Potential value of the calibrated automated thrombogram in patients after a cerebral venous sinus thrombosis; an exploratory study
Tóm tắt
Cerebral venous sinus thrombosis (CVST) is a relatively rare, but potentially lethal condition. In approximately 15% of the patients, the cause of CVST remains unclear. Conventional clotting tests such as prothrombin time and activated partial thromboplastin time are not sensitive enough to detect prothrombotic conditions nor mild haemostatic abnormalities. The calibrated automated thrombogram (CAT) is a physiological function test that might be able to detect minor aberrations in haemostasis. Therefore, we aimed to detect the presence of a prothrombotic state in patients who endured idiopathic CVST with the CAT assay. Five adult patients with an idiopathic, radiologically proven CVST that had been admitted during the past 3 years were included in this study. The control group consisted of five age/gender matched healthy volunteers. Exclusion criteria were known haematological disorders, malignancy (current/past) or hormonal and anticoagulant therapy recipients. We obtained venous blood samples from all participants following cessation of anticoagulation. Using the CAT assay, we determined lag time, normalized endogenous thrombin potential (ETP), ETP reduction and normalized peak height. In addition, prothrombin concentrations were determined. We found no significant differences in lag time (4.7 min [4.5–4.9] vs 5.3 min [3.7–5.7], p = 0.691), normalized ETP (142% [124–148] vs 124% [88–138], p = 0.222), ETP reduction (29% [26–35] vs 28% [24–58], p > 0.999), and normalized peak height (155% [153–175] vs 137 [94–154], p = 0.056) between patients and their age/gender matched controls. In addition, prothrombin concentrations did not significantly differ between patients and controls (120% [105–132] vs 127% [87–139], p > 0.999). Reasons for absent overt hypercoagulability within this study population may be the small patient sample, long time since the event (e.g. 3 years) and avoidance of acquired risk factors like oral contraception. Given the fact that CVST is a serious condition with a more than negligible risk of venous thrombosis event recurrence, exclusion of clinically relevant hypercoagulability remains a challenging topic to further study at the acute and later time points, particularly in patients with idiopathic CVST.
Tài liệu tham khảo
Weimar C. Diagnosis and treatment of cerebral venous and sinus thrombosis. Curr Neurol Neurosci Rep. 2014;14(1):417.
Silvis SM, de Sousa DA, Ferro JM, Coutinho JM. Cerebral venous thrombosis. Nat Rev Neurol. 2017;13(9):555–65.
Gao L, Xu W, Li T, Yu X, Cao S, Xu H, et al. Accuracy of magnetic resonance venography in diagnosing cerebral venous sinus thrombosis. Thromb Res. 2018;167:64–73.
Ferro JM, Canhao P, Stam J, Bousser MG, Barinagarrementeria F, Investigators I. Prognosis of cerebral vein and dural sinus thrombosis: results of the international study on cerebral vein and Dural sinus thrombosis (ISCVT). Stroke. 2004;35(3):664–70.
Breteau G, Mounier-Vehier F, Godefroy O, Gauvrit JY, Mackowiak-Cordoliani MA, Girot M, et al. Cerebral venous thrombosis 3-year clinical outcome in 55 consecutive patients. J Neurol. 2003;250(1):29–35.
Gameiro J, Ferro JM, Canhao P, Stam J, Barinagarrementeria F, Lindgren A, et al. Prognosis of cerebral vein thrombosis presenting as isolated headache: early vs. late diagnosis. Cephalalgia. 2012;32(5):407–12.
Franchini M, Liumbruno GM, Pezzo M. COVID-19 vaccine-associated immune thrombosis and thrombocytopenia (VITT): Diagnostic and therapeutic recommendations for a new syndrome. Eur J Haematol. n/a(n/a).
Dentali F, Crowther M, Ageno W. Thrombophilic abnormalities, oral contraceptives, and risk of cerebral vein thrombosis: a meta-analysis. Blood. 2006;107(7):2766–73.
Luo Y, Tian X, Wang X. Diagnosis and treatment of cerebral venous sinus thrombosis: a review. Front Aging Neurosci. 2018;10:2.
Coutinho JM, Stam J. How to treat cerebral venous and sinus thrombosis. J Thromb Haemost. 2010;8(5):877–83.
Palazzo P, Agius P, Ingrand P, Ciron J, Lamy M, Berthomet A, et al. Venous thrombotic recurrence after cerebral venous thrombosis: a long-term follow-up study. Stroke. 2017;48(2):321–6.
Dielis AWJHCE, Spronk HMH, van Oerle R, Hamulya'k K, Cate t, Rosing J. Coagulation factors and the protein C system as determinants of thrombin generation in a normal population. Thromb Haemost. 2008;6(1):125–31.
