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Published in: International Journal of Hematology 5/2015

01-11-2015 | Original Article

Bleeding complications in BCR-ABL negative myeloproliferative neoplasms: prevalence, type, and risk factors in a single-center cohort

Authors: Elizabeth M. Kander, Sania Raza, Zheng Zhou, Juehua Gao, Anaadriana Zakarija, Brandon J. McMahon, Brady L. Stein

Published in: International Journal of Hematology | Issue 5/2015

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Abstract

The BCR-ABL1-negative myeloproliferative neoplasms (MPN) share an increased risk of thrombotic and hemorrhagic complications. Risk factors for hemorrhage are less well defined than those for thrombosis. Because patients with CALR mutations have higher platelet counts compared to JAK2 V617F-mutated patients, bleeding rates may be increased in this group. Our aim was to retrospectively evaluate whether acquired von Willebrand disease (AvWD), thrombocytosis, mutational status, or treatment history are associated with bleeding in a cohort of MPN patients. Using an electronic database, MPN patients seen between 2005 and 2013 were retrospectively identified using ICD-9 codes and billing records. A bleeding event was defined as one that was identified in the medical record and graded based on the Common Terminology Criteria for Adverse Event (CTCAE) version 4.0. Among 351 MPN patients, 15.6 % experienced 64 bleeding event types. There was no association of bleeding with mutational status, gender, MPN subtype, aspirin use, prior thrombosis, or platelet count at presentation. There was an association between bleeding and older age at diagnosis. aVWD was identified in six patients. In this single-center retrospective study, bleeding events were identified in 15 % of patients, and associated with older age at diagnosis. aVWD was rarely tested for in this cohort.
Literature
1.
go back to reference Tefferi A. Polycythemia vera and essential thrombocythemia: 2013 update on diagnosis, risk-stratification, and management. Am J Hematol. 2013;88:508–16. Tefferi A. Polycythemia vera and essential thrombocythemia: 2013 update on diagnosis, risk-stratification, and management. Am J Hematol. 2013;88:508–16.
2.
go back to reference Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodegherio F, et al. Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 891 patients. Blood. 2011;117:2813–6.CrossRef Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodegherio F, et al. Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 891 patients. Blood. 2011;117:2813–6.CrossRef
3.
go back to reference Elliott MA, Tefferi A. Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol. 2005;128:275–90.CrossRefPubMed Elliott MA, Tefferi A. Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol. 2005;128:275–90.CrossRefPubMed
4.
go back to reference Duan Y, Nie J, Zhang Z, Ji C. Acquired von Willebrand syndrome in a case of polycythemia vera resulting in recurrent and massive bleeding events in the pleural and abdominal cavity. Blood Coagul Fibrinolysis. 2015;26(1):101–3.CrossRefPubMed Duan Y, Nie J, Zhang Z, Ji C. Acquired von Willebrand syndrome in a case of polycythemia vera resulting in recurrent and massive bleeding events in the pleural and abdominal cavity. Blood Coagul Fibrinolysis. 2015;26(1):101–3.CrossRefPubMed
5.
go back to reference Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, et al. Incidence and risk factors for bleeding in 1104 patients with essential thrombocythemia or prefibrotic myelofibrosis diagnosed according to the 2008 WHO criteria. Leukemia. 2012;26(4):716–9.CrossRefPubMed Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, et al. Incidence and risk factors for bleeding in 1104 patients with essential thrombocythemia or prefibrotic myelofibrosis diagnosed according to the 2008 WHO criteria. Leukemia. 2012;26(4):716–9.CrossRefPubMed
