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A cohort study on blood coagulation in childhood cancer survivors
Andrew D Meyer1, Tyler B Hughes1, Anjana R Rishmawi1
1Division of Critical Care, Department of Pediatrics, Long School of Medicine at The University of Texas Health Science Center, San Antonio, TX, United States of America.
Insights
Pediatric cancer survivors exhibit a persistent procoagulant imbalance, indicated by elevated thrombin-antithrombin complexes (TAT) and plasminogen activator inhibitor (PAI). This imbalance, present years after diagnosis, may increase their risk of thromboembolism.
Area of Science:
- Hematology
- Pediatric Oncology
- Thrombosis Research
Background:
- Pediatric cancer survivors face a higher risk of thromboembolism than the general pediatric population.
- Anticoagulant therapy is used to mitigate thromboembolism risk in cancer patients.
- A chronically hypercoagulable state may underlie the increased thromboembolism risk in survivors.
Purpose of the Study:
- To test the hypothesis that pediatric cancer survivors are in a chronically hypercoagulable state.
- To compare coagulation parameters in long-term pediatric cancer survivors versus healthy controls.
- To identify specific coagulation markers associated with past cancer therapy.
Main Methods:
- Compared 47 pediatric cancer survivors (≥5 years post-diagnosis) with 37 healthy controls.
- Assessed coagulation via platelet count, thrombin-antithrombin complexes (TAT), plasminogen activator inhibitor (PAI), routine assays, and thrombin generation.
- Excluded participants with recent NSAID use or history of coagulopathy.
Main Results:
- Cancer survivors had significantly lower platelet counts and shorter prothrombin times (PT) than controls.
- Elevated biomarkers of the procoagulant state, including TAT and PAI, were significantly higher in survivors.
- Logistic regression confirmed low platelet count, short PT, and elevated TAT/PAI associated with past cancer therapy.
Conclusions:
- Pediatric cancer survivors demonstrate a persistent procoagulant imbalance for over five years post-diagnosis.
- This imbalance is characterized by lower platelet counts, shorter PT, and elevated TAT and PAI levels.
- Further research is warranted to determine if this procoagulant imbalance elevates thromboembolism risk.
Abstract:
Cancer survivors are at an increased risk of thromboembolism compared to the general pediatric population. Anticoagulant therapy decreases the risk of thromboembolism in cancer patients. We hypothesized that pediatric cancer survivors are in a chronically hypercoagulable state compared to healthy controls. Children who survived for more than five years from cancer diagnosis at the UT Health Science Center at San Antonio Cancer Survivorship Clinic were compared to healthy controls. The exclusion criteria were recent NSAID use or a history of coagulopathy. Coagulation analysis included platelet count, thrombin-antithrombin complexes (TAT), plasminogen activator inhibitor (PAI), routine coagulation assays, and thrombin generation with and without thrombomodulin. We enrolled 47 pediatric cancer survivors and 37 healthy controls. Platelet count was significantly lower in cancer survivors at a mean of 254 × 109/L (95%CI: 234-273 × 109/L) compared at 307 × 109/L (283-331 × 109/L) in healthy controls (p < 0.001), although not outside the normal range. Routine coagulation assays showed no differences, except for a significantly lower prothrombin time (PT) in cancer survivors (p < 0.004). Cancer survivors has significantly elevated biomarkers of the procoagulant state, such as TAT and PAI, compared to healthy controls (p < 0.001). A multiple logistic regression model controlling for age, BMI, gender, and race/ethnicity documented that a low platelet count, short prothrombin clot time, and higher procoagulant biomarkers (TAT and PAI) were significantly associated with past cancer therapy. Survivors of childhood cancer have a persistent procoagulant imbalance for more than five years after diagnosis. Further studies are needed to establish whether procoagulant imbalance increases the risk of thromboembolism in childhood cancer survivors.
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