Whole Blood Viscosity as a Marker of Thrombosis in Cushing’s Disease: An Actor or Ineffective Factor

Abstract views: 49 / PDF downloads: 25





Cushing’s disease, hypercoagulability, shear stress, whole blood viscosity


Objective: There is a tendency for thromboembolic events (TE) in Cushing’s disease (CD) because of the cortisol excess itself and associated risk factors for TE. Whole blood viscosity (WBV) as a measure of hemorheological features may impact the development of TE. However, limited data are available on the status of these changes in CD. Herein, we aimed to compare WBV between patients with CD and the control group and evaluate the impact of CD treatment on WBV. Methods: A total of 34 patients with CD without prior TE history and 30 subjects as the control group were enrolled between 2015 and 2020. Demographic, clinical, and laboratory characteristics of the study groups were recorded. WBV was calculated using the de Simone formula. Results: Among the corticotroph pituitary adenomas of the CD group, 32 of 34 were microadenomas, and 2 were macroadenomas. Postoperative remission was achieved in all patients. However, a recurrence was observed in 10 patients at 5.8±3.2 year follow-up. There was no difference between baseline WBV, at both low and high shear rates, between the CD and control groups (p>0.05). Furthermore, the WBVs at both low and high shear rates were also similar before and after treatment in the CD group (16.3±1.8 versus 15.4±1.7, p=0.2, for WBV at the high shear rate; 40.5±38.2 versus 25.4±35.2, p=0.23, at the low shear rate). Conclusion: In this small-sized preliminary study, the WBV at both shear rates revealed no difference between the CD and control groups. There was also no impact of CD treatment on WBV at follow-up. However, further large-scale studies are necessary to confirm our study findings.


Metrics Loading ...


Boscaro M, Sonino N, Scarda A, Barzon L, Fallo F, Sartori MT, et al. Anticoagulant prophylaxis markedly reduces thromboembolic complications in Cushing's syndrome. J Clin Endocrinol Metab 2002; 87: 3662-6. https://doi.org/10.1210/jcem.87.8.8703

Manetti L, Bogazzi F, Giovannetti C, Raffaelli V, Genovesi M, Pellegrini G, et al. Changes in coagulation indexes and occurrence of venous thromboembolism in patients with Cushing's syndrome: results from a prospective study before and after surgery. Eur J Endocrinol 2010; 163: 783-91. https://doi.org/10.1530/EJE-10-0583

Güneş H, Kirişci M. The Relationship Between Whole Blood Viscosity and Deep Vein Thrombosis. Turkiye Klinikleri J Cardiovasc Sci 2018; 30: 6-12. https://doi.org/10.5336/cardiosci.2018-61921

Toraldo DM, Peverini F, De Benedetto M, De Nuccio F. Obstructive sleep apnea syndrome: blood viscosity, blood coagulation abnormalities, and early atherosclerosis. Lung 2013; 191: 1-7. https://doi.org/10.1007/s00408-012-9427-3

Weidman J, Sloop G, St Cyr JA. Validated formulae for estimation of whole blood viscosity underestimate the influence of erythrocyte aggregation and deformability. Ther Adv Cardiovasc Dis 2016; 10: 271-3. https://doi.org/10.1177/1753944716642676

Nieman LK, Biller BM, Findling JW, Murad MH, Newell-Price J, Savage MO, et al. Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2015; 100: 2807-31. https://doi.org/10.1210/jc.2015-1818

Szakacs Z, Csiszar B, Kenyeres P, Sarlós P, Erőss B, Hussain A, et al. Haemorheological and haemostatic alterations in coeliac disease and inflammatory bowel disease in comparison with non-coeliac, non-IBD subjects (HERMES): a case-control study protocol. BMJ open 2019; 9: e026315. https://doi.org/10.1136/bmjopen-2018-026315

Suarez MG, Stack M, Hinojosa-Amaya JM, Mitchell MD, Varlamov EV, Yedinak CG, et al. Hypercoagulability in Cushing Syndrome, Prevalence of Thrombotic Events: A Large, Single-Center, Retrospective Study. J Endocr Soc 2020; 4: bvz033. https://doi.org/10.1210/jendso/bvz033

Casonato A, Pontara E, Boscaro M, Sonino N, Sartorello F, Ferasin S, et al. Abnormalities of von Willebrand factor are also part of the prothrombotic state of Cushing's syndrome. Blood Coagul Fibrinolysis 1999; 10: 145-51. https://doi.org/10.1097/00001721-199904000-00006

Van Zaane B, Nur E, Squizzato A, Dekkers OM, Twickler MTB, Fliers E, et al. Hypercoagulable state in Cushing's syndrome: a systematic review. J Clin Endocrinol Metab 2009; 94: 2743-50. https://doi.org/10.1210/jc.2009-0290

