Assessment of Blood Loss With a Point Of Care Device

Study Overview
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Brief Summary
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Main Objective: The purpose of this study is to demonstrate whether there is a correlation between perioperative blood loss and the degree of platelet inhibition assessed by a point of care assay in patients undergoing hip or knee arthroplasty and treated by antiplatelet mono/bi-therapy

Detailed Description
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Type of study : Prospective, non-interventional, multicenter registry Principal Investigator: Collet Jean-Philippe Rational: Discontinuation of antiplatelet therapy in patients with established coronary artery disease (CAD) has become an increasingly important concern given the risk of recurrent arterial event. Exaggerated concern about increased procedure-related bleeding remains the major factor for premature discontinuation of APT. Interruption modalities and their impact on perioperative bleeding has never been prospectively evaluated and it is accepted that the maximum duration of interruption should not exceed 5 days for Clopidogrel/Ticagrelor and 7 days for Prasugrel given the fact that the remaining antiplatelet effect of APT is observed in less than 50% of patients after 3 days of interruption. Resuming APT after the operation has never been studied and remains a complex situation during anticoagulation is often prescribed to prevent deep vein thrombosis further increasing perioperative bleeding. Hypotheses: (i) the volume of perioperative blood loss is correlated to the degree of platelet inhibition. (ii) Clopidogrel metabolizer status as defined by genetic profile is also correlated to perioperative blood loss. (iii) Resuming antiplatelet therapy during the perioperative period is not associated with a significant recovery of the antiplatelet effect. Primary endpoint: Perioperative (day 1-day 5) blood loss in mL assessed by NADLER & Mercurial formula* and PRU** (for patients under Clopidogrel/ARU*** as measured using the VerifyNow®P2Y12 and aspirin assays at baseline. Secondary objectives: (i) to evaluate the correlation between clopidogrel genetic metabolizer status**** and perioperative blood loss. To evaluate antiplatelet pharmacodynamic response at discharge according to metabolizer status. Definition*Blood loss in mL of Red Blood Cell (RBC) = Compensated RBC Volume (1 Pack=150mL) + Non Compensated RBC Vol. (Total Blood Loss : Ht D-1-Ht D+5). *PRU=Platelet Reaction Unit. It is a specific measure of on-clopidogrel platelet reactivity. Cut-off value is for defining high-on clopidogrel platelet reactivity is 230. **ARU=Aspirin Reaction Unit. It is a specific measure of on-aspirin platelet reactivity. Cutoff value to identify high on-aspirin platelet reactivity is 550. ***Clopidogrel Metabolizer Phenotype is defined according to the carriage of the loss/gain-of function allele 2C19*2-*8/*17 as follows: SM for slow metabolizer: (*2-*8/*2-*8) ; Ultrafast Metabolizer (FM): (*17/*17) ; Normal/intermediate (M): (wt/wt, wt/*17, *2-*8/*17 or *2-*8/wt) Number of subjects : 200 patients Study duration: Two years. Study duration per subject: length of hospital stay with a maximum duration of 30 days.

Official Title
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Assessment of Blood Loss With a Point Of Care Device During Hip/Knee Surgery Performed On Dual/Single Antiplatelet Therapy

Conditions
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Acute or Programmed Hip Replacement (Gamma Nail, Total Prosthesis or Throuhg DHS) / Knee Surgery

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years Patient in antiplatelet monotherapy (aspirin or clopidogrel) or dual therapy (aspirin + clopidogrel / prasugrel / ticagrelor) in the context of secondary prevention after: acute coronary syndrome and / or intracoronary stenting Planned or urgent hip (gamma nail, total prosthesis or through DHS) or knee arthroplasty Informed consent of the participant Patient receiving a social security scheme or entitled Exclusion Criteria: Polytrauma Anemia <9g/dL Indication for oral anticoagulation Pelvic fracture justifying complex surgery Ongoing or recent major bleeding or recent major surgery (< 3 weeks) Liver failure Thrombopenia <80 000/µl Lack of health insurance Mental disability Participation to any other research protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Planned hip or knee arthroplasty<br>Patients with planned hip or knee arthroplasty | |
| urgent hip or knee arthroplasty<br>Patients with hip or knee arthroplasty in emergency. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perioperative blood loss in mL assessed by NADLER & Mercurial formula* and PRU**/ARU*** as measured using the VerifyNow®P2Y12 and aspirin assays at baseline | Perioperative (day 1-day 5) blood loss in mL assessed by NADLER & Mercuriali formula* and PRU**/ARU*** as measured using the VerifyNow®P2Y12 and aspirin assays at baseline. | day 1- day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the correlation between clopidogrel genetic metabolizer status**** and perioperative blood loss. | When the patient discharges of surgery department | up to 10 days | 
| To evaluate clopidogrel and aspirin pharmacodynamic response at discharge according to metabolizer status. | When the patient discharges of surgery department | up to 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antiplatelet therapy, Surgery, Bleeding, Platelet aggregation