RESULTS AND DISCUSSION
In 95 pediatric patients undergoing CCVR for craniosynostosis, 47 patients received EACA and 48 patients received TXA. There were no differences in demographics, procedure category, operative time, or CBL between antifibrinolytic groups (Supplemental Table 1).24 Perioperative hematologic and coagulation laboratory values were reviewed and the minimum or maximum value for each was recorded (Table 1). Preoperative laboratory values were within normal range on all patients and there were no differences between antifibrinolytic cohorts. Postoperative laboratory parameters are depicted in spaghetti plots in Supplemental Figure 1. Intraoperative hematocrit fell as expected with appreciated BL and did not fully recover for most patients, despite RBC transfusion intraoperatively in 59 patients (62%) and postoperatively in 22 patients (23%). No patients developed significant thrombocytopenia perioperatively. Hypofibrinogenemia was not seen and fibrinogen activity tended to increase postoperatively. PT and PTT were prolonged, consistent with TIC in this patient population; though reflecting only loss of procoagulant proteins. There was a trend toward a small peak in PT around 24-36 hours postoperatively, but this varied with several outliers. PTT tended to rise with time in the postoperative period but was only collected on a few patients (n=11).
CBL and transfusion rates in our cohort were similar to that reported in other large cohorts.3,14,16,17,25 Intraoperative CBL for the cohort was 34 mL/kg, reflecting a percentage of total blood volume (BV) loss of 44%. Postoperative CBL was 12 mL/kg ( total BV loss of 15%). We evaluated laboratory parameters to determine if they could be predictive of BL (Table 2). Intraoperative laboratory values did predict perioperative CBL. A lower intraoperative platelet count and fibrinogen predicted lower intraoperative CBL; lower intraoperative platelet count also predicted lower postoperative CBL. However, it is important to note that none of these patients were thrombocytopenic nor hypofibrinogenemic. In contrast, a higher intraoperative PT was associated with increased intraoperative CBL and a higher postoperative PTT was associated with increased postoperative CBL, possibly reflecting procoagulant protein losses or a more abnormal coagulation state. Postoperative laboratory values were not predictive of postoperative BL.
In our laboratory analysis, there was no significant difference in hematologic or coagulation laboratory parameters between patients receiving EACA vs. TXA. While there were no differences in laboratory parameters between the two cohorts, postoperative laboratory trends suggest ongoing disturbance of the hemostatic system beyond the operative period (Supplemental Figure 1). This includes an expected fall in hematocrit with a delayed improvement despite transfusion, a continuous rise in fibrinogen postoperatively, and in some patients, a persistently prolonged PTT. These results were limited by sampling in this observational study, not providing mechanistic data, but may provide an impetus for future laboratory investigation in this population.
Prior groups have looked at viscoelastic assays in pediatric CCVR as a potential alternative to monitoring standard coagulation assays.19,21,30,31 Global assays of hemostasis, such as thromboelastography, potentially provide more useful information, but have their own limitations.20,21,30–32 This testing was not performed routinely in our cohort. Our data set was insufficient to draw firm conclusions about coagulopathy but suggests that future prospective laboratory-based studies looking at alternative coagulation assays may help elucidate some of the mechanisms of surgically-induced coagulopathy. Better understanding of the mechanisms of coagulopathy in CCVR has the potential to improve BL and surgical outcomes for children with craniosynostosis. A prospective study analyzing additional perioperative laboratory markers such as plasminogen activity, plasmin-antiplasmin complexes, markers of platelet activation by flow cytometry, and inflammatory cytokines would be beneficial in improving our understanding of TIC and BL in craniofacial surgery.