46 POSTER PRESENTATIONS P-VI Fibrinolysis in Vascular Diseases

152 HEMOSTATIC MAKERS INCREASED SIGUNIFICANTLY AFTER HANSHIN-AWAJI EARTHQUAKE IN JAPAN

1 Kobayashi H, 1 Suzuki S, 1 Matuo T, and 2 Kario K

1 Hyougo Prefectural Awaji Hospital, Sumoto, Japan.

2 Awaji-Hokudan Public Clinic, Hokudan, Japan.

On Jan. 17, 1995, the south part of Hyougo Prefecture was struck by major earthquake. In the our Hokudan town where was the epicenter, the number of the cardiovascular and sudden deaths duadng the 6 weeks after the quake increased at 3.3 times, compared to the same period in the previous year. To clarify a role hemostatic activation in cardiovascular accidents, we compared coagulation and fibrinolytic parameters before and after the quake. Blood samples were collected from 42 outpatients with well-controlled hypertension who lived near the epicenter. After the quake, all subjects showed a significant increase in blood pressure, hematocrit and fibrinogen. Hemostatic activation makers (D-dimer and plasmin-= 2plasmin inhibiter complex ), and endothelial cell-derived markers (tissue-type plasminogen activator antigen and von Willebrand factor) increased significantly after the quake. High-stress subjects who experienced total loss of housing and injury or death in family member had greater hemostatic activation than low-stress subjects. The quake induces hemostatic activation in hypertensive patients with the risk factors. Hemostatic activation may contribute to the increased incidence of cardiovascular accidents after the quake.

153 FIBRINOLYSIS IN CORONARY ARTERY DISEASE. INFLUENCE OF POSTMENOPAUSAL STATUS. ~Estellds A, 2Tormo G, tGilabert J, 1Falc6 C, 'Espafia F, 2Rodriguez J, ~'l'ormo V and ~Aznar J. ~Hospital Universitario La Fe, and 2Hospital General, Valencia. Spain.

The incidence of coronary artery disease (CAD) is higher in postmenopausal that in premenopeusal women, and there is evidence that the estrogen protects against CAD in premenopause. We have previously described a decrease in fibrinolytic activity and an increase in lipoprotein (a) [Lp(a)] in healthy postmenopausal women in comparison with healthy premenopausal women (Am J Obstet Gynecol, 1995). We have also observed an increase in fibrinolytic activity and a decrease in Lp(a) levels in women under hormone replacement therapy (HRT) and these modifications could help to decrease the risk of CAD associated with postmenopausal status. The aim of the present study is to evaluate several components of the fibrinolytic system and lipid profile in postmenopausal women with CAD and to compare them with premenopausal women with CAD (patient groups), and with healthy pre and postmenopausal women (control groups). A decrease in fibrinolytic activity due to an increase in PAl-1 levels was observed in patient groups in comparison with control groups, but the PAl-1 levels were more elevated in the postmenopausal patient group (patient groups: postmenopause 44+17 ng/ml, premenopause 34_+24 ng/ml; control groups: postmenopause 28_+18 ng/ml, premenopause 16_+7 ng/ml). Lp(a) levels are increased in postmenopausal status in both healthy and CAD women. Our preliminary data indicate that after 3 months of HRT there was an increase in plasma fibrinolytic activity mainly due to a decrease in PAl-1 and in Lp(a) plasma levels. In conclusion, women with CAD show a decrease in fibrinolytic activity due to increased PAl-1 levels. This alteration is more evident in postmenopause. The influence of HRT is under study. (FIS 96/1256).

