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Erschienen in: Current Hematologic Malignancy Reports 5/2017

25.09.2017 | Myeloproliferative Neoplasms (B Stein, Section Editor)

Risk Factors for and Management of MPN-Associated Bleeding and Thrombosis

verfasst von: Karlyn Martin

Erschienen in: Current Hematologic Malignancy Reports | Ausgabe 5/2017

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Abstract

Purpose of the Review

The Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are characterized by both thrombotic and bleeding complications. The purpose of this review is to describe the risk factors associated with bleeding and thrombosis in MPN, as well as to review prevention strategies and management of these complications.

Recent Findings

Well-described risk factors for thrombotic complications include older age and history of prior thrombosis, along with traditional cardiovascular and venous thromboembolic risk factors. More recently, JAK2 V617F mutation has been found to carry an increased risk of thrombotic complications, whereas CALR has a lower risk than JAK2 mutation. Factors associated with an increased risk of bleeding in MPN include a prior history of bleeding, acquired von Willebrand syndrome, and primary myelofibrosis. Recent findings suggest that thrombocytosis carries a higher risk of bleeding than thrombosis in MPN, and aspirin may exacerbate this risk of bleeding, particularly in CALR-mutated ET.

Summary

Much of the management of MPN focuses on predicting risk of bleeding and thrombosis and initiating prophylaxis to prevent complications in those at high risk of thrombosis. Emerging evidence suggests that sub-populations may have bleeding risk that outweighs thrombotic risk, particularly in setting of antiplatelet therapy. Future work is needed to better characterize this balance. At present, a thorough assessment of the risks of bleeding and thrombosis should be undertaken for each patient, and herein, we review risk factors for and management of these complications.
Literatur
1.
Zurück zum Zitat 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
2.
Zurück zum Zitat • Appelmann I, Kreher S, Parmentier S, Wolf HH, Bisping G, Kirschner M, et al. Diagnosis, prevention, and management of bleeding episodes in Philadelphia-negative myeloproliferative neoplasms: recommendations by the hemostasis working party of the German Society of Hematology and Medical Oncology (DGHO) and the Society of Thrombosis and Hemostasis Research (GTH). Ann Hematol. 2016;95(5):707–18. Recommendations by DGHO and GTH for the diagnosis and management of bleeding in MPN. PubMedCrossRef • Appelmann I, Kreher S, Parmentier S, Wolf HH, Bisping G, Kirschner M, et al. Diagnosis, prevention, and management of bleeding episodes in Philadelphia-negative myeloproliferative neoplasms: recommendations by the hemostasis working party of the German Society of Hematology and Medical Oncology (DGHO) and the Society of Thrombosis and Hemostasis Research (GTH). Ann Hematol. 2016;95(5):707–18. Recommendations by DGHO and GTH for the diagnosis and management of bleeding in MPN. PubMedCrossRef
3.
Zurück zum Zitat • Kaifie A, Kirschner M, Wolf D, Maintz C, Hänel M, Gattermann N, et al. Bleeding, thrombosis, and anticoagulation in myeloproliferative neoplasms (MPN): analysis from the German SAL-MPN-registry. Journal of hematology & oncology. 2016;9:18. Practice-based data from prospective MPN registry of German Leukemia Alliance to describe the frequency of and risk factors for bleeding and thrombotic complications. CrossRef • Kaifie A, Kirschner M, Wolf D, Maintz C, Hänel M, Gattermann N, et al. Bleeding, thrombosis, and anticoagulation in myeloproliferative neoplasms (MPN): analysis from the German SAL-MPN-registry. Journal of hematology & oncology. 2016;9:18. Practice-based data from prospective MPN registry of German Leukemia Alliance to describe the frequency of and risk factors for bleeding and thrombotic complications. CrossRef
4.
Zurück zum Zitat 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. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005;23(10):2224–32.CrossRef 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. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005;23(10):2224–32.CrossRef
5.
