Kumar Rahul, Katare Parmeshwar B, Lentz Steven R, Modi Arunkumar J, Sharathkumar Anjali A, Dayal Sanjana
Department of Internal Medicine University of Iowa Iowa City IA USA.
Department of Pediatrics University of Iowa Iowa City IA USA.
Res Pract Thromb Haemost. 2021 Jul 26;5(5):e12557. doi: 10.1002/rth2.12557. eCollection 2021 Jul.
Thromboembolism affects up to 30% of children undergoing treatment for acute lymphoblastic leukemia (ALL). Increased thrombin generation has been reported in ALL, but the mechanisms remain elusive.
We aimed to show that extracellular traps and cell-free DNA (cfDNA) promote thrombin generation in pediatric ALL.
In a longitudinal single-center study, we recruited 17 consecutive pediatric ALL patients. Serial blood samples were collected at diagnosis and weekly during the 4-week induction phase of antileukemic chemotherapy. Healthy children (n = 14) and children with deep vein thrombosis (DVT; n = 7) or sepsis (n = 5) were recruited as negative and positive controls, respectively. In plasma, we measured endogenous thrombin generation potential (ETP) and components of extracellular traps, including cfDNA.
In patients with ALL, ETP was increased at baseline and remained significantly elevated throughout the induction therapy. Plasma levels of cfDNA were increased at baseline and during the first 3 weeks of induction therapy. The extent of enhancement of ETP and plasma cfDNA in patients with ALL was similar to that seen in patients with DVT or sepsis. Treatment of plasma with DNase 1 lowered ETP in patients with ALL at each time point but did not affect ETP in healthy controls.
We conclude that childhood ALL is associated with a prothrombotic milieu at the time of diagnosis that continues during induction chemotherapy, and cfDNA contributes to increased thrombogenic potential.
血栓栓塞影响高达30%正在接受急性淋巴细胞白血病（ALL）治疗的儿童。ALL患者中已报道凝血酶生成增加，但机制仍不清楚。
我们旨在表明细胞外陷阱和游离DNA（cfDNA）促进儿童ALL中的凝血酶生成。
在一项纵向单中心研究中，我们招募了17例连续的儿童ALL患者。在诊断时以及抗白血病化疗4周诱导期的每周采集系列血样。分别招募健康儿童（n = 14）和患有深静脉血栓形成（DVT；n = 7）或脓毒症（n = 5）的儿童作为阴性和阳性对照。在血浆中，我们测量内源性凝血酶生成潜力（ETP）和细胞外陷阱的成分，包括cfDNA。
ALL患者中，ETP在基线时升高，并在整个诱导治疗期间持续显著升高。cfDNA的血浆水平在基线时和诱导治疗的前3周升高。ALL患者中ETP和血浆cfDNA的增强程度与DVT或脓毒症患者相似。用DNA酶1处理血浆可降低ALL患者在每个时间点的ETP，但不影响健康对照的ETP。
我们得出结论，儿童ALL在诊断时与促血栓形成环境相关，在诱导化疗期间持续存在，且cfDNA有助于增加血栓形成潜力。
