Patient outcomes in myeloproliferative neoplasm-related thrombosis: Insights from the National Inpatient Sample

      Highlights

      • Thrombosis in myeloproliferative neoplasms increases mortality and cost of care.
      • There is an inverse relationship between age and cost of care in thrombosis.
      • Length-of-stay is unaffected by the presence or absence of thrombosis.
      • Correlation of patient age and Elixhauser comorbidity index predicts survival.
      • Thrombosis-related hospitalizations among patients with MPNs are on the decline.

      Abstract

      Background

      Philadelphia-negative myeloproliferative neoplasms (MPNs) – polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) – often present with thrombosis. We aimed to determine the inpatient mortality, cost of care, and length-of-stay among individuals with Philadelphia-negative MPNs who had arterial or venous thrombosis associated with admission versus those who were admitted for non-thrombosis-related events.

      Methods

      Using ICD-10M coding, we identified 7,128,770 patients from the National Inpatient Sample (NIS) database who were hospitalized in 2016. 31,302 patients had a diagnosis of a Philadelphia-negative MPN. Mortality, length-of-stay, and cost of care were compared between patients who had thrombosis included among the top three diagnoses and those who were admitted for other reasons. Chi-squared test for categorical variables and t-test for continuous variables were used to compare baseline characteristics. Final multivariable models were constructed to determine predictors of outcomes.

      Results

      Inpatient mortality was significantly higher among individuals with Philadelphia-negative MPN who had thrombosis associated with admission as compared to those who were hospitalized for other reasons (5.7% versus 3.1%, P < 0.001). Unadjusted cost of care was also significantly higher for patients with thrombosis as compared to those without thrombosis ($25,539.06 versus $19,002.72 USD, respectively, P < 0.001). Length-of-stay was longer among the former group as compared to the latter (8.26 versus 7.95 days, P = 0.0963). However, this finding did not reach statistical significance.

      Conclusions

      Hospitalization for MPN-related thrombotic events is associated with excess inpatient mortality and higher cost of care. However, thrombosis has no statistically significant effect on length-of-stay among this population. The underlying causes of mortality and cost disparities among patients with MPN-associated thrombosis warrant further investigation.

