PB2209 RISK FACTORS OF THROMBOSIS AFTER MPN DIAGNOSIS: A RETROSPECTIVE COHORT OF MPN PATIENTS IN BRAZIL
Authors: Teixeira L.L.C. , Silva W.F. , da Rosa L.I. , Zeinad‐Vallim A.K. , Bendit I. , Rocha V. , Seguro F.S. 
Published: June 2019

Background:

Myeloproliferative Ph‐negative neoplasms (MPN) are a group of heterogeneous clonal hematopoietic disorders with high risk for thrombotic events. Hemorrhage can also occurs, particularly associated with the treatment.

Aims:

Describe risk factors for thrombosis and bleeding in patients with Ph‐negative MPN in a single center in Brazil.

Methods:

We analyzed retrospectively data of 334 patients older than 18 years old, with diagnosis of polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and unclassifiable MPN (U‐MPN) defined by the 2008 WHO criteria from 2012 to 2017. Unadjusted and adjusted analyses were conducted by using Logistic Regression models to determine the association of covariates with binary outcome. All statistical analyses were performed using SAS software (SAS Institute Inc, Cary, NC). The primary endpoint was risk of thrombotic event at any time and secondary endpoints were risk of thrombotic event after the diagnosis and the incidence of major bleeding (MB) events defined by the ISTH criteria.

Results:

Overall, 334 patients with Ph‐negative MPN were recruited. The majority was diagnosed with TE (159/47,6%), followed by PV (92/27,54%), PMF (71/21,26%) and U‐MPN (12/3,6%). The female sex was prevalent (66%) and, at the time of diagnosis, the median age was 56 years. The median follow‐up was 4.9 years (1.3 – 7.7). At least one thrombotic event was found in 42% of the patients during the follow‐up. Among these events, 19% occurred after the MPN diagnosis and arterial thrombosis was more prevalent (61%) being stroke the most frequent event followed by acute coronary syndrome. A subsequent event occurred in less than one third of patients. MB events were seen in just 5%, with 67% related with gastrointestinal bleedings. The incidence of thrombosis and MB was similar among the PV, ET, PMF and U‐MPN as shown in table 1. In a multivariable logistic regression model for thrombosis, age ≥60y (OR 3.01, 95%CI 1.83‐4.95) and JAK2 V617 mutation (OR 3.03 CI 1.81‐5.08) were associated with increased risk of thrombosis at any time. For thrombosis after the diagnosis of MPN, WBC ≥ 7x109/L (OR 2.44, 95%CI 1.03‐5.8), age ≥60y (OR 2.58, 95% CI 1.04‐6.4) and 2 or more CV risk factors (OR 2.4 95% CI 1.02‐5.66) had statistical significance. In our center, all patients with PV have received cytoreductive therapy and none were exclusively treated with phlebotomy, although some patients were defined as low‐risk. Only 4% of the patients with ET received only low‐dose aspirin. Also 43% of the patients harboring a JAK2 V617F mutation already had a thrombotic event before the MPN diagnosis and were treated as high risk.

Summary/Conclusion:

The incidence of thrombosis and MB were similar among all subtypes of MPN as reported by previous studies. In our population, we confirmed that age ≥ 60 years and JAK2 V617F mutation were associated with increased risk of thrombosis at any time. Seemingly, the presence of JAK2 V617F mutation did not increase the risk of thrombosis after the diagnosis of MPN. Since these patients were mostly treated with cytoreductive therapy, we hypothesize that this strategy may abrogate the negative impact of JAK2 mutation reported in previous cohorts. To the best of our knowledge, this is one of the largest cohorts of patients with MPN ever reported in Latin America. Organizing cooperative study groups in Latin America is an urgent need for improving the knowledge in this field.

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