Carbon Monoxide Releasing Molecule-2 Enhances Coagulation and Diminishes Fibrinolytic Vulnerability in Subjects Exposed to Warfarin

被引:12
作者
Nielsen, Vance G. [1 ]
Khan, Ejaz S. [1 ]
Kirklin, James K. [2 ]
George, James F. [2 ]
机构
[1] Drexel Univ, Coll Med, Dept Anesthesiol, Philadelphia, PA 19102 USA
[2] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA
关键词
Carbon monoxide releasing molecule; Warfarin; International Normalized Ratio; Thrombelastography; DEFICIENT PLASMAS; THROMBUS GROWTH; FACTOR-VII; INCREASES; STRENGTH; VELOCITY;
D O I
10.1016/j.thromres.2010.03.011
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Introduction: It has been recently demonstrated that a carbon monoxide releasing molecule (tricarbonyldichlororuthenium (II) dimer; CORM-2) enhances coagulation and attenuates vulnerability to fibrinolysis in normal and hemophiliac human plasma. We tested the hypothesis that plasma obtained from warfarin-treated subjects would demonstrate improved coagulation and decreased fibrinolytic vulnerability following exposure to CORM-2. Materials and Methods: Anonymous donor plasma samples with international normalized ratios (INR) values ranging from 1.5-5.4 were exposed to 0 or 100 mu M CORM-2 and activated with tissue factor (12 samples). Additional samples within the same INR range were exposed to 0 or 100 mu M CORM-2 and 0 or 100 U/ml tissue-type plasminogen activator (tPA) to assess fibrinolytic vulnerability (8 samples). Thrombelasto-graphic data were collected until either clot strength stabilized or clot lysis occurred as appropriate. Results and Conclusions: In the absence of tPA, all but one sample (INR=1.5) demonstrated a marked increase in the velocity of clot formation (40-577%) and strength (42-180%) following CORM- 2 exposure. Of interest, in the presence of tPA, all samples (including the previously unresponsive sample) were noted to have an increase in the velocity of clot formation and strength, coupled with a prolonged onset to maximal rate of clot lysis (60-242%) and increased clot lysis time (74-149%). As with normal and hemophilic plasma, both enhancement of coagulation and attenuation of fibrinolysis occur following CORM-2 exposure in plasma from warfarin-treated subjects. Future investigation must determine if carbon monoxide releasing molecules could be used therapeutically to control bleeding in warfarin-treated patients. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:68 / 73
页数:6
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