Zurück zum Zitat Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, et al. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005;353(1):33–45.PubMedCrossRef Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, et al. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005;353(1):33–45.PubMedCrossRef
6.
Zurück zum Zitat Barbui T, Carobbio A, Cervantes F, Vannucchi AM, Guglielmelli P, Antonioli E, et al. Thrombosis in primary myelofibrosis: incidence and risk factors. Blood. 2010;115(4):778–82.PubMedCrossRef Barbui T, Carobbio A, Cervantes F, Vannucchi AM, Guglielmelli P, Antonioli E, et al. Thrombosis in primary myelofibrosis: incidence and risk factors. Blood. 2010;115(4):778–82.PubMedCrossRef
7.
Zurück zum Zitat Tefferi A, Rumi E, Finazzi G, Gisslinger H, Vannucchi AM, Rodeghiero F, et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia. 2013;27(9):1874–81.PubMedPubMedCentralCrossRef Tefferi A, Rumi E, Finazzi G, Gisslinger H, Vannucchi AM, Rodeghiero F, et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia. 2013;27(9):1874–81.PubMedPubMedCentralCrossRef
8.
Zurück zum Zitat Bonicelli G, Abdulkarim K, Mounier M, Johansson P, Rossi C, Jooste V, et al. Leucocytosis and thrombosis at diagnosis are associated with poor survival in polycythaemia vera: a population-based study of 327 patients. Br J Haematol. 2013;160(2):251–4.PubMedCrossRef Bonicelli G, Abdulkarim K, Mounier M, Johansson P, Rossi C, Jooste V, et al. Leucocytosis and thrombosis at diagnosis are associated with poor survival in polycythaemia vera: a population-based study of 327 patients. Br J Haematol. 2013;160(2):251–4.PubMedCrossRef
9.
Zurück zum Zitat Barbui T, Thiele J, Passamonti F, Rumi E, Boveri E, Ruggeri M, et al. Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2011;29(23):3179–84.CrossRef Barbui T, Thiele J, Passamonti F, Rumi E, Boveri E, Ruggeri M, et al. Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2011;29(23):3179–84.CrossRef
10.
Zurück zum Zitat • De Stefano V, Ruggeri M, Cervantes F, Alvarez-Larrán A, Iurlo A, Randi ML, et al. High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with vitamin K antagonists. Leukemia. 2016;30(10):2032–8. Demonstrated that vitamin K antagonists (VKA) significantly reduce recurrent VTE, with incidence rates of recurrent MPN doubling after stopping VKA. PubMedCrossRef • De Stefano V, Ruggeri M, Cervantes F, Alvarez-Larrán A, Iurlo A, Randi ML, et al. High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with vitamin K antagonists. Leukemia. 2016;30(10):2032–8. Demonstrated that vitamin K antagonists (VKA) significantly reduce recurrent VTE, with incidence rates of recurrent MPN doubling after stopping VKA. PubMedCrossRef
11.
Zurück zum Zitat • Barbui T, Carobbio A, Rumi E, Finazzi G, Gisslinger H, Rodeghiero F, et al. In contemporary patients with polycythemia vera, rates of thrombosis and risk factors delineate a new clinical epidemiology. Blood. 2014;124(19):3021–3. Describes frequency of arterial and venous thrombotic events, risk factors for such, and sites and frequency of recurrent thrombosis in PV as defined by WHO criteria. PubMedCrossRef • Barbui T, Carobbio A, Rumi E, Finazzi G, Gisslinger H, Rodeghiero F, et al. In contemporary patients with polycythemia vera, rates of thrombosis and risk factors delineate a new clinical epidemiology. Blood. 2014;124(19):3021–3. Describes frequency of arterial and venous thrombotic events, risk factors for such, and sites and frequency of recurrent thrombosis in PV as defined by WHO criteria. PubMedCrossRef
12.
