Vol.15, No 2, 2008 pp. 41 - 45
UC 616-005.6:616.155.392-085:[615.31:577.161.1
THROMBOSIS IN ACUTE PROMYELOCYTIC LEUKEMIA
PATIENTS TREATED BY ALL-TRANS RETINOIC ACID (ATRA) –
A PROSPECTIVE RESEARCH THROMBOSIS INDUCED
BY ATRA TREATMENT
Lana Đ. Mačukanović-Golubović1,
Ankica V. Jelenković1, Mladen M. Milenović1,
Goran Marjanović1, Emina Dimitrijević2
1Clinic of Hematology Niš, University
of Niš, Faculty of Medicine, Serbia
2Clinic of Cardiovascular Diseases,
University of Niš, Faculty of Medicine, Serbia
E-mail: golubovicz@bankerinter.net
Summary. Acute promyelocytic leukemia (APL) is characterized by
clone proliferation and accumulation of promyelocytes with characteristic
morphology, fibrinolysis, proteolysis and disseminated intravascular coagulation.
It is accepted that all-trans retinoic acid (ATRA) alone or combined with
cytostatics, has to be used in the first swing of APL, in APL resistant
to cytostatics and in relapse of APL treated by cytostatics. Though usually
well tolerated, ATRA can induce side effects known as ATRA syndrome. Deep
vein thrombosis is a rare complication of ATRA treatment. In a four years
long prospective research, we determined the incidence and the risk of
thrombosis in APL patients treated by ATRA. The study involved 12 APL patients
of both gender, with median age of 47.8 years. All patients received 110995
mg of ATRA in total, 9246.25 mg per person IN average. A deep vein thrombosis
developed in one patient (8.3 %) after receiving ATRA cumulative dose of
2700 mg. The drug was immediately withdrawn and was reintroduced when thrombosis
disappeared. Thrombosis was probably the consequence of transitory hypercoagulability
caused by the drug. In further three years of ATRA treatment, thrombosis
did not reappear. The patient is still in remission. Careful observation
of each APL patient treated by ATRA is necessary, as well as the early
diagnosis and adequate treatment of ATRA-caused thrombosis.
Key words: Acute promyelocytic
leukemia, ATRA (all-trans retinoic acid), ATRA syndrome, thrombosis
TROMBOZA KOD PACIJENATA SA AKUTNOM PROMIJELOCITNOM
LEUKEMIJOM TRETIRANIH
ALL - TRANS RETINOIČNOM KISELINOM (ATRA)
- PROSPEKTIVNO ISPITIVANJE
Kratak sadržaj: Akutna promijelocitna leukemija (APL) se karakteriše
klonalnom proliferacijom i akumulacijom promijelocita karakteristične
morfologije, fibrinolizom, proteolizom i diseminovanom intravaskulnom koagulacijom.
Opšte je prihvaćeno da se all-trans retinoična kiselina (ATRA), sama
ili u kombinaciji sa citostaticima, koristi u indukciji lečenja APL-a,
u APL rezistentnom na citostatike i u relapsu APL-a tretiranom citostaticima.
Iako se dobro toleriše, ATRA može izazvati neke neželjene efekte, poznate
kao ATRA sindrom. Duboka venska tromboza je retka komplikacija lečenja
ATRA-om. Za četiri godine dugog prospektivnog istraživanja, utvrdili
smo incidencu i rizik od tromboza kod APL bolesnika tretiranih ATRA-om.
Studija je uključivala 12 APL bolesnika, oba pola, prosečnog uzrasta
48,7g. Svi pacijenti, primili su, 110995mg ATRA-e ukupno, 9246,25mg po
osobi u proseku. Duboka venska tromboza razvila se kod jednog pacijenta
(8,3%) posle primanja kumulativne doze od 2700mg ATRA-e. Lek je momentalno
obustavljen i po izlečenju duboke venske tromboze ponovo uključen. Tromboza
je verovatno izazvana tranzitornom hiperkoagulabilnošću krvi izazvane
lekom. U sledeće tri godine ATRA tretmana, tromboza se više nije pojavljivala.
Pacijent je još uvek u remisiji, iako je u poslednjih 12 meseci bez APL
terapije. Neophodna je pažljiva opservacija svakog pacijenta tretiranog
ATRA-om, kao i rana dijagnoza i adekvatno lečenje ATRA-om izazvane tromboze.
Ključne reči: akutna promijelocitna
leukemija, ATRA (all-trans retinoična kiselina), ATRA sindrom, tromboza
