Impact of Thrombosis and Bleeding on Survival of Older People with Myelodysplastic Syndromes (MDS): A Population Analysis

Introduction:

Thrombotic and hemostatic complications are challenging in people with MDS. Thrombotic and bleeding events occurring during the first year after diagnosis may have an impact on outcomes as they shape early therapy, however there is little understanding of their impact on overall survival of MDS.

Objective:

First, we will determine the impact on survival of a VTE or severe bleeding event during the first year following a diagnosis of MDS. Second, we will determine risk factors for VTE and bleeding in this population.

Methods:

Incident MDS cases between 2007 and 2017 were identified in the SEER-Medicare database using published methods. Subjects were followed from the time of diagnosis to up to 2 years for bleeding, VTE, and death. Demographics, baseline comorbidities and validated claim-based risk stratification for MDS (SMMRS) were assessed at diagnosis. Within the first year after diagnosis, incident VTE and bleeding were identified using codes through previously validated algorithms. Subjects with VTE or bleeding one year prior to the MDS diagnosis were excluded. Survival was analyzed as a dichotomous variable at 2 years from diagnosis. We used logistic regression models adjusted for age, sex, race, socioeconomic status, geographic region, comorbidity, and SMMRS to assess the impact of VTE or bleeding on 2-year overall survival of people with MDS. Similarly, we used logistic regression to identify potential risk factors for VTE and bleeding in this population.

Results:

We identified 15,277 MDS subjects with MDS; median age was 82 years and 46% were female. A total of 605 (4%) subjects had VTE and 916 (6%) had hospitalized bleeding during the first year after MDS diagnosis. The 2-year death rate was 59% for those with a VTE event (vs. 52% without VTE) and 70% for those with a bleeding event (vs. 50% for those without bleeding). After adjusting for other risk factors, a VTE event within 1 year after MDS diagnosis was not clearly associated with significant increase in 2-year mortality (OR 1.17, 95% CI 0.97- 1.41), however a severe bleeding event was associated with 68% increased odds of 2-year mortality (OR 1.68, 95% CI 1.43 - 1.97). Compared to White subjects, Blacks had a 76% increased of risk of VTE (OR 1.76, 95% CI 1.31 – 2.36), but there was no race difference in bleeding. Higher comorbidity burden was associated with higher risk of both VTE and bleeding (Charlson Index ≥3, OR 1.80, 95% CI 1.44 - 2.26 and OR 1.89, 95% CI 1.57 - 2.27, respectively). Notably, hypertension (OR 1.33, 95% CI 1.12 - 1.58), diabetes (OR 1.32, 95% CI 1.15 - 1.53) and liver disease (OR 1.47, 95% CI 1.12 - 1.93) were associated with an increased risk of bleeding but not VTE. Higher MDS risk was associated with increased risk of both VTE and bleeding, (SMMRS high risk OR 2.02,95% CI, 1.55 - 2.63 for VTE and OR 4.27, 95% CI 3.37 - 5.41 for bleeding). Recent anticoagulant use increased the bleeding risk by 65% (OR 1.65, 95% CI 1.36 - 2.01) and had no impact on the risk of VTE. Hypomethylating agent (HMA) and erythropoietin stimulating agent use had no impact on VTE or bleeding risk, but lenalidomide use was associated with 56% increased risk of VTE and 36% lower risk of bleeding (OR 1.56 95% CI 1.18 - 2.08 and OR 0.64, 95% CI 0.46 - 0.90, respectively).

Conclusion:

Bleeding but not VTE within the first year of diagnosis in people with MDS is associated with worse survival. While this could be due baseline differences in comorbidity and MDS risk, it could also result from the consequences of bleeding versus VTE on clinical management, with bleeding events more significantly impacting use of disease-modifying therapy such as HMA. We identified risk factors for VTE and bleeding, which may help refine risk assessment and potentially preventing these adverse events.