Platelet Functions in Recombinant Hirudin-Anticoagulated Blood

Abstract

The influence of genetically engineered recombinant hirudin (r-hirudin) on platelet functions was studied. Depending on the concentration, r-hirudin inhibits the thrombin-induced aggregation and ¹⁴C-serotonin secretion to the same extent as native hirudin. Comparative studies in blood anticoagulated by r-hirudin, heparin or citrate show a significantly lower spontaneous platelet aggregation in r-hirudinized blood. The extent of the ADP-induced aggregation is nearly the same in r-hirudinized, heparinized or citrated plasma. In r-hirudinized plasma, however, aggregation is reversible. In contrast to heparinized or citrated plasma, adrenaline causes only a very slight aggregation in r-hirudinized plasma. ADP- or adrenaline-induced secretion of ¹⁴C-serotonin do not occur in r-hirudinized plasma. The collagen- as well as the PAF-induced aggregation and ¹⁴C-serotonin release in hirudinized plasma do not differ significantly from those in heparinized or citrated plasma. r-Hirudin is a suitable anticoagulant for studying platelet functions because it does not produce any alterations in platelet reactions and does not provoke any changes in the ionized calcium concentration in blood.

Comparison of Two Different Blood Sample Tubes for Platelet Function Analysis with the Multiplate® System

“…Previous studies have established direct thrombin inhibitors such as lepirudin as anticoagulants for platelet function studies because these inhibitors, in contrast to citrate, keep up physiological levels of calcium ions and have no direct effect on platelets [4,[6][7][8]. In both sample tubes of this comparative study, lepirudin was used -in a liquid form in one tube and in a spray dried form in the other.…”

Effects of Recombinant Hirudin on D Dimer Levels before and after Experimental Venous Thrombosis

“…The analysis of the anticoagulant effects of hirudins showed that they are thrombin-spe cific inhibitors, which form tight stoichiomet ric complexes with thrombin whereby the ac tive center of the enzyme is blocked [10]. Thus, hirudin prevents not only fibrinogen clotting but also other thrombin-catalyzed haemostatic reactions such as activation of both clotting factors and platelets [11], The thrombin-induced platelet aggregation and re lease reaction are prevented in hirudinized blood [12][13][14], However, no references have been found in the literature about the effects of hirudin on the fibrinolytic system.…”

Hirudin as Anticoagulant in Experimental Hemodialysis

“…To prevent thrombotic occlusion in extracorporeal circulation, higher hirudin doses are required than are necessary for the inhibition of venous thrombosis, as has al ready been demonstrated in rat models of arteriovenous shunt thrombosis [7], In our opinion, this is due to the role platelets play in thrombus formation. Because of the high affinity of thrombin for platelet membrane receptors, the platelet reaction initiated by thrombin is inhibited at higher r-hirudin concentrations only [10]. The platelet reac tion caused by collagen, ADP and other sub stances is not influenced by r-hirudin [11], Hirudin as anticoagulant in hemodialysis compares well with heparin, which has pre dominantly been used for this purpose so far.…”