The impact of vitamin K-dependent factor depletion by warfarin on platelet-rich thrombosis after deep arterial injury

Robert D. McBane, N. L. Hassinger, D. E. Grill, J. H. Chesebro

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Although the central role of thrombin in arterial thrombosis is well established, the efficacy of vitamin K-dependent factor depletion by warfarin at preventing this process has not been established. To assess the efficacy of warfarin in the prevention of arterial thrombosis, two intensities of anticoagulation were compared in a well-characterized porcine model of carotid angioplasty. For 10 days prior to angioplasty, pigs received either high-dose warfarin (n = 9), low-dose warfarin plus aspirin (n = 9), or control tablets (n = 10). Injured arteries were assessed for 111In-platelet (× 106 cm-2) and 125I-fibrin(ogen) (molecules × 1012 cm-2) deposition and the incidence of macroscopic thrombus. Platelet (30 ± 7 vs. 332 ± 137; P = 0.001) and fibrinogen (156 ± 17 vs. 365 ± 90; P < 0.05) deposition were significantly reduced in animals receiving high-intensity warfarin whereas low-intensity warfarin/ASA (520 ± 240 and 1193 ± 638) was similar to control (P = NS). At the time of angioplasty, the PT-INR and vitamin K-dependent factors varied over a broad range. The greatest reduction of platelet and fibrinogen deposition occurred as the PT-INR increased from 1.0 to 2.2. Increasing the PT-INR beyond 3.0 resulted in little, if any, incremental reduction of either platelet or fibrinogen deposition. Macroscopic thrombus was abolished at PT-INR > 2.2. Despite a broad range of vitamin K factor activities, no single factor was predictive of either platelet or fibrinogen deposition. Warfarin at PT-INR > 2.2 effectively eliminates thrombosis following deep arterial injury. Arterial thrombosis correlates poorly with any single vitamin K-dependent factor but rather appears to be a function of the entire extrinsic coagulation pathway as measured by the PT-INR.

Original languageEnglish (US)
Pages (from-to)1834-1841
Number of pages8
JournalJournal of Thrombosis and Haemostasis
Volume2
Issue number10
DOIs
StatePublished - Oct 1 2004

Keywords

  • Coagulation
  • Platelets
  • Thrombosis
  • Warfarin

ASJC Scopus subject areas

  • Hematology

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