Facebook
Twitter
LinkedIn
Email
 |
Checking for direct PDF access through Ovid | |
Excerpt
Since aprotinin reduces microvascular bleeding, the drug may have procoagulant properties. However, Despotis et al. [1] report that aprotinin perturbs the activated partial thromboplastin time (APTT) as an apparent anticoagulant, and they see no procoagulant effect on the prothrombin time (PT). A clotting test, which, unlike the APTT and PT, is accelerated by aprotinin might indicate a mechanism for the hemostatic activity of aprotinin. As shown in Figure 1, aprotinin does hasten clotting time in a modified PT test performed in the presence of activated protein C (APC).
This test has been proposed as a means to screen for the hyper-coagulable condition caused by rare hereditary resistance to APC [2]. APC is an anticoagulant plasma enzyme that functions to oppose vascular thrombosis and that prolongs clotting times of normal plasma [2]. However, effective activation of the protein C zymogen requires an endothelial cofactor [3], and protein C effects are not manifest on the traditional APTT and PT because endothelial cells are not included in those tests. Figure 1 outlines an experiment in which APC is added to PT reagents in sufficient quantity to nearly double plasma clotting time. This prolongation of the clotting time is completely blocked at an aprotinin concentration of 167 KIU/mL.
Aprotinin inhibits hydrolysis of small artificial molecules by APC [4]. As shown here, clinically achieved concentrations of aprotinin block the anticoagulant effect of APC. APC is probably a clinically important receptor for aprotinin.
Theodore A.
