Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
Department of Orthopaedics, Vanderbilt University Medical Center, Nashville, TN, USA.
Spine Deform. 2022 Jul;10(4):841-851. doi: 10.1007/s43390-022-00489-6. Epub 2022 Mar 5.
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.
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.
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 (R = 0.400, 0.264; P < 0.01), transfusions (R = 0.388; P < 0.01), and complement activation (R = 0.346, P < 0.05).
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 II-diagnostic.
后路脊柱融合术（PSF）可激活纤溶蛋白酶尿激酶，其与失血和输血有关。虽然抗纤溶药物已改善失血和减少输血，但在接受相同剂量抗纤溶药物治疗的类似 PSF 手术中，仍观察到不同程度的失血。然而，导致这种情况的原因以及确定 PSF 高失血手术中抗纤溶疗效的适当措施尚不清楚，这使得优化 PSF 中抗纤溶药物剂量的临床试验变得困难。我们假设接受 PSF 的患者对抗纤溶药物的剂量反应不同，导致失血程度不同，并且纤溶酶活性的特定诊断标志物将准确测量 PSF 中抗纤溶药物的疗效。
对 17 例行择期 PSF 手术且 TXA 剂量方案相同的患者进行前瞻性研究。在围手术期血样中全面分析手术诱导的尿激酶活性，并将其与炎症、出血和输血的测量值相关联。
尽管体内尿激酶激活的标志物（PAP 和 D-二聚体）表明存在显著的突破性尿激酶激活和纤溶作用（P<0.01），但包括 TEG 在内的体外尿激酶测定并未检测到尿激酶的激活。体内突破性尿激酶激活的测量值与失血（R=0.400，0.264；P<0.01）、输血（R=0.388；P<0.01）和补体激活（R=0.346，P<0.05）相关。
尽管所有患者均接受高剂量 TXA 治疗，但由于术中尿激酶活性显著，其疗效在患者之间存在差异。体内尿激酶激活的标志物与临床结果相关性最佳。这些发现表明，在未来的研究中，PSF 手术中抗纤溶治疗抑制尿激酶的疗效应通过体内尿激酶激活的标志物来确定。
II 级诊断。
