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Erschienen in: International Journal of Hematology 5/2017

05.08.2017 | Original Article

Elevated plasma levels of procoagulant microparticles are a novel risk factor for thrombosis in patients with myeloproliferative neoplasms

verfasst von: Yasuhiro Taniguchi, Hirokazu Tanaka, Espinoza J. Luis, Kazuko Sakai, Takahiro Kumode, Keigo Sano, Kentarou Serizawa, Shinya Rai, Yasuyoshi Morita, Hitoshi Hanamoto, Kazuo Tsubaki, Kazuto Nishio, Itaru Matsumura

Erschienen in: International Journal of Hematology | Ausgabe 5/2017

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Abstract

Myeloproliferative neoplasms (MPNs), including polycythemia vera and essential thrombocythemia, are frequently associated with thrombotic complications. Prevention of thrombotic events is thus a primary aim of the current treatment for these disorders. Although it is known that microparticles (MPs), which are small vesicles released from cell membranes and circulate in the blood, directly contribute to thrombosis via their procoagulant activity, potential associations between plasma levels of MPs and the risk of thrombotic events in MPNs have not been reported. In the present study, we characterized plasma levels of MPs and assessed their potential association with the occurrence of thrombotic events in 59 patients with MPNs. Plasma levels of procoagulant MPs expressing tissue factor (TF+ MPs) were significantly higher in patients suffering thrombotic events than in patients without such events (median/μl plasma: 33.8 vs 47.2, p = 0.02). Among patients who developed thrombotic events, irrespective of patients’ blood counts, TF+ MP were significantly higher in patients without cytoreductive therapy than in those receiving cytoreductive therapy (101.2 vs. 42.5, p < 0.001). These results suggest that elevated levels of TF+ MP may be considered as a novel surrogate marker for thrombotic events in MPN patients. Further studies are needed to clarify the mechanism involved.
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Literatur
1.
Zurück zum Zitat Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405.CrossRefPubMed Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405.CrossRefPubMed
2.
Zurück zum Zitat Schnittger S, Bacher U, Haferlach C, Geer T, Müller P, Mittermüller J, Petrides P, Schlag R, Sandner R, Selbach J, et al. Detection of JAK2 exon 12 mutations in 15 patients with JAK2V617F negative polycythemia vera. Haematologica. 2009;94(3):414–8.CrossRefPubMedPubMedCentral Schnittger S, Bacher U, Haferlach C, Geer T, Müller P, Mittermüller J, Petrides P, Schlag R, Sandner R, Selbach J, et al. Detection of JAK2 exon 12 mutations in 15 patients with JAK2V617F negative polycythemia vera. Haematologica. 2009;94(3):414–8.CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Milosevic JD, Kralovics R. Genetic and epigenetic alterations of myeloproliferative disorders. Int J Hematol. 2013;97(2):183–97.CrossRefPubMed Milosevic JD, Kralovics R. Genetic and epigenetic alterations of myeloproliferative disorders. Int J Hematol. 2013;97(2):183–97.CrossRefPubMed
4.
Zurück zum Zitat Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, Avezov E, Li J, Kollmann K, Kent DG, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013;369(25):2391–405.CrossRefPubMedPubMedCentral Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, Avezov E, Li J, Kollmann K, Kent DG, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013;369(25):2391–405.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Imai M, Araki M, Komatsu N. Somatic mutations of calreticulin in myeloproliferative neoplasms. Int J Hematol. 2017;105(6):743–7.CrossRefPubMed Imai M, Araki M, Komatsu N. Somatic mutations of calreticulin in myeloproliferative neoplasms. Int J Hematol. 2017;105(6):743–7.CrossRefPubMed
6.
Zurück zum Zitat Ma W, Zhang X, Wang X, Zhang Z, Yeh CH, Uyeji J, Albitar M. MPL mutation profile in JAK2 mutation-negative patients with myeloproliferative disorders. Diagn Mol Pathol. 2011;20(1):34–9.CrossRefPubMed Ma W, Zhang X, Wang X, Zhang Z, Yeh CH, Uyeji J, Albitar M. MPL mutation profile in JAK2 mutation-negative patients with myeloproliferative disorders. Diagn Mol Pathol. 2011;20(1):34–9.CrossRefPubMed
7.
