Plasma Proteolytic Cascade Activation during Neonatal Cardiopulmonary Bypass Surgery

Abstract

The most striking changes were observed following heparin administration and were associated with the appearance of inactive forms of anti-thrombin and an increase in the plasma concentration of TFPI. Changes in anti-thrombin and TFPI remained evident throughout surgery and into the post-operative period but were not different between patients with or without post-operative bleeding. The concentration of antitrypsin decreased across surgery, but there was no significant accumulation of inactive conformations of any inhibitor besides anti-thrombin, indicating that widespread cross-activation of other plasma proteolytic cascades by coagulation proteases did not occur.

Platelet Function Changes during Neonatal Cardiopulmonary Bypass Surgery: Mechanistic Basis and Lack of Correlation with Excessive Bleeding

“…1,2,4,5,14,19,[49][50][51] In this study, which included only neonates, the demographic and surgical characteristics that were strongly associated with excessive bleeding included shorter height, higher incidence of exposure to DHCA, and decreased likelihood of undergoing ASO procedures. A previous study of these same patients 21 did not evaluate differences in the incidences of exposure to DHCA or ASO procedures, and did not find a significant difference in height between patients who bled excessively and those who did not. A possible explanation for the latter disparity is that our study adopted a literal definition of excessive bleeding that resulted in inclusion of one more patient in the excessive bleeding group than was included in the previous study.…”

“…The choice was also made because platelet P-selectin exposure is thought to be relatively insensitive to changes in platelet count, 42 which are known to occur over the course of CPB surgery in our patients. 21 Platelet aggregation in response to stimulation with U46619 or TRAP is known to require amplification of the initial platelet activating signal by secondary agonists like ADP and epinephrine, which are released from platelet granules, bind to G αi/z -coupled P2Y 12 , and α 2 -adrenergic receptors, respectively, and inhibit adenylate cyclase. [43][44][45] Similarly, U46619-induced release of plate-let granule contents, of which P-selectin exposure is a measure, has been shown to require binding of released ADP to the P2Y 12 receptor .…”

“…The study protocol, patient demographics, and clinical characteristics of patients with normal versus excessive levels of postoperative bleeding have been described previously. 20,21 Briefly, surgery was performed with CPB on heparinized patients under hypothermic conditions. All patients were transfused with onefourth unit of apheresis-derived single donor platelets (SDPs) and 1 unit of cryoprecipitate after aortic cross-clamp (AoX) removal and rewarming to 32°C but prior to termination of CPB.…”

“…5,[14][15][16][17][18][19] Transfusion with appropriate blood products has been shown to correct CPB-induced defects in platelet count, coagulation factor levels, and in vitro measures of hemostasis, but was only partially effective at decreasing perioperative bleeding and reducing the requirement for additional transfusions in the postoperative period for pediatric cardiac surgery patients. 14,15,20,21 The factors responsible for excessive post-CPB bleeding in children despite apparent normalization of hemostatic parameters with blood product transfusion are not well characterized.…”

“…The goal of this study was to explore the contribution of platelet count and function defects to excessive bleeding following CPB surgery in neonates treated with protocolized platelet and cryoprecipitate transfusions to correct platelet and fibrinogen deficiencies. 20,21 We examined the responsiveness of platelets to agonist stimulation in blood samples obtained at various times before, during, and after CPB surgery. We describe the mechanisms that underlie changes in agonist-induced platelet responsiveness at different times during surgery and clarify the extent to which decreases in platelet count and changes in platelet function correlate with excessive postoperative bleeding in this highrisk population.…”