Management of Venous Thromboembolism (VTE) in Patients with Acute Leukemia: Results from a Multicenter Study

Background

In the last decades, evaluation of thrombotic complications secondary to acute leukemia (AL) has been poorly investigated. Only scant data are available on management and prevention of thrombosis in this setting. We performed a multicenter retrospective study with the aim to evaluate the management of venous thromboembolism (VTE) in patients with AL and to report the most commonly adopted regimens of treatment.

Materials and methods

Available clinical records of out and in-patients diagnosed with AL from January 2008 to June 2013 in 7 Reference Regional Hospitals were analyzed. Cases of VTE, including thrombosis in atypical sites [Retinal occlusion (RO) and Cerebral Sinus Thrombosis (SCT)], were reported. All data were recorded in a dedicated electronic database. The patient’s basic demographic data (age, gender, race), medical history, disease-related information, and laboratory data were extracted. Instrumental diagnosis of deep vein thrombosis (DVT), pulmonary embolism (PE) and RO and SCT was performed according to ACCP guidelines. Data were collected and analysed by the IBM SPSS Software 21.0 version (SPSS, Inc., Chicago, Ill, US) and the Epi Info software, version 3.2.2, (Centers for Disease Control and Prevention). Statistical analysis of quantitative and qualitative data, included descriptive statistics, was performed for all the items.

Results

Over a population of 1461 patients with AL, 99 (6.8%) cases of VTE were recorded, mainly in hospitalized patients: 72 cases were associated with Acute Myeloid Leukemia (AML) and 27 with Acute Lymphoblastic Leukemia (ALL), with a mean age of 52.2 ± 15.4 years (median age: 53years). In particular the incidence/ratio over the sub-population of AML-patients was 6.0%, that is 72/1191 cases; with a mean age of 54.7 ± 14.3 years (median age: 57 years). VTE occurred during chemotherapy (CHT) in 90/99 (90%) cases, mainly during the induction phase of treatment (in 70% of cases ),the remaining 9 cases were diagnosed in concomitance with acute leukemia. In both subgroups with VT, there was no statistical significant difference between time at diagnosis of VT and time at diagnosis of AL. Treatment of VTE was mainly based on Low Molecular Weight Heparin (LMWH), in accordance with results from previous studies and current guidelines (full dosage for the first month from diagnosis and reduced dosage at 75% for the following months). Thrombocytopenia occurred in 55 patients at diagnosis of AL, in 33 cases platelets were <50x10⁹/L. Most VTE episodes (73/99, 73.7%) were treated with LMWH as above reported . In patients with moderate/severe thrombocytopenia, a dose adjusted to platelet count was adopted; most of the investigators used LMWH at prophylactic dosage. Two cases received fondaparinux, one patient was treated with unfractioned heparin; six cases did not receive any treatment due to severe thrombocytopenia. No cases of VT–related deaths nor fatal complications during treatment for VTE were reported. All treatments with LMWH lasted from 3 to 6 months. All patients clinically recovered from VTE, only 2 late recurrences (PEs) were observed.

Conclusion

VTE can complicate the clinical course of AL in a not negligible percentage of cases. Anticoagulant treatment schedules and duration in patients with AL are influenced by many factors, mainly related to chemotherapy and severe thrombocytopenia. In the analyzed subset of patients, full dose treatment with LMWH for at least one month followed by a dose reduction for at least three months was appropriate.