Clinical bleeding events and laboratory coagulation profiles in acute promyelocytic leukemia

Chang, Hong-Yeh; Kuo, Ming‐Chung; Shih, Lee‐Yung; Dunn, Po; Wang, Po‐Nan; Wu, Jin‐Hou; Lin, Tung‐Liang; Hung, Yu‐Shin; Tang, Tzung‐Chih

doi:10.1111/j.1600-0609.2011.01747.x

Cited by 83 publications

(52 citation statements)

References 21 publications

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“…Coagulation disorders are frequently observed in APL and can also occur in other AL subtypes (28)(29)(30). The pathogenic mechanism underlying the blood coagulation disorder in these patients is complex.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of D-dimer and lactate dehydrogenase plasma levels in patients with relapsed acute leukemia

Wang

Yang

2016

Oncology Letters

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Abstract. Despite the outstanding advances made over the past decade regarding our knowledge of acute leukemia (AL), relapsed AL remains to be associated with a dismal prognosis. A better understanding of AL relapse and monitoring of the D-dimer and lactate dehydrogenase (LDH) plasma levels following chemotherapy may aid clinicians in determining whether relapse may occur in the subsequent phases of the disease. The present study evaluated D-dimer and LDH levels in 204 patients with relapsed AL. Data were collected at the initial onset of AL, at complete remission (CR) and in patients with relapsed AL. D-dimer plasma levels were significantly increased in patients with initial AL and in patients with relapsed AL (P=0.005 and P=0.007, respectively) but not in those with CR. LDH levels were significantly increased in AL patients at the initial onset of disease and at relapse compared with patients achieving CR, irrespective of cell type. Plasma prothrombin time, activated partial thromboplastin time and fibrinogen levels were not significantly different across patients (with the exception of acute promyelocytic leukemia patients) at the initial onset, relapsed AL or CR. Routine hematological parameters (white blood cell count, hemoglobin, platelet count) were significantly different at the initial onset of AL (P=0.002, P<0.001 and P=0.001, respectively) and during relapsed AL (P=0.009, P=0.003 and P<0.001, respectively) compared with patients achieving CR, suggesting an association between D-dimer, LDH and relapsed AL. These results also indicate that determination of D-dimer and LDH levels may be useful for predicting the probability of relapse during chemotherapy, but should also be combined with routine hematological parameters.

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Section: Discussionmentioning

confidence: 99%

Evaluation of D-dimer and lactate dehydrogenase plasma levels in patients with relapsed acute leukemia

Wang

Yang

2016

Oncology Letters

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“…11,13,14,[19][20][21] The risk factors identified as independent predictors of severe bleeding in multivariate analysis vary between published studies, and only 3 of those cohorts have .200 participants. With this in mind, uncertainty persists as to what are the best independent predictors of bleeding mortality during induction chemotherapy for APL.…”

Section: Introductionmentioning

confidence: 99%

Determinants of fatal bleeding during induction therapy for acute promyelocytic leukemia in the ATRA era

Mantha¹,

Goldman

Devlin

et al. 2017

Blood

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• High WBC is an independent predictor of early HD in APL.Acute promyelocytic leukemia (APL) is commonly complicated by a complex coagulopathy. Uncertainty remains as to which markers of bleeding risk are independent predictors. Drawing from 5 large clinical trials that included all-trans retinoic acid (ATRA) as part of induction, we assessed known determinants of bleeding at baseline and evaluated them as potential predictors of hemorrhagic death (HD) in the first 30 days of treatment. The studies included were ALLG APML3 (single arm of ATRA 1 idarubicin 6 prednisone), ALLG APML4 (single arm of ATRA 1 idarubicin 1 arsenic trioxide 1 prednisone), CALGB C9710 (single arm of ATRA 1 cytarabine 1 daunorubicin), Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) E2491 (intergroup I0129, consisting of daunorubicin 1 cytarabine vs ATRA), and SWOG S0521 (single-arm induction of ATRA 1 cytarabine 1 daunorubicin). A total of 1009 patients were included in the original trials, of which 995 had sufficient data to be included in our multivariate analysis. In this final cohort, there were 37 HD cases during the first 30 days following induction, for an estimated cumulative incidence of 3.7% (95% confidence interval [CI], 2.6% to 5.0%). Using multivariate Cox proportional hazards regression, the hazard ratio of HD in the first 30 days was 2.17 (95% CI, 0.84-5.62) for an ECOG performance status of 3-4 vs 0-2 and 5.20 (95% CI, 2.70-10.02) for a white blood cell count of ‡20 000/mL vs <20 000/mL. In this large cohort of APL patients, high white blood cell count emerged as an independent predictor

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“…The most important clinical feature of APL is life-threatening hemorrhage, which is caused mainly by enhanced fibrinolytic-type disseminated intravascular coagulation (DIC). Although the true incidence of DIC in APL patients is unknown, a recent epidemiological survey conducted in Taiwan found that 90 (77.6 %) of 116 APL patients developed overt DIC [3].…”

Section: Introductionmentioning

confidence: 99%

Pathogenesis of disseminated intravascular coagulation in patients with acute promyelocytic leukemia, and its treatment using recombinant human soluble thrombomodulin

Ikezoe

2013

Int J Hematol

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Acute promyelocytic leukemia (APL) is an uncommon subtype of acute myelogenous leukemia characterized by the proliferation of blasts with distinct morphology, a specific balanced reciprocal translocation t(15;17), and life-threatening hemorrhage caused mainly by enhanced fibrinolytic-type disseminated intravascular coagulation (DIC). The introduction of all-trans retinoic acid (ATRA) into anthracycline-based induction chemotherapy regimens has dramatically improved overall survival of individuals with APL, although hemorrhagerelated death during the early phase of therapy remains a serious problem. Moreover, population-based studies have shown that the incidence of early death during induction chemotherapy is nearly 30 %, and the most common cause of death is associated with hemorrhage. Thus, development of a novel treatment strategy to alleviate abnormal coagulation in APL patients is urgently required. Recombinant human soluble thrombomodulin (rTM) comprises the active extracellular domain of TM, and has been used for treatment of DIC since 2008 in Japan. Use of rTM in combination with remission induction chemotherapy, including ATRA, produces potent resolution of DIC without exacerbation of bleeding tendency in individuals with APL. This review article discusses the pathogenesis and features of DIC caused by APL, as well as the possible anticoagulant and anti-leukemic action of rTM in APL patients.

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Clinical bleeding events and laboratory coagulation profiles in acute promyelocytic leukemia

Cited by 83 publications

References 21 publications

Evaluation of D-dimer and lactate dehydrogenase plasma levels in patients with relapsed acute leukemia

Evaluation of D-dimer and lactate dehydrogenase plasma levels in patients with relapsed acute leukemia

Determinants of fatal bleeding during induction therapy for acute promyelocytic leukemia in the ATRA era

Pathogenesis of disseminated intravascular coagulation in patients with acute promyelocytic leukemia, and its treatment using recombinant human soluble thrombomodulin

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