Thrombotic potential during pediatric acute lymphoblastic leukemia induction: Role of cell-free DNA.
Thrombotic potential during pediatric acute lymphoblastic leukemia induction: Role of cell-free DNA.
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DOI：
10.1002/rth2.12557
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发表时间：
2021-07
影响因子：
4.6
通讯作者：
Dayal S
中科院分区：
文献类型：
--
作者：
Kumar R;Katare PB;Lentz SR;Modi AJ;Sharathkumar AA;Dayal S
在接受急性淋巴细胞白血病（ALL）治疗的儿童中，血栓栓塞的发生率高达30%。据报道，在ALL中凝血酶生成增加，但其机制仍不清楚。我们的目的是证明细胞外陷阱和无细胞DNA（cfDNA）促进儿科ALL中凝血酶的生成。在一项纵向单中心研究中，我们招募了17名连续的儿童ALL患者。在诊断时和抗白血病化疗的4周诱导期每周采集一次连续血样。健康儿童（n = 14）和患有深静脉血栓形成（DVT; n = 7）或脓毒症的儿童（n = 5）分别被招募作为阴性和阳性对照。在血浆中，我们测量了内源性凝血酶生成潜力（ETP）和细胞外陷阱的组分，包括cfDNA。在ALL患者中，ETP在基线时增加，并在整个诱导治疗期间保持显著升高。cfDNA的血浆水平在基线和诱导治疗的前3周期间增加。ALL患者ETP和血浆cfDNA的增强程度与DVT或脓毒症患者相似。用DNA酶1处理血浆在每个时间点降低ALL患者的ETP，但不影响健康对照的ETP。我们得出结论，儿童ALL与诊断时的血栓前环境相关，该环境在诱导化疗期间持续存在，cfDNA有助于增加血栓形成的可能性。
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.
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