Casonato A, Daidone V, Sartorello F, Albiger N, Romualdi C, Mantero F, et al. Polymorphisms in von Willebrand factor gene promoter influence the glucocorticoid-induced increase in von Willebrand factor: the lesson learned from Cushing syndrome. Br J Haematol 2008; 140: 230-5. https://doi.org/10.1111/j.1365-2141.2007.06907.x

van der Pas R, Leebeek FW, Hofland LJ, de Herder WW, Feelders RA. Hypercoagulability in Cushing's syndrome: prevalence, pathogenesis and treatment. Clin Endocrinol 2013; 78: 481-8. https://doi.org/10.1111/cen.12094

Halleux CM, Declerck PJ, Tran SL, Detry R, Brichard SM. Hormonal control of plasminogen activator inhibitor-1 gene expression and production in human adipose tissue: stimulation by glucocorticoids and inhibition by catecholamines. J Clin Endocrinol Metab 1999; 84: 4097-105. https://doi.org/10.1210/jc.84.11.4097

Dintenfass L. Viscosity and Clotting of Blood in Venous Thrombosis and Coronary Occlusions. Circ Res 1964; 14: 1-16. https://doi.org/10.1161/01.RES.14.1.1

Larcan A, Laprevote-Heully MC, Stoltz JF, Bollaert PE. [Rheologic particulars of venous flow. Physiopathologic consequences]. J Mal Vasc 1989; 14: 107-10.

Barakat AI. A model for shear stress-induced deformation of a flow sensor on the surface of vascular endothelial cells. J Theor Biol 2001; 210: 221-36. https://doi.org/10.1006/jtbi.2001.2290

Ring CP, Pearson TC, Sanders MD, Wetherley-Mein G. Viscosity and retinal vein thrombosis. Br J Ophthalmol 1976; 60: 397-410. https://doi.org/10.1136/bjo.60.6.397

Cetin MS, Ozcan Cetin EH, Canpolat U, Aydın S, Temizhan A, Topaloglu S, et al. An overlooked parameter in coronary slow flow phenomenon: whole blood viscosity. Biomark Med 2015; 9: 1311-21. https://doi.org/10.2217/bmm.15.92

Booth S, Chohan S, Curran JC, Karrison T, Schmitz A, Utset TO. Whole blood viscosity and arterial thrombotic events in patients with systemic lupus erythematosus. Arthritis Rheum 2007; 57: 845-50. https://doi.org/10.1002/art.22766

Duyuler PT, Duyuler S, Ileri M, Demir M, Dolu AK, Basyigit F. Evaluation of Whole Blood Viscosity in Patients with Aortic Sclerosis. J Tehran Heart Cent 2017; 12: 6-10.

Lowe GD, Lee AJ, Rumley A, Price JF, Fowkes FG. Blood viscosity and risk of cardiovascular events: the Edinburgh Artery Study. Br J Haematol 1997; 96: 168-73. https://doi.org/10.1046/j.1365-2141.1997.8532481.x

Tamariz LJ, Young JH, Pankow JS, Yeh HC, Schmidt MI, Astor B, et al. Blood viscosity and hematocrit as risk factors for type 2 diabetes mellitus: the atherosclerosis risk in communities (ARIC) study. Am J Epidemiol 2008; 168: 1153-60. https://doi.org/10.1093/aje/kwn243

Simmons PS, Miles JM, Gerich JE, Haymond MW. Increased proteolysis. An effect of increases in plasma cortisol within the physiologic range. J Clin Invest 1984; 73: 412-20. https://doi.org/10.1172/JCI111227

Putignano P, Kaltsas GA, Korbonits M, Jenkins PJ, Monson JP, Besser GM, et al. Alterations in serum protein levels in patients with Cushing's syndrome before and after successful treatment. J Clin Endocrinol Metab 2000; 85: 3309-12. https://doi.org/10.1210/jcem.85.9.6833

van Gool J, Boers W, Sala M, Ladiges NC. Glucocorticoids and catecholamines as mediators of acute-phase proteins, especially rat alpha-macrofoetoprotein. Biochem J 1984; 220: 125-32. https://doi.org/10.1042/bj2200125

Leberbauer C, Boulme F, Unfried G, Huber J, Beug H, Mullner EW. Different steroids co-regulate long-term expansion versus terminal differentiation in primary human erythroid progenitors. Blood 2005; 105: 85-94. https://doi.org/10.1182/blood-2004-03-1002

Gursoy A, Dogruk Unal A, Ayturk S, Karakus S, Izol AN, Tutuncu NB, et al. Polycythemia as the first manifestation of Cushing's disease. J Endocrinol Invest 2006; 29: 742-4. https://doi.org/10.1007/BF03344186




How to Cite

Canpolat, A. G., Tan Öksüz, S. B., Demir, Özgür, & Çorapçıoğlu, D. (2021). Whole Blood Viscosity as a Marker of Thrombosis in Cushing’s Disease: An Actor or Ineffective Factor. European Journal of Therapeutics, 27(1), 73–77. https://doi.org/10.5152/eurjther.2021.20132



Original Articles