6.
go back to reference van Genderen PJ, Michiels JJ. Erythromelalgic, thrombotic and haemorrhagic manifestations of thrombocythaemia. Presse Med. 1994;23(2):73–7.PubMed van Genderen PJ, Michiels JJ. Erythromelalgic, thrombotic and haemorrhagic manifestations of thrombocythaemia. Presse Med. 1994;23(2):73–7.PubMed
7.
go back to reference Papadakis E, Hoffman R, Brenner B. Thrombohemorrhagic complications of myeloproliferative disorders. Blood Rev. 2010;24(6):227–32.CrossRefPubMed Papadakis E, Hoffman R, Brenner B. Thrombohemorrhagic complications of myeloproliferative disorders. Blood Rev. 2010;24(6):227–32.CrossRefPubMed
8.
go back to reference Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and Important changes. Blood. 2009;114:937–51.CrossRefPubMed Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and Important changes. Blood. 2009;114:937–51.CrossRefPubMed
9.
go back to reference Ng C, Motto DG, Di Paola J. Diagnostic approach to von Willebrand disease. Blood. 2015;125(13):2029–37.CrossRefPubMed Ng C, Motto DG, Di Paola J. Diagnostic approach to von Willebrand disease. Blood. 2015;125(13):2029–37.CrossRefPubMed
10.
go back to reference McMahon B, Stein BL. Thrombotic and bleeding complications in classical myeloproliferative neoplasms. Semin Thromb Hemost. 2013;39(1):101–11.PubMed McMahon B, Stein BL. Thrombotic and bleeding complications in classical myeloproliferative neoplasms. Semin Thromb Hemost. 2013;39(1):101–11.PubMed
11.
go back to reference De Stefano V, Za T, Rossi E, Vannucchi AM, Ruggeri M, Elli E, et al. Recurrent thrombosis in patients with polycythemia vera and essential thrombocythemia: incidence, risk factors, and effect of treatments. Haematologica. 2008;93(3):372–80.CrossRefPubMed De Stefano V, Za T, Rossi E, Vannucchi AM, Ruggeri M, Elli E, et al. Recurrent thrombosis in patients with polycythemia vera and essential thrombocythemia: incidence, risk factors, and effect of treatments. Haematologica. 2008;93(3):372–80.CrossRefPubMed
12.
13.
go back to reference Chim CS, Kwong YL, Lie AK, Ma SK, Chan CC, Wong LG, et al. Long-term outcome of 231 patients with essential thrombocythemia: prognostic factors for thrombosis, bleeding, myelofibrosis, and leukemia. Arch Intern Med. 2005;165(22):2651–8.CrossRefPubMed Chim CS, Kwong YL, Lie AK, Ma SK, Chan CC, Wong LG, et al. Long-term outcome of 231 patients with essential thrombocythemia: prognostic factors for thrombosis, bleeding, myelofibrosis, and leukemia. Arch Intern Med. 2005;165(22):2651–8.CrossRefPubMed
14.
go back to reference Campbell PJ, MacLean C, Beer PA, Buck G, Wheatley K, Kiladjian JJ, et al. Correlation of blood counts with vascular complications in essential thrombocythemia: analysis of the prospective PT1 cohort. Blood. 2012;120(7):1409–11.PubMedCentralCrossRefPubMed Campbell PJ, MacLean C, Beer PA, Buck G, Wheatley K, Kiladjian JJ, et al. Correlation of blood counts with vascular complications in essential thrombocythemia: analysis of the prospective PT1 cohort. Blood. 2012;120(7):1409–11.PubMedCentralCrossRefPubMed
15.
go back to reference Marchioli R, Finazzi G, Landolfi R, Kutti J, Gisslinger H, Patrono C, et al. Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol. 2005;23(10):2224–32.CrossRefPubMed Marchioli R, Finazzi G, Landolfi R, Kutti J, Gisslinger H, Patrono C, et al. Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol. 2005;23(10):2224–32.CrossRefPubMed
16.
go back to reference Colombi M, Radaelli F, Zocchi L, Maiolo AT. Thrombotic and hemorrhagic complications in essential thrombocythemia. A retrospective study of 103 patients. Cancer. 1991;67(11):2926–30.CrossRefPubMed Colombi M, Radaelli F, Zocchi L, Maiolo AT. Thrombotic and hemorrhagic complications in essential thrombocythemia. A retrospective study of 103 patients. Cancer. 1991;67(11):2926–30.CrossRefPubMed
17.
