A Novel Fibrinolysis Resistance Capacity Assay Can Detect Fibrinolytic Phenotypes in Trauma Patients.

IF 5 2区医学 Q1 HEMATOLOGY Thrombosis and haemostasis Pub Date : 2025-01-21 DOI:10.1055/a-2508-3424

Christopher D Barrett, Yuko Suzuki, Ernest E Moore, Hunter B Moore, Elizabeth R Maginot, Collin M White, Halima Siddiqui, Flobater I Gawargi, James G Chandler, Angela Sauaia, Tetsumei Urano

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Abstract

Background: To evaluate residual fibrinolysis resistance activity (FRA) in plasma, a detergent-modified plasma clot lysis assay time (dPCLT) was established in which α2-antiplasmin (A2AP) and plasminogen activator inhibitor type 1 (PAI-1) are inactivated without impacting protease activity. We applied this novel assay to severely injured trauma patients' plasma.

Material and methods: Tissue-type plasminogen activator (tPA)-induced plasma clot lysis assays were conducted after detergents- (dPCLT) or vehicle- (sPCLT) treatment, and time to 50% clot lysis was measured ("transition midpoint", T _m). Residual FRA was then calculated as ([sPCLT T _m] - [dPCLT T _m]/[sPCLT T _m]) x100% = Δ T_m PCLT (%). Assay results were compared to rapid thromboelastography (TEG) LY30, tPA TEG LY30, and plasma fibrinolysis biomarkers in polytrauma patients' plasma (N=43).

Results: Δ T_m PCLT(%) in normal plasma (N=5) was 63.0 ± 8.3 whereas in A2AP-depleted plasma was -19.1 ± 1.3%, Plasmin-antiplasmin (PAP) complex increased after complete lysis of sPCLT, whereas that in dPCLT was negligible in normal plasma. In trauma plasma, significant correlations between Δ T_m PCLT and active PAI-1 (r = 0.85, p<0.0001), PAP complex (r = -0.85, p<0.0001), free A2AP (r = 0.66, p<0.0001), total A2AP levels (r = 0.52, p=0.001) and tPA TEG LY30 (r = -0.85, p<0.0001) were found. dPCLT in hyperfibrinolysis patients diagnosed by tPA TEG was significantly shorter than those with low fibrinolysis [10.2 ± 6.4 minutes versus 20.2 ± 2.1 minutes, p=0.0006].

Conclusion: Hyperfibrinolysis after trauma is significantly related to exhaustion of FRA, and our novel assay appears to quickly assess this state and may be a useful clinical diagnostic after additional validation.

Key points: · We established a new clot lysis assay to measure residual fibrinolysis resistance activity after inactivating PAI-1 and A2AP by detergents without impacting protease function.. · This novel clot lysis assay unmasked the mechanism of hyperfibrinolysis after trauma as exhaustion of fibrinolysis resistance activity, and appeared useful in quickly identifying these patients..

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一种新的抗纤溶能力测定方法可以检测创伤患者的纤溶表型。

背景：为了评估血浆中残余纤维蛋白溶解抵抗活性（FRA），建立了一种清洁剂修饰的血浆凝块溶解测定时间（dPCLT），其中α - 2抗纤溶蛋白（A2AP）和纤溶酶原激活物抑制剂1型（PAI-1）失活而不影响蛋白酶活性。我们将这种新方法应用于严重创伤患者的血浆。材料和方法：在清洁剂- (dPCLT)或载体- (sPCLT)处理后，进行组织型纤溶酶原激活剂（tPA）诱导的血浆凝块溶解试验，测量到50%凝块溶解的时间（“过渡中点”，Tm），然后计算残余FRA （[sPCLT Tm] - [dPCLT Tm]/[sPCLT Tm]） × 100% = Δ Tm PCLT（%）。将检测结果与多发外伤患者血浆中的快速血栓弹性成像（TEG） LY30、tPA TEG LY30和血浆纤维蛋白溶解生物标志物进行比较（N=43）。结果：正常（N=5）血浆中Δ Tm PCLT（%）为63.0±8.3，而a2ap缺失血浆中PCLT（%）为-19.1±1.3%，sPCLT完全溶解后Plasmin-antiplasmin （PAP）复合物升高，而dPCLT在正常血浆中可忽略。在创伤血浆中，Δ Tm PCLT和活性PAI-1之间存在显著相关性（r = 0.85）。结论：创伤后高纤溶与FRA衰竭显著相关，我们的新检测方法似乎可以快速评估这种状态，并可能在进一步验证后成为有用的临床诊断方法。·我们建立了一种新的凝块溶解实验，在不影响蛋白酶功能的情况下，用洗涤剂灭活PAI-1和A2AP后，测量残余的纤维蛋白溶解抵抗活性。·这种新颖的凝块溶解试验揭示了创伤后高纤溶的机制是纤维蛋白溶解抵抗活性的衰竭，并有助于快速识别这些患者。

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来源期刊

Thrombosis and haemostasis 医学-外周血管病

CiteScore

11.90

自引率

9.00%

发文量

140

审稿时长

1 months

期刊介绍： Thrombosis and Haemostasis publishes reports on basic, translational and clinical research dedicated to novel results and highest quality in any area of thrombosis and haemostasis, vascular biology and medicine, inflammation and infection, platelet and leukocyte biology, from genetic, molecular & cellular studies, diagnostic, therapeutic & preventative studies to high-level translational and clinical research. The journal provides position and guideline papers, state-of-the-art papers, expert analysis and commentaries, and dedicated theme issues covering recent developments and key topics in the field.