Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Center for Theoretical Problems of Physicochemical Pharmacology, Moscow, Russia.
PLoS One. 2018 Jun 28;13(6):e0199900. doi: 10.1371/journal.pone.0199900. eCollection 2018.
Heparin therapy and prophylaxis may be accompanied by bleeding and thrombotic complications due to individual responses to treatment. Dosage control based on standard laboratory assays poorly reflects the effect of the therapy. The aim of our work was to compare the heparin sensitivity of new thrombodynamics (TD) assay with sensitivity of other standard and global coagulation tests available to date.
A total of 296 patients with high risk of venous thromboembolism (deep vein thrombosis (DVT), early postoperative period, hemoblastosis) were enrolled in the study. We used a case-crossover design to evaluate the sensitivity of new thrombodynamics assay (TD) to the hemostatic state before and after unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) therapy/prophylaxis and to compare it with the activated partial thromboplastin time (APTT), anti-Xa activity test, thrombin generation test (TGT) and thromboelastography (TEG). A receiver operating characteristic (ROC) curve analysis was used to evaluate changes before and after heparin prophylaxis and therapy. Blood was sampled before heparin injection, at the time of maximal blood heparin concentration and before the next injection.
Hypercoagulation before the start of heparin treatment was detected by TD, TGT and TEG but not by APTT. The area under the ROC curve (AUC) was maximal for TD and anti-Xa, intermediate for TGT and TEG and minimal for APTT.
These results indicate that TD has a high sensitivity to the effects of UFH and LMWH after both prophylactic and therapeutic regimes and may be used for heparin monitoring.
肝素治疗和预防可能会因个体对治疗的反应而出现出血和血栓并发症。基于标准实验室检测的剂量控制并不能很好地反映治疗效果。我们的工作旨在比较新的血栓动力学(TD)检测与迄今为止可用的其他标准和全球凝血检测对肝素的敏感性。
共纳入 296 例静脉血栓栓塞高风险患者(深静脉血栓形成(DVT)、早期术后、血液病)。我们采用病例交叉设计来评估新的血栓动力学检测(TD)在未分级肝素(UFH)和低分子肝素(LMWH)治疗/预防前后对止血状态的敏感性,并将其与活化部分凝血活酶时间(APTT)、抗 Xa 活性检测、凝血酶生成试验(TGT)和血栓弹力图(TEG)进行比较。使用受试者工作特征(ROC)曲线分析来评估肝素预防和治疗前后的变化。在肝素注射前、最大血液肝素浓度时和下次注射前采集血液样本。
TD、TGT 和 TEG 检测到肝素治疗前的高凝状态,但 APTT 检测不到。ROC 曲线下面积(AUC)在 TD 和抗 Xa 中最大,在 TGT 和 TEG 中中等,在 APTT 中最小。
这些结果表明,TD 对 UFH 和 LMWH 的预防和治疗后均具有高敏感性,可用于肝素监测。