Zurück zum Zitat Ageno W, Dentali F, Pomero F, Fenoglio L, Squizzato A, Pagani G, et al. Incidence rates and case fatality rates of portal vein thrombosis and Budd-Chiari syndrome. Thromb Haemost. 2017;117(4):794–800.PubMedCrossRef Ageno W, Dentali F, Pomero F, Fenoglio L, Squizzato A, Pagani G, et al. Incidence rates and case fatality rates of portal vein thrombosis and Budd-Chiari syndrome. Thromb Haemost. 2017;117(4):794–800.PubMedCrossRef
13.
Zurück zum Zitat Sekhar M, McVinnie K, Burroughs AK. Splanchnic vein thrombosis in myeloproliferative neoplasms. Br J Haematol. 2013;162(6):730–47.PubMedCrossRef Sekhar M, McVinnie K, Burroughs AK. Splanchnic vein thrombosis in myeloproliferative neoplasms. Br J Haematol. 2013;162(6):730–47.PubMedCrossRef
14.
Zurück zum Zitat Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, et al. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004;350(2):114–24.PubMedCrossRef Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, et al. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004;350(2):114–24.PubMedCrossRef
15.
Zurück zum Zitat Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, et al. Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 891 patients. Blood. 2011;117(22):5857–9.PubMedCrossRef Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, et al. Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 891 patients. Blood. 2011;117(22):5857–9.PubMedCrossRef
16.
Zurück zum Zitat Barbui T, Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, et al. Development and validation of an international prognostic score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). Blood. 2012;120(26):5128–33. quiz 252 PubMedCrossRef Barbui T, Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, et al. Development and validation of an international prognostic score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). Blood. 2012;120(26):5128–33. quiz 252 PubMedCrossRef
17.
Zurück zum Zitat • Barbui T, Vannucchi AM, Carobbio A, Rumi E, Finazzi G, Gisslinger H, et al. The effect of arterial hypertension on thrombosis in low-risk polycythemia vera. Am J Hematol. 2017;92(1):E5–6. Demonstrate arterial hypertension is associated with a significant reduction in thrombosis-free survival in low-risk PV. PubMedCrossRef • Barbui T, Vannucchi AM, Carobbio A, Rumi E, Finazzi G, Gisslinger H, et al. The effect of arterial hypertension on thrombosis in low-risk polycythemia vera. Am J Hematol. 2017;92(1):E5–6. Demonstrate arterial hypertension is associated with a significant reduction in thrombosis-free survival in low-risk PV. PubMedCrossRef
18.
Zurück zum Zitat • Barbui T, De Stefano V. Management of venous thromboembolism in myeloproliferative neoplasms. Curr Opin Hematol. 2017;24(2):108–14. Describes frequency, patterns, and management of primary and recurrent venous thromboembolic events in MPN. PubMedCrossRef • Barbui T, De Stefano V. Management of venous thromboembolism in myeloproliferative neoplasms. Curr Opin Hematol. 2017;24(2):108–14. Describes frequency, patterns, and management of primary and recurrent venous thromboembolic events in MPN. PubMedCrossRef
19.
Zurück zum Zitat Ruggeri M, Rodeghiero F, Tosetto A, Castaman G, Scognamiglio F, Finazzi G, et al. Postsurgery outcomes in patients with polycythemia vera and essential thrombocythemia: a retrospective survey. Blood. 2008;111(2):666–71.PubMedCrossRef Ruggeri M, Rodeghiero F, Tosetto A, Castaman G, Scognamiglio F, Finazzi G, et al. Postsurgery outcomes in patients with polycythemia vera and essential thrombocythemia: a retrospective survey. Blood. 2008;111(2):666–71.PubMedCrossRef
20.