Zurück zum Zitat Kim SY, Im K, Park SN, Kwon J, Kim JA, Lee DS. CALR, JAK2, and MPL mutation profiles in patients with four different subtypes of myeloproliferative neoplasms: primary myelofibrosis, essential thrombocythemia, polycythemia vera, and myeloproliferative neoplasm, unclassifiable. Am J Clin Pathol. 2015;143(5):635–44.CrossRefPubMed Kim SY, Im K, Park SN, Kwon J, Kim JA, Lee DS. CALR, JAK2, and MPL mutation profiles in patients with four different subtypes of myeloproliferative neoplasms: primary myelofibrosis, essential thrombocythemia, polycythemia vera, and myeloproliferative neoplasm, unclassifiable. Am J Clin Pathol. 2015;143(5):635–44.CrossRefPubMed
8.
Zurück zum Zitat Casini A, Fontana P, Lecompte TP. Thrombotic complications of myeloproliferative neoplasms: risk assessment and risk-guided management. J Thromb Haemost. 2013;11(7):1215–27.CrossRefPubMed Casini A, Fontana P, Lecompte TP. Thrombotic complications of myeloproliferative neoplasms: risk assessment and risk-guided management. J Thromb Haemost. 2013;11(7):1215–27.CrossRefPubMed
9.
Zurück zum Zitat Barbui T. How to manage thrombosis in myeloproliferative neoplasms. Curr Opin Oncol. 2011;23(6):654–8.CrossRefPubMed Barbui T. How to manage thrombosis in myeloproliferative neoplasms. Curr Opin Oncol. 2011;23(6):654–8.CrossRefPubMed
10.
Zurück zum Zitat Barbui T, Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, Randi ML, Bertozzi I, 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 5252).CrossRefPubMed Barbui T, Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, Randi ML, Bertozzi I, 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 5252).CrossRefPubMed
11.
Zurück zum Zitat Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, Randi ML, Bertozzi I, Vannucchi AM, Antonioli E, 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.CrossRefPubMed Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, Randi ML, Bertozzi I, Vannucchi AM, Antonioli E, 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.CrossRefPubMed
12.
Zurück zum Zitat Görtzen J, Hunka LM, Vonnahme M, Praktiknjo M, Kaifie A, Fimmers R, Jansen C, Heine A, Lehmann J, Goethert JR, et al. γ-Glutamyl transferase is an independent biomarker of splanchnic thrombosis in patients with myeloproliferative neoplasm. Medicine (Baltimore). 2016;95(20):e3355.CrossRef Görtzen J, Hunka LM, Vonnahme M, Praktiknjo M, Kaifie A, Fimmers R, Jansen C, Heine A, Lehmann J, Goethert JR, et al. γ-Glutamyl transferase is an independent biomarker of splanchnic thrombosis in patients with myeloproliferative neoplasm. Medicine (Baltimore). 2016;95(20):e3355.CrossRef
13.
Zurück zum Zitat Barbui T, Thiele J, Passamonti F, Rumi E, Boveri E, Ruggeri M, Rodeghiero F, d’Amore ES, Randi ML, Bertozzi I, et al. Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol. 2011;29(23):3179–84.CrossRefPubMed Barbui T, Thiele J, Passamonti F, Rumi E, Boveri E, Ruggeri M, Rodeghiero F, d’Amore ES, Randi ML, Bertozzi I, et al. Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol. 2011;29(23):3179–84.CrossRefPubMed
14.
Zurück zum Zitat Rumi E, Pietra D, Ferretti V, Klampfl T, Harutyunyan AS, Milosevic JD, Them NC, Berg T, Elena C, Casetti IC, et al. JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood. 2014;123(10):1544–51.CrossRefPubMedPubMedCentral Rumi E, Pietra D, Ferretti V, Klampfl T, Harutyunyan AS, Milosevic JD, Them NC, Berg T, Elena C, Casetti IC, et al. JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood. 2014;123(10):1544–51.CrossRefPubMedPubMedCentral
15.
16.
Zurück zum Zitat Geddings JE, Mackman N. Tumor-derived tissue factor-positive microparticles and venous thrombosis in cancer patients. Blood. 2013;122(11):1873–80.CrossRefPubMedPubMedCentral Geddings JE, Mackman N. Tumor-derived tissue factor-positive microparticles and venous thrombosis in cancer patients. Blood. 2013;122(11):1873–80.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Lacroix R, Dubois C, Leroyer AS, Sabatier F, Dignat-George F. Revisited role of microparticles in arterial and venous thrombosis. J Thromb Haemost. 2013;11(Suppl 1):24–35.CrossRefPubMed Lacroix R, Dubois C, Leroyer AS, Sabatier F, Dignat-George F. Revisited role of microparticles in arterial and venous thrombosis. J Thromb Haemost. 2013;11(Suppl 1):24–35.CrossRefPubMed
