Background: The International Society of Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) score is widely used to predict mortality in critically ill - typically septic - patients. DIC is an acquired condition characterized by systemic activation of coagulation, intravascular fibrin degeneration, consumption of platelets and coagulation factors along with fibrinolytic imbalance. The intravascular coagulation may disseminate and cause a variety of severe and potentially fatal clinical manifestations including major bleedings and thromboembolic events. Patients with hematological malignancies (HM) can present with DIC as defined by the evidence of coagulative disorders, in the absence of thrombo-hemorrhagic manifestations. Despite several studies have already investigated the association between HM, including Acute Myeloid Leukemia (AML) and DIC in adults, which factors and their specific degree of contribution to a worse outcome is still a matter of debate.
Aims: The aim of the present analysis was to investigate whether the ISTH DIC score can be used to predict the 30-day mortality from disease presentation in patients with non-promielocytic (non-M3) AML.
Methods: In this monocentric retrospective study, we included consecutive adult patients (≥18 years of age) who were diagnosed with non-M3 AML between 2010 and 2020. Patients were stratified according to European Leukemia Net 2017 genetic/cytogenetic risk stratification. Patients with documented sepsis at AML presentation were excluded from the study. The ISTH DIC 2018 score was calculated at AML presentation as follows: platelet count (≥100 x 109/L = 0; 50-99,999 x 109/L = 1; <50 x 109/L = 2), fibrinogen level (≥100 mg/dL = 0; <100 mg/dL = 1), PT prolongation above upper limit of normal (ULN) (<3 seconds = 0, 3-6 seconds = 1, >6 seconds = 2), and D-dimer (<3 µg/ml = 0, 3-7 µg/ml = 2, >7 µg/ml = 3). A score sum ≥ 4 identified high-risk patient.
Results: A total of 300 patients were included in this study (39% female; median age 64 years, range 21-90 years). Of them, 174 were treated with intensive chemotherapy, 57 with low intensive therapy and 69 received only supportive care. Seventy-five patients (25%) presented with DIC score ≥ 4 at AML onset. Several factors were significantly associated with DIC score ≥ 4, including diabetes (p=0.038), FLT3 and NPM1 mutations (p=0.024 and p=0.017, respectively), elevated serum LDH (p<0.001) and a leukocyte count above 50x109/L (p=0.002). The 30-days mortality rate was 14,7% (44/300), with 16 patients dying from hemorrhagic or thrombotic complications. A DIC-score ≥ 4 was associated with a significantly higher 30-day mortality rate (28% vs. 9,8%, HR 3.307 95%CI 1.818-6.015; p < 0.001, Figure 1). The independent role of DIC score (0=0.017) and leukocytosis above 50x109/L (p=0.001) in influencing 30-day mortality rate was confirmed in multivariable analysis.
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Summary/Conclusion: The ISTH-DIC score is easy to assess, and this study suggests that it accurately predicts 30-day mortality risk of AML patients, regardless of age and cytogenetic risk. A potential role of DIC score is to select patients who are at high-risk of fatal bleeding and therefore in need of aggressive transfusion support. Further studies on larger population are needed to confirm the findings, and to incorporate DIC score in prognostic models.