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Effect of hirudin vs heparin on haemostatic activity in patients with acute coronary syndromes; the GUSTO-IIb haemostasis substudy.

Publication ,  Journal Article
Kottke-Marchant, K; Bahit, MC; Granger, CB; Zoldhelyi, P; Ardissino, D; Brooks, L; Griffin, JH; Potthoff, RF; Van de Werf, F; Califf, RM; Topol, EJ
Published in: Eur Heart J
August 2002

AIMS: We compared the effects of hirudin and heparin on thrombin generation and activity among 350 patients with acute coronary syndromes enrolled in the GUSTO-IIb trial. METHODS AND RESULTS: We obtained blood at baseline; at 4, 8, and 24h into infusion; at drug termination; and 6 and 24h after termination. We assayed for thrombin activity (fibrinopeptide A, activated protein C, thrombin-antithrombin complex), thrombin generation (prothrombin fragment 1.2), and platelet activation (platelet factor 4). Median baseline fibrinopeptide A and platelet factor 4 levels were elevated. Thrombin formation tended to increase with hirudin and decrease with heparin; by 8h into infusion, thrombin formation was significantly less for heparin (P<0.01). Most patients showed reduced thrombin activity and platelet activation during infusion of either agent. Hirudin-assigned patients had significantly lower fibrinopeptide A levels during infusion. Six h post-termination, both groups had increased thrombin activity. Thrombin formation was increased in heparin patients (P<0.0001), significantly more than with hirudin (P=0.005). Higher values of haemostasis markers tended to be associated with poorer 30-day outcomes. CONCLUSION: Although hirudin did not prevent generation of new thrombin, it appeared to inhibit thrombin activity more than did heparin and produced slower increases in thrombin formation after discontinuation. The reelevation of thrombotic markers after stopping intravenous antithrombin therapy and the tendency toward increased thrombotic events with post-treatment increases in marker levels suggest an ongoing, clinically significant prothrombotic state. These results raise the possibility of improving on current antithrombotics by preventing thrombin generation and thrombin activity and by sustained suppression of the prothrombotic state.

Duke Scholars

Published In

Eur Heart J

DOI

ISSN

0195-668X

Publication Date

August 2002

Volume

23

Issue

15

Start / End Page

1202 / 1212

Location

England

Related Subject Headings

  • Treatment Outcome
  • Thrombin
  • Syndrome
  • Middle Aged
  • Male
  • Humans
  • Hirudins
  • Hirudin Therapy
  • Heparin
  • Hemostasis
 

Citation

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Kottke-Marchant, K., Bahit, M. C., Granger, C. B., Zoldhelyi, P., Ardissino, D., Brooks, L., … Topol, E. J. (2002). Effect of hirudin vs heparin on haemostatic activity in patients with acute coronary syndromes; the GUSTO-IIb haemostasis substudy. Eur Heart J, 23(15), 1202–1212. https://doi.org/10.1053/euhj.2001.3074
Kottke-Marchant, K., M. C. Bahit, C. B. Granger, P. Zoldhelyi, D. Ardissino, L. Brooks, J. H. Griffin, et al. “Effect of hirudin vs heparin on haemostatic activity in patients with acute coronary syndromes; the GUSTO-IIb haemostasis substudy.Eur Heart J 23, no. 15 (August 2002): 1202–12. https://doi.org/10.1053/euhj.2001.3074.
Kottke-Marchant K, Bahit MC, Granger CB, Zoldhelyi P, Ardissino D, Brooks L, et al. Effect of hirudin vs heparin on haemostatic activity in patients with acute coronary syndromes; the GUSTO-IIb haemostasis substudy. Eur Heart J. 2002 Aug;23(15):1202–12.
Kottke-Marchant, K., et al. “Effect of hirudin vs heparin on haemostatic activity in patients with acute coronary syndromes; the GUSTO-IIb haemostasis substudy.Eur Heart J, vol. 23, no. 15, Aug. 2002, pp. 1202–12. Pubmed, doi:10.1053/euhj.2001.3074.
Kottke-Marchant K, Bahit MC, Granger CB, Zoldhelyi P, Ardissino D, Brooks L, Griffin JH, Potthoff RF, Van de Werf F, Califf RM, Topol EJ. Effect of hirudin vs heparin on haemostatic activity in patients with acute coronary syndromes; the GUSTO-IIb haemostasis substudy. Eur Heart J. 2002 Aug;23(15):1202–1212.
Journal cover image

Published In

Eur Heart J

DOI

ISSN

0195-668X

Publication Date

August 2002

Volume

23

Issue

15

Start / End Page

1202 / 1212

Location

England

Related Subject Headings

  • Treatment Outcome
  • Thrombin
  • Syndrome
  • Middle Aged
  • Male
  • Humans
  • Hirudins
  • Hirudin Therapy
  • Heparin
  • Hemostasis