Effect of Chronic Stress on Coagulation Parameters in Warfarin-Treated Male Rats

stress & coagulation in warfarin-treated rats

Abstract

Objective: Chronic stress affects coagulation system, thus, can potentially interact with oral anticoagulation therapy. Clinically, it can be difficult to induce or quantify stress in human subjects. Therefore, this study proposed to evaluate the effects of chronic stress on coagulation parameters in warfarin-treated rats under controlled conditions.

Materials and Method: Forty male Wistar rats were divided into unstressed and stressed groups. Rats in unstressed group were assigned to control and normal plus warfarin treatment (N-WT) subgroups (n = 10 each). Rats in stressed group underwent chronic mild stress (CMS) and were assigned to CMS and CMS plus warfarin treatment (CMS-WT) subgroups (n = 10 each).

On the 28^th day and after completion of the CMS induction procedure, serum corticosterone was used to confirm CMS induction. Also, the coagulation parameters-prothrombin time (PT), partial prothrombin time (PTT), International normalized ratio (INR) and prothrombinlevels-were assessed by biochemical methods

Results: Comparison of changes in PT, PTT and INR values between two groups of N-WT and CMS-WT showed significant increase in PT, PTT and INR values in the CMS-WT(PT:6.6 ± 3.23, p<0.001; PTT: 4.4 ± 3.8, p=0.01 and INR: 0.51 ± 0.23, p<0.001).Prothrombin was significantly higher in CMS group that shows hypercoagulable state. Prothrombin was significantly lower in CMS-WT group which can be due to reduced metabolism of warfarin in this group (0.54 ± 0.017,p<0.001).

Conclusion: CMS decreases prothrombin levels and leads to an increase in measures of timed coagulation parameters (PT, PTT and INR), but in no warfarin treated rats leads to hypercoagulable state.