KIDNEY DYSFUNCTION IS ASSOCIATED WITH INCREASED THROMBOSIS BUT NOT SEVERE BLEEDING EVENTS IN PATIENTS WITH MYELOPROLIFERATIVE NEOPLASMS: AN ANALYSIS FROM THE GERMAN GSG-MPN BIOREGISTRY
Author(s): ,
Judith Gecht
Affiliations:
Dept. of Hematology, Oncology, Hemostaseology, and SCT,Faculty of Medicine, RWTH Aachen University,Aachen,Germany
,
Ioannis Tsoukakis
Affiliations:
Dept. of Hematology, Oncology, Hemostaseology, and SCT,Faculty of Medicine, RWTH Aachen University,Aachen,Germany;Department of Medicine, Hematology/Oncology,Goethe-University,Frankfurt,Germany
,
Kim Kricheldorf
Affiliations:
Dept. of Hematology, Oncology, Hemostaseology, and SCT,Faculty of Medicine, RWTH Aachen University,Aachen,Germany
,
Frank Stegelmann
Affiliations:
Department of Internal Medicine III,University Hospital of Ulm,Ulm,Germany
,
Martine Klausmann
Affiliations:
Studienzentrum Aschaffenburg,Aschaffenburg,Germany
,
Martin Griesshammer
Affiliations:
Johannes Wesling Medical Center Minden, University Clinic for Hematology, Oncology, Hemostaseology, and Palliative Care, UKRUB,University of Bochum,Minden,Germany
,
Holger Schulz
Affiliations:
Oncological Practice,Frechen,Germany
,
Wiebke Hollburg
Affiliations:
HOPA-Hämatologisch-Onkologische Praxis Altona,Hamburg,Germany
,
Joachim R. Göthert
Affiliations:
Department of Hematology,University Hospital Essen,Essen,Germany
,
Katja Sockel
Affiliations:
Medical Clinic and Policlinic I,University Hospital Carl Gustav Carus, TU Dresden,Dresden,Germany
,
Florian H. Heidel
Affiliations:
Department of Hematology/Oncology, Clinic of Internal Medicine II,Jena University Hospital,Jena,Germany
,
Norbert Gattermann
Affiliations:
Department of Hematology, Oncology, and Clinical Immunology,Heinrich Heine University Düsseldorf,Düsseldorf,Germany
,
Christoph Maintz
Affiliations:
MWZ-West Hematology-Oncology,Würselen,Germany
,
Haifa K. Al-Ali
Affiliations:
Department of Hematology/Oncology,University Hospital Halle,Halle,Germany
,
Uwe Platzbecker
Affiliations:
Medical Clinic and Policlinic I, Hematology and Cellular Therapy,Leipzig University Hospital,Leipzig,Germany
,
Richard Hansen
Affiliations:
Oncological Practice Dres. Hansen & Reeb,Kaiserslautern,Germany
,
Mathias Hänel
Affiliations:
Department of Internal Medicine III,Klinikum Chemnitz,Chemnitz,Germany
,
Stefani Parmentier
Affiliations:
Department of Hematology and Oncology,Rems-Murr-Klinikum Winnenden,Winnenden,Germany
,
Martin Bommer
Affiliations:
Department of Hematology, Oncology, Infectious Diseases and Palliative Care,Alb-Fils-Kliniken,Göppingen,Germany
,
Heike L. Pahl
Affiliations:
Department of Medicine I, Hematology and Oncology,University Medical Center Freiburg, Faculty of Medicine, University of Freiburg,Freiburg,Germany
,
Fabian Lang
Affiliations:
Department of Medicine, Hematology/Oncology,Goethe-University,Frankfurt,Germany
,
Susanne Isfort
Affiliations:
Dept. of Hematology, Oncology, Hemostaseology, and SCT,Faculty of Medicine, RWTH Aachen University,Aachen,Germany
,
Tim H. Brümmendorf
Affiliations:
Dept. of Hematology, Oncology, Hemostaseology, and SCT,Faculty of Medicine, RWTH Aachen University,Aachen,Germany
,
Konstanze Döhner
Affiliations:
Department of Internal Medicine III,University Hospital of Ulm,Ulm,Germany
Steffen Koschmieder
Affiliations:
Dept. of Hematology, Oncology, Hemostaseology, and SCT,Faculty of Medicine, RWTH Aachen University,Aachen,Germany
EHA Library. Koschmieder S. 06/12/20; 293589; EP1100
Prof. Dr. Steffen Koschmieder
Prof. Dr. Steffen Koschmieder
Contributions
Abstract

Abstract: EP1100

Type: e-Poster

Presentation during EHA25: All e-Poster presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

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

Abstract: EP1100

Type: e-Poster

Presentation during EHA25: All e-Poster presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

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

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