EFFECTS OF STANDARD HEPARIN AND A LOW MOLECULAR WEIGHT HEPARIN (KABI 2165) ON PLASMA LEVEL OF t-PA AND PA INHIBITOR

Previous and recent reports have suggested a fibrinolysis-enhancing property of standard heparin (SH) and low molecular weight heparin (LMWH) but these observations have never been confirmed in a clinical study fulfilling appropriate methodological criteria.Aim of this study was to evaluate in a cross-over double blind placebo-controlled study the effect of SH and LMWH (K 2165) on fibrinolysis. Six healthy volunteers (age 22-30) received a bolus dose of the following treatments: l)Placebo, 2)Kabi SH,5000 I.U., 3) Kabi 2165,5000 anti Xa U, 4)Kabi 2165, 10000 anti Xa U. A 4 day wash-out period was adopted.The volunteers had been fasting for at least 12 hours before the infusion and were sitting during the experiment.Before starting the infusion and at 1,2,5,10,15,30,60,120 minutes thereafter, blood samples were collected for the assay of t-PA activity, PA inhibitor activity, plasminogen, alfa2-antiplasmin, fibrinplate lysis area (FPLA), fibrinogen, aPTT, antithrombin III and anti-Xa activity. Placebo and Kabi 2165,5000 U had no effect on t-PA plasma level, however both SH and Kabi 2165,10000 U produced a statistically significant increase of t-PA level at 1 hour after the infusion. The t-PA increase lasted for at least 2 hours after the infusion; at that time the average t-PA activity was 0.14 U/ml for SH and 0.09 U/ml for Kabi 2165,10000 U (p<0.05, AN0VA,average pre-infusion level and placebo at 2 hours:0.01 U/ml).At that time plasma anti-Xa was 0.11 U/ml for SH and 1.05 U/ml for Kabi 2165,10000 U. SH and Kabi,10000 produced no effect on PA inhibitor.No effect of any treatment on fibrinogen,alfa2-antiplasmin,plasminogen, FPLA and antithrombin III was observed. We conclude that in this study both SH and Kabi 2165 produced a delayed and sustained increase of t-PA. The relevance of this effect remains to be established.