Lymphoblasts Express Hemostatic Factors: A Mechanism for Hypercoagulability in Pediatric Acute Lymphoblastic Leukemia.

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: · Leukemic lymphoblasts express hemostatic system factors at gene and protein levels.. · Leukemic lymphoblasts lysis directly contributes to hypercoagulability and hypofibrinolysis in thrombin and fibrin generation assays..