154 FOLLOWING PTCA A SIGNIFICANT AND SUSTAINED CLOTTING ACTIVATION OCCURS AFTER ttEPARIN DIS CON TIN U ATION Prisco D, Simonetti I, Dabizzi RP, Margheri M, Giglioli C, Antonucci E, Capanni M, Chiarugi L, Abbate R, Gensini GF. Istituto di Clinica Medica e Cardiologia, Universit~ di Firenze Italy

Percutaneous transluminal coronary angioplasty (PTCA) is still affected by acute complications (2-8%) and restenosis (30-40%). A study was undertaken in order to evaluate the changes of hemostatic tactors in relation to PTCA procedure. Thirty-one patients (27 M, 4 F) undergoing elective PTCA were enrolled. All were on chronic oral treatment with aspirin (ASA, 325 rag/day) in addition to standard medications (nitrates and/or calcium blockers and/or beta-blockers), and received heparin (10,000 - I5,000 U i.v.) plus ASA 500 mg i.v. during the procedure. Post-PTCA drug regimen included heparin infusion ( 1,000-1,200 U/hour) for 12-18 hours, and oral treatment with ASA (325 rag/day) and standard anti-anginal therapy. PTCA was successful in 29 patients, while it was not successful in 2, whose diameter stenosis was 100%. In successful PTCA, mean diameter stenosis was 73+12% before, and 24+10% after PTCA. Clotting activation (Prothrombin fragment 1+2, Thrombin-antithrombin complex) and fibrinolysis (Euglobulin Lysis Time, Plasminogen Actiwtto, Inhibitor-1 activity and D-dimer) were tested in peripheral venous blood before, immediately after PTCA, 48 hours and 7 days later No clotting activation was detectable at the end of the procedure, btit such phenomenon occurred in 85% of patients at 48 hours and 7 days. A marked fibrinolysis activation was observed during PTCA, followed by a further increase in D-dimer after 2 and 7 days. We conclude that in most patients who undergo PTCA signs of clotting activation become evident after discontinuation of heparin and are still detectable 7 days after the procedure. An impaired fibfinolytic reaction could accotllqt for acute or subacute closure in case of suboptimal PTCA result.

155 DISTURBANCES IN THE TUSSUE PLASMINOGEN

ACTIVATOR/PLASMINOGEN ACTIVATOR INHIBITOR ( TPA/PAI ) SYSTEM IN LUPUS NEPHRITIS (LN).

IBobkova 1, 1Tareyeva I., 1Polyantseva L., 2Podorolskaya L., 2Andreenko (7.

1Moscow Medical Academy and 2Moscow State University, Moscow, Russia.

Activity and antigen level of endothelium-derived fibrinolytic factors ( TPA, PAl) were evaluated in plasma and urine of 53 patients with active LN ( I group- LN without nephrotie syndrome (NS) in 20 pts, II- LN with NS in 17 pts, III- rapidly progressive LN (RPLN) in 16 pts ) and 15 healthy controls (group IY). Venous occlusion (VO) test was performed also. Plasma and urine TPA activity in patients with active LN was significantly lower than in healthy controls (plasma: I- 5,6+1,2; II- 3,25_+1,1; III- 1,5+0,6; IY- 17,3_+1,0 mm 2 ; urine: I -147,9_+17,5; II- 131,2_+19,6; III- 174,0_+53,9; IY- 201,1_+32,0 mm2). Correlation was found between decrease of plasma and urine TPA activity and LN severity. Plasma and urine PAI levels were abnormally high in active LN( plasma: I- 4,9_+0,2; II- 5,9+0,4; III- 5,4_+0,4; IY- 3,1_+0,4 ng/ml; urine: I- 1,5_+0,2; 11- 3,1+0,2; III- 3,6_+0,2; IY- 0,96+0,2 ng/ml). Negative reversive correlations were revealed betweeen decrease of plasma and urine TPA activity and high levels of plasma and urine PAl. After VO plasma and urinary TPA activity increased in healthy controls and patients without NS ( plasma: Y- 362% to basal level, IY- 331%, 1- 199%; urine: Y- 160%, IY- 150%, I- 145% to basal level). In pts with NS and RPLN VO test revealed reduced response of plasma and urinary TPA ( plasma: II- 99%, III- 64%; urine: II- 106, IlI- 64%). Thus, these results reflect the change of endothelium functional phenotype: the decrease of fibrinolytic activity and stimulation of procoagulant pathways. We consider, that endothelium disfunction may be secondary to its damage.