Understanding Thrombosis and Hemorrhage in Myeloproliferative Neoplasms through a Nationwide Study

Introduction

The incidence of Myeloproliferative Neoplasms (MPNs), including Essential Thrombocythemia (ET), Polycythemia Vera (PV), and Primary Myelofibrosis (PMF) are increased. Thrombosis and hemorrhage are major complications of ET and PV. Leukemic transformation is a rare but fatal complication of MPNs. However, their incidence and risk factors of thrombosis and hemorrhage in a nationwide population are not fully known.

Methods

This study used nationwide data from the Korean National Health Insurance System (NHIS). We assessed thrombosis, hemorrhage, and leukemic transformation events in a cohort of all 9,779 patients diagnosed with MPNs during 2011-2016. A Big data formed by the NHIS contains demographic, clinical characteristics (smoking, body mass index, dates of birth, last follow up date, gender), health care utilization, treatment medication and health screening for the whole Korean population (Table 1).

Results

Of total 9,779 patients with MPNs, 5,970 (61.04%) had ET, 2,655(27.2%) PV, 586 (5.9%) PMF, and 568 (5.8%) unspecified MPN (MPN-U). 2,187 (22.4%) patients were diagnosed arterial thromboembolism including cerebral infarction and other thromboembolism during follow-up. And 1,029 (10.5%) patients were diagnosed venous thrombus including pulmonary thromboembolism. 254 (2.6%) patients were diagnosed intracerebral hemorrhage. Secondary leukemia (acute myeloid leukemia (n=482, 4.9%), acute lymphocytic leukemia (n=38, 0.4%), chronic myeloid leukemia (n=423, 4.3%), and chronic lymphocytic leukemia (n=22, 0.2%)) arising from MPNs were noted. Secondary myelofibrosis was noted in 321 (3.3%) patients with MPNs. Multivariate analysis revealed several risk factors for thrombosis and hemorrhage in patients with PV and ET. In patients with PV, age over 60 years (hazard ratio [HR]=2.199, 95% confidence interval [CI]=1.863-2.596, p<0.001), hypertension (HR=1.519, 95% CI=1.269-1.818, p<0.001), and atrial fibrillation/flutter (HR=1.561, 95% CI=1.088-2.241, p=0.016) were identified as significant risk factors for thrombosis. Additionally, age over 60 years (HR=2.896, 95% CI=1.637-5.123, p<0.001) was associated with an increased risk of hemorrhage in patients with PV. In patients with ET, multivariate analysis identified age over 60 years (HR=2.495, 95% CI=2.217-2.809, p<0.001), male sex (HR=1.147, 95% CI=1.034-1.271, p=0.009), hypertension (HR=1.563, 95% CI=1.385-1.764, p<0.001), dyslipidemia (HR=1.216, 95% CI=1.084-1.364, p=0.001), atrial fibrillation/flutter (HR=1.537, 95% CI=1.091-2.165, p=0.014), and hematologic malignancy (HR=1.294, 95% CI=1.097-1.527, p=0.002) as significant risk factors for thrombosis. Moreover, age over 60 years (HR=2.657, 95% CI=1.744-4.048, p<0.001) and hypertension (HR=1.775, 95% CI=1.161-2.713, p=0.008) were found to be significant risk factors for hemorrhage in patients with ET.

Conclusions

This is the first Korean nationwide study to understand thrombosis and hemorrhage in patients with MPNs. This set of data can be utilized to compare the Asian patients with MPNs to international data and guidelines.