28. a new fibrinogen immunoprecipitation test (fipt) predicts prevalence of cardiovascular disease...

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3rd International Fibrinogen Symposium 9 zation. In patients with clinically manifested atherosclerosis an open prospective trial (planned patient number: 100) comparing ultrasonographic findings with scintigraphy of 123I-fibrinogen labelling has been performed. Preliminary data of this comparative study will be presented. The experi- mental data indicate that fibrinogen deposition in the arte- rial wall is strongly associated with Lp(a)-entry as well as to a lesser extent to LDL. The clinical study will provide the in vivo information in patients whether 123I-fibrinogen is a reliable radioimaging agent and whether there is a correla- tion to sonographic data. 28. A new fibrinogen immunoprecipitation test (FIFr) predicts prevalence of cardiovascular disease in the Framingham offspring population J. J. Stec, H. Silbershatz, T. H. Matheney, P. Suthedand, I. Lipinska, P. Wilson, J. E. Muller, R. B. D'Agostino, G. H. Toiler Deaconess Hospital and Framingham Heart Study, Boston, MA, USA Although fibrinogen has been shown to be an independent risk factor for cardiovascular disease, it has not yet been determined which fibrinogen assay is optimal for population screening. We compared FIPT (American Biogenetic Sciences) to the commonly used Clauss functional method. FIPT utilizes a monoclonal antibody that specifically recog- nizes the intact fibrinogen molecule and is not influenced by fibrin degradation products. The ability to run multiple sam- ples concurrently make it suitable for population testing. Fibrinogen levels were measured using both methods in 1814 subjects of the Framingham Offspring Population to determine whether the methods predicted the prevalence of cardiovascular disease (CVD). The study population con- sisted of 869 men, 95 with CVD and 945 women, 51 with CVD. Values are mean + standard deviation of mean. Men Method CVD noCVD p-value p-value* FIPT (mg/dl) 356+_73 322_+77 0.001 0.034 Clauss (mg/dl) 326+_56 299+_56 0.001 0.061 Women FIPT (mg/dl) 383+_93 317+_80 0.001 0.009 Clauss (mg/dl) 344+_69 310+_57 0.001 0.189 *adjusted for age, body mass index, smoking and diabetes After adjustment, FIPT remained significantly correlated to CVD in both men and women while the Clauss method did not. These data support prior findings that fibrinogen levels are predictive of CVD and also suggest that FIPT will be use- ful in routine cardiovascular risk assessment and population screening. 29. Fibrinogen function versus antigen concentration ratio in thromboembolic disease M. Steiner, B. Krammer-Steiner 1, C. Burstein, M. Freund 1 Institute of Clinical Chemistry, 1Department of Internal Medicine, University of Rostock, Germany © Pearson Professional Ltd 1996 Increased fibrinogen concentration is an established risk fac- tor for the development of myocardial infarction and stroke whereas its role in venous thromboembolism is less clear. Since different methods result in varying fibrinogen concen- trations, we used the fibrinogen function versus antigen con- centration ratio as a measure of fibrinogen functionality which is in addition not influenced by ongoing acute phase response. This approach was applied to a cohort of 114 patients with thromboembolic disease (deep vein thrombo- sis n=32, stroke n=34, acute myocardial infarction n=48). Fibrinogen was analysed by a clotting method (Clauss, KC 10) and by automated nephelometry (Behring BN 100) at the time of admission to the hospital. The fibrinogen functional- ity ratio was calculated (functional/nephelometric). Patients with stroke demonstrated significantly higher fibrinogen concentrations in both assays when compared to DVT patients (4.47 vs 3.77 g/1 Clauss; 3.79 vs 3.08 g/1 nephelo- metric). No significant changes were observed for fibrinogen concentrations in AMI patients compared to DVT or stroke. Varying proportions of ongoing acute phase response as ver- ified by analysis of CRP (69% in DVT patients, 47% in stroke patients, and 33% in AMI patients) might partly account for the different fibrinogen concentrations. In contrast, the fib- rinogen functionality ratio was 1.206+0.447 for DVT, 1.71+_0.263 for stroke and 1.206_+0.383 for AMI without sig- nificant differences between groups. The data indicate that irrespective of fibrinogen concentrations the mean fibrino- gen functionality is not different between DVT, stroke, and AMI patients. 30. Effect of Bezafibrate on fibrinogen binding to platelets in patients with hyperlipidemia Y. Wul, J. Li 1, L. Zuo 2, X. Cao 1 IDept. of Medicine Fourth Affiliated Hospital of Hebei Medical University, 2Dept. of Cytology, Hebei Cancer Research Institute, 5 Jiankang Road, 050011 Shifiazhuang, P. R. China Disturbances of lipid metabolism may increase platelet aggregability, which is one of major mechanism by which hyperlipoidemia may contribute to atherothrombotic com- plications. More and more evidence suggest that lipid-lower- ing agent Bezafibrate (BZF) has positive action to inhibit platelet aggregability, but its exact mechanism is unknown. Having observed effect of BZF on platelet membrane glyco- protein (GP)IIIa and fibrinogen (F) binding to platelets in patients with hyperlipidemia, we try to investigate the mech- anism of BZF inhibiting platelet aggregability. According to single-blinded placebo design, 40 hyperlipidemic patients were divided into two groups. Platelet membrane GPIIIa and F binding to platelet were measured by flow cytometry 0enning's and Warkentin's methods), before treatment and after 6 weeks of treatment with 400 mg BZF retard once a day. Plasma F level was also determined. Treatment with BZF decreased significantly: F binding to platelets, -12% (p<0.05); plasma F level, -38°/0 (p<0.01). GPIIIa was not affected by BZF. Each index was not changed in placebo con- trol group. This study suggests that through inhibiting F receptor express BZF reduces F binding to platelet, which is maybe the basic mechanism of lowering platelet aggregabil- ity by itself. BZF does not affect the number of GPIIb-IIIa complex. Decrement of plasma F level is maybe one cause for BZF reducing F binding to platelets. Fibrinolysis (1996) 10, Suppl. 1, 1-58

