Ruiz-Llobet Anna, Gassiot Susanna, Sarrate Edurne, Zubicaray Josune, Rives Susana, Suleman Warda, Berrueco Rubén
Pediatric Hematology Department, Hospital Sant Joan de Déu Barcelona, Institut de Recerca Pediàtrica, Hospital San Joan de Déu de Barcelona (IRP-HSJD), Esplugues de Llobregat, Universitat de Barcelona, Barcelona, Spain.
Instituto Nacional de Investigación Biomédica en Enfermedades Raras (CIBER ER), Instituto de Salud Carlos III, Madrid, Spain.
Thromb Haemost. 2024 Oct;124(10):973-985. doi: 10.1055/a-2316-4547. Epub 2024 Apr 29.
Venous thromboembolism (VTE) etiology in children with acute lymphoblastic leukemia (ALL) is multifactorial. The use of global assays of hemostasis as a thrombin generation test (TGT) is useful to individualize VTE risk in adult patients. This prospective cohort study aimed to evaluate the usefulness of an automated TGT to evaluate VTE risk during ALL treatment in children.
TGT (automated analyzer ST Genesia; ThromboScreen) and pro- and anticoagulant plasma proteins were analyzed during ALL treatment in pediatric patients following LAL-SEHOP-PETHEMA-2013 guidelines. Results were compared with a series of pediatric normal controls and evaluated according to pegylated asparaginase PEG-ASP administration and to VTE risk factors.
The study included 67 patients: males = 35, B-ALL ( = 60). None had a VTE during the evaluated period. Compared to healthy controls, the normalized endogenous thrombin potential (N-ETP) ratio in patients was higher and ETP inhibition (ETP-inh) was lower, especially after PEG-ASP administration. Plasmatic protein C and protein S levels decreased after PEG-ASP administration, but antithrombin mean level did not. A bivariant analysis showed that ETP-inh was lower in patients >10 years old ( = 0.05) and in those with non-O blood type ( = 0.005). A linear mixed model also showed a higher TGT prothrombotic profile in patients with inherited thrombophilia.
TGT could be a biomarker of a high VTE risk in ALL pediatric patients. Non-O blood group and inherited thrombophilia were associated with a significantly higher thrombotic profile, and an increased profile was also observed after administration of PEG-ASP.
急性淋巴细胞白血病（ALL）患儿发生静脉血栓栓塞（VTE）的病因是多因素的。使用凝血酶生成试验（TGT）等整体止血检测方法有助于个体化评估成年患者的VTE风险。这项前瞻性队列研究旨在评估自动化TGT在评估ALL患儿治疗期间VTE风险方面的实用性。
按照LAL-SEHOP-PETHEMA-2013指南，在儿科ALL患者治疗期间分析TGT（自动化分析仪ST Genesia；ThromboScreen）以及促凝血和抗凝血血浆蛋白。将结果与一组儿科正常对照进行比较，并根据聚乙二醇化天冬酰胺酶（PEG-ASP）的使用情况和VTE风险因素进行评估。
该研究纳入67例患者：男性35例，B-ALL 60例。在评估期间均未发生VTE。与健康对照相比，患者的标准化内源性凝血酶潜力（N-ETP）比值较高，而ETP抑制率（ETP-inh）较低，尤其是在使用PEG-ASP后。PEG-ASP使用后血浆蛋白C和蛋白S水平降低，但抗凝血酶平均水平未降低。双变量分析显示，10岁以上患者（P = 0.05）和非O血型患者（P = 0.005）的ETP-inh较低。线性混合模型还显示，遗传性易栓症患者的TGT促血栓形成特征较高。
TGT可能是ALL儿科患者VTE高风险的生物标志物。非O血型和遗传性易栓症与显著较高的血栓形成特征相关，使用PEG-ASP后也观察到血栓形成特征增加。
