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Published in: Annals of Hematology 1/2019

01-01-2019 | Original Article

High risk of recurrent venous thromboembolism in BCR-ABL-negative myeloproliferative neoplasms after termination of anticoagulation

Authors: Kai Wille, Parvis Sadjadian, Tatjana Becker, Vera Kolatzki, Anette Horstmann, Christiane Fuchs, Martin Griesshammer

Published in: Annals of Hematology | Issue 1/2019

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Abstract

Venous thromboembolism (VTE) is a major burden in patients with BCR-ABL-negative myeloproliferative neoplasms (MPN). In addition to cytoreductive treatment anticoagulation is mandatory, but optimal duration of anticoagulation is a matter of debate. In our single center study, we retrospectively included 526 MPN patients. In total, 78 of 526 MPN patients (14.8%) had 99 MPN-associated VTE. Median age at first VTE was 52.5 years (range 23–81). During a study period of 3497 years, a VTE event rate of 1.7% per patient/year was detected. 38.4% (38/99) of all VTEs appeared before or at MPN diagnosis and 55.6% (55/99) occurred at “uncommon” sites like splanchnic or cerebral veins. MPN patients with VTEs were significantly more female (p = 0.028), JAK2 positive (p = 0.018), or had a polycythemia vera (p = 0.009). MPN patients without VTEs were more often CALR positive (p = 0.023). Total study period after first VTE was 336 years with 20 VTE recurrences accounting for a recurrence rate of 6% per patient/year. In 36 of 71 MPN patients with anticoagulation therapy after first VTE event (50.7%), prophylactic anticoagulation was terminated after a median time of 6 months (range 1–61); 13 of those 36 patients (36.1%) had a VTE recurrence after a median of 13 months (range 4–168). In contrast, only three of 35 (8.6%) patients with ongoing anticoagulation had a VTE recurrence (p = 0.0127). Thus, termination of prophylactic anticoagulation was associated with a significantly higher risk of VTE recurrence. Our data suggest that in MPN patients with VTE, a prolonged duration of anticoagulation may be beneficial.
Literature
1.
go back to reference Hultcrantz M, Wilkes SR, Kristinsson SY et al (2015) Risk and cause of death in patients diagnosed with myeloproliferative neoplasms in Sweden between 1973 and 2005: a population-based study. J Clin Oncol 33(20):2285–2295CrossRef Hultcrantz M, Wilkes SR, Kristinsson SY et al (2015) Risk and cause of death in patients diagnosed with myeloproliferative neoplasms in Sweden between 1973 and 2005: a population-based study. J Clin Oncol 33(20):2285–2295CrossRef
2.
go back to reference Kaifie A, Kirschner M, Wolf D et al (2016a) Bleeding, thrombosis, and anticoagulation in myeloproliferative neoplasms (MPN): analysis from the German SAL-MPN-registry. J Hematol Oncol 9:18CrossRefPubMedPubMedCentral Kaifie A, Kirschner M, Wolf D et al (2016a) Bleeding, thrombosis, and anticoagulation in myeloproliferative neoplasms (MPN): analysis from the German SAL-MPN-registry. J Hematol Oncol 9:18CrossRefPubMedPubMedCentral
3.
go back to reference Landolfi R, Marchiolo R, Kutti J et al (2004) Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med 350:114–124CrossRefPubMed Landolfi R, Marchiolo R, Kutti J et al (2004) Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med 350:114–124CrossRefPubMed
4.
go back to reference Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, Wilkins BS, van der Walt JD, Reilly JT, Grigg AP, Revell P, Woodcock BE, Green AR (2005) Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med 353:33–45CrossRefPubMed Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, Wilkins BS, van der Walt JD, Reilly JT, Grigg AP, Revell P, Woodcock BE, Green AR (2005) Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med 353:33–45CrossRefPubMed
5.
go back to reference Goldhaber SZ (2012) Venous thromboembolism: epidemiology and magnitude of the problem. Best Pract Res Clin Haematol 25(3):235–242CrossRefPubMed Goldhaber SZ (2012) Venous thromboembolism: epidemiology and magnitude of the problem. Best Pract Res Clin Haematol 25(3):235–242CrossRefPubMed
6.
