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Risk factors for DIC in paediatric APL: Insights from the CCLG-APL 2016 study
Qingyuan Xu1, Linya Wang1, Shaoyan Hu2
1Hematology Center, National Key Discipline of Pediatric Hematology, National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, Xicheng District, China.
Insights
Low initial platelet counts increase the risk of disseminated intravascular coagulation (DIC) in children with acute promyelocytic leukemia (APL). Realgar-indigo naturalis formula (RIF) therapy shows protective effects against DIC.
Area of Science:
- Pediatric Hematology Oncology
- Leukemia Research
- Coagulation Disorders
Background:
- Disseminated intravascular coagulation (DIC) is a severe complication in pediatric acute promyelocytic leukemia (APL).
- Identifying early risk factors for DIC is crucial for timely intervention and improved patient outcomes.
- Understanding the role of specific genetic mutations and treatment modalities in DIC development is essential.
Purpose of the Study:
- To identify early risk factors for DIC, especially severe grades (4-5), in pediatric APL patients undergoing induction therapy.
- To evaluate the impact of initial patient characteristics and treatment regimens on DIC occurrence and severity.
- To compare the efficacy of arsenic trioxide (ATO) and realgar-indigo naturalis formula (RIF) in preventing DIC.
Main Methods:
- A cohort of 186 pediatric APL patients from the CCLG-APL 2016 study was analyzed.
- Patients were categorized based on the occurrence and severity of DIC during induction therapy.
- Multivariate analysis was employed to identify independent risk factors and protective factors for DIC.
Main Results:
- DIC occurred in 52.2% of patients, with 7.5% experiencing grade 4-5 DIC.
- Initial low platelets (PLT ≤26×10^9/L) were an independent risk factor for DIC (OR=2.679).
- Realgar-indigo naturalis formula (RIF) induction therapy demonstrated a protective effect (OR=0.465).
- For grade 4-5 DIC, independent risk factors included FLT3 mutation (OR=11.742), initial PLT ≤26×10^9/L (OR=13.784), and initial bone marrow blasts ≥90% (OR=5.289).
Conclusions:
- Initial low platelet count is a significant independent risk factor for DIC in pediatric APL.
- RIF therapy may serve as a protective factor against DIC during induction therapy.
- FLT3 mutation, very low initial platelet count, and high bone marrow blast percentage are critical risk factors for severe DIC in pediatric APL.
Abstract:
To identify early risk factors for disseminated intravascular coagulation (DIC), particularly severe DIC (grade 4-5), in paediatric acute promyelocytic leukaemia (APL). One hundred and eighty-six paediatric APL patients enrolled in the Chinese Children Leukemia Group (CCLG)-APL 2016 study across 38 hospitals nationwide were grouped based on the occurrence and severity of DIC during induction therapy. DIC occurred in 52.2% of patients during induction therapy, with 7.5% developing grade 4-5 DIC. Significant differences were observed between the DIC and non-DIC groups in the proportion of patients with initial white blood cells (WBC) ≥5 × 109/L, initial platelets (PLT) ≤26 × 109/L and arsenic trioxide (ATO) use (p < 0.05). Multivariate analysis identified initial PLT ≤26 × 109/L (p = 0.002, odds ratio [OR] = 2.679, 95% confidence interval [CI]: 1.438-4.992) as an independent risk factor, while induction therapy using realgar-indigo naturalis formula (RIF) was a protective factor (p = 0.030, OR = 0.465, 95% CI: 0.232-0.929). Further analysis revealed that Fms-like tyrosine kinase 3 (FLT3) mutation (p = 0.023, OR = 11.742, 95% CI: 1.405-98.149), initial PLT ≤26 × 109/L (p = 0.017, OR = 13.784, 95% CI: 1.598-118.905) and initial bone marrow blasts ≥90% (p = 0.030, OR = 5.289, 95% CI: 1.178-23.744) were significant risk factors for grade 4-5 DIC. Initial WBC ≥5 × 109/L and PLT ≤26 × 109/L are associated with an increased risk of DIC, with PLT ≤26 × 109/L as an independent risk factor. Compared with ATO, RIF is a protective factor during induction therapy. Additionally, FLT3 mutation, PLT ≤26 × 109/L and initial bone marrow blasts ≥90% are independent risk factors for grade 4-5 DIC.
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