Zurück zum Zitat Gangat N, Wolanskyj AP, Schwager SM, Mesa RA, Tefferi A. Estrogen-based hormone therapy and thrombosis risk in women with essential thrombocythemia. Cancer. 2006;106(11):2406–11.PubMedCrossRef Gangat N, Wolanskyj AP, Schwager SM, Mesa RA, Tefferi A. Estrogen-based hormone therapy and thrombosis risk in women with essential thrombocythemia. Cancer. 2006;106(11):2406–11.PubMedCrossRef
21.
Zurück zum Zitat De Stefano V, Za T, Rossi E, Fiorini A, Ciminello A, Luzzi C, et al. Influence of the JAK2 V617F mutation and inherited thrombophilia on the thrombotic risk among patients with essential thrombocythemia. Haematologica. 2009;94(5):733–7.PubMedPubMedCentralCrossRef De Stefano V, Za T, Rossi E, Fiorini A, Ciminello A, Luzzi C, et al. Influence of the JAK2 V617F mutation and inherited thrombophilia on the thrombotic risk among patients with essential thrombocythemia. Haematologica. 2009;94(5):733–7.PubMedPubMedCentralCrossRef
22.
Zurück zum Zitat Ruggeri M, Gisslinger H, Tosetto A, Rintelen C, Mannhalter C, Pabinger I, et al. Factor V Leiden mutation carriership and venous thromboembolism in polycythemia vera and essential thrombocythemia. Am J Hematol. 2002;71(1):1–6.PubMedCrossRef Ruggeri M, Gisslinger H, Tosetto A, Rintelen C, Mannhalter C, Pabinger I, et al. Factor V Leiden mutation carriership and venous thromboembolism in polycythemia vera and essential thrombocythemia. Am J Hematol. 2002;71(1):1–6.PubMedCrossRef
23.
Zurück zum Zitat Gisslinger H, Müllner M, Pabinger I, Heis-Vahidi-Fard N, Gisslinger B, Brichta A, et al. Mutation of the prothrombin gene and thrombotic events in patients with polycythemia vera or essential thrombocythemia: a cohort study. Haematologica. 2005;90(3):408–10.PubMed Gisslinger H, Müllner M, Pabinger I, Heis-Vahidi-Fard N, Gisslinger B, Brichta A, et al. Mutation of the prothrombin gene and thrombotic events in patients with polycythemia vera or essential thrombocythemia: a cohort study. Haematologica. 2005;90(3):408–10.PubMed
24.
Zurück zum Zitat Landolfi R, Di Gennaro L, Barbui T, De Stefano V, Finazzi G, Marfisi R, et al. Leukocytosis as a major thrombotic risk factor in patients with polycythemia vera. Blood. 2007;109(6):2446–52.PubMedCrossRef Landolfi R, Di Gennaro L, Barbui T, De Stefano V, Finazzi G, Marfisi R, et al. Leukocytosis as a major thrombotic risk factor in patients with polycythemia vera. Blood. 2007;109(6):2446–52.PubMedCrossRef
25.
Zurück zum Zitat De Stefano V, Za T, Rossi E, Vannucchi AM, Ruggeri M, Elli E, et al. Leukocytosis is a risk factor for recurrent arterial thrombosis in young patients with polycythemia vera and essential thrombocythemia. Am J Hematol. 2010;85(2):97–100.PubMed De Stefano V, Za T, Rossi E, Vannucchi AM, Ruggeri M, Elli E, et al. Leukocytosis is a risk factor for recurrent arterial thrombosis in young patients with polycythemia vera and essential thrombocythemia. Am J Hematol. 2010;85(2):97–100.PubMed
26.
Zurück zum Zitat Barbui T, Carobbio A, Rambaldi A, Finazzi G. Perspectives on thrombosis in essential thrombocythemia and polycythemia vera: is leukocytosis a causative factor? Blood. 2009;114(4):759–63.PubMedPubMedCentral Barbui T, Carobbio A, Rambaldi A, Finazzi G. Perspectives on thrombosis in essential thrombocythemia and polycythemia vera: is leukocytosis a causative factor? Blood. 2009;114(4):759–63.PubMedPubMedCentral
27.