go back to reference Sekhar M, McVinnie K, Burroughs AK (2013) Splanchnic vein thrombosis in myeloproliferative neoplasms. Br J Haematol 162(6):730–747CrossRefPubMed Sekhar M, McVinnie K, Burroughs AK (2013) Splanchnic vein thrombosis in myeloproliferative neoplasms. Br J Haematol 162(6):730–747CrossRefPubMed
7.
go back to reference De Stefano V, Martinelli I (2010) Splanchnic vein thrombosis: clinical presentation, risk factors and treatment. Intern Emerg Med 5(6):487–494CrossRefPubMed De Stefano V, Martinelli I (2010) Splanchnic vein thrombosis: clinical presentation, risk factors and treatment. Intern Emerg Med 5(6):487–494CrossRefPubMed
8.
go back to reference Bertozzi I, Bogoni G, Biagetti G, Duner E, Lombardi AM, Fabris F, Randi ML (2017) Thromboses and hemorrhages are common in MPN patients with high JAK2V617F allel burden. Ann Hematol 96(8):1297–1302CrossRefPubMed Bertozzi I, Bogoni G, Biagetti G, Duner E, Lombardi AM, Fabris F, Randi ML (2017) Thromboses and hemorrhages are common in MPN patients with high JAK2V617F allel burden. Ann Hematol 96(8):1297–1302CrossRefPubMed
9.
go back to reference Pei YQ, Wu Y, Wang F, Cui W (2016) Prognostic value of CALR vs. JAK2V617F mutations on splenomegaly, leukemic transformation, thrombosis, and overall survival in patients with primary fibrosis: a meta-analysis. Ann Hematol 95(9):1391–1398CrossRefPubMed Pei YQ, Wu Y, Wang F, Cui W (2016) Prognostic value of CALR vs. JAK2V617F mutations on splenomegaly, leukemic transformation, thrombosis, and overall survival in patients with primary fibrosis: a meta-analysis. Ann Hematol 95(9):1391–1398CrossRefPubMed
10.
go back to reference De Stefano V, Ruggeri M, Cervantes F et al (2016a) High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with vitamin K antagonists. Leukemia 30(10):2032–2038CrossRefPubMed De Stefano V, Ruggeri M, Cervantes F et al (2016a) High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with vitamin K antagonists. Leukemia 30(10):2032–2038CrossRefPubMed
11.
go back to reference Bauersachs R, Berkowitz SD, Brenner B et al (2010) Oral Rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 363(26):2499–2510CrossRef Bauersachs R, Berkowitz SD, Brenner B et al (2010) Oral Rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 363(26):2499–2510CrossRef
12.
go back to reference Buller HR, Prins MH, Lensin AW et al (2012) Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 366(14):1287–1297CrossRefPubMed Buller HR, Prins MH, Lensin AW et al (2012) Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 366(14):1287–1297CrossRefPubMed
13.
go back to reference Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI (2013) Oral Apixaban for the treatment of acute venous thromboembolism. N Engl J Med 369(9):799–808CrossRef Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI (2013) Oral Apixaban for the treatment of acute venous thromboembolism. N Engl J Med 369(9):799–808CrossRef
14.
go back to reference Buller HR, Decousus H, Grosso MA et al (2013) Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 369(15):1406–1415CrossRefPubMed Buller HR, Decousus H, Grosso MA et al (2013) Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 369(15):1406–1415CrossRefPubMed
15.
go back to reference Hernandez-Boluda JC, Arellano-Rodrigo E, Cervantes F et al (2015) Oral anticoagulation to prevent thrombosis recurrence in polycythemia vera and essential thrombocythemia. Ann Hematol 94(6):911–918CrossRefPubMed Hernandez-Boluda JC, Arellano-Rodrigo E, Cervantes F et al (2015) Oral anticoagulation to prevent thrombosis recurrence in polycythemia vera and essential thrombocythemia. Ann Hematol 94(6):911–918CrossRefPubMed
16.
go back to reference Ellis MH, Lavi N, Vannucchi A, Harrison C (2014) Treatment of thrombembolic events coincident with the diagnosis of myeloproliferative neoplasms: a physicians survey. Thromb Res 134:251–254CrossRefPubMed Ellis MH, Lavi N, Vannucchi A, Harrison C (2014) Treatment of thrombembolic events coincident with the diagnosis of myeloproliferative neoplasms: a physicians survey. Thromb Res 134:251–254CrossRefPubMed
17.
