Thrombolytic and haemorrhagic effects of bolus doses of rt-PA and A hybrid plasminogen activator with prolonged plasma half-life (K 2 tu-PA: CGP 42935)

ABSTRACTS OF 12TH NATIONAL CONGRESS Vol. 70, zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Suppl. 1 s91 c 180 HEMORHEOLOGICAL EFFECTS OF A VERY LOW CALORIE DIET (VLCD) IN OBESE SUBJECTS. Poegi, Biagi R, Babini AC (l), Baraldi L (l), Parenti M (l), Palareti G, Coccheri S. Dept. Angiology and Blood Coagulation, (1) Inst. Internal Medicine, University Hospital S. Orsola, Bologna, Italy Hemorheologic tests were performed in 52 obese healthy subjects (OB; 31 females, age range 14-56,), with body mass index (BMI) ranging between 3254, before (TO) and after 3 months (T3) of VLCD (470 Kcal/day), and in a control group (CG) of 28 (12 females) non obese age-matched individuals. Compared to CG male OBs had higher levels of Hematocrit (Ht, p< 0,05), plasma viscosity (PLV, p<O,OOl), erythrocyte aggregation index (EAI, Rheoaggregometer Myrenne, p<O,OOl) and fibrinogen (Fgn, p<O,OOl). Female OBs had higher PLV (p<O,Ol), EAI (pcO,O5) and Fgn @<O,OOl) levels. Three months VLCD induced a significant reduction in BMI (from 37.920.2 to 32.021.1, p<O.OOl) and EAI (from 35.421.9 AU to 28.621.9, p<O.OOl). In male OBs Ht was also reduced (~~0.05). In female OBs a reduction in total proteins @<O.Ol) with increased albumin/globulin ratio (pcO.001) was recorded. No changes in Fgn and PLV levels were observed. In conclusion, marked obesity is associated with alterations of some hemorheologic parameters; a prolonged period of very low calorie diet improved erythrocyte aggregability (probably due to improved albumin/globulin ratio) while not affecting Fgn and PLV levels. C 182 THROMBOLYTIC AND HAEMORRHAGIC EFFECTS OF BOLUS DOSES OF MA AND A HYBRID PLASMINOGEN ACTIVATOR WITH PROLONGED PLASMA HALF-LIFE (Kltu-PA: CGP 42935). /&t&l ,G. Agnellil, G. G. Nencil, A. Mele2, R. BiirgP,J. Hein?, ‘Institute of zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA /nterna/ and Vascular Medicine, UniweMy of Pen,@, ha/y. 2Menarini Ricerche Sud, Rome, Italy. %iba Geigy, &ml, Switzerland. K2tu-PA is a hybrid plasminogen activator linking the kringle 2 domain of t-PA to the catalytic protease domain scu-PA. Kptu-PA has a plasma half-life of over 30 minutes. The aim of this study was to compare the effects of bolus doses of &PA and K2tu_PA, on: 1) lysis of pm-formed thrombi (fibrinolysis), 2) accretion of new fibrin on pre-existing thrombi during fibrinolysis (thrombus growth), 3) systemic plasma proteolysis and blood Ices from a standard wound. A jugular vein thrombosis and an ear bleeding model were adopted in rabbits. Saline produced 11*2% fibrindysis. &PA, 0.2 mg/Kg, 0.4 mg/kg and 0.8 mg/Kg produced 35*4%, 54*4Oh and 78&% fibrinolysis,respectively. K2tuPA! at the same doses, produced 396%, 576% and 83&% fibrinolysis, respectively. Injection of saline was followed by an accretion of 56.4k5.9 pg of radioactive new f&tin on the thrombi. The injection of the three increasing doses of &PA was followed by an accretion of 54.9k5.3 pg, 49.lti.lpg and 47.2k4.8 pg. The injection of three increasing doses of K2tu-PA was fdlowed by an accretionof 38.1 k3.4 pg, 29.b 2.5 pg and 17.1* 3.4 pg. At each of the three doses, K2tu-PAwas more effective than &PA in reducing the accretion of new fibrin on the thrombi (~0.01) and, as a consequence, in reducing thrombus weight (pcO.01). The two lower doses of rt-PA and K2tu-PA did not produce systemic proteolysis and bleeding. The highest dose of K2tu-PA produced a statistically significant more intense systemic proteolysis and bleedi than the highest dose of rt-PA. This study demonstrates that bolus doses of K2tu-Pn! and &PA produce a similar degree of fibrinolysis. K2tu-PA is more efficient than rt-PA in inhibiting accretion of new fibrin on the thrombi during thrombolysis. The potential increased risk of bleeding with a bolus of high doses of l$tu-PA has to be seen in view of the advantage of avoiding the concomitant use of heparin.