Zurück zum Zitat Carobbio A, Antonioli E, Guglielmelli P, Vannucchi AM, Delaini F, Guerini V, et al. Leukocytosis and risk stratification assessment in essential thrombocythemia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2008;26(16):2732–6.CrossRef Carobbio A, Antonioli E, Guglielmelli P, Vannucchi AM, Delaini F, Guerini V, et al. Leukocytosis and risk stratification assessment in essential thrombocythemia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2008;26(16):2732–6.CrossRef
28.
Zurück zum Zitat 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
29.
Zurück zum Zitat Buxhofer-Ausch V, Gisslinger H, Thiele J, Gisslinger B, Kvasnicka HM, Müllauer L, 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(7):669–72.PubMedCrossRef Buxhofer-Ausch V, Gisslinger H, Thiele J, Gisslinger B, Kvasnicka HM, Müllauer L, 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(7):669–72.PubMedCrossRef
30.
Zurück zum Zitat Ziakas PD. Effect of JAK2 V617F on thrombotic risk in patients with essential thrombocythemia: measuring the uncertain. Haematologica. 2008;93(9):1412–4.PubMedCrossRef Ziakas PD. Effect of JAK2 V617F on thrombotic risk in patients with essential thrombocythemia: measuring the uncertain. Haematologica. 2008;93(9):1412–4.PubMedCrossRef
31.
Zurück zum Zitat Dahabreh IJ, Zoi K, Giannouli S, Zoi C, Loukopoulos D, Voulgarelis M. Is JAK2 V617F mutation more than a diagnostic index? A meta-analysis of clinical outcomes in essential thrombocythemia. Leuk Res. 2009;33(1):67–73.PubMedCrossRef Dahabreh IJ, Zoi K, Giannouli S, Zoi C, Loukopoulos D, Voulgarelis M. Is JAK2 V617F mutation more than a diagnostic index? A meta-analysis of clinical outcomes in essential thrombocythemia. Leuk Res. 2009;33(1):67–73.PubMedCrossRef
32.
Zurück zum Zitat Takata Y, Seki R, Kanajii T, Nohara M, Koteda S, Kawaguchi K, et al. Association between thromboembolic events and the JAK2 V617F mutation in myeloproliferative neoplasms. The Kurume medical journal. 2014;60(3–4):89–97.PubMedCrossRef Takata Y, Seki R, Kanajii T, Nohara M, Koteda S, Kawaguchi K, et al. Association between thromboembolic events and the JAK2 V617F mutation in myeloproliferative neoplasms. The Kurume medical journal. 2014;60(3–4):89–97.PubMedCrossRef
33.
Zurück zum Zitat Lussana F, Caberlon S, Pagani C, Kamphuisen PW, Büller HR, Cattaneo M. Association of V617F Jak2 mutation with the risk of thrombosis among patients with essential thrombocythaemia or idiopathic myelofibrosis: a systematic review. Thromb Res. 2009;124(4):409–17.PubMedCrossRef Lussana F, Caberlon S, Pagani C, Kamphuisen PW, Büller HR, Cattaneo M. Association of V617F Jak2 mutation with the risk of thrombosis among patients with essential thrombocythaemia or idiopathic myelofibrosis: a systematic review. Thromb Res. 2009;124(4):409–17.PubMedCrossRef
34.
Zurück zum Zitat Passamonti F, Rumi E, Pietra D, Elena C, Boveri E, Arcaini L, et al. A prospective study of 338 patients with polycythemia vera: the impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications. Leukemia. 2010;24(9):1574–9.PubMedCrossRef Passamonti F, Rumi E, Pietra D, Elena C, Boveri E, Arcaini L, et al. A prospective study of 338 patients with polycythemia vera: the impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications. Leukemia. 2010;24(9):1574–9.PubMedCrossRef
35.
