Hydroxyurea prevents arterial and late venous thrombotic recurrences in patients with myeloproliferative neoplasms but fails in the splanchnic venous district. Pooled analysis of 1500 cases

Blood Cancer Journal - Tập 8 Số 11
Valerio De Stefano1, Elena Rossi1, Alessandra Carobbio2, Arianna Ghirardi2, Silvia Betti1, Guido Finazzi3, Alessandro M. Vannucchi4, Tiziano Barbui2
1Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
2FROM Research Foundation, Papa Giovanni XXIII Hospital, Bergamo, Italy
3Division of Hematology, Papa Giovanni XXIII Hospital, Bergamo, Italy
4CRIMM-Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, and Department Experimental and Clinical Medicine, University of Florence, Firenze, Italy

Tóm tắt

AbstractWe collected 1500 patients with myeloproliferative neoplasms (MPN) and arterial or venous thrombosis (935/565), pooling three independent cohorts previously reported. Long-term treatment with antiplatelet drugs or vitamin K-antagonists (VKA) was given to 1391 (92.7%) patients; 975 (65%) patients received hydroxyurea (HU). We recorded 348 recurrences (venous in 142 cases) over 6075 patient-years, with an incidence rate of 5.7 per 100 pt-years (95% CI 5.1–6.4). The site of the first thrombosis predicted the site of recurrence. Independent factors influencing the rate of novel arterial thrombosis were HU (HR 0.67, 95% CI 0.46–0.98), antiplatelet treatment (HR 0.54, 95% CI 0.35–0.82), and VKA (HR 0.58, 95% CI 0.35–0.96). On the contrary, the recurrence of venous thromboses was significantly diminished only by VKA (HR 0.60, 95% CI 0.37–0.95), while HU prevented late but not early recurrences after venous thrombosis at common sites. Of note, we failed to demonstrate a positive effect of HU in the prevention of recurrent splanchnic vein thrombosis. In conclusion, in MPN patients, HU plays a role in the prevention of arterial thrombosis, together with aspirin and VKA, whereas its action in the prevention of recurrent venous thrombosis is uncertain. Such findings call for future studies to optimize and personalize secondary prophylaxis after MPN-related thrombosis.

Từ khóa


Tài liệu tham khảo

Hultcrantz, M. et al. Risk for arterial and venous thrombosis in patients with myeloproliferative neoplasms: a population-based cohort study. Ann. Intern. Med. 168, 317–325 (2018).

Patrono, C., Rocca, B. & De Stefano, V. Platelet activation and inhibition in polycythemia vera and essential thrombocythemia. Blood 121, 1701–1711 (2013).

Barbui, T., Finazzi, G. & Falanga, A. Myeloproliferative neoplasms, and thrombosis. Blood 122, 2176–2184 (2013).

De Stefano, V. et al. Benefit-risk profile of cytoreductive drugs along with antiplatelet and antithrombotic therapy after transient ischemic attack or ischemic stroke in myeloproliferative neoplasms. Blood Cancer J. 8, 25 (2018).

De Stefano, V. et al. Recurrent thrombosis in patients with polycythemia vera and essential thrombocythemia: incidence, risk factors, and effect of treatments. Haematologica 93, 372–380 (2008).

Hernández-Boluda, J. C. et al. Oral anticoagulation to prevent thrombosis recurrence in polycythemia vera and essential thrombocythemia. Ann. Hematol. 94, 911–918 (2015).

De Stefano, V. et al. High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with vitamin K antagonists. Leukemia 30, 2032–2038 (2016).

De Stefano, V. et al. Splanchnic vein thrombosis in myeloproliferative neoplasms: risk factors for recurrences in a cohort of 181 patients. Blood Cancer J. 6, e493 (2016).

Cortelazzo, S. et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N. Engl. J. Med. 332, 1132–1136 (1995).

Harrison, C. N. et al. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N. Engl. J. Med. 353, 33–45 (2005).

Gisslinger, H. et al. Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial. Blood 121, 1720–1728 (2013).

Barbui, T. et al. A reappraisal of the benefit-risk profile of hydroxyurea in polycythemia vera: a propensity-matched study. Am. J. Hematol. 92, 1131–1136 (2017).

Barbui, T., et al. Different effect of hydroxyurea and phlebotomy on prevention of arterial and venous thrombosis in polycythemia vera. Blood Cancer J., in press.

Barbui, T. et al. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia 32, 1057–1069 (2018).

Franchini, M. & Mannucci, P. M. Association between venous and arterial thrombosis: clinical implications. Eur. J. Intern. Med. 23, 333–337 (2012).

Spronk, H.M.H. et al. Atherothrombosis and thromboembolism: position paper from the Second MaastrichtConsensus Conference on thrombosis. Thromb. Haemost 118, 229–250 (2018).

Maugeri, N. et al. Inhibition of tissue factor expression by hydroxyurea in polymorphonuclear leukocytes from patients with myeloproliferative disorders: a new effect for an old drug? J. Thromb. Haemost. 4, 2593–2598 (2006).

Swystun, L. L. & Liaw, P. C. The role of leukocytes in thrombosis. Blood 128, 753–762 (2016).

Nahrendorf, M. Myeloid cell contributions to cardiovascular health and disease. Nat. Med. 24, 711–720 (2018).

Landolfi, R. et al. Leukocytosis as a major thrombotic risk factor in patients with polycythemia vera. Blood 109, 2446–2452 (2007).

Carobbio, A. et al. Leukocytosis and risk stratification assessment in essential thrombocythemia. J. Clin. Oncol. 26, 2732–2736 (2008).

Carobbio, A. et al. Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 891 patients. Blood 117, 5857–5859 (2011).

Kyrle, P. A. et al. The long-term recurrence risk of patients with unprovoked venous thromboembolism: an observational cohort study. J. Thromb. Haemost. 14, 2402–2409 (2016).

Chait, Y. et al. Relevance of the criteria commonly used to diagnose myeloproliferative disorder in patients with splanchnic vein thrombosis. Br. J. Haematol. 129, 553–560 (2005).

Sozer, S. et al. The presence of JAK2 V617F mutation in the liver endothelial cells of patients with Budd-Chiari syndrome. Blood 113, 5246–5249 (2009).

Rosti, V. et al. Spleen endothelial cells from patients with myelofibrosis harbor the JAK2V617F mutation. Blood 121, 360–368 (2013).

Robertson, L., Yeoh, S. E. & Ramli, A. Secondary prevention of recurrent venous thromboembolism after initial oral anticoagulation therapy in patients with unprovoked venous thromboembolism. Cochrane Database Syst. Rev. 12, CD011088 (2017).

Thông tin
Thông tin xuất bản

Blood Cancer Journal

Tập 8 Số 11

Thông tin tác giả