PB0331 - Chacma baboon natural anticoagulants and factor VIII activities: implications for thrombin generation and haemostatic disease models

Background: Non-human primates are useful models of human haemostasis, but distinctions do exist. Chacma baboons have a lower peak thrombin height and slower time-to-peak but a greater overall thrombin generation potential than humans – primarily due to a prolonged thrombin “tail”.

Aims: To explore whether Chacma baboon factor VIII and natural anticoagulants, which may impact thrombin generation, are different from those of humans.

Methods: Activated protein C (APC), antithrombin, factor VIII, clotting protein S and free protein S were measured using chromogenic and clot-based assays in 40 ABO typed (30 group O and 10 non-O), male (n=14) and female (n=26) Chacma baboon platelet poor plasma samples, and compared with human reference intervals.

Results: APC (baboon: 111–200%; human: 70–130%), free protein S (male: 44–55%; men: 70–148%; female: 25–67%; women: 50–134%) clotting protein S (male: 44–56%; men: 77–143%; female: 38–82%; women: 55–123%) and factor VIII activity (baboon: 51–135%; human: 70–150%) revealed differences, while antithrombin was similar to humans. Between sexes, reference intervals largely overlapped, but were wider for female baboons’ free and clotting protein S; only free protein S was not significantly (p>0.05) different. Factor VIII activity was 14% lower in group O baboons. The APC kinetic ratio increases in baboons were higher compared to humans before ±55 minutes, explaining the slower time-to-peak and decreased thrombin peak.

Conclusion(s): Largely, these findings support the use of Papio ursinus as a pre-clinical model for novel drug testing and pre-clinical coagulation studies. The greater APC kinetic ratio increases explains the slower time-to-peak and decreased thrombin peak in Chacma baboons. The prolonged thrombin tail is likely explained by the early consumption of the reduced protein S available, leaving APC without its cofactor, allowing thrombin generation to continue unabated.