Abstract: EP1100

Type: e-Poster

Background
Patients (pts) with Myeloproliferative neoplasms (MPN) are at an increased risk for both thrombosis/thromboembolism and severe bleeding events. Risk factors for thrombosis in MPNs include an age above 60 years, a history of thrombosis, elevated leukocyte counts, and the presence of the JAK2V617F mutation. In the general population, the risk of venous thrombosis is increased by chronic kidney dysfunction (CKD). Retrospective analyses have shown that CKD occurs in a significant proportion of MPN pts and that the estimated glomerular filtration rate (eGFR) may decline during the course of the MPN. However, it is not known whether CKD is associated with thrombosis in MPN nor what the risk factors for decreased kidney function are.

Aims

To assess the prevalence of CKD in MPN pts, its association with thrombosis and bleeding events,  and the risk factors for decreased kidney function.

Methods
This retrospective analysis includes 1979 MPN pts enrolled in 52 centers within the German Study Group for MPN (GSG-MPN) Bioregistry. Pts were subdivided into three subgroups eGFR1, eGFR2, and eGFR3, according to their calculated eGFR (simplified MDRD formula) of >90ml/min, 60-90ml/min, and <60ml/min, resp., and they were assessed for age, sex, the MPN subtype, the presence of thrombosis/thromboembolism (both arterial or venous), severe bleeding, the presence of diabetes mellitus, blood cell parameters (leukocytes, hematocrit, platelets, absolute monocytes, absolute neutrophils), JAK2V617F status, and parameters of proliferative activity and inflammation (LDH, C-reactive protein [CRP], uric acid). Descriptive statistics included chi-square testing and univariate as well as multivariable logistic regression analyses. Probability values of <0.05 were considered significant.

Results
Among, the 1979 pts, 556 had a documented thrombosis/thromboembolism, while 77 pts had documented severe bleeding. 1420 of the pts had classic MPNs: polycythemia vera (PV; 34% of pts), essential thrombocythemia (ET; 38%), or myelofibrosis (MF, comprising pts with PMF/post-PV MF/post-ET MF; 28%). Univariate analysis identified male sex, JAK2V617F positivity, high uric acid, lower platelets, and eGF3 but not age as significant risk factors for thrombosis in this cohort. eGFR1, eGFR2, and eGFR3 comprised 21%, 56%, and 22% of pts, resp., and pts in eGFR3 had significantly more thromboses than those in eGFR1 or eGFR2 (p=0.0044; odds ratios (ORs) of 1.6 and 1.5, resp.). This was particularly evident in pts with PV. Conversely, the rate of severe bleeding was not significantly different among the three eGFR groups. Univariate analysis for factors that are associated with an eGFR <60ml/min and MPN showed significant ORs for elevated LDH, uric acid, CRP, leukocytes, monocytes, neutrophils, platelets, and co-existing diabetes mellitus (age and sex were not included since they are included in the eGFR formula). Of these, LDH and uric acid remained significant upon multivariable regression analysis. Intriguingly, the frequency of JAK2V617F positivity increased from 55% to 62% to 77% in eGFR1, 2, and 3, resp., in ET, but not PV or MF.

Conclusion
In pts with MPN, chronic kidney dysfunction as defined by an eGFR below 60 ml/min is associated with increased thrombosis/thromboembolism but not severe bleeding events. Renal dysfunction was associated with elevated LDH and uric acid serum levels, suggesting that cell hyperproliferation may be causally implicated. Thus, renal dysfunction should not be underestimated in MPN pts, as these pts may require closer monitoring and, possibly, early thromboprophylaxis.

Session topic: 16. Myeloproliferative neoplasms - Clinical

Keyword(s): Myeloproliferative disorder, Renal impairment, Risk factor, Thrombosis