To study the in vivo effect of
all-trans-retinoic acid (ATRA) and
arsenic trioxide (
As(2)O(3)) on the expression of
tissue factor (TF) and the other
hemostatic disturbance, a series of parameters were measured either in bone marrow blasts or plasma from
acute promyelocytic leukemia (APL) patients. The plasma parameters were measured by ELISA or chromogenic studies. The TF transcription was assessed using reverse transcription-polymerase chain reaction (RT-PCR) technique. The results indicated that the blast cell procoagulant activity (PCA),
TF antigen of APL cell lysate, as well as the transcription of APL TF
mRNA elevated at diagnosis, were reduced after ATRA or
As(2)O(3)
therapy. The plasma level of
P-selectin, TF,
thrombin-antithrombin complex (TAT), soluble
fibrinmonomer complex,
thrombomodulin (TM),
tissue factor pathway inhibitor (
TFPI),
plasmin-
antiplasmin complex,
tissue plasminogen activator (t-PA) activity,
urokinase plasminogen activator (
u-PA) and its receptor (u-PAR), and
D-dimer (
D-D) significantly increased.
Fibrinogen (Fg),
antigen level of
protein C (PC),
plasminogen (PLG) activity, alpha(2)-plasminogen inhibitor activity (alpha(2)-PI), and
plasminogen activator inhibitor (PAI) activity were decreased at diagnosis. The
protein C activity (PC:A) and
protein S (PS) remained unchanged. All the parameters were restored to normal ranges after complete remission (CR) except elevation of TF and TAT in both groups, as well as PC:A, PS, and t-PA in the ATRA group. In conclusion, there existed activation of platelets and consumption of
anticoagulants as well as activation of coagulation and fibrinolytic system before treatment. Both ATRA and
As(2)O(3)
therapy downregulated the expression of TF
mRNA, decreased the PCA and TF level in APL cells, significantly inhibited coagulation activation, corrected secondary hyperfibrinolysis and the other
hemostatic abnormalities, and thus greatly improved the
bleeding symptom in early stage of the treatment.