Effects of anticoagulation on markers of activation of clotting following major orthopedic surgery

M M Bern, D Hazel, D T Reilly, D M Adcock, L Hou, M M Bern, D Hazel, D T Reilly, D M Adcock, L Hou

Abstract

Introduction: This study examines makers of activation of clotting following three chemoprophylactic regimens used for prevention of postoperative venous thromboembolic disease (TED) following high-risk surgery for TED.

Methods: Patients having elective primary knee or hip replacement surgery received variable dose warfarin (target international normalized ratios 2.0-2.5), 1 mg warfarin daily starting 7 days preoperatively or aspirin 325 mg daily starting on the day of surgery. Twelve patients in each group were treated for 28 ± 2 days. Thrombin-antithrombin (T-AT) and prothrombin fragment F1 + 2 were measured at baseline and postoperative days 3 and 28 ± 2.

Results: Thrombin-antithrombin and F1 + 2 on postoperative day 3 were equal for the study groups. By days 28 ± 2, variable dose warfarin therapy group suppressed production of F1 + 2 (P = 0.002) with no difference in the T-AT accumulation. F1 + 2 for other patients overlapped the normal range.

Conclusion: The signals of activated clotting following surgery did not differentiate the three regimens on postoperative day 3. Variable dose warfarin was associated with suppression of F1 + 2 after 1 month of therapy, with no effect on accumulation of T-AT. Fixed low-dose warfarin started 7 days prior to surgery and aspirin are not inferior on postoperative day 3, but appear to be inferior over a longer treatment.

Trial registration: ClinicalTrials.gov NCT00767559.

Keywords: Arthroplasty; aspirin; markers of activated clotting; prothrombin fragment F1 + 2; thrombin-antithrombin complex; thromboembolism; warfarin.

© 2015 The Authors. International Journal of Laboratory Hematology Published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
International Normalized Ratios for the patients taking the fixed low dose warfarin and for those taking the variable dose warfarin for weeks 1, 2, 3 and 4. Box plot demonstrates the range from first to third quartiles, plus outliers. The symbol within the box represents the mean value.
Figure 2
Figure 2
Prothrombin in Vitamin K Absence II results for the patients taking the fixed low dose or variable dose warfarin, at baseline, on operating room (OR) day and after 3 and 28 ± 2 days following surgery. (ng/mL, mean ± 1 SD in graph and mean in the table below).
Figure 3
Figure 3
Thrombin–antithrombin complex for each study group at baseline, on operating room (OR) day and after 3 and 28 ± 2 days following surgery. (ng/mL, mean ± 1 SD).
Figure 4
Figure 4
Prothrombin fragment F1 + 2 (F1 + 2) for each study group at baseline, on operating room day and after 3 and 28 ± 2 days following surgery. (pmol/L, mean ± 1 SD).
Figure 5
Figure 5
Box plot of the prothrombin fragment F1 + 2 (F1 + 2) results on postoperative day 28 ± 2 for each study group, first to third quartiles, and outliers. The symbol within the box represents the mean value.

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