Thrombotic events in acute promyelocytic leukemia

Mitrović, Mirjana; Suvajdžić, Nada; Elezović, Ivo; Bogdanović, Andrija; Djordjević, Valentina; Miljić, Predrag; Đjunić, Irena; Gvozdenov, Maja; Čolović, Nataša; Virijevic, Marijana; Leković, Danijela; Vidović, Ana; Tomin, Dragica

doi:10.1016/j.thromres.2014.11.026

Cited by 51 publications

(52 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A) Increased occurrence of thrombotic events, as supported by an initial study of Breccia an coworkers on 135 APL patients [43] and recently confirmed by Mitrovic and coworkers on 63 APL patients [44]; the majority of these thrombotic events occurs during the induction phase of treatment. B) Increased white blood cell counts (WBC), as initially described by Kiyoi and coworkers who reported increased WBC counts, as well as peripheral leukemia cell counts, and high LDH levels [39] and confirmed in numerous other studies [45,46].…”

Section: Molecular Prognostic Markersmentioning

confidence: 81%

Prognostic factors in acute promyelocytic leukemia: strategies to define high-risk patients

Testa

Lo‐Coco

2016

Ann Hematol

View full text Add to dashboard Cite

All trans retinoic acid (ATRA) has revolutionized the therapy of acute promyelocytic leukemia (APL). Treatment of this leukemia with ATRA in combination with chemotherapy has resulted in complete remission rates >90 % and long-term remission rates above 80 %. Furthermore, the combination of ATRA and arsenic trioxide (ATO) was shown to be safe and effective in frontline treatment and, for patients with low and intermediate risk disease, possibly superior to the standard ATRA and anthracycline-based regimen. However, in spite of this tremendous progress, APL still remains associated with a high incidence of early death due to the frequent occurrence of an abrupt bleeding diathesis. This hemorrhagic syndrome more frequently develops in high-risk APL patients, currently defined as those exhibiting >10 × 10(9)/L WBC at presentation. In addition to high WBC count, other molecular and immunophenotypic features have been associated with high-risk APL. Among them, the expression in APL blasts of the stem/progenitor cell antigen CD34, the neural adhesion molecule (CD56), and the T cell antigen CD2 help to identify a subset of patients at higher risk of relapse and often the expression of these markers is associated with high WBC count. At the molecular level, the short PML/RARA isoform and FLT3-internal tandem duplication (ITD) mutations have been associated with increased relapse risk. These observations indicate that extended immunophenotypic and molecular characterization of APL at diagnosis including evaluation of CD2, CD56, and CD34 antigens and of FLT3 mutations may help to better design risk-adapted treatment in this disease.

show abstract

Section: Molecular Prognostic Markersmentioning

confidence: 81%

Prognostic factors in acute promyelocytic leukemia: strategies to define high-risk patients

Testa

Lo‐Coco

2016

Ann Hematol

View full text Add to dashboard Cite

show abstract

“…A number of thrombosis risk factors have been identified 16,22 . These risk factors are higher white blood count, bcr 3 isoform of PML/RARA, Internal tandem duplications of FLT3 (FLT3-ITD), plasminogen activator inhibitor-1 (PAI-1) 4G/4G polymorphism, 101 high International Society of Thrombosis and Hemostasis (ISTH) disseminated intravascular coagulation (DIC) score, 102 and coexisting morbidity, such as infection.…”

Section: Thrombosismentioning

confidence: 99%

The Role of Abnormal Hemostasis and Fibrinolysis in Morbidity and Mortality of Acute Promyelocytic Leukemia

Kwaan

Weiss

Tallman

2019

Semin Thromb Hemost

View full text Add to dashboard Cite

Despite the improved therapeutic advances in the management of acute promyelocytic leukemia (APL), a significant early mortality during induction, also referred to as early death (ED), remains an obstacle for further improvement in outcome. Hemorrhagic complications are the most common cause of morbidity and mortality. Perturbed hemostatic dysfunction is present as the result of abnormalities in both the coagulation and the fibrinolytic systems. The activation of coagulation is distinct from the classical disseminated intravascular coagulation. Multiple abnormalities in the fibrinolytic system have recently been identified. The most significant change is increased production of tissue plasminogen activator (tPA) and its receptor annexin A2 by the APL promyelocytes. Among the hemorrhagic complications, intracranial hemorrhage predominates. The pathogenesis of this catastrophic event is elucidated by new evidence of adverse effect of tissue plasminogen activator (tPA) on the brain, including both the plasmin-dependent and plasmin-independent pathways. In order to address the hemorrhagic complications, a thorough understanding of the hemostatic dysfunction is essential. In this article, our current concept of the abnormal hemostasis in APL is reviewed. The failure to reduce the early death rate, despite the introduction of effective therapy, will also be discussed.

show abstract

“…Some series report the thrombotic manifestation of APL with a frequency as high as 2-10% (Chang et al, 2013;Mitrovic et al, 2015). We did not come across any such findings which is rather unusual.…”

Section: Discussionmentioning

confidence: 46%