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3rd International Fibrinogen Symposium 9

zation. In patients with clinically manifested atherosclerosis an open prospective trial (planned patient number: 100) comparing ultrasonographic findings with scintigraphy of 123I-fibrinogen labelling has been performed. Preliminary data of this comparative study will be presented. The experi- mental data indicate that fibrinogen deposition in the arte- rial wall is strongly associated with Lp(a)-entry as well as to a lesser extent to LDL. The clinical study will provide the in vivo information in patients whether 123I-fibrinogen is a reliable radioimaging agent and whether there is a correla- tion to sonographic data.

28. A n e w f ib r i nogen immunoprecipitation test (FIFr) predicts prevalence of c a r d i o v a s c u l a r disease in the Framingham offspring population

J. J. Stec, H. Silbershatz, T. H. Matheney, P. Suthedand, I. Lipinska, P. Wilson, J. E. Muller, R. B. D'Agostino, G. H. Toiler Deaconess Hospital and Framingham Heart Study, Boston, MA, USA

Although fibrinogen has been shown to be an independent risk factor for cardiovascular disease, it has not yet been determined which fibrinogen assay is optimal for population screening. We compared FIPT (American Biogenetic Sciences) to the commonly used Clauss functional method. FIPT utilizes a monoclonal antibody that specifically recog- nizes the intact fibrinogen molecule and is not influenced by fibrin degradation products. The ability to run multiple sam- ples concurrently make it suitable for population testing. Fibrinogen levels were measured using both methods in 1814 subjects of the Framingham Offspring Population to determine whether the methods predicted the prevalence of cardiovascular disease (CVD). The study population con- sisted of 869 men, 95 with CVD and 945 women, 51 with CVD. Values are mean + standard deviation of mean.

