Breanne H Y Gibson1, Matthew T Duvernay2, Lydia J McKeithan3, Teresa A Benvenuti2, Tracy A Warhoover2, Jeffrey E Martus2,4, Gregory A Mencio2,4, Brian R Emerson5, Stephanie N Moore-Lotridge2,6, Alexandra J Borst4,7, Jonathan G Schoenecker8,9,10,11,12,13. 1. Department of Pharmacology, Vanderbilt University, Nashville, TN, USA. 2. Department of Orthopaedics, Vanderbilt University Medical Center, Nashville, TN, USA. 3. Vanderbilt University School of Medicine, Nashville, TN, USA. 4. Department of Pediatrics, Vanderbilt University Medical Center, 1155 MRBIV, 2215B Garland Ave, Nashville, TN, 37232, USA. 5. Department of Pediatric Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, USA. 6. Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN, USA. 7. Department of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, TN, USA. 8. Department of Pharmacology, Vanderbilt University, Nashville, TN, USA. jon.schoenecker@vumc.org. 9. Department of Orthopaedics, Vanderbilt University Medical Center, Nashville, TN, USA. jon.schoenecker@vumc.org. 10. Department of Pediatrics, Vanderbilt University Medical Center, 1155 MRBIV, 2215B Garland Ave, Nashville, TN, 37232, USA. jon.schoenecker@vumc.org. 11. Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA. jon.schoenecker@vumc.org. 12. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. jon.schoenecker@vumc.org. 13. Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN, USA. jon.schoenecker@vumc.org.
Abstract
PURPOSE: Posterior spinal fusion (PSF) activates the fibrinolytic protease plasmin, which is implicated in blood loss and transfusion. While antifibrinolytic drugs have improved blood loss and reduced transfusion, variable blood loss has been observed in similar PSF procedures treated with the same dose of antifibrinolytics. However, both the cause of this and the appropriate measures to determine antifibrinolytic efficacy during high-blood-loss spine surgery are unknown, making clinical trials to optimize antifibrinolytic dosing in PSF difficult. We hypothesized that patients undergoing PSF respond differently to antifibrinolytic dosing, resulting in variable blood loss, and that specific diagnostic markers of plasmin activity will accurately measure the efficacy of antifibrinolytics in PSF. METHODS: A prospective study of 17 patients undergoing elective PSF with the same dosing regimen of TXA was conducted. Surgery-induced plasmin activity was exhaustively analyzed in perioperative blood samples and correlated to measures of inflammation, bleeding, and transfusion. RESULTS: While markers of in vivo plasmin activation (PAP and D-dimer) suggested significant breakthrough plasmin activation and fibrinolysis (P < 0.01), in vitro plasmin assays, including TEG, did not detect plasmin activation. In vivo measures of breakthrough plasmin activation correlated with blood loss (R2 = 0.400, 0.264; P < 0.01), transfusions (R2 = 0.388; P < 0.01), and complement activation (R2 = 0.346, P < 0.05). CONCLUSIONS: Despite all patients receiving a high dose of TXA, its efficacy among patients was variable, indicated by notable intra-operative plasmin activity. Markers of in vivo plasmin activation best correlated with clinical outcomes. These findings suggest that the efficacy of antifibrinolytic therapy to inhibit plasmin in PSF surgery should be determined by markers of in vivo plasmin activation in future studies. LEVEL OF EVIDENCE: Level II-diagnostic.
PURPOSE: Posterior spinal fusion (PSF) activates the fibrinolytic protease plasmin, which is implicated in blood loss and transfusion. While antifibrinolytic drugs have improved blood loss and reduced transfusion, variable blood loss has been observed in similar PSF procedures treated with the same dose of antifibrinolytics. However, both the cause of this and the appropriate measures to determine antifibrinolytic efficacy during high-blood-loss spine surgery are unknown, making clinical trials to optimize antifibrinolytic dosing in PSF difficult. We hypothesized that patients undergoing PSF respond differently to antifibrinolytic dosing, resulting in variable blood loss, and that specific diagnostic markers of plasmin activity will accurately measure the efficacy of antifibrinolytics in PSF. METHODS: A prospective study of 17 patients undergoing elective PSF with the same dosing regimen of TXA was conducted. Surgery-induced plasmin activity was exhaustively analyzed in perioperative blood samples and correlated to measures of inflammation, bleeding, and transfusion. RESULTS: While markers of in vivo plasmin activation (PAP and D-dimer) suggested significant breakthrough plasmin activation and fibrinolysis (P < 0.01), in vitro plasmin assays, including TEG, did not detect plasmin activation. In vivo measures of breakthrough plasmin activation correlated with blood loss (R2 = 0.400, 0.264; P < 0.01), transfusions (R2 = 0.388; P < 0.01), and complement activation (R2 = 0.346, P < 0.05). CONCLUSIONS: Despite all patients receiving a high dose of TXA, its efficacy among patients was variable, indicated by notable intra-operative plasmin activity. Markers of in vivo plasmin activation best correlated with clinical outcomes. These findings suggest that the efficacy of antifibrinolytic therapy to inhibit plasmin in PSF surgery should be determined by markers of in vivo plasmin activation in future studies. LEVEL OF EVIDENCE: Level II-diagnostic.
Authors: Andrew L Alejo; Scott McDermott; Yusuf Khalil; Hope C Ball; Gabrielle T Robinson; Ernesto Solorzano; Amanda M Alejo; Jacob Douglas; Trinity K Samson; Jesse W Young; Fayez F Safadi Journal: J Orthop Sports Med Date: 2022-09-05