go back to reference De Stefano V, Za T, Rossi E et al (2008) Recurrent thrombosis in patients with polycythemia vera and essential thrombocythemia: incidence, risk factors and effect of treatments. Haematologica 93(3):372–380CrossRefPubMed De Stefano V, Za T, Rossi E et al (2008) Recurrent thrombosis in patients with polycythemia vera and essential thrombocythemia: incidence, risk factors and effect of treatments. Haematologica 93(3):372–380CrossRefPubMed
19.
go back to reference Kreher S, Ochsenreither S, Trappe RU, Pabinger I, Bergmann F, Petrides PE, Koschmieder S, Matzdorff A, Tiede A, Griesshammer M, Riess H (2014) Prophylaxis and management of venous thromboembolism in patients with myeloproliferative neoplasm: consensus statement of DGHO, ÖGHO and GTH. Ann Hematol 93(12):1953–1963CrossRefPubMed Kreher S, Ochsenreither S, Trappe RU, Pabinger I, Bergmann F, Petrides PE, Koschmieder S, Matzdorff A, Tiede A, Griesshammer M, Riess H (2014) Prophylaxis and management of venous thromboembolism in patients with myeloproliferative neoplasm: consensus statement of DGHO, ÖGHO and GTH. Ann Hematol 93(12):1953–1963CrossRefPubMed
20.
go back to reference Tefferi A, Barbui T (2017) Polycythemia vera and essential thrombocythemia: 2017 update on diagnosis, risk-stratification and management. Am J Hematol 92(1):94–108CrossRefPubMed Tefferi A, Barbui T (2017) Polycythemia vera and essential thrombocythemia: 2017 update on diagnosis, risk-stratification and management. Am J Hematol 92(1):94–108CrossRefPubMed
21.
go back to reference Kaatz S, Ahmad D, Spyropoulos AC, Schulman S, the Subcommittee on Control of Anticoagulation (2015) Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost 13:2119–2126CrossRef Kaatz S, Ahmad D, Spyropoulos AC, Schulman S, the Subcommittee on Control of Anticoagulation (2015) Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost 13:2119–2126CrossRef
22.
go back to reference Marchioli R, Finazzi G, Landolfi R, Kutti J, Gisslinger H, Patrono C, Marilus R, Villegas A, Tognoni G, Barbui T (2005) Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol 23(10):2224–2232CrossRefPubMed Marchioli R, Finazzi G, Landolfi R, Kutti J, Gisslinger H, Patrono C, Marilus R, Villegas A, Tognoni G, Barbui T (2005) Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol 23(10):2224–2232CrossRefPubMed
23.
go back to reference Marchioli R, Finazzi G, Specchia G, Cacciola R, Cavazzina R, Cilloni D, de Stefano V, Elli E, Iurlo A, Latagliata R, Lunghi F, Lunghi M, Marfisi RM, Musto P, Masciulli A, Musolino C, Cascavilla N, Quarta G, Randi ML, Rapezzi D, Ruggeri M, Rumi E, Scortechini AR, Santini S, Scarano M, Siragusa S, Spadea A, Tieghi A, Angelucci E, Visani G, Vannucchi AM, Barbui T (2013) Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med 368(1):22–33CrossRefPubMed Marchioli R, Finazzi G, Specchia G, Cacciola R, Cavazzina R, Cilloni D, de Stefano V, Elli E, Iurlo A, Latagliata R, Lunghi F, Lunghi M, Marfisi RM, Musto P, Masciulli A, Musolino C, Cascavilla N, Quarta G, Randi ML, Rapezzi D, Ruggeri M, Rumi E, Scortechini AR, Santini S, Scarano M, Siragusa S, Spadea A, Tieghi A, Angelucci E, Visani G, Vannucchi AM, Barbui T (2013) Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med 368(1):22–33CrossRefPubMed
24.
go back to reference Gissliner H, Gotic M, Holowiecki J et al (2013) Anagrelid compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial. Blood 121(10):1720–1728CrossRef Gissliner H, Gotic M, Holowiecki J et al (2013) Anagrelid compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial. Blood 121(10):1720–1728CrossRef
25.
go back to reference Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, Randi ML, Bertozzi I, Vannucchi AM, Antonioli E, Gisslinger H, Buxhofer-Ausch V, Finazzi G, Gangat N, Tefferi A, Barbui T (2011) Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 891 patients. Blood 117(22):5857–5859CrossRefPubMed Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, Randi ML, Bertozzi I, Vannucchi AM, Antonioli E, Gisslinger H, Buxhofer-Ausch V, Finazzi G, Gangat N, Tefferi A, Barbui T (2011) Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 891 patients. Blood 117(22):5857–5859CrossRefPubMed
26.