go back to reference Passamoni F, Brusamolino E, Lazzarino M, Baraté C, Klersky C, Orlandi E, et al. Efficacy of pipobroman in the treatment of polycythemia vera: long-term results in 163 patients. Haematologica. 2000;85(10):1011–8. Passamoni F, Brusamolino E, Lazzarino M, Baraté C, Klersky C, Orlandi E, et al. Efficacy of pipobroman in the treatment of polycythemia vera: long-term results in 163 patients. Haematologica. 2000;85(10):1011–8.
18.
go back to reference Borowczyk M, Wotjtaszewska M, Lewandowski K, Gil L, Lewandowska M, Lehmann-Kopydlowska L, et al. The JAK2 eV617F 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(2):272–80.CrossRefPubMed Borowczyk M, Wotjtaszewska M, Lewandowski K, Gil L, Lewandowska M, Lehmann-Kopydlowska L, et al. The JAK2 eV617F 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(2):272–80.CrossRefPubMed
19.
go back to reference Rumi E, Pietra D, Pascutto C, Guglielmelli P, Martinez-Trillos A, Casetti I, et al. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Blood. 2014;124(7):1062–9.PubMedCentralCrossRefPubMed Rumi E, Pietra D, Pascutto C, Guglielmelli P, Martinez-Trillos A, Casetti I, et al. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Blood. 2014;124(7):1062–9.PubMedCentralCrossRefPubMed
20.
go back to reference Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369(25):2379–90.CrossRefPubMed Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369(25):2379–90.CrossRefPubMed
21.
go back to reference Tefferi A, Guglielmelli P, Larson DR, Finke C, Wassie EA, Pieri L, et al. Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood. 2014;124(16):2507–13.PubMedCentralCrossRefPubMed Tefferi A, Guglielmelli P, Larson DR, Finke C, Wassie EA, Pieri L, et al. Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood. 2014;124(16):2507–13.PubMedCentralCrossRefPubMed
22.
go back to reference Rotunno G, Mannarelli C, Guglielmelli P, Pacilli A, Pancrazzi A, Pieri L, et al. Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia. Blood. 2014;123(10):1552–5.CrossRefPubMed Rotunno G, Mannarelli C, Guglielmelli P, Pacilli A, Pancrazzi A, Pieri L, et al. Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia. Blood. 2014;123(10):1552–5.CrossRefPubMed
23.
go back to reference Budde U, van Genderen PJ. Acquired von Willebrand Disease in Patients with High Platelet Counts. Semin Thromb Hemost. 1997;23(5):425–31.CrossRefPubMed Budde U, van Genderen PJ. Acquired von Willebrand Disease in Patients with High Platelet Counts. Semin Thromb Hemost. 1997;23(5):425–31.CrossRefPubMed
24.
go back to reference Budde U, Scharf RE, Franke P, Hartmann-Budde K, Dent J, Ruggeri ZM. Elevated platelet count as a cause of abnormal von Willebrand factor multimer distribution in plasma. Blood. 1993;82(6):1749–57.PubMed Budde U, Scharf RE, Franke P, Hartmann-Budde K, Dent J, Ruggeri ZM. Elevated platelet count as a cause of abnormal von Willebrand factor multimer distribution in plasma. Blood. 1993;82(6):1749–57.PubMed
25.
go back to reference Mital A, Prejzner W, Wsiatkowska-Stodulska R, Hellmann A. Factors predisposing to acquired von Willebrand syndrome during the course of polycythemia vera—retrospective analysis of 142 consecutive cases. Thromb Res. 2015 (epub ahead of print). Mital A, Prejzner W, Wsiatkowska-Stodulska R, Hellmann A. Factors predisposing to acquired von Willebrand syndrome during the course of polycythemia vera—retrospective analysis of 142 consecutive cases. Thromb Res. 2015 (epub ahead of print).
Metadata
Title
Bleeding complications in BCR-ABL negative myeloproliferative neoplasms: prevalence, type, and risk factors in a single-center cohort
Authors
Elizabeth M. Kander
Sania Raza
Zheng Zhou
Juehua Gao
Anaadriana Zakarija
Brandon J. McMahon
Brady L. Stein
Publication date
01-11-2015
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 5/2015
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-015-1871-4

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