The Plasma Hemostatic Proteome: Thrombin Generation in Healthy Individuals

Overview

Journal J Thromb Haemost

Publisher Elsevier

Specialty Hematology

Date 2005 Jun 28

PMID 15978105

Citations 34

Authors

K Brummel-Ziedins

C Y Vossen

F R Rosendaal

K Umezaki

K G Mann

Affiliations

Soon will be listed here.

Abstract

Background And Objectives: The range of plasma concentrations of hemostatic analytes in the population is wide. In this study these components of blood coagulation phenotype are integrated in an attempt to predict clinical risk.

Methods: We modeled tissue factor (TF)-induced thrombin generation in the control population (N = 473) from the Leiden Thrombophilia Study utilizing a numerical simulation model. Hypothetical thrombin generation curves were established by modeling pro- and anticoagulant factor levels for each individual. These curves were evaluated using parameters which describe the initiation, propagation and termination phases of thrombin generation, i.e. time to 10 nm thrombin (approximate clot time), total thrombin and the maximum rates and levels of thrombin generated.

Results And Conclusions: The time to 10 nm thrombin varied over a 3-fold range (2.9-9.5 min), maximum levels varied over a approximately 4-fold range (200-800 nm), maximum rates varied approximately 4.8-fold (90-435 nm min(-1)) and total thrombin varied approximately 4.5-fold (39-177 microm s(-1)) within this control population. Thrombin generation curves, defined by the clotting factor concentrations, were distinguished by sex, age, alcohol consumption, body mass index (BMI) and oral contraceptive (OC) use (OC > sex > BMI > age). Our results show that the capacity for thrombin generation in response to a TF challenge may represent a method to identify an individual's propensity for developing thrombosis.

Citing Articles

Orthostatic Challenge-Induced Coagulation Activation in Young and Older Persons.

Schlagenhauf A, Steuber B, Kneihsl M, Gattringer T, Koestenberger M, Tsiountsioura M Biomedicines. 2022; 10(11).

PMID: 36359289 PMC: 9687232. DOI: 10.3390/biomedicines10112769.

Differences in thrombin and plasmin generation potential between East African and Western European adults: The role of genetic and non-genetic factors.

Temba G, Vadaq N, Wan J, Kullaya V, Huskens D, Pecht T J Thromb Haemost. 2022; 20(5):1089-1105.

PMID: 35102686 PMC: 9305795. DOI: 10.1111/jth.15657.

In vitro methodology for medical device material thrombogenicity assessments: A use condition and bioanalytical proof-of-concept approach.

Wolf M, Girdhar G, Anderson A, Ubl S, Thinamany S, Jeffers H J Biomed Mater Res B Appl Biomater. 2020; 109(3):358-376.

PMID: 32929881 PMC: 7821245. DOI: 10.1002/jbm.b.34705.

Mathematical model of thrombin generation and bleeding phenotype in Amish carriers of Factor IX:C deficiency vs. controls.

Gupta S, Bravo M, Heiman M, Nakar C, Brummel-Ziedins K, Miller C Thromb Res. 2019; 182:43-50.

PMID: 31446339 PMC: 7071813. DOI: 10.1016/j.thromres.2019.07.020.

Comparison of Effects of Anti-thrombin Aptamers HD1 and HD22 on Aggregation of Human Platelets, Thrombin Generation, Fibrin Formation, and Thrombus Formation Under Flow Conditions.

Derszniak K, Przyborowski K, Matyjaszczyk K, Moorlag M, de Laat B, Nowakowska M Front Pharmacol. 2019; 10:68.

PMID: 30842734 PMC: 6391317. DOI: 10.3389/fphar.2019.00068.

