Objectives: To study the changes of tissue factor expression and hemostatic molecular markers in acute promyelocytic leukemia during all-trans retinoic acid (ATRA) or arsenic trioxide (AS(2)O(3)) treatment.
Methods: The plasma level of tissue factor (TF), tissue factor pathway inhibitor(TFPI), thrombin antithrombin complex(TAT), plasmin antiplasmin complex(PAP), urokinase type plasminogen activator(u-PA), urokinase type plasminogen activator receptor(u-PAR) and the TF level of bone marrow blasts lysate were measured by ELISA. Transcription of TF mRNA was detected by RT-PCR.
Results: The plasma levels of TF [(98.3 +/- 19.8) ng/L, (89.6 +/- 15.2) ng/L], TFPI [(94.4 +/- 37.0) mg/L, (93.5 +/- 36.4) mg/L], TAT [(21.9 +/- 9.6) microg/L, (18.2 +/- 9.7) microg/L[, PAP [(0.73 +/- 0.26) mg/L, (0.63 +/- 0.33) mg/L], u-PA [(0.63 +/- 0.23) microg/L, (0.57 +/- 0.01) microg/L] and u-PAR [(0.41 +/- 0.14) microg/L, (0.47 +/- 0.16) microg/L], the TF of bone marrow blasts lysate [(680.24 +/- 456.61) pg/10(7), (368.02 +/- 151.2) pg/10(7)] and transcription of mRNA were all remarkably elevated at the time of diagnosis. They all decreased after ATRA and AS(2)O(3) administration.
Conclusions: There is over expression of TF, activation of coagulation system and hyperfibrinolysis, in patients with acute promyelocytic leukemia, these can be ameliorated with clinical improvement. All-trans retinoic acid and arsenic trioxide down-regulate the expression of TF mRNA and decrease the TF contents in APL blasts. However, there is also high plasma level of TF and TAT indicating the existence of hypercoagulability after remission.