Influence of therapy on the plasma hemostasis in patients with polycythemia vera
Russian Research Institute of hematology and Transfusiology, St. Petersburg, Russia
Polycythemia vera (PV) is a clonal disease that belongs to the group of myeloproliferative neoplasms. The most patients with PV have a somatic mutation JAK2V617F. This mutation plays a common role in the etiology and pathogenesis of disease and as a risk factor of thrombosis. Unsafe and effective prevention of thromboembolic complications remains a major question in the management of these patients.
Aim to evaluate the effect of cytoreductive and / or antiplatelet therapy on the plasma hemostasis in patients with polycythemia vera.
Materials and methods. 38 patients with PV were examined. 18 people were treated with antiplatelet therapy with acetylsalicylic acid in prophylactic doses (group 1) and 20 patients were on cytoreductive therapy (17 of them received hydroxyurea, and 3 - interferon alpha ) in combination with the administration of prophylactic doses of acetylsalicylic acid (group 2). A history of thrombosis was found in 5 (28.0%) and 7 (35.0%) people in the first and the second groups respectively. The control group consisted of 77 healthy individuals. Activated partial thromboplastin time ratio (APTT), the Quick prothrombin test (PT), fibrinogen concentration, factor VIII activity (f.VIII), ristocetin cofactor activity and von Willebrand factor level (fW and Ag fW respectively), natural anticoagulants antithrombin (AT) and protein C activities (PC), the level of free protein S (PS) were determined. The thrombin generation test (TGT) parameters were used with or without thrombomodulin (TM). Statistical data processing was performed using the programs Microsoft office Excel and STATISTICA 12.0.
Results. The patients with PV had a decrease of PT. At the same time fibrinogen concentration and factor VIII activity were higher than reference parameters. The sighs of endothelial dysfunction in patients on antiplatelet with cytoreductive therapy were expressed in increasing of level and activity of von Willebrand factor. The level of free protein S decline were obtained in the same patients. Quantitative parameters of TGT were significantly lower than in controls. Sensitivity to TM was significantly reduced in patients of both groups, but in patients of the second group it was most significant.
Conclusion. Patients with PV were treated by antiplatelet or antiplatelet in combination with cytoreductive therapy. The all patients had an imbalance of the plasma hemostasis system. There were hypocoagulation disorders and at the same time the failure of the anticoagulant system of protein C, damage to the vascular wall, which was generally recognized risk factors for thrombotic complications. The procoagulant state of plasma hemostasis was further developed with cytoreductive therapy. Thus, it is necessary to estimate both the procoagulant and anticoagulant components of the patient?s hemostatic system to evaluate of individual state of thrombotic complications.
2. Dentali F., Pegoraro S., Barco S. et al. Clinical course of isolated distal deep vein thrombosis in patients with active cancer: a multicenter cohort study. - Journal of thrombosis and haemostasis - 2017. - ?15. - P. 1757-1763.
3. Mihaila R-G. Thrombin generation - a potentially useful biomarker of thromboyic risk in Philadelphia-negative myeloproliferative neoplasms - Biomed. Pap. Med. Fac. Univ. Palacky Olomouc. Czech Repub. - 2017. - ?161, Vol. 1. - P. 50-53.
4. Marchioli R., Finazzi G., Landolfi R. et al. Vascular and neoplastic risk in a large cohort in patients with polycythemia vera. - J. Clin. Oncol. - 2005. - ?23, Vol. 10. - P. 2224-2232.
5. Lussana F., Carobbio A., Salmoiraghi S. et al. Driver munations (JAK2V617F, MPLW515L/K or CALR), pentraxin-3 and C-reactive protein in essential thrombocythemia and polycythemia vera. - Journal of Hematology and Oncology. - 2017. - ?10. - P. 54-61.
6. Duchemin J., Ugo V., Ianotto J-C. et al. Increased circulating procoagulant activity and thrombin generation in patients with myeloproliferative neoplasms. - Thrombosis Research. - 2010. - ?126. - P. 238-242.
7. Landolfi R., Di Gennaro L. Pathophysiology of thrombosis in myeloproliferative neoplasms. - 2011. - ?96. - P. 183-186.
8. Microparticle phenotypes are associated with driver mutations and distinct thrombotic risks in essential thrombocythemia. - Haematologica. - 2016. - ? 101. - P. 365-368.
9. The effects of JAK inhibitor therapy upon novel markers of thrombosis in myeloproliferative neoplasms. - Haematologica. - 2015. - ? 100. - P. 348-350.
10. Kreher S., Ochsenreither S., Trappe R.U. et al. Prophylaxis and management of venous thromboembolism in patients with myeloproliferative neoplasms: consensus statement of the Haemostasis Working Party of the German Society of Hematology and Oncology (DGHO), the Austrian Society of Hematology and Oncology (ÖGHO) and Society of Thrombosis and Haemostasis Research (GTH e. V.). - Ann. Hematol. - 2014. - ?93. - P. 1953-1963.
11. Arber D.A., Orazi A., Hasserjian R. et al. The 2016 revision of the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127(20): 2391-2405. PMID: 27069254 DOI: 10.1182/blood-2016-03-643544.
12. Hemker H.C., Giesen P., Al Dieri R. et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb. 2003; 33(1): 4-15. PMID: 12853707 DOI: 10.1159/000071636.