References

Hemker H, Wielders S, Kessels H, Beguin S . Continuous registration of thrombin generation in plasma, its use for the determination of the thrombin potential. Thromb Haemost. 1993; 70(4):617-24. View

Lawson J, Kalafatis M, Stram S, Mann K . A model for the tissue factor pathway to thrombin. I. An empirical study. J Biol Chem. 1994; 269(37):23357-66. View

Jones K, Mann K . A model for the tissue factor pathway to thrombin. II. A mathematical simulation. J Biol Chem. 1994; 269(37):23367-73. View

Lu D, Bovill E, Long G . Molecular mechanism for familial protein C deficiency and thrombosis in protein CVermont (Glu20-->Ala and Val34-->Met). J Biol Chem. 1994; 269(46):29032-8. View

Koster T, Rosendaal F, Reitsma P, van der Velden P, Briet E, Vandenbroucke J . Factor VII and fibrinogen levels as risk factors for venous thrombosis. A case-control study of plasma levels and DNA polymorphisms--the Leiden Thrombophilia Study (LETS). Thromb Haemost. 1994; 71(6):719-22. View

Koster T, Blann A, Briet E, Vandenbroucke J, Rosendaal F . Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet. 1995; 345(8943):152-5. DOI: 10.1016/s0140-6736(95)90166-3. View

Rand M, Lock J, Vant Veer C, Gaffney D, Mann K . Blood clotting in minimally altered whole blood. Blood. 1996; 88(9):3432-45. View

Poort S, Rosendaal F, Reitsma P, Bertina R . A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood. 1996; 88(10):3698-703. View

Rosing J, Tans G, Nicolaes G, Thomassen M, van Oerle R, van der Ploeg P . Oral contraceptives and venous thrombosis: different sensitivities to activated protein C in women using second- and third-generation oral contraceptives. Br J Haematol. 1997; 97(1):233-8. DOI: 10.1046/j.1365-2141.1997.192707.x. View

10.

van der Meer F, Koster T, Vandenbroucke J, Briet E, Rosendaal F . The Leiden Thrombophilia Study (LETS). Thromb Haemost. 1997; 78(1):631-5. View

11.

van Boven H, Lane D . Antithrombin and its inherited deficiency states. Semin Hematol. 1997; 34(3):188-204. View

12.

Butenas S, DiLorenzo M, Mann K . Ultrasensitive fluorogenic substrates for serine proteases. Thromb Haemost. 1997; 78(4):1193-201. View

13.

Doggen C, Cats V, Bertina R, Rosendaal F . Interaction of coagulation defects and cardiovascular risk factors: increased risk of myocardial infarction associated with factor V Leiden or prothrombin 20210A. Circulation. 1998; 97(11):1037-41. DOI: 10.1161/01.cir.97.11.1037. View

14.

Cawthern K, van t Veer C, Lock J, DiLorenzo M, Branda R, Mann K . Blood coagulation in hemophilia A and hemophilia C. Blood. 1998; 91(12):4581-92. View

15.

Franco R, Trip M, ten Cate H, van den Ende A, Prins M, Kastelein J . The 20210 G-->A mutation in the 3'-untranslated region of the prothrombin gene and the risk for arterial thrombotic disease. Br J Haematol. 1999; 104(1):50-4. DOI: 10.1046/j.1365-2141.1999.01149.x. View

16.

Vuori I, Pasanen M . Public health burden of coronary heart disease risk factors among middle-aged and elderly men. Prev Med. 1999; 28(4):343-8. DOI: 10.1006/pmed.1998.0426. View

17.

Kamphuisen P, Eikenboom J, Vos H, Pablo R, Sturk A, Bertina R . Increased levels of factor VIII and fibrinogen in patients with venous thrombosis are not caused by acute phase reactions. Thromb Haemost. 1999; 81(5):680-3. View

18.

Rosing J, Tans G . Effects of oral contraceptives on hemostasis and thrombosis. Am J Obstet Gynecol. 1999; 180(6 Pt 2):S375-82. DOI: 10.1016/s0002-9378(99)70699-x. View

19.

Butenas S, Vant Veer C, Mann K . "Normal" thrombin generation. Blood. 1999; 94(7):2169-78. View

20.

LANGDELL R, Wagner R, Brinkhous K . Effect of antihemophilic factor on one-stage clotting tests; a presumptive test for hemophilia and a simple one-stage antihemophilic factor assy procedure. J Lab Clin Med. 1953; 41(4):637-47. View