Long-term Follow-up of Hemostatic Molecular Markers during Remission Induction Therapy with All-Trans Retinoic Acid for Acute Promyelocytic Leukemia

Reiko Watanabe; Mitsuru Murata; Nobuyuki Takayama; Michihide Tokuhira; Masahiro Kizaki; Shinichiro Okamoto; Yohko Kawai; Kiyoaki Watanabe; Hiroshi Murakami; Masao Kikuchi; Shin Nakamura; Yasuo Ikeda; For Keio Hematology-Oncology Cooperative Study Group (KHOCS)

doi:10.1055/s-0038-1656026

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1997; 77(04): 641-645
DOI: 10.1055/s-0038-1656026

Clinical Studies

Schattauer GmbH Stuttgart

Long-term Follow-up of Hemostatic Molecular Markers during Remission Induction Therapy with All-Trans Retinoic Acid for Acute Promyelocytic Leukemia

Reiko Watanabe

¹The Department of internal Medicine, School of Medicine, Keio University, Tokyo

,

Mitsuru Murata

¹The Department of internal Medicine, School of Medicine, Keio University, Tokyo

,

Nobuyuki Takayama

¹The Department of internal Medicine, School of Medicine, Keio University, Tokyo

,

Michihide Tokuhira

¹The Department of internal Medicine, School of Medicine, Keio University, Tokyo

,

Masahiro Kizaki

¹The Department of internal Medicine, School of Medicine, Keio University, Tokyo

,

Shinichiro Okamoto

¹The Department of internal Medicine, School of Medicine, Keio University, Tokyo

,

Yohko Kawai

²The Department of Laboratory Medicine, School of Medicine, Keio University, Tokyo

,

Kiyoaki Watanabe

²The Department of Laboratory Medicine, School of Medicine, Keio University, Tokyo

,

Hiroshi Murakami

³The Tachikawa-Kyosai Hospital, Tokyo

,

Masao Kikuchi

³The Tachikawa-Kyosai Hospital, Tokyo

,

Shin Nakamura

⁴The Primate Research Institute, Kyoto University, Kyoto, Japan

,

Yasuo Ikeda

¹The Department of internal Medicine, School of Medicine, Keio University, Tokyo

,

For Keio Hematology-Oncology Cooperative Study Group (KHOCS)

› Author Affiliations

Abstract

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Summary

Hemostatic molecular markers were serially monitored in a prospective fashion during remission induction therapy with all-trans retinoic acid (ATRA) in sixteen patients with acute promyelocytic leukemia (APL). One patient with leukocytosis before treatment and three patients who later developed hyperleukocytosis also received chemotherapy with behenoyl Ara-C and daunorubicin. Plasma levels of E-fragment of fibrin and fibrinogen degradation product (FDP-E), FDP-D dimer (D-D), thrombin-antithrombin complex (TAT), and plasmin-α₂ plasmin inhibitor complex (PIC) were markedly elevated in all but one patient before treatment, and these parameters decreased to normal or near normal ranges in most patients within the first 7 days of treatment. Interestingly, we have found that these parameters were again elevated during the later course of ATRA therapy (after day +7) in eleven patients for various reasons including cytotoxic chemotherapy (3 cases), fever (5 cases; 2 cases with apparent infection, 3 cases without known etiology), Caesarean section (1 case), and no apparent etiology (2 cases). Three patients showed bleeding complications during reelevation of molecular markers, but none developed thrombosis. Plasma elastase-α₁ proteinase inhibitor complex (E-α₁PI) was markedly elevated in all patients at diagnosis and did not decrease significantly during ATRA therapy. Plasma tissue factor antigen was mildly elevated in one out of four patients studied, and thrombomodulin was elevated in two out of ten patients tested. These results confirmed the rapid normalization of coagulopathy during the early phase of remission induction therapy with ATRA but suggest that re-elevation of molecular markers occurs frequently during the later course of ATRA therapy.

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References

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