Monitoring of heparin therapy and establishment of an optimal therapy scheme for thrombosis prophylaxis in a pig model for human catheter interventions

Abstract

This study aims to investigate variables suitable for monitoring of unfractionated heparin (UFH) therapy and establishment of an optimal therapy scheme in pigs. This is a prospective study of 32 pigs undergoing catheterization for endovascular embolization of experimentally induced arteriovenous malformation. Pigs were assigned to four groups receiving different UFH treatment during catheter intervention. In groups 1 and 2, UFH was applied as a bolus of either 100 IU/kg (n = 6) and 200 IU/kg (n = 6). Groups 3 and 4 received a continuous infusion of 66 IU/kg/h UFH (n = 10) and 100 IU/kg/h (n = 10), respectively, which was applied 20 min after an initial bolus of 100 IU/kg. Blood samples were taken 0, 10, 20, 40, 60, 100, and 140 min after starting catheterization (groups 1 + 2) and after 0, 10, 20, 30, 40, 50, 60, 80, 100, 120, and 140 min, respectively (groups 3 + 4). High/low range activated coagulation time (LR-ACT), activated partial thromboplastin time (aPTT), prothrombin time, fibrinogen, and anti-FactorXa activity (FXa) activity were assessed. Based on anti-FXa activity, bolus injection of 100 and 200 IU/kg UFH had a mean half-life of 28.43 ± 8.85 and 57.05 ± 12.42 min, however, an aPTT exceeding 999 s was present in four of seven pigs in group 2. In group 3, aPTT increased from baseline 15 ± 2 s to a steady state ranging from 30 to 33 s. In group 4, there was an increase of aPTT to 58 ± 23 s 140 min after initiation of treatment. Suitable variables for monitoring UFH therapy included anti-FXa activity, aPTT, and LR-ACT. An initial bolus of 100 IU/kg followed by a continuous UFH infusion of 66 IU UFH/kg/h can be recommended as antithrombotic therapy during catheterization.