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Published on: October 17, 2025
Coagulation profile during induction chemotherapy in childhood acute lymphoblastic leukemia
Shivali Sehgal1, Sunita Sharma1, Jagdish Chandra2
1Department of Pathology, Lady Hardinge Medical College, Kalawati Saran Children's Hospital, New Delhi, India.
Insights
Pediatric acute lymphoblastic leukemia (ALL) patients exhibit a hypercoagulable state. Induction chemotherapy further enhances this prothrombotic condition by activating thrombin and decreasing natural inhibitors.
Area of Science:
- Pediatric Hematology
- Hemostasis and Thrombosis
- Oncology
Background:
- Thromboembolism is a significant concern in pediatric acute lymphoblastic leukemia (ALL), often occurring after antileukemic therapy initiation.
- This suggests a complex interplay between the disease process and therapeutic interventions on coagulation.
- Understanding these changes is crucial for managing thrombotic risks in young ALL patients.
Purpose of the Study:
- To investigate the impact of induction chemotherapy on coagulation parameters in pediatric ALL patients.
- To assess changes in specific markers of coagulation, anticoagulation, and fibrinolysis during the initial phase of ALL treatment.
- To differentiate the effects of the malignant process from those of chemotherapy on hemostasis.
Main Methods:
- A cohort of 37 newly diagnosed pediatric ALL patients and 30 age/sex-matched controls were studied.
- Coagulation parameters including PT, APTT, fibrinogen, Protein C, Protein S, and Antithrombin were measured.
- D-dimer, tPA, and PAI-1 levels were also assessed using ELISA, with sequential analysis during induction chemotherapy.
Main Results:
- Fibrinogen levels significantly declined post-L-asparaginase, while D-dimer levels were markedly elevated throughout induction.
- Natural anticoagulants (Protein C, Protein S, Antithrombin) initially decreased but later rose towards baseline levels.
- Tissue plasminogen activator (tPA) levels were significantly reduced, and PAI-1 showed an increasing trend during therapy.
Conclusions:
- Pediatric ALL is inherently a hypercoagulable state, influenced by both the malignancy and induction chemotherapy.
- Chemotherapy contributes to thrombin activation, reduced natural inhibitors, and hypofibrinolysis, exacerbating the prothrombotic risk.
- These findings highlight the need for careful monitoring of coagulation status in pediatric ALL patients undergoing induction therapy.
Context:
Thromboembolism in children with acute lymphoblastic leukemia (ALL) is most commonly reported after the initiation of antileukemic therapy, indicating a possible interaction of disease and therapy.
Aims:
To study the effect of induction chemotherapy on coagulation parameters in pediatric ALL patients.
Settings And Design:
Thirty-seven newly diagnosed patients of ALL up to 18 years of age were evaluated along with 30 age- and sex-matched controls.
Subjects And Methods:
At the time of diagnosis (day 0), various coagulation parameters were tested. These were sequentially analyzed on day 14 (after the completion of L-asparaginase doses) and on day 28 of therapy (after the completion of induction). Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, protein C (PC) activity, and protein S (PS) activity were done by a clot-based method. Antithrombin (AT) assay was performed by chromogenic method. D-dimer (D-DI), tissue plasminogen activator (tPA), and plasminogen activator inhibitor type 1 (PAI-1) levels were assayed by ELISA method.
Statistical Analysis Used:
The statistical analysis was done using Statistical Package for Social Sciences version 17.0.
Results:
No major change in PT and APTT was observed during chemotherapy; however, fibrinogen levels declined significantly (P = 0.04), following L-asparaginase treatment. D-DI levels were significantly raised at diagnosis (P < 0.001) and throughout induction therapy (P < 0.001). PC, PS, and AT were reduced in the initial part of induction, followed by a rise in the second half of therapy, reaching their respective baseline levels (P < 0.05). The tPA levels were significantly reduced in the patients at diagnosis and throughout therapy (P < 0.001). PAI-1 levels were comparable to controls at presentation and showed a rising trend during therapy.
Conclusions:
The results of this study indicated that both the malignant process and the drugs used in combined chemotherapy cause thrombin activation, decrease in natural inhibitors, and hypofibrinolysis, resulting in hypercoagulability. Thus, ALL per se is a hypercoagulable state and the prothrombotic condition at the time of diagnosis gets enhanced during induction chemotherapy.
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