Duarte RCF, Ferreira CN, Rios DRA, Reis HJD, Carvalho MDG. Thrombin generation assays for global evaluation of the hemostatic system: perspectives and limitations. Rev Bras Hematol Hemoter. 2017;39(3):259–65.
Hemker HC, Giesen P. AR, Regnault V, de Smed E, Lecompte T, Béguin S. the calibrated automated Thrombogram (CAT) a universal routine test for hyper- and hypocoagulability. Pathophysiol Haemost Thromb. 2002;32(5–6):249–53.
Bloemen S, Zwaveling S, Ten Cate H, Ten Cate-Hoek A, de Laat B. Prediction of bleeding risk in patients taking vitamin K antagonists using thrombin generation testing. PLoS One. 2017;12(5):e0176967.
Hemker HC, Al Dieri R, Beguin S. Thrombin generation assays: accruing clinical relevance. Curr Opin Hematol. 2004;11(3):170–5.
Ten Cate H. Thrombin generation in clinical conditions. Thromb Res. 2012;129(3):367–70.
Loeffen R, Kleinegris MC, Loubele ST, Pluijmen PH, Fens D, van Oerle R, et al. Preanalytic variables of thrombin generation: towards a standard procedure and validation of the method. J Thromb Haemost. 2012;10(12):2544–54.
Spronk HM, Dielis AW, De Smedt E, van Oerle R, Fens D, Prins MH, et al. Assessment of thrombin generation II: validation of the calibrated automated Thrombogram in platelet-poor plasma in a clinical laboratory. Thromb Haemost. 2008;100(2):362–4.
Wexels F, Dahl OE, Pripp AH, Seljeflot I. Thrombin generation in patients with suspected venous thromboembolism. Clin Appl Thromb Hemost. 2017;23(5):416–21.
Kremers BMM, Birocchi S, van Oerle R, Zeerleder S, Spronk HMH, Mees BME, et al. Searching for a Common Thrombo-Inflammatory Basis in Patients With Deep Vein Thrombosis or Peripheral Artery Disease. Front Cardiovasc Med. 2019;6(33).
Butenas S, van't Veer C, Mann KG. "Normal" thrombin generation. Blood. 1999;94(7):2169–78.
Hemker HC, Beguin S. Thrombin generation in plasma: its assessment via the endogenous thrombin potential. Thromb Haemost. 1995;74(1):134–8.
ten Cate-Hoek AJ, Dielis AW, Spronk HM, van Oerle R, Hamulyak K, Prins MH, et al. Thrombin generation in patients after acute deep-vein thrombosis. Thromb Haemost. 2008;100(2):240–5.
Lutsey PL, Folsom AR, Heckbert SR, Cushman M. Peak thrombin generation and subsequent venous thromboembolism: the longitudinal investigation of thromboembolism etiology (LITE) study. Thromb Haemost. 2009;7(10):1639–48.
Machlus KR, Colby EA, Wu JR, Koch GG, Key NS, Wolberg AS. Effects of tissue factor, thrombomodulin and elevated clotting factor levels on thrombin generation in the calibrated automated thrombogram. Thromb Haemost. 2009;102(5):936–44.
Joly BS, Sudrie-Arnaud B, Barbay V, Borg JY, Le Cam Duchez V. Thrombin generation test as a marker for high risk venous thrombosis pregnancies. J Thromb Thrombolysis. 2018;45(1):114–21.
Park MS, Spears GM, Bailey KR, Xue A, Ferrara MJ, Headlee A, et al. Thrombin generation profiles as predictors of symptomatic venous thromboembolism after trauma: a prospective cohort study. J Trauma Acute Care Surg. 2017;83(3):381–7.
Riva N, Vella K, Hickey K, Bertu L, Zammit D, Spiteri S, et al. Biomarkers for the diagnosis of venous thromboembolism: D-dimer, thrombin generation, procoagulant phospholipid and soluble P-selectin. J Clin Pathol. 2018;71(11):1015–22.
Voils SA, Lemon SJ, Jordan J, Riley P, Frye R. Early thrombin formation capacity in trauma patients and association with venous thromboembolism. Thromb Res. 2016;147:13–5.
Lippi G, Danese E, Favaloro EJ, Montagnana M, Franchini M. Diagnostics in venous thromboembolism: from origin to future prospects. Semin Thromb Hemost. 2015;41(4):374–81.
Miranda B, Ferro JM, Canhao P, Stam J, Bousser MG, Barinagarrementeria F, et al. Venous thromboembolic events after cerebral vein thrombosis. Stroke. 2010;41(9):1901–6.