Zurück zum Zitat Carobbio A, Finazzi G, Antonioli E, Guglielmelli P, Vannucchi AM, Dellacasa CM, et al. JAK2V617F allele burden and thrombosis: a direct comparison in essential thrombocythemia and polycythemia vera. Exp Hematol. 2009;37(9):1016–21.PubMedPubMedCentralCrossRef Carobbio A, Finazzi G, Antonioli E, Guglielmelli P, Vannucchi AM, Dellacasa CM, et al. JAK2V617F allele burden and thrombosis: a direct comparison in essential thrombocythemia and polycythemia vera. Exp Hematol. 2009;37(9):1016–21.PubMedPubMedCentralCrossRef
36.
Zurück zum Zitat Vannucchi AM, Antonioli E, Guglielmelli P, Rambaldi A, Barosi G, Marchioli R, et al. Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera or essential thrombocythemia. Blood. 2007;110(3):840–6.PubMedCrossRef Vannucchi AM, Antonioli E, Guglielmelli P, Rambaldi A, Barosi G, Marchioli R, et al. Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera or essential thrombocythemia. Blood. 2007;110(3):840–6.PubMedCrossRef
37.
Zurück zum Zitat Vannucchi AM, Pieri L, Guglielmelli P. JAK2 allele burden in the myeloproliferative neoplasms: effects on phenotype, prognosis and change with treatment. Ther Adv Hematol. 2011;2(1):21–32.PubMedPubMedCentralCrossRef Vannucchi AM, Pieri L, Guglielmelli P. JAK2 allele burden in the myeloproliferative neoplasms: effects on phenotype, prognosis and change with treatment. Ther Adv Hematol. 2011;2(1):21–32.PubMedPubMedCentralCrossRef
38.
Zurück zum Zitat • 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. Describes clinical characteristics associated with CALR mutation in ET, including higher platelet count and lower rate of thrombosis compared to patients with JAK2 and MPL mutations. PubMedCrossRef • 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. Describes clinical characteristics associated with CALR mutation in ET, including higher platelet count and lower rate of thrombosis compared to patients with JAK2 and MPL mutations. PubMedCrossRef
39.
Zurück zum Zitat • Jaiswal S, Natarajan P, Silver AJ, Gibson CJ, Bick AG, Shvartz E, et al. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N Engl J Med. 2017;377(2):111–21. Demonstrate that clonal hematopoiesis of indeterminate potential as well as mutations in DNMT3A , TET2 , ASXL1 , and JAK2 are associated with coronary heart disease and myocardial infarctions. PubMedCrossRef • Jaiswal S, Natarajan P, Silver AJ, Gibson CJ, Bick AG, Shvartz E, et al. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N Engl J Med. 2017;377(2):111–21. Demonstrate that clonal hematopoiesis of indeterminate potential as well as mutations in DNMT3A , TET2 , ASXL1 , and JAK2 are associated with coronary heart disease and myocardial infarctions. PubMedCrossRef
40.
Zurück zum Zitat • Chu DK, Hillis CM, Leong DP, Anand SS, Siegal DM. Benefits and risks of antithrombotic therapy in essential thrombocythemia: a systematic review. Ann Intern Med. 2017;167(3):170–180. Systematic review of risk/benefit of aspirin in essential thrombocythemia. • Chu DK, Hillis CM, Leong DP, Anand SS, Siegal DM. Benefits and risks of antithrombotic therapy in essential thrombocythemia: a systematic review. Ann Intern Med. 2017;167(3):170–180. Systematic review of risk/benefit of aspirin in essential thrombocythemia.
41.
Zurück zum Zitat Alvarez-Larrán A, Cervantes F, Pereira A, Arellano-Rodrigo E, Pérez-Andreu V, Hernández-Boluda JC, et al. Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia. Blood. 2010;116(8):1205–10. quiz 387 PubMedCrossRef Alvarez-Larrán A, Cervantes F, Pereira A, Arellano-Rodrigo E, Pérez-Andreu V, Hernández-Boluda JC, et al. Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia. Blood. 2010;116(8):1205–10. quiz 387 PubMedCrossRef
42.
