Disseminated intravascular coagulation at diagnosis is a strong predictor for thrombosis in acute myeloid leukemia

Abstract

Key Points• A high D-dimer level strongly predicts symptomatic venous and arterial thrombosis in newly diagnosed AML.• Thrombosis occurs in up to 10% of patients with newly diagnosed AML.Venous thromboembolism is a common complication in patients with cancer, but only limited data are available in acute myeloid leukemia (AML). In a prospective study in a cohort of 272 adult patients (aged 18-65) and an independent validation cohort of 132 elderly adults (aged >60) with newly diagnosed AML, we assessed markers of disseminated intravascular coagulation (DIC) (fibrinogen, D-dimer, a-2-antiplasmin, antitrombin, prothrombin time, and platelet count) and the DIC score according the International Society of Thrombosis and Haemostasis and their associations with the occurrence of venous and arterial thrombosis during follow-up. The prevalence of thrombosis was 8.7% (4.7% venous, 4.0% arterial) in the younger adults over a median follow-up of 478 days and 10.4% (4.4% venous, 5.9% arterial) in elderly patients. Most thrombotic events (66%) occurred before the start of the second course of chemotherapy. The calculated DIC score significantly predicted venous and arterial thrombosis with a hazard ratio (HR) for a high DIC score ( ‡5) of 4.79 (1.71-13.45). These results were confirmed in the validation cohort of elderly patients with AML ). Among all DIC parameters, D-dimer levels are most predictive for thrombosis with an HR of 12.3 (3.39-42.64) in the first cohort and an HR of 7.82 (1.95-31.38) in validation cohort for a D-dimer >4 mg/L vs £4 mg/L. It is concluded that venous and arterial thrombosis may develop in ∼10% of AML patients treated with intensive chemotherapy, which to a large extent can be predicted by the presence of DIC at time of AML diagnosis.

A minor role of asparaginase in predisposing to cerebral venous thromboses in adult acute lymphoblastic leukemia patients

“…Regrettably, antithrombin levels that have been shown to increase the risk of thrombosis were not routinely collected at the time of patient enrolment in this study . A recent study on acute myeloid leukemia patients suggests that a situation parallel with disseminated intravascular coagulopathy (i.e., low platelet count, low TT%, and high D‐dimer) could increase the risk of venous thrombosis . Unfortunately, although our CVT patients showed a decreased level of platelets and elevated level of D‐dimer, no TT% was measured at the time of ALL diagnosis.…”

Validation of the Khorana Score in Acute Myeloid Leukemia Patients: A Single Institution Experience

“…In addition to previously known prognostic factors, independent risk factors for thrombosis also include increasing age and cytogenetic risk [32,33]. Recently, disseminated intravascular coagulation was found to be significantly predictive of venous and arterial thrombosis, with thrombosis incidence being approximately 10% among patients who were treated with multiple rounds of chemotherapy [34]. Recent data suggest that malignant leukocytes mediate both disseminated intravascular coagulation and primary hyperfibrinolysis in acute promyelocytic leukemia [35].…”

Can Biomarkers of Coagulation, Platelet Activation, and Inflammation Predict Venous Thromboembolism in Patients with Haematological Malignancies?

“…Concerning haematological malignancies, some predictive models have been developed to identify patients at risk of VTE development, such as the ThroLy score, which was validated by Antic et al [24] in lymphoma patients with variables including previous venous and/or arterial events, mediastinal involvement, BMI > 30, reduced mobility, extranodal localization, development of neutropenia, and haemoglobin < 100 g/L. In newly diagnosed acute myeloid leukaemia (AML) patients, Libourel et al [25] showed that disseminated intravascular coagulation (DIC) markers at diagnosis are strong predictors for both arterial and venous thrombosis.…”