Hemostatic abnormalities associated with acute promyelocytic leukemia and corrective effects of all-trans-retinoic acid or arsenic trioxide treatment.
OBJECTIVE
To study in vivo effect of all-trans-retinoic acid (ATRA) or arsenic trioxide (As2O3) on the expression of tissue factor (TF) and the hemostatic disorders, a series of parameters were measured in bone marrow blasts and plasma from acute promyelocytic leukemia (APL) patients.


METHODS
The plasma variables were measured by ELISA or chromogenic study. The TF transcription was assessed using reverse transcription-polymerase chain reaction technique (RT-PCR).


RESULTS
The blast cell procoagulant activity (PCA), TF antigen of APL cell lysates, as well as the transcription of APL TF mRNA elevated at diagnosis, were reduced after ATRA or As2O3 therapy. The plasma level of platelet alpha-granular membrane protein-140, soluble fibrinomonomer complex, thrombomodulin, tissue plasminogen activator and D-dimer significantly increased, fibrinogen, antigen level of protein C, plasminogen, alpha 2-plasminogen inhibitor and plasminogen activator inhibitor decreased at diagnosis, were restored to normal after complete remission but protein C activity and protein S remained elevated in ATRA group.


CONCLUSIONS
There existed activation of platelets and consumption of anticoagulants as well as activation of coagulation and fibrinolytic system before treatment. Both ATRA and As2O3 therapy down-regulated the expression of TF mRNA, decreased the PCA and TF level in APL cells, inhibited coagulation activation, secondary hyperfibrinolysis and recorrected other hemostatic abnormalities, thus greatly improved the bleeding symptom in early stage of the treatment.
Zhao
W
W
Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Wang
X
X
Guo
W
W
Qu
B
B
Wang
H
H
Shen
Z
Z
Chen
Z
Z
Wang
Z
Z
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use*; D001779:Blood Coagulation Factors / Q000032:analysis; D005260:Female; D006487:Hemostasis; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000627:therapeutic use*; D013925:Thromboplastin / Q000032:analysis / Q000235:genetics; D014212:Tretinoin / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001152:Arsenicals; D001779:Blood Coagulation Factors; D010087:Oxides; C045071:leukocyte procoagulant activity; D014212:Tretinoin; D013925:Thromboplastin; D000077237:Arsenic Trioxide