Abstract

In the nonbleeding patient, constant low-level activation of coagulation enables a quick procoagulant response upon an injury. Conversely, local activation of coagulation might influence the systemic activity level of coagulation. To characterize this interaction in more detail, activity pattern analysis was performed in patients undergoing elective surgeries. Blood samples were taken before, during, and 24 hours after surgery from 35 patients undergoing elective minor ( n = 18) and major ( n = 17) orthopaedic surgeries. Plasma levels of thrombin and activated protein C (APC) were measured using oligonucleotide-based enzyme capture assays, while those of prothrombin fragment 1.2, thrombin–antithrombin-complexes, and D-dimer were measured using commercially available enzyme-linked immunosorbent assays. In vitro thrombin generation kinetics were recorded using calibrated automated thrombography. Results showed that median plasma levels of up to 20 pM thrombin and of up to 12 pM APC were reached during surgery. D-dimer levels started to increase at the end of surgery and remained increased 24 hours after surgery, while all other parameters returned to baseline. Peak levels showed no significant differences between minor and major surgeries and were not influenced by the activity state at baseline. In vitro thrombin generation kinetics remained unchanged during surgery. In summary, simultaneous monitoring of the procoagulant and anticoagulant pathways of coagulation demonstrates that surgical trauma is associated with increased systemic activities of both pathways. Activity pattern analysis might be helpful to identify patients at an increased risk for thrombosis due to an imbalance between surgery-related thrombin formation and the subsequent anticoagulant response.

Highlights

  • Coagulation is a dynamic and temporal-spatial controlled process that becomes activated after vessel wall injury byà These authors contributed to the study.complex formation between activated factor VII (FVIIa) and tissue factor (TF).[1]

  • The resulting thrombin–AT (TAT) complex circulates in blood with a half-life of 44 minutes.[5]. Another fraction of the blood-born thrombin binds to thrombomodulin (TM) on the surface of endothelial cells where it becomes an anticoagulant through conversion of protein C (PC) into the active enzyme activated protein C (APC).[6]

  • According to the guidelines for perioperative care published by the American College of Cardiology (ACA) and the American Heart Association (AHA), the surgeries were graded into minor and major surgeries depending on magnitude, type, duration, blood loss, and transfusion requirements.[12]

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Summary

Introduction

Coagulation is a dynamic and temporal-spatial controlled process that becomes activated after vessel wall injury byà These authors contributed to the study.complex formation between activated factor VII (FVIIa) and tissue factor (TF).[1]. Surgical Trauma Increases Systemic Coagulation Activity Friedrich et al e351 thrombin formation through a series of acceleration steps resulting in peak thrombin levels of approximately 800 nM as measured through in vitro monitoring of TF-induced coagulation activation.[3] Since formation of a stable clot is achieved at thrombin concentrations between 10 and 20 nM, it is concluded that 96% of thrombin is generated after the wound-sealing clot has been formed. Part of this thrombin is released into the flowing blood, since thrombin, unlike other activated coagulation factors, contains no phospholipidbinding sites. Despite this short half-life, the results of numerical simulation of thrombin profiles have predicted thrombin blood levels reaching low nanomolar concentrations downstream a wounded area.[8,9] localized coagulation activation should induce a systemic coagulation response

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