Artificial plasma expanders (PEs) are widely used in modern transfusion medicine. PEs do not contain components of the coagulation system, so their infusion in large volumes causes haemodilution and affects haemostasis. However, the existing information on this effect is contradictory. We studied the effect of the very process of plasma dilution on coagulation and tested the hypothesis that moderate dilution with a PE should accelerate clotting owing to a decrease in concentration of coagulation inhibitors. The standard clotting times, a thrombin generation test, and the spatial rate of clot growth (test of thrombodynamics) were used to assess donor plasma diluted in vitro with various PEs. The pH value and Ca+2 concentration were maintained strictly constant in all samples. The effect of thrombin inhibitors on dilution-induced hypercoagulation was also examined. It was shown that coagulation was enhanced in plasma diluted up to 2.0–2.5-fold with any PE. This enhancement was due to the dilution of coagulation inhibitors in plasma. Their addition to plasma or PE could partially prevent the hypercoagulation shift.

Investigation of inhibitory effect of two single-stranded DNA thrombin-inhibiting aptamers (15TBA and 31TBA) on fibrin polymerization in fibrinogen solutions and comparison of anticoagulant properties of these aptamers by a new global coagulation test of thrombodynamics. Measurement of aptamers' functional stability in human plasma and blood in vitro in order to investigate the involvement of 3'-exonuclease in fast decrease of aptamers' functional activity in vivo. Thrombin inhibition activity was measured in a buffer system in vitro as effects of aptamers on fibrin polymerization. Anticoagulant activity was investigated by measuring the spatial clot growth rate in the presence of aptamers. The stability of aptamers during incubation in human plasma was investigated in vitro by measuring activated partial thromboplastin time. Both aptamers dose-dependently inhibit fibrin polymerization in a buffer solution (IC50=10 nm for 15TBA and 3 nm for 31TBA) and are effective anticoagulants in human plasma (IC50 for spatial clot growth rate decreasing are 9.5 μmol/l and 4.0 μmol/l for 15TBA and 31TBA, correspondingly). Both aptamers remain stable in plasma or whole blood in vitro for at least 4 h. It was shown that 31TBA was 2-3 times more effective than 15TBA. Both aptamers were stable in human plasma and whole blood in vitro. So, the 3'-exonuclease could not be the reason for fast decrease of aptamers' functional activity in vivo. The main role in the removal of oligonucleotides from the circulation is played obviously by the liver.