Zurück zum Zitat • Alvarez-Larrán A, Pereira A, Guglielmelli P, Hernández-Boluda JC, Arellano-Rodrigo E, Ferrer-Marín F, et al. Antiplatelet therapy versus observation in low-risk essential thrombocythemia with a CALR mutation. Haematologica. 2016;101(8):926–31. Assessed the risks and benefits of aspirin according to mutation status in patients with low-risk ET and demonstrated that aspirin was associated with a higher incidence of bleeding but had no effect on thrombotic risk for patients with CALR mutation. PubMedPubMedCentralCrossRef • Alvarez-Larrán A, Pereira A, Guglielmelli P, Hernández-Boluda JC, Arellano-Rodrigo E, Ferrer-Marín F, et al. Antiplatelet therapy versus observation in low-risk essential thrombocythemia with a CALR mutation. Haematologica. 2016;101(8):926–31. Assessed the risks and benefits of aspirin according to mutation status in patients with low-risk ET and demonstrated that aspirin was associated with a higher incidence of bleeding but had no effect on thrombotic risk for patients with CALR mutation. PubMedPubMedCentralCrossRef
43.
Zurück zum Zitat Tartaglia AP, Goldberg JD, Berk PD, Wasserman LR. Adverse effects of antiaggregating platelet therapy in the treatment of polycythemia vera. Semin Hematol. 1986;23(3):172–6.PubMed Tartaglia AP, Goldberg JD, Berk PD, Wasserman LR. Adverse effects of antiaggregating platelet therapy in the treatment of polycythemia vera. Semin Hematol. 1986;23(3):172–6.PubMed
44.
Zurück zum Zitat Marchioli R, Finazzi G, Specchia G, Cacciola R, Cavazzina R, Cilloni D, et al. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013;368(1):22–33.PubMedCrossRef Marchioli R, Finazzi G, Specchia G, Cacciola R, Cavazzina R, Cilloni D, et al. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013;368(1):22–33.PubMedCrossRef
45.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
46.
Zurück zum Zitat Cortelazzo S, Finazzi G, Ruggeri M, Vestri O, Galli M, Rodeghiero F, et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med. 1995;332(17):1132–6.PubMedCrossRef Cortelazzo S, Finazzi G, Ruggeri M, Vestri O, Galli M, Rodeghiero F, et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med. 1995;332(17):1132–6.PubMedCrossRef
47.
Zurück zum Zitat Gisslinger H, Gotic M, Holowiecki J, Penka M, Thiele J, Kvasnicka HM, et al. Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET study, a randomized controlled trial. Blood. 2013;121(10):1720–8.PubMedPubMedCentralCrossRef Gisslinger H, Gotic M, Holowiecki J, Penka M, Thiele J, Kvasnicka HM, et al. Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET study, a randomized controlled trial. Blood. 2013;121(10):1720–8.PubMedPubMedCentralCrossRef
48.
Zurück zum Zitat Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015;372(5):426–35.PubMedPubMedCentralCrossRef Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015;372(5):426–35.PubMedPubMedCentralCrossRef
49.
Zurück zum Zitat Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, et al. Ruxolitinib versus best available therapy in patients with polycythemia vera: 80-week follow-up from the RESPONSE trial. Haematologica. 2016;101(7):821–9.PubMedPubMedCentralCrossRef Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, et al. Ruxolitinib versus best available therapy in patients with polycythemia vera: 80-week follow-up from the RESPONSE trial. Haematologica. 2016;101(7):821–9.PubMedPubMedCentralCrossRef
50.
