Tags

Type your tag names separated by a space and hit enter

Thrombin generation and fibrinolysis in anti-factor IX treated blood and plasma spiked with factor VIII inhibitor bypassing activity or recombinant factor VIIa.
Haemophilia 2010; 16(3):510-7H

Abstract

Activated prothrombin complex concentrates (aPCC) and recombinant activated factor VIIa (rFVIIa) are two important therapies in haemophilia patients with inhibitors and improve clot stability. We hypothesized that potential differences in procoagulant and fibrinolytic actions of aPCC and rFVIIa may lie in the clot stability against fibrinolytic activation. We used thrombin generation, fluorescence detection and thromboelastometry in anti-factor IXa (FIXa) aptamer-treated whole blood (WB) and plasma to evaluate: (i) generation of thrombin and activated factor X (FXa) and (ii) viscoelastic properties of blood clots in the presence of tissue plasminogen activator (tPA) after addition of aPCC (0.4 U mL(-1)) or rFVIIa (60 nm). Peak thrombin generation increased from 85 +/- 19 nm in aptamer-treated plasma to 276 +/- 83 nm and 119 +/- 22 nm after addition of aPCC and rFVIIa respectively (P < 0.001). FXa activity increased within 20 min by 87 +/- 6% and by 660 +/- 97% after addition of aPCC and rFVIIa respectively (P < 0.001). TPA-induced lysis time increased from 458 +/- 378 s in aptamer-treated WB to 1597 +/- 366 s (P = 0.001) and 1132 +/- 214 s (P = 0.075), after addition of aPCC and rFVIIa respectively. In this haemophilia model using the anti-FIXa aptamer, the larger amount of thrombin was generated with aPCC compared with rFVIIa, while FXa generation was more rapidly increased in the presence of rFVIIa. Furthermore, clot formation in anti-FIXa aptamer-treated WB was less susceptible to tPA-induced fibrinolysis after adding aPCC compared with rFVIIa.

Authors+Show Affiliations

Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20050927

Citation

Bolliger, D, et al. "Thrombin Generation and Fibrinolysis in Anti-factor IX Treated Blood and Plasma Spiked With Factor VIII Inhibitor Bypassing Activity or Recombinant Factor VIIa." Haemophilia : the Official Journal of the World Federation of Hemophilia, vol. 16, no. 3, 2010, pp. 510-7.
Bolliger D, Szlam F, Molinaro RJ, et al. Thrombin generation and fibrinolysis in anti-factor IX treated blood and plasma spiked with factor VIII inhibitor bypassing activity or recombinant factor VIIa. Haemophilia. 2010;16(3):510-7.
Bolliger, D., Szlam, F., Molinaro, R. J., Escobar, M. A., Levy, J. H., & Tanaka, K. A. (2010). Thrombin generation and fibrinolysis in anti-factor IX treated blood and plasma spiked with factor VIII inhibitor bypassing activity or recombinant factor VIIa. Haemophilia : the Official Journal of the World Federation of Hemophilia, 16(3), pp. 510-7. doi:10.1111/j.1365-2516.2009.02164.x.
Bolliger D, et al. Thrombin Generation and Fibrinolysis in Anti-factor IX Treated Blood and Plasma Spiked With Factor VIII Inhibitor Bypassing Activity or Recombinant Factor VIIa. Haemophilia. 2010;16(3):510-7. PubMed PMID: 20050927.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thrombin generation and fibrinolysis in anti-factor IX treated blood and plasma spiked with factor VIII inhibitor bypassing activity or recombinant factor VIIa. AU - Bolliger,D, AU - Szlam,F, AU - Molinaro,R J, AU - Escobar,M A, AU - Levy,J H, AU - Tanaka,K A, Y1 - 2009/12/29/ PY - 2010/1/7/entrez PY - 2010/1/7/pubmed PY - 2010/9/18/medline SP - 510 EP - 7 JF - Haemophilia : the official journal of the World Federation of Hemophilia JO - Haemophilia VL - 16 IS - 3 N2 - Activated prothrombin complex concentrates (aPCC) and recombinant activated factor VIIa (rFVIIa) are two important therapies in haemophilia patients with inhibitors and improve clot stability. We hypothesized that potential differences in procoagulant and fibrinolytic actions of aPCC and rFVIIa may lie in the clot stability against fibrinolytic activation. We used thrombin generation, fluorescence detection and thromboelastometry in anti-factor IXa (FIXa) aptamer-treated whole blood (WB) and plasma to evaluate: (i) generation of thrombin and activated factor X (FXa) and (ii) viscoelastic properties of blood clots in the presence of tissue plasminogen activator (tPA) after addition of aPCC (0.4 U mL(-1)) or rFVIIa (60 nm). Peak thrombin generation increased from 85 +/- 19 nm in aptamer-treated plasma to 276 +/- 83 nm and 119 +/- 22 nm after addition of aPCC and rFVIIa respectively (P < 0.001). FXa activity increased within 20 min by 87 +/- 6% and by 660 +/- 97% after addition of aPCC and rFVIIa respectively (P < 0.001). TPA-induced lysis time increased from 458 +/- 378 s in aptamer-treated WB to 1597 +/- 366 s (P = 0.001) and 1132 +/- 214 s (P = 0.075), after addition of aPCC and rFVIIa respectively. In this haemophilia model using the anti-FIXa aptamer, the larger amount of thrombin was generated with aPCC compared with rFVIIa, while FXa generation was more rapidly increased in the presence of rFVIIa. Furthermore, clot formation in anti-FIXa aptamer-treated WB was less susceptible to tPA-induced fibrinolysis after adding aPCC compared with rFVIIa. SN - 1365-2516 UR - https://www.unboundmedicine.com/medline/citation/20050927/Thrombin_generation_and_fibrinolysis_in_anti_factor_IX_treated_blood_and_plasma_spiked_with_factor_VIII_inhibitor_bypassing_activity_or_recombinant_factor_VIIa_ L2 - https://doi.org/10.1111/j.1365-2516.2009.02164.x DB - PRIME DP - Unbound Medicine ER -