Your browser does not support JavaScript!

Home    Εκτίμηση της πηκτικότητας του αίματος σε ασθενείς υψηλού κινδύνου για θρομβοεμβολική νόσο που λαμβάνουν προφύλαξη με ηπαρίνη χαμηλού μοριακού βάρους  

Results - Details

Add to Basket
[Add to Basket]
Identifier 000390771
Title Εκτίμηση της πηκτικότητας του αίματος σε ασθενείς υψηλού κινδύνου για θρομβοεμβολική νόσο που λαμβάνουν προφύλαξη με ηπαρίνη χαμηλού μοριακού βάρους
Alternative Title Thrombin generation mechanism in high risk patients for vte receiving thrompoprophylaxis with LMWH
Author Γκιώνης, Μιχάλης
Thesis advisor Χρήστος, Ιωάννου
Reviewer Αστέριος, Κατσαμούρης
Ελένη, Παπαδάκη
Abstract Introduction: The recommended duration of post-operative Low-Molecular-Weight- Heparins (LMWHs) thromboprophylaxis in high risk for VTE surgical patients (as those who undergo Total-Hip-Replacement (THR) and Total-Knee-Replacement (TKR) surgery) is controversial. Our aim is to study the thrombin generation (TG) modifications induced by surgery and to evaluate the effect of LMWH on TG during and after the recommended duration, as well as to investigate biological resistance to enoxaparin’s antithrombotic action, and rebound effect in reactivation of coagulation mechanism after thromboprophylaxis withdrawal, using Thrombin Generation (TG) assay. Finally, we aimed to evaluate antiplatelet effect as adjuvant antithrombotic treatment in TG modifications during the LMWH somministration period and after LMWH’s withdrawal. Patients/Methods: 1st category (Orthopaedic-THR vs TKR- patients):Thirty-one patients received 4000IU anti-Xa/day of enoxaparin, 8-hours postoperatively (15 THR for 30-days and 16 TKR for 15-days). TG assay sensitive to enoxaparin was performed, preoperatively (D0), 7-hours post-surgery (D1), 8-days post-surgery (D8), and 2-days after thromboprophylaxis withdrawal (D32 and D17), evaluating: lag-time, endogenous thrombin potential (ETP), peak amount of generated thrombin (Peak), time-to-Peak (tt-Peak), and the Mean- Rate-Index [MRI=Peak/(tt-Peak-lag-time)]. 2nd category (Orthopaedic vs Vascular patients): Fifteen-patients undergoing femoro-popliteal bypass grafting (receiving enoxaparin 4000 antiXa IU + 75 mg clopidogrel), and 15-patients undergoing total-hipreplacement (THR) (receiving enoxaparin alone). TG-assay parameters [lag-time, Endogenous-Thrombin-Potential, Peak-, time-to- Peak, and Mean-Rate-Index] were assessed to investigate heparin resistance and rebound [76] effect after prophylaxis interruption. Measurements were obtained pre-op, 7-hours post-op and before prophylaxis initiation, 8-days post-op, and 48-hours after anticoagulant withdrawal (Day 32). Results: 1st category :TKR surgery decreased lag-time and tt-Peak and increased MRI on D1vs.D0 (p&λτ0.05). In contrast, THR did not significantly modify TG. Enoxaparin effectively reduced thrombin generation in both groups. Thromboprophylaxis withdrawal resulted in rebound increase of TG in the TKR patients (ETP, Peak & MRI increased on D17vs.D0;p΄&λτ0.05, and vs.D1;p΄&λτ0.05) but not in THR patients. Variability in the response to enoxaparin was observed among patients of the same group. 2nd category : Surgery increased TG in vascular patients despite intra-operative unfractioned heparin administration when compared to orthopaedic patients (MRI:p=0.039, ETP:p=0.001, PGT:p=0.003), but this peri-operative pro-thrombotic status was reversed by post-operative thromboprophylaxis. No arterial or venous thrombotic events were observed. Vascular patients were adequately protected after prophylaxis withdrawal, probably due to the synergic action of clopidogrel (similar TG parameters between the 8th and 32nd post-op day), while orthopaedic patients increased TG on Day-32 compared to the 8th post-op day (p=0.03, for both lag-time and ttPeak). Furthermore, on the 32nd, a prothrombotic status (increased TG) was observed in the orthopaedic patients (p=0.034, and 0.004 for ttPeak and lag-time, respectively) compared to the vascular patients. Inter-individual variability to enoxaparin response was observed in both groups: 7/15 vascular and 10/15 orthopaedic patients increased TG despite anticoagulant administration, which reveals resistance to heparin (HR). Among the HR patients 4 of the Vascular and 6 of the Orthopaedic further increased TG after anticoagulant withdrawal depicting a rebound effect in activation of coagulation. [77] Conclusions: TKR surgery is more thrombogenic than THR surgery. In THR patients TG was efficiently inhibited by 30-day thromboprophylaxis, whereas, in TKR patients treated for 15-days TG was not effectively inhibited. Individual variability of the response to enoxaparin was observed in both groups revealing some form of biological resistance to enoxaparin. TG assay may represent the breakthrough step to efficient antithrombotic strategy in clinical settings with high thrombotic risk. Additonally, Heparin Resistance is not a rare phenomenon in clinical practice and was found in a considerable percentage of our patients. A rebound effect of coagulation activation after thromboprophylaxis withdrawal is observed in the extended post-operative period. This phenomenon is attenuated with the addition of concomitant anti-platelet (clopidogrel) treatment.
Language Greek
Subject High risk surgical patients
Thrombinogenesis
Θρομβινογένεση
Χαμηλού μοριακού βάρους ηπαρίνη
Χειρουργικοί ασθενείς υψηλού κινδύνου
Issue date 2015-03-31
Collection   School/Department--School of Medicine--Department of Medicine--Doctoral theses
  Type of Work--Doctoral theses
Views 260

Digital Documents
No preview available

Download document
View document
Views : 2