Impact of Hematocrit on Coagulation Measured by Rotational Thromboelastometry in Healthy Subjects and Patients with Polycythemia

Abstract

Thrombotic and cardiovascular events are among the leading causes of death for patients with polycythemia, more specifically for those with primary origin. It has been suggested that the high hematocrit (Hct) would favor hypercoagulability. However, the impact of Hct on coagulation in patients with polycythemia has not been investigated so far. The aim of our study was to compare the coagulation profiles of healthy subjects and patients with polycythemia and to evaluate the in vitro impact of Hct on coagulation. Blood from healthy individuals (n = 100 for blood viscosity; n = 19 for coagulation) and patients with primary/secondary polycythemia (n = 29 for blood viscosity; n = 20 for coagulation) was used to perform measurements at native Hct. The impact of Hct modulation (20% vs. 50%) on coagulation was tested in vitro in 9 healthy subjects and 19 patients with polycythemia. Blood viscosity was measured by viscosimetry and coagulation and fibrinolysis by rotational thromboelastometry. In patients with polycythemia, Hct, and blood viscosity were higher, clotting time was prolonged and clot lysis was faster compared to healthy individuals. Our in vitro results showed that the clotting time was faster and the clot firmness higher at 20% versus 50% Hct for both populations, without any difference between the two populations at a given Hct. Our findings suggest that the interpretation of thromboelastometry results should be approached with caution in patients with high Hct. The in vivo hypercoagulable state of patients with polycythemia is probably the consequence of changes in hemodynamic conditions attributed to blood hyper-viscosity, that may promote venous stasis and platelet margination.

Keywords

hematocrit - thromboelastometry - polycythemia - clot

^* These authors contributed equally to this article.