19.
Zurück zum Zitat Trappenburg MC, van Schilfgaarde M, Marchetti M, Spronk HM, ten Cate H, Leyte A, Terpstra WE, Falanga A. Elevated procoagulant microparticles expressing endothelial and platelet markers in essential thrombocythemia. Haematologica. 2009;94(7):911–8.CrossRefPubMedPubMedCentral Trappenburg MC, van Schilfgaarde M, Marchetti M, Spronk HM, ten Cate H, Leyte A, Terpstra WE, Falanga A. Elevated procoagulant microparticles expressing endothelial and platelet markers in essential thrombocythemia. Haematologica. 2009;94(7):911–8.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Kissova J, Ovesna P, Bulikova A, Zavřelova J, Penka M. Increasing procoagulant activity of circulating microparticles in patients with Philadelphia-negative myeloproliferative neoplasms: a single-centre experience. Blood Coagul Fibrinolysis. 2015;26(4):448–53.CrossRefPubMed Kissova J, Ovesna P, Bulikova A, Zavřelova J, Penka M. Increasing procoagulant activity of circulating microparticles in patients with Philadelphia-negative myeloproliferative neoplasms: a single-centre experience. Blood Coagul Fibrinolysis. 2015;26(4):448–53.CrossRefPubMed
21.
Zurück zum Zitat Dey-Hazra E, Hertel B, Kirsch T, Woywodt A, Lovric S, Haller H, Haubitz M, Erdbruegger U. Detection of circulating microparticles by flow cytometry: influence of centrifugation, filtration of buffer, and freezing. Vasc Health Risk Manag. 2010;6:1125–33.PubMedPubMedCentral Dey-Hazra E, Hertel B, Kirsch T, Woywodt A, Lovric S, Haller H, Haubitz M, Erdbruegger U. Detection of circulating microparticles by flow cytometry: influence of centrifugation, filtration of buffer, and freezing. Vasc Health Risk Manag. 2010;6:1125–33.PubMedPubMedCentral
22.
Zurück zum Zitat Hemker HC, Al Dieri R, De Smedt E, Béguin S. Thrombin generation, a function test of the haemostatic-thrombotic system. Thromb Haemost. 2006;96(5):553–61.PubMed Hemker HC, Al Dieri R, De Smedt E, Béguin S. Thrombin generation, a function test of the haemostatic-thrombotic system. Thromb Haemost. 2006;96(5):553–61.PubMed
23.
Zurück zum Zitat Zubairova LD, Nabiullina RM, Nagaswami C, Zuev YF, Mustafin IG, Litvinov RI, Weisel JW. Circulating microparticles alter formation, structure, and properties of fibrin clots. Sci Rep. 2015;5:17611.CrossRefPubMedPubMedCentral Zubairova LD, Nabiullina RM, Nagaswami C, Zuev YF, Mustafin IG, Litvinov RI, Weisel JW. Circulating microparticles alter formation, structure, and properties of fibrin clots. Sci Rep. 2015;5:17611.CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48(3):452–8.CrossRefPubMed Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48(3):452–8.CrossRefPubMed
25.
Zurück zum Zitat Price GL, Davis KL, Karve S, Pohl G, Walgren RA. Survival patterns in United States (US) medicare enrollees with non-CML myeloproliferative neoplasms (MPN). PLoS One 2014;9(3):e90299.CrossRefPubMedPubMedCentral Price GL, Davis KL, Karve S, Pohl G, Walgren RA. Survival patterns in United States (US) medicare enrollees with non-CML myeloproliferative neoplasms (MPN). PLoS One 2014;9(3):e90299.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Hultcrantz M, Wilkes SR, Kristinsson SY, Andersson TM, Derolf Å, Eloranta S, Samuelsson J, Landgren O, Dickman PW, Lambert PC et al. Risk and Cause of Death in Patients Diagnosed With Myeloproliferative Neoplasms in Sweden Between 1973 and 2005: A Population-Based Study. J Clin Oncol. 2015;33(20):2288–95.CrossRefPubMed Hultcrantz M, Wilkes SR, Kristinsson SY, Andersson TM, Derolf Å, Eloranta S, Samuelsson J, Landgren O, Dickman PW, Lambert PC et al. Risk and Cause of Death in Patients Diagnosed With Myeloproliferative Neoplasms in Sweden Between 1973 and 2005: A Population-Based Study. J Clin Oncol. 2015;33(20):2288–95.CrossRefPubMed
27.
Zurück zum Zitat Borowczyk M, Wojtaszewska M, Lewandowski K, Gil L, Lewandowska M, Lehmann-Kopydłowska A, Kroll-Balcerzak R, Balcerzak A, Iwoła M, Michalak M 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(2):272–80.CrossRefPubMed Borowczyk M, Wojtaszewska M, Lewandowski K, Gil L, Lewandowska M, Lehmann-Kopydłowska A, Kroll-Balcerzak R, Balcerzak A, Iwoła M, Michalak M 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(2):272–80.CrossRefPubMed
28.
