinolysis and transient platelet function defect [2,11-15]. …”

Fresh frozen plasma does not reduce in vivo thrombin formation after neonatal cardiopulmonary bypass surgery

“…Theaim to alleviate thrombin generation after open heartsurgeryi si ntuitivelyd esirable.B esidest hrombin'sa pparent contribution in clinicalthrombosis, studies on human adults as well as animals suggest thathigh thrombin activity maybeharmful to the functioning of the heartand vasculature (3,7). In newborns postoperative thrombin generation is high (5,(8)(9)(10)enabling the harmful effects of thrombin.…”