Publikationsverlauf

Eingereicht: 06. Dezember 2024

Angenommen: 31. März 2025

Accepted Manuscript online:
01. April 2025

Artikel online veröffentlicht:
25. April 2025

• References

• 1 Kroll MH, Michaelis LC, Verstovsek S. Mechanisms of thrombogenesis in polycythemia vera. Blood Rev 2015; 29 (04) 215-221
• 2 Barbui T, Thiele J, Gisslinger H, Finazzi G, Vannucchi AM, Tefferi A. The 2016 revision of WHO classification of myeloproliferative neoplasms: clinical and molecular advances. Blood Rev 2016; 30 (06) 453-459
• 3 Mithoowani S, Laureano M, Crowther MA, Hillis CM. Investigation and management of erythrocytosis. CMAJ 2020; 192 (32) E913-E918
• 4 Shibata J, Hasegawa J, Siemens HJ. et al. Hemostasis and coagulation at a hematocrit level of 0.85: functional consequences of erythrocytosis. Blood 2003; 101 (11) 4416-4422
• 5 Griesshammer M, Kiladjian JJ, Besses C. Thromboembolic events in polycythemia vera. Ann Hematol 2019; 98 (05) 1071-1082
• 6 Gordeuk VR, Key NS, Prchal JT. Re-evaluation of hematocrit as a determinant of thrombotic risk in erythrocytosis. Haematologica 2019; 104 (04) 653-658
• 7 Schwarcz TH, Hogan LA, Endean ED, Roitman IT, Kazmers A, Hyde GL. Thromboembolic complications of polycythemia: polycythemia vera versus smokers' polycythemia. J Vasc Surg 1993; 17 (03) 518-522 , discussion 522–523
• 8 Tefferi A, Barbui T. Polycythemia vera: 2024 update on diagnosis, risk-stratification, and management. Am J Hematol 2023; 98 (09) 1465-1487
• 9 Kwaan HC, Wang J. Hyperviscosity in polycythemia vera and other red cell abnormalities. Semin Thromb Hemost 2003; 29 (05) 451-458
• 10 Lowe GD, Fowkes FG, Dawes J, Donnan PT, Lennie SE, Housley E. Blood viscosity, fibrinogen, and activation of coagulation and leukocytes in peripheral arterial disease and the normal population in the Edinburgh Artery Study. Circulation 1993; 87 (06) 1915-1920
• 11 Windberger U, Dibiasi C, Lotz EM. et al. The effect of hematocrit, fibrinogen concentration and temperature on the kinetics of clot formation of whole blood. Clin Hemorheol Microcirc 2020; 75 (04) 431-445
• 12 Champigneulle B, Brugniaux JV, Stauffer E. et al. Expedition 5300: limits of human adaptations in the highest city in the world. J Physiol 2024; 602 (21) 5449-5462
• 13 (GEHT) Gdéslhelt. Recommandation pré-analytique en hémostase. In. Révision partielle octobre 2015 (mise à jour mai 2017) ed. France; 2017. Accessed at: https://www.chu-tours.fr/wp-content/uploads/2020/01/MP-recommandations-preanalytiques-hemostase-GEHT.pdf
• 14 Baskurt OK, Boynard M, Cokelet GC. et al; International Expert Panel for Standardization of Hemorheological Methods. New guidelines for hemorheological laboratory techniques. Clin Hemorheol Microcirc 2009; 42 (02) 75-97
• 15 Georgiadou P, Sokou R, Tsantes AG. et al. The non-activated thromboelastometry (NATEM) assay's application among adults and neonatal/pediatric population: a systematic review. Diagnostics (Basel) 2022; 12 (03) 658
• 16 Nougier C, Benoit R, Simon M. et al. Hypofibrinolytic state and high thrombin generation may play a major role in SARS-COV2 associated thrombosis. J Thromb Haemost 2020; 18 (09) 2215-2219
• 17 Tripodi A, Chantarangkul V, Gianniello F. et al. Global coagulation in myeloproliferative neoplasms. Ann Hematol 2013; 92 (12) 1633-1639
• 18 Roh DJ, Chang TR, Kumar A. et al. Hemoglobin concentration impacts viscoelastic hemostatic assays in ICU admitted patients. Crit Care Med 2023; 51 (02) 267-278
• 19 Stauffer E, Loyrion E, Hancco I. et al. Blood viscosity and its determinants in the highest city in the world. J Physiol 2020; 598 (18) 4121-4130
• 20 Nagler M, Kathriner S, Bachmann LM, Wuillemin WA. Impact of changes in haematocrit level and platelet count on thromboelastometry parameters. Thromb Res 2013; 131 (03) 249-253
• 21 Westbury SK, Lee K, Reilly-Stitt C, Tulloh R, Mumford AD. High haematocrit in cyanotic congenital heart disease affects how fibrinogen activity is determined by rotational thromboelastometry. Thromb Res 2013; 132 (02) e145-e151
• 22 Casini A, Fontana P, Lecompte TP. Thrombotic complications of myeloproliferative neoplasms: risk assessment and risk-guided management. J Thromb Haemost 2013; 11 (07) 1215-1227
• 23 Meli A, Grasselli G, Panigada M. Hemoglobin concentration and viscoelastic tests: remember to consider fibrinogen and platelets. Crit Care Med 2023; 51 (05) e122-e123
• 24 Lim HY, Ng C, Rigano J. et al. An evaluation of global coagulation assays in myeloproliferative neoplasm. Blood Coagul Fibrinolysis 2018; 29 (03) 300-306
• 25 Kumar DR, Hanlin E, Glurich I, Mazza JJ, Yale SH. Virchow's contribution to the understanding of thrombosis and cellular biology. Clin Med Res 2010; 8 (3-4): 168-172
• 26 Lowe GD. Virchow's triad revisited: abnormal flow. Pathophysiol Haemost Thromb 2003; 33 (5-6): 455-457
• 27 Baskurt OK, Meiselman HJ. Blood rheology and hemodynamics. Semin Thromb Hemost 2003; 29 (05) 435-450
• 28 Connes P, Alexy T, Detterich J, Romana M, Hardy-Dessources MD, Ballas SK. The role of blood rheology in sickle cell disease. Blood Rev 2016; 30 (02) 111-118
• 29 Reasor Jr DA, Mehrabadi M, Ku DN, Aidun CK. Determination of critical parameters in platelet margination. Ann Biomed Eng 2013; 41 (02) 238-249
• 30 Goldsmith HL, Bell DN, Braovac S, Steinberg A, McIntosh F. Physical and chemical effects of red cells in the shear-induced aggregation of human platelets. Biophys J 1995; 69 (04) 1584-1595
• 31 Abbitt KB, Nash GB. Rheological properties of the blood influencing selectin-mediated adhesion of flowing leukocytes. Am J Physiol Heart Circ Physiol 2003; 285 (01) H229-H240
• 32 Gangat N, Strand J, Li CY, Wu W, Pardanani A, Tefferi A. Leucocytosis in polycythaemia vera predicts both inferior survival and leukaemic transformation. Br J Haematol 2007; 138 (03) 354-358
• 33 Neunteufl T, Heher S, Stefenelli T, Pabinger I, Gisslinger H. Endothelial dysfunction in patients with polycythaemia vera. Br J Haematol 2001; 115 (02) 354-359
• 34 Boyer L, Chaar V, Pelle G. et al. Effects of polycythemia on systemic endothelial function in chronic hypoxic lung disease. J Appl Physiol 2011; 110 (05) 1196-1203
• 35 Aoyama R, Kubota Y, Tara S. et al. Vascular endothelial dysfunction in myeloproliferative neoplasms and gene mutations. Int Heart J 2022; 63 (04) 661-668
• 36 Kitchen S, Adcock DM, Dauer R. et al. International Council for Standardisation in Haematology (ICSH) recommendations for collection of blood samples for coagulation testing. Int J Lab Hematol 2021; 43 (04) 571-580
• 37 Volod O, Bunch CM, Zackariya N. et al. Viscoelastic hemostatic assays: a primer on legacy and new generation devices. J Clin Med 2022; 11 (03) 860