      Keywords

      To read this article in full you will need to make a payment
      Subscribe to Thrombosis Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Arber D.A.
        • Orazi A.
        • Hasserjian R.
        • et al.
        The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia.
        Blood. 2016; 127: 2391-2405
        • Mehta J.
        • Wang H.
        • Iqbal S.U.
        • et al.
        Epidemiology of myeloproliferative neoplasms in the United States.
        Leuk Lymphoma. 2014; 55: 595-600
        • Hultcrantz M.
        • Kristinsson S.Y.
        • Andersson T.M.
        • et al.
        Patterns of survival among patients with myeloproliferative neoplasms diagnosed in Sweden from 1973 to 2008: a population-based study.
        J Clin Oncol. 2012; 30: 2995-3001
        • Emanuel R.M.
        • Dueck A.C.
        • Geyer H.L.
        • et al.
        Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs.
        J Clin Oncol. 2012; 30: 4098-4103
        • Casini A.
        • Fontana P.
        • Lecompte T.P.
        Thrombotic complications of myeloproliferative neoplasms: risk assessment and risk-guided management.
        J Thromb Haemost. 2013; 11: 1215-1227https://doi.org/10.1111/jth.12265
        • Barbui T.
        • Carobbio A.
        • Cervantes F.
        • et al.
        Thrombosis in primary myelofibrosis: incidence and risk factors.
        Blood. 2010; 115: 778-782https://doi.org/10.1182/blood-2009-08-238956
        • Tefferi A.
        • Elliott M.
        Thrombosis in myeloproliferative disorders: prevalence, prognostic factors, and the role of leukocytes and JAK2V617F.
        Semin Thromb Hemost. 2007; 33: 313-320https://doi.org/10.1055/s-2007-976165
        • Hulcrantz M.
        • Andersson T.M.
        • Landgren O.
        • et al.
        Risk of arterial and venous thrombosis in 11,155 patients with myeloproliferative neoplasms and 44,620 matched controls: a population-based study.
        Blood. 2014; 124: 632https://doi.org/10.1182/blood.V124.21.632.632
        • Marchioli R.
        • Finazzi G.
        • Landolfi R.
        • et al.
        Vascular and neoplastic risk in a large cohort of patients with polycythemia vera.
        J Clin Oncol. 2005; 23: 2224-2232https://doi.org/10.1200/JCO.2005.07.062
        • Carobbio A.
        • Thiele J.
        • Passamonti F.
        • et al.
        Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 891 patients.
        Blood. 2011; 117: 5857-5859https://doi.org/10.1182/blood-2011-02-339002
        • Buxhofer-Ausch V.
        • Gisslinger H.
        • Thiele J.
        • et al.
        Leukocytosis as an important risk factor for arterial thrombosis in WHO-defined early/prefibrotic myelofibrosis: an international study of 264 patients.
        Am J Hematol. 2012; 87: 669-672https://doi.org/10.1002/ajh.23217
        • McMullin M.F.
        • Mead A.J.
        • Ali S.
        • et al.
        A guideline for management of specific situations in polycythaemia vera and secondary erythrocytosis: a British Society for Haematology Guideline.
        Br J Haematol. 2019; 184: 161-175https://doi.org/10.1111/bjh.15647
        • Reikvam H.
        • Tiu R.V.
        Venous thromboembolism in patients with essential thrombocythemia and polycythemia vera.
        Leukemia. 2012; 26: 563-571https://doi.org/10.1038/leu.2011.314
        • Wendelboe A.M.
        • Raskob G.E.
        Global burden of thrombosis: epidemiologic aspects.
        Circ Res. 2016; 118: 1340-1347https://doi.org/10.1161/CIRCRESAHA.115.306841
        • Grosse S.D.
        • Nelson R.E.
        • Nyarko K.A.
        • et al.
        The economic burden of incident venous thromboembolism in the United States: a review of estimated attributable healthcare costs.
        . 2016; 137: 3-10https://doi.org/10.1016/j.thromres.2015.11.033
        • Mahan C.E.
        • Borrego M.E.
        • Woersching A.L.
        • et al.
        Venous thromboembolism: annualised United States models for total, hospital-acquired and preventable costs utilising long-term attack rates.
        Thromb Haemost. 2012; 108: 291-302https://doi.org/10.1160/TH12-03-0162
        • Quan H.
        • Sundararajan V.
        • Halfon P.
        • et al.
        Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data.
        Med Care. 2005; 43: 1130-1139https://doi.org/10.1097/01.mir.0000182534.19832.83
        • Archer K.J.
        • Lemeshow S.
        Goodness-of-fit test for a logistic regression model fitted using survey sample data.
        The Stata Journal. 2006; 6: 97-105
      1. U.S. Census Bureau. Census 2010 Redistricting Data (Public Law 94-171) Summary File, Tables P1 and P2.

