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Loss of blast cell procoagulant activity and improvement of hemostatic
variables in patients with acute promyelocytic leukemia administered
all-trans-retinoic acid
A Falanga, L Iacoviello, V Evangelista, D Belotti, R Consonni, A D'Orazio, L Robba, MB Donati and T Barbui
Hematology Division, Ospedali Riuniti, Bergamo, Italy.
All-trans-retinoic acid (ATRA) induces complete remission (CR) in up to 90%
of acute promyelocytic leukemia (APL) patients with rapid amelioration of
the bleeding syndrome. Previous studies indicate that ATRA treatment in
vitro of the APL NB4 cell line can affect their procoagulant activity
(PCA). To assess whether ATRA has this effect also in vivo, we
prospectively studied the PCA of bone marrow blasts from APL patients on
therapy with ATRA alone or associated with chemotherapy. Samples were
obtained before, during, and after ATRA. To characterize the coagulopathy,
we measured a series of plasma hemostatic variables before and during the
first two weeks of therapy, as follows: (1) markers of hypercoagulability;
(2) natural anticoagulants; (3) fibrinolysis proteins; and (4) elastase.
The results by enzymatic and immunologic methods show that both total
(tissue factor-like) and factor VII-independent (cancer procoagulant- like)
blast cell PCAs, present before therapy, were reduced during (69% and 65%
decrement, respectively) and virtually undetectable after ATRA. The plasma
hemostatic assessment of patients before treatment was elevated
hypercoagulability markers, low mean protein C, normal fibrinolysis
proteins, and increased elastase. After starting ATRA, hypercoagulability
markers were reduced within 4 to 8 days, protein C augmented, the overall
fibrinolytic balance was unmodified, and elastase remained elevated. These
results were not different either with or without chemotherapy and are
consistent with the clinical findings of rapid improvement of the
coagulopathy.
Volume 86,
Issue 3,
pp. 1072-1081,
08/01/1995
Copyright © 1995 by The American Society of Hematology
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