Because the release of leukemic cell components during ATRA treatment is slow when compared to massive cell death induced by CT, no exacerbation of the bleeding tendency is observed in APL patients undergoing ATRA therapy. In the European APL 91 trial, median time to disappearance of significant coagulopathy was 6 days after CT alone and 3 days in the ATRA group (p = 0.001) . ATRA therapy may be especially important in reducing the severity of the bleeding tendency in hyperleukocytic APL patients, a population still at a relatively high risk of early death with CT alone [6, 7, 118].
In APL patients treated with ATRA alone, primary fibrinogenolysis disappears during the first 5 days of treatment, while DIC and leukocyte-mediated proteolysis seem to persist during the first 2 or 3 weeks of ATRA therapy. This could lead to a transient period of hypercoagulability, which could explain the few well-documented cases of thromboembolic events in APL patients treated with ATRA [119-121].
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