Abstract
Background
Venous thromboembolism (VTE) is a serious complication of pediatric acute lymphoblastic
leukemia (ALL), primarily occurring during induction therapy and associated with acquired
hemostatic abnormalities. However, the contribution of leukemic lymphoblasts to hypercoagulability
remains unexplored. This study aimed to determine whether leukemic lymphoblasts express
hemostatic factors that promote a hypercoagulable state and to assess the functional
impact of lysed lymphoblasts on thrombin and fibrin generation.
Methods
We examined the expression of 28 hemostatic factors at both mRNA and protein levels
in four pediatric leukemic cell lines (T-ALL and B-ALL) and normal lymphocytes using
RT-PCR and immunoblotting. To evaluate the overall functional effect, we conducted
thrombin and fibrin generation assays by adding cell lysates to platelet-poor plasma
in the absence of exogenous tissue factor or phospholipids.
Results
Leukemic lymphoblasts constitutively expressed the procoagulants tissue factor, factor
VIII and factor XIIIa; the coagulation inhibitors antithrombin, ADAMTS13 and TFPI;
and the pro-fibrinolytic and antifibrinolytic proteins uPA, TAFI, and α2-AP. Lysed,
but not intact, leukemic lymphoblasts enhanced thrombin and fibrin generation, indicating
a procoagulant state. Additionally, leukemic lysates exhibited a hypo-fibrinolytic
state, as evidenced by prolonged fibrin clot lysis times.
Conclusion
These findings suggest that leukemic lymphoblasts actively contribute to a hypercoagulable
state in pediatric ALL by simultaneously increasing procoagulant activity and impairing
fibrinolysis. This study provides novel insights into the mechanisms underlying VTE
risk in pediatric ALL, highlighting the role of leukemic lymphoblasts in disrupting
the hemostatic balance.
Key Points
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Leukemic lymphoblasts express hemostatic system factors at gene and protein levels.
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Leukemic lymphoblasts lysis directly contributes to hypercoagulability and hypofibrinolysis
in thrombin and fibrin generation assays.
Keywords
venous thrombosis - hypercoagulability - pediatric acute lymphoblastic leukemia -
hypofibrinolysis