go back to reference Barbui T, Carobbio A, Cervantes F, Vannucchi AM, Guglielmelli P, Antonioli E, Alvarez-Larran A, Rambaldi A, Finazzi G, Barosi G (2010) Thrombosis in primary myelofibrosis: incidence and risk factors. Blood 115(4):778–782CrossRefPubMed Barbui T, Carobbio A, Cervantes F, Vannucchi AM, Guglielmelli P, Antonioli E, Alvarez-Larran A, Rambaldi A, Finazzi G, Barosi G (2010) Thrombosis in primary myelofibrosis: incidence and risk factors. Blood 115(4):778–782CrossRefPubMed
27.
go back to reference Kaifie A, Kirschner M, Wolf D et al (2016) Bleeding, thrombosis, and anticoagulation in myeloproloferative neoplasms (MPN): analysis from the German SAL-MPN-registry. J Hematol Oncol 9:18CrossRefPubMedPubMedCentral Kaifie A, Kirschner M, Wolf D et al (2016) Bleeding, thrombosis, and anticoagulation in myeloproloferative neoplasms (MPN): analysis from the German SAL-MPN-registry. J Hematol Oncol 9:18CrossRefPubMedPubMedCentral
28.
go back to reference Cervantes F, Alvarez-Larran A, Arellano-Rodrigo E et al (2006) Frequency and risk factors for thrombosis in idiopathic myelofibrosis: analysis in a serie of 155 patients from a single institution. Leukemia 20(1):55–60CrossRefPubMed Cervantes F, Alvarez-Larran A, Arellano-Rodrigo E et al (2006) Frequency and risk factors for thrombosis in idiopathic myelofibrosis: analysis in a serie of 155 patients from a single institution. Leukemia 20(1):55–60CrossRefPubMed
29.
go back to reference De Stefano V, Vannucchi AM, Ruggeri M et al (2016b) Splanchnic vein thrombosis in myeloproliferative neoplasms: risk factors for recurrences in a cohort of 181 patients. Blood Cancer J 6(11):e493CrossRefPubMedPubMedCentral De Stefano V, Vannucchi AM, Ruggeri M et al (2016b) Splanchnic vein thrombosis in myeloproliferative neoplasms: risk factors for recurrences in a cohort of 181 patients. Blood Cancer J 6(11):e493CrossRefPubMedPubMedCentral
30.
go back to reference Haider M, Gangat N, Lasho T, Abou Hussein AK, Elala YC, Hanson C, Tefferi A (2016) Validation of the revised international prognostic score of thrombosis for essential thrombocythemia (IPSET-thrombosis) in 585 Mayo Clinic patients. Am J Hematol 91:390–394CrossRefPubMed Haider M, Gangat N, Lasho T, Abou Hussein AK, Elala YC, Hanson C, Tefferi A (2016) Validation of the revised international prognostic score of thrombosis for essential thrombocythemia (IPSET-thrombosis) in 585 Mayo Clinic patients. Am J Hematol 91:390–394CrossRefPubMed
31.
go back to reference Kearon C, Ginsberg JS, Anderson DR et al (2003) Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thrombembolism. N Engl J Med 349(7):631–639CrossRefPubMed Kearon C, Ginsberg JS, Anderson DR et al (2003) Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thrombembolism. N Engl J Med 349(7):631–639CrossRefPubMed
32.
go back to reference Lussana F, Caberlon S, Pagani C, Kamphuisen PW, Büller HR, Cattaneo M (2009) Association of V617F JAK2 mutation with the risk of thrombosis among patients with essential thrombocythemia or idiopathic myelofibrosis: a systematic review. Thromb Res 124(4):409–417CrossRefPubMed Lussana F, Caberlon S, Pagani C, Kamphuisen PW, Büller HR, Cattaneo M (2009) Association of V617F JAK2 mutation with the risk of thrombosis among patients with essential thrombocythemia or idiopathic myelofibrosis: a systematic review. Thromb Res 124(4):409–417CrossRefPubMed
33.
go back to reference Finazzi MC, Carobbio A, Cervantes F, Isola IM, Vannucchi AM, Guglielmelli P, Rambaldi A, Finazzi G, Barosi G, Barbui T (2015) CALR mutation, MPL mutation and triple negativitiy identify patients with lowest vascular risk in primary myelofibrosis. Leukemia 29(5):1209–1210CrossRefPubMed Finazzi MC, Carobbio A, Cervantes F, Isola IM, Vannucchi AM, Guglielmelli P, Rambaldi A, Finazzi G, Barosi G, Barbui T (2015) CALR mutation, MPL mutation and triple negativitiy identify patients with lowest vascular risk in primary myelofibrosis. Leukemia 29(5):1209–1210CrossRefPubMed
Metadata
Title
High risk of recurrent venous thromboembolism in BCR-ABL-negative myeloproliferative neoplasms after termination of anticoagulation
Authors
Kai Wille
Parvis Sadjadian
Tatjana Becker
Vera Kolatzki
Anette Horstmann
Christiane Fuchs
Martin Griesshammer
Publication date
01-01-2019
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology / Issue 1/2019
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-018-3483-6

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