Zurück zum Zitat Samuelson BT, Vesely SK, Chai-Adisaksopha C, Scott BL, Crowther M, Garcia D. The impact of ruxolitinib on thrombosis in patients with polycythemia vera and myelofibrosis: a meta-analysis. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. 2016;27(6):648–52.CrossRef Samuelson BT, Vesely SK, Chai-Adisaksopha C, Scott BL, Crowther M, Garcia D. The impact of ruxolitinib on thrombosis in patients with polycythemia vera and myelofibrosis: a meta-analysis. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. 2016;27(6):648–52.CrossRef
51.
Zurück zum Zitat • Hernández-Boluda JC, Arellano-Rodrigo E, Cervantes F, Alvarez-Larrán A, Gómez M, Barba P, et al. Oral anticoagulation to prevent thrombosis recurrence in polycythemia vera and essential thrombocythemia. Ann Hematol. 2015;94(6):911–8. Demonstrated that vitamin K antagonists reduce recurrent thrombotic events in PV and ET without a significant increase in the rate of major bleeding. PubMedCrossRef • Hernández-Boluda JC, Arellano-Rodrigo E, Cervantes F, Alvarez-Larrán A, Gómez M, Barba P, et al. Oral anticoagulation to prevent thrombosis recurrence in polycythemia vera and essential thrombocythemia. Ann Hematol. 2015;94(6):911–8. Demonstrated that vitamin K antagonists reduce recurrent thrombotic events in PV and ET without a significant increase in the rate of major bleeding. PubMedCrossRef
52.
Zurück zum Zitat Tefferi A, Barbui T. Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk-stratification and management. Am J Hematol. 2015;90(2):162–73.PubMedCrossRef Tefferi A, Barbui T. Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk-stratification and management. Am J Hematol. 2015;90(2):162–73.PubMedCrossRef
53.
Zurück zum Zitat Barbui T, Barosi G, Birgegard G, Cervantes F, Finazzi G, Griesshammer M, et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol. 2011;29(6):761–70.PubMedPubMedCentralCrossRef Barbui T, Barosi G, Birgegard G, Cervantes F, Finazzi G, Griesshammer M, et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol. 2011;29(6):761–70.PubMedPubMedCentralCrossRef
54.
Zurück zum Zitat Papadakis E, Hoffman R, Brenner B. Thrombohemorrhagic complications of myeloproliferative disorders. Blood Rev. 2010;24(6):227–32.PubMedCrossRef Papadakis E, Hoffman R, Brenner B. Thrombohemorrhagic complications of myeloproliferative disorders. Blood Rev. 2010;24(6):227–32.PubMedCrossRef
55.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
56.
Zurück zum Zitat Buss DH, Stuart JJ, Lipscomb GE. The incidence of thrombotic and hemorrhagic disorders in association with extreme thrombocytosis: an analysis of 129 cases. Am J Hematol. 1985;20(4):365–72.PubMedCrossRef Buss DH, Stuart JJ, Lipscomb GE. The incidence of thrombotic and hemorrhagic disorders in association with extreme thrombocytosis: an analysis of 129 cases. Am J Hematol. 1985;20(4):365–72.PubMedCrossRef
57.
Zurück zum Zitat Tefferi A, Barbui T. Personalized management of essential thrombocythemia-application of recent evidence to clinical practice. Leukemia. 2013;27(8):1617–20.PubMedPubMedCentralCrossRef Tefferi A, Barbui T. Personalized management of essential thrombocythemia-application of recent evidence to clinical practice. Leukemia. 2013;27(8):1617–20.PubMedPubMedCentralCrossRef
Metadaten
Titel
Risk Factors for and Management of MPN-Associated Bleeding and Thrombosis
verfasst von
Karlyn Martin
Publikationsdatum
25.09.2017
Verlag
Springer US
Erschienen in
Current Hematologic Malignancy Reports / Ausgabe 5/2017
Print ISSN: 1558-8211
Elektronische ISSN: 1558-822X
DOI
https://doi.org/10.1007/s11899-017-0400-3

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