Men Method CVD noCVD p-value p-value* FIPT (mg/dl) 356+_73 322_+77 0.001 0.034 Clauss (mg/dl) 326+_56 299+_56 0.001 0.061

Women FIPT (mg/dl) 383+_93 317+_80 0.001 0.009 Clauss (mg/dl) 344+_69 310+_57 0.001 0.189

*adjusted for age, body mass index, smoking and diabetes

After adjustment, FIPT remained significantly correlated to CVD in both men and women while the Clauss method did not. These data support prior findings that fibrinogen levels are predictive of CVD and also suggest that FIPT will be use- ful in routine cardiovascular risk assessment and population screening.

29. Fibrinogen function versus antigen concentration ra t io in thromboembolic disease

M. Steiner, B. Krammer-Steiner 1, C. Burstein, M. Freund 1 Institute of Clinical Chemistry, 1Department of Internal Medicine, University of Rostock, Germany

© Pearson Professional Ltd 1996

Increased fibrinogen concentration is an established risk fac- tor for the development of myocardial infarction and stroke whereas its role in venous thromboembolism is less clear. Since different methods result in varying fibrinogen concen- trations, we used the fibrinogen function versus antigen con- centration ratio as a measure of fibrinogen functionality which is in addition not influenced by ongoing acute phase response. This approach was applied to a cohort of 114 patients with thromboembolic disease (deep vein thrombo- sis n=32, stroke n=34, acute myocardial infarction n=48). Fibrinogen was analysed by a clotting method (Clauss, KC 10) and by automated nephelometry (Behring BN 100) at the time of admission to the hospital. The fibrinogen functional- ity ratio was calculated (functional/nephelometric). Patients with stroke demonstrated significantly higher fibrinogen concentrations in both assays when compared to DVT patients (4.47 vs 3.77 g/1 Clauss; 3.79 vs 3.08 g/1 nephelo- metric). No significant changes were observed for fibrinogen concentrations in AMI patients compared to DVT or stroke. Varying proportions of ongoing acute phase response as ver- ified by analysis of CRP (69% in DVT patients, 47% in stroke patients, and 33% in AMI patients) might partly account for the different fibrinogen concentrations. In contrast, the fib- rinogen functionality ratio was 1.206+0.447 for DVT, 1.71+_0.263 for stroke and 1.206_+0.383 for AMI without sig- nificant differences between groups. The data indicate that irrespective of fibrinogen concentrations the mean fibrino- gen functionality is not different between DVT, stroke, and AMI patients.

30. Effect of Bezafibrate on fibrinogen binding to platelets in patients with hyperlipidemia

Y. Wul , J. Li 1, L. Zuo 2, X. Cao 1 I Dept. of Medicine Fourth Affiliated Hospital of Hebei Medical University, 2Dept. of Cytology, Hebei Cancer Research Institute, 5 Jiankang Road, 050011 Shifiazhuang, P. R. China

Disturbances of lipid metabolism may increase platelet aggregability, which is one of major mechanism by which hyperlipoidemia may contribute to atherothrombotic com- plications. More and more evidence suggest that lipid-lower- ing agent Bezafibrate (BZF) has positive action to inhibit platelet aggregability, but its exact mechanism is unknown. Having observed effect of BZF on platelet membrane glyco- protein (GP)IIIa and fibrinogen (F) binding to platelets in patients with hyperlipidemia, we try to investigate the mech- anism of BZF inhibiting platelet aggregability. According to single-blinded placebo design, 40 hyperlipidemic patients were divided into two groups. Platelet membrane GPIIIa and F binding to platelet were measured by flow cytometry 0enning's and Warkentin's methods), before treatment and after 6 weeks of treatment with 400 mg BZF retard once a day. Plasma F level was also determined. Treatment with BZF decreased significantly: F binding to platelets, -12% (p<0.05); plasma F level, -38°/0 (p<0.01). GPIIIa was not affected by BZF. Each index was not changed in placebo con- trol group. This study suggests that through inhibiting F receptor express BZF reduces F binding to platelet, which is maybe the basic mechanism of lowering platelet aggregabil- ity by itself. BZF does not affect the number of GPIIb-IIIa complex. Decrement of plasma F level is maybe one cause for BZF reducing F binding to platelets.

Fibrinolysis (1996) 10, Suppl. 1, 1-58