Zurück zum Zitat Tefferi A. Myeloproliferative neoplasms: a decade of discoveries and treatment advances. Am J Hematol. 2016;91(1):50–8.CrossRefPubMed Tefferi A. Myeloproliferative neoplasms: a decade of discoveries and treatment advances. Am J Hematol. 2016;91(1):50–8.CrossRefPubMed
29.
Zurück zum Zitat Falchi L, Bose P, Newberry KJ, et al. Approach to patients with essential thrombocythaemia and very high platelet counts: what is the evidence for treatment? Br J Haematol. 2017;176(3):352–64.CrossRefPubMed Falchi L, Bose P, Newberry KJ, et al. Approach to patients with essential thrombocythaemia and very high platelet counts: what is the evidence for treatment? Br J Haematol. 2017;176(3):352–64.CrossRefPubMed
30.
Zurück zum Zitat Mallat Z, Benamer H, Hugel B, Benessiano J, Steg PG, Freyssinet JM, Tedgui A. Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. Circulation 2000;101(8):841–43.CrossRefPubMed Mallat Z, Benamer H, Hugel B, Benessiano J, Steg PG, Freyssinet JM, Tedgui A. Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. Circulation 2000;101(8):841–43.CrossRefPubMed
31.
Zurück zum Zitat Morel O, Hugel B, Jesel L, Lanza F, Douchet MP, Zupan M, Chauvin M, Cazenave JP, Freyssinet JM, Toti F. Sustained elevated amounts of circulating procoagulant membrane microparticles and soluble GPV after acute myocardial infarction in diabetes mellitus. Thromb Haemost. 2004; 91(2):345–53.PubMed Morel O, Hugel B, Jesel L, Lanza F, Douchet MP, Zupan M, Chauvin M, Cazenave JP, Freyssinet JM, Toti F. Sustained elevated amounts of circulating procoagulant membrane microparticles and soluble GPV after acute myocardial infarction in diabetes mellitus. Thromb Haemost. 2004; 91(2):345–53.PubMed
32.
Zurück zum Zitat Bharthuar A, Khorana AA, Hutson A, Wang JG, Key NS, Mackman N, Iyer RV. Circulating microparticle tissue factor, thromboembolism and survival in pancreaticobiliary cancers. Thromb Res. 2013;132(2):180–4.CrossRefPubMed Bharthuar A, Khorana AA, Hutson A, Wang JG, Key NS, Mackman N, Iyer RV. Circulating microparticle tissue factor, thromboembolism and survival in pancreaticobiliary cancers. Thromb Res. 2013;132(2):180–4.CrossRefPubMed
33.
Zurück zum Zitat Tan X, Shi J, Fu Y, Gao C, Yang X, Li J, Wang W, Hou J, Li H, Zhou J. Role of erythrocytes and platelets in the hypercoagulable status in polycythemia vera through phosphatidylserine exposure and microparticle generation. Thromb Haemost. 2013;109(6):1025–32.CrossRefPubMed Tan X, Shi J, Fu Y, Gao C, Yang X, Li J, Wang W, Hou J, Li H, Zhou J. Role of erythrocytes and platelets in the hypercoagulable status in polycythemia vera through phosphatidylserine exposure and microparticle generation. Thromb Haemost. 2013;109(6):1025–32.CrossRefPubMed
34.
Zurück zum Zitat Bellucci S, Legrand C, Boval B, Drouet L, Caen J. Studies of platelet volume, chemistry and function in patients with essential thrombocythaemia treated with Anagrelide. Br J Haematol. 1999;104(4):886–92.CrossRefPubMed Bellucci S, Legrand C, Boval B, Drouet L, Caen J. Studies of platelet volume, chemistry and function in patients with essential thrombocythaemia treated with Anagrelide. Br J Haematol. 1999;104(4):886–92.CrossRefPubMed
35.
Zurück zum Zitat Cacciola RR, Francesco ED, Giustolisi R, Cacciola E. Effects of anagrelide on platelet factor 4 and vascular endothelial growth factor levels in patients with essential thrombocythemia. Br J Haematol. 2004;126(6):885–6.CrossRefPubMed Cacciola RR, Francesco ED, Giustolisi R, Cacciola E. Effects of anagrelide on platelet factor 4 and vascular endothelial growth factor levels in patients with essential thrombocythemia. Br J Haematol. 2004;126(6):885–6.CrossRefPubMed
Metadaten
Titel
Elevated plasma levels of procoagulant microparticles are a novel risk factor for thrombosis in patients with myeloproliferative neoplasms
verfasst von
Yasuhiro Taniguchi
Hirokazu Tanaka
Espinoza J. Luis
Kazuko Sakai
Takahiro Kumode
Keigo Sano
Kentarou Serizawa
Shinya Rai
Yasuyoshi Morita
Hitoshi Hanamoto
Kazuo Tsubaki
Kazuto Nishio
Itaru Matsumura
Publikationsdatum
05.08.2017
Verlag
Springer Japan
Erschienen in
International Journal of Hematology / Ausgabe 5/2017
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-017-2302-5

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