        • Rungjirajittranon T.
        • Owattanapanich W.
        • Ungprasert P.
        • et al.
        A systematic review and meta-analysis of the prevalence of thrombosis and bleeding at diagnosis of Philadelphia-negative myeloproliferative neoplasms.
        BMC Cancer. 2019; 19: 184https://doi.org/10.1186/s12885-019-5387-9
        • Vazquez-Garza E.
        • Jerjes-Sanchez C.
        • Navarrete A.
        • et al.
        Venous thromboembolism: thrombosis, inflammation, and immunothrombosis for clinicians.
        J Thromb Thrombolysis. 2017; 44: 377-385https://doi.org/10.1007/s11239-017-1528-7
        • Falanga A.
        • Marchetti M.
        Thrombosis in myeloproliferative neoplasms.
        Semin Thromb Hemost. 2014; 40: 348-358https://doi.org/10.1055/s-0034-1370794
        • De Stefano V.
        • Ghirardi A.
        • Masciuli A.
        • et al.
        Arterial thrombosis in Philadelphia-negative myeloproliferative neoplasms predicts second cancer: a case-control study.
        Blood. 2020; 135: 381-386https://doi.org/10.1182/blood.2019002614
        • Katiyar V.
        • Uprety A.
        • Mendez-Hernandez A.
        • et al.
        Trends and inpatient outcomes of venous thromboembolism-related admissions in patients with Philadelphia-negative myeloproliferative neoplasms.
        TH Open. 2019; 3: e203-e209https://doi.org/10.1055/s-0039-1692988
        • Bak M.
        • Flachs E.M.
        • Zwisler A.
        • et al.
        Comorbidity and its impact on all-cause mortality in Danish patients with myeloproliferative neoplasms from 1994-2013: a population-based matched cohort study.
        Haematologica. 2015; 100: 99
        • Fernandez M.M.
        • Hogue S.
        • Preblick R.
        • et al.
        Review of the cost of venous thromboembolism.
        Clinicoecon Outcomes Res. 2015; 7: 451-462https://doi.org/10.2147/CEOR.S85635
        • Fanikos J.
        • Rao A.
        • Seger A.C.
        • et al.
        Hospital costs of acute pulmonary embolism.
        Am J Med. 2013; 126: 127-132https://doi.org/10.1016/j.amjmed.2012.07.025
        • Elting L.S.
        • Escalante C.P.
        • Cooksley C.
        • et al.
        Outcomes and cost of deep venous thrombosis among patients with cancer.
        Arch Intern Med. 2004; 164: 1653-1661https://doi.org/10.1001/archinte.164.15.1653
        • Cowper P.A.
        • Knight J.D.
        • Davidson-Ray L.
        • et al.
        Acute and 1-year hospitalization costs for acute myocardial infarction treated with percutaneous coronary intervention: results from the TRANSLATE-ACS registry.
        J Am Heart Assoc. 2019; 8e011322https://doi.org/10.1161/JAHA.118.011322
        • Mehta J.
        • Wang H.
        • Fryzek J.P.
        • et al.
        Health resource utilization and cost associated with myeloproliferative neoplasms in a large United States health plan.
        Leuk Lymphoma. 2014; 55: 2368-2374https://doi.org/10.3109/10428194.2013.879127
        • Tefferi A.
        • Vannucchi A.M.
        • Barbui T.
        Essential thrombocythemia treatment algorithm 2018.
        Blood Cancer J. 2018; 8: 2https://doi.org/10.1038/s41408-017-0041-8
        • Tefferi A.
        • Vannucchi A.M.
        • Barbui T.
        Polycythemia vera treatment algorithm 2018.
        Blood Cancer J. 2018; 8: 3https://doi.org/10.1038/s41408-017-0042-7
        • De Stefano V.
        • Za T.
        • Rossi E.
        • et al.
        Recurrent thrombosis in patients with polycythemia vera and essential thrombocythema: incidence, risk factors, and effect of treatments.
        Haematologica. 2008; 93: 372-380https://doi.org/10.3324/haematol.12053
        • Hernández-Boluda J.C.
        • Arellano-Rodrigo E.
        • Cervantes F.
        • et al.
        Oral anticoagulation to prevent thrombosis recurrence in polycythemia vera and essential thrombocythemia.
        Ann Hematol. 2015; 94: 911-918https://doi.org/10.1007/s00277-015-2330-2
        • Verstovsek S.
        • Vannucchi A.M.
        • Griesshammer M.
        • et al.
        Ruxolitinib versus best available therapy in patients with polycythemia vera: 80-week follow-up from the RESPONSE trial.
        Haematologica. 2016; 101: 821-829https://doi.org/10.3324/haematol.2016.143644
        • Bose P.
        • Verstovsek S.
        JAK2 inhibitors for myeloproliferative neoplasms: what is next?.
        Blood. 2017; 130: 115-125https://doi.org/10.1182/blood-2017-04-742288
        • Borowcyzk M.
        • Wojtaszewska M.
        • Lewandowski K.
        • et al.
        The JAK2 V617F mutational status and allele burden may be related with the risk of venous thromboembolic events in patients with Philadelphia-negative myeloproliferative neoplasms.
        Thromb Res. 2015; 135: 272-280https://doi.org/10.1016/j.thromres.2014.11.006
        • Falchi L.
        • Kantarjian H.M.
        • Verstovsek S.
        Assessing the thrombotic risk of patients with essential thrombocythemia in the genomic era.
        Leukemia. 2017; 31: 1845-1854https://doi.org/10.1038/leu.2017.150