Altered fibrin clot structure in patients with advanced coronary artery disease: a role of C‐reactive protein, lipoprotein(a) and homocysteine

Abstract

To cite this article: Undas A, Plicner D, Stępień E, Drwiła R, Sadowski J. Altered fibrin clot structure in patients with advanced coronary artery disease: a role of C-reactive protein, lipoprotein(a) and homocysteine. J Thromb Haemost 2007; 5: 1988-90. Evidence for a role of fibrin clot structure/function in coronary artery disease (CAD) is scarce [1]. Factors that determine unfavorable fibrin clot properties in CAD patients are poorly understood. We have demonstrated that C-reactive protein (CRP) [2], lipoprotein(a) [Lp(a)] [3] and total homocysteine (tHcy) [4] are associated with decreased clot permeability and susceptibility to lysis. However, these findings are derived from small studies in patients aged < 60 years with a variable extent of CAD. The aim of the current study was to evaluate fibrin clot properties in middle-aged and elderly patients with advanced CAD.We studied 133 patients with angiographically proven CAD ( ‡ 70% stenosis), who qualified for elective coronary artery bypass grafting surgery. Exclusion criteria were: any acute illness; cancer; hepatic or renal dysfunction; anticoagulant therapy; acute coronary syndrome within the previous 6 weeks; or previous venous thromboembolism. Medications were administered in unchanged doses for at least 2 weeks. Apparently healthy, age-and sex-matched individuals (n = 100) served as controls.Fibrinogen and high-sensitivity CRP were measured by nephelometry (Dade Behring, Marburg, Germany). Fasting plasma tHcy levels were measured using the IMX System (Abbott Diagnostics, Wiesbaden, Germany). Serum Lp(a) levels were determined by ELISA (Biopool, Umea, Sweden).Fibrin clot permeability, expressed as a permeation coefficient (K s ), which indicates the pore size, was determined as described [5]. Clot lysis times were determined using a turbidity assay with slight modifications. Citrated plasma was diluted with the Tris buffer, containing 20 mmol L -1 CaCl 2 , 1 U mL -1 human thrombin (Sigma) and 1 lg mL -1 recombinant tissue plasminogen activator, rtPA (Boerhinger Ingelheim, Ingelheim, Germany). The time required for a 50% decrease in clot turbidity (t 50% ) was determined [6]. Assembly kinetics were monitored at 405 nm. The intra-assay and interassay coefficients of variation for all the measures were 4-7%.Clots from CAD patients with fibrinogen within the reference range were fixed, further processed by dehydration and photographed digitally in six different areas with a Hitachi S-4700 scanning electron microscopy (SEM) [5].Data are given as mean ± SD or median (interquartile range). Inter-group comparisons were performed using the Mann-Whitney U-test and correlations were assessed by the SpearmanÕs rank-correlation coefficient. Multiple linear regression analysis was used to determine predictors of K s and lysis times. A value of P < 0.05 was considered significant.The CAD group consisted of 133 patients (94 male, 39 female), aged 62 (59-67) years, including 53 (40%) smokers and 28 (21%) diabetics. Seventy-eight (59%) of the patients had previous MI; ...

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