Evaluation of the Effect of Dextran Sulphate on Anti-Xa Activities Measured (DEXHEP)

Evaluation of the Effect of Dextran Sulphate on Anti-Xa Activities Measured in Patients Treated With Unfractionated Heparin in Different Indications-DEXHEP

The measurement of anti-Xa activity is classically used for the dose adjustement of unfractionated heparin (UFH) treatment and to monitor reversal of UFH by protamine during cardiac surgery with cardiopulmonary bypass (CPB). Three categories of reagents are currently available in France for the measurement of anti-Xa activity: antithrombin-containing reagents (very little used), antithrombin-free reagents and antithrombin-free reagents with dextran sulphate. Significant differences in anti-Xa results based on the reagents used were described, particularly after protamine neutralization in CPB. Indeed, dextran sulphate, contained in some reagents, could dissociate the heparin/protamine complex contributing to the higher levels of anti-Xa with these reagents. The differences observed in these patients are likely related to the presence of platelet factor 4 (PF4) in the samples from either PF4 present in vivo in patients or released in vitro after blood collection. These differences may lead to different therapeutic attitudes, including the re-administration of protamine to neutralize heparin at the end of CBP

Study Overview

• Status: Completed
• Conditions: Unfractionated Heparin Treatment
• Intervention / Treatment: Biological: measurement of anti-Xa activities

Detailed Description

Any hospitalized patient receiving UFH in the intensive, cardiac surgery and medicine departments of the participating centres will be offered the study by investigator. It will be included in the study after validation of the selection criteria and after collecting its non-opposition. This participation will not change the medical care of the participants.

Patients will be divided into four groups:

• Group 1: patients with cardiac surgery with CBP. Blood samples in the operating room, 5 to 10 minutes after neutralization of heparin by protamine.
• Group 2: patients who had cardiac surgery with CBP, between day 1 and day 5 after surgery.
• Group 3: hospitalized patients in intensive care unit, including patients on extracorporeal life support (ECLS).

Group 4: patients hospitalized in a medical non-intensive care ward.

The response to heparin treatment varies considerably depending on the clinical situation. The results found in one indication are not transposable to another indication. The 4 patient groups will provide a comprehensive response to situations in which heparin is used.

For each patient, during the usual follow-up of anti-Xa activity, and only once per patient, 3 to 4 additional blood tubes - 1 citrate tube (0.109 M) of 5 mL or 2 citrate tubes of 3 mL and 2 tubes CTAD (Citrate-Theophylline, Adenosine, Dipyrioledam) of 3 mL - will be taken during a blood test carried out in common practice. Thus, no additional invasive gestures are added by this search. CTAD contains, in addition to citrate, a platelet activation inhibitor and thus limits the in-vitro activation of platelets and thus the release of PF4.

Blood samples will be handle according to the usual procedures of each centre. All plasma will be aliquoted and stored at -80oC, until the end of inclusions in the hematology laboratories of each center.

At the end of the inclusion period, the aliquotes will be sent to the hematology laboratories of the Necker University Hospital and the University Hospital of Rennes for centralized testing.

The measurement of anti-Xa activities will be carried out on frozen-defrosted citrate and CTAD plasma with with 4 reagents:

• STA-Liquid anti-Xa (STAGO) (not containing dextran)
• Biophen Heparin LRT (Hyphen) (containing dextran)
• Berichrom (Siemens) with dextran
• Berichrom (Siemens) without dextran

The dosage of platelet factor 4 and beta-TG will be performed on frozen-defrosted plasma with CTAD with asserachrom PF4 and Asserachrom beta-TG (Diagnostica Stago) kits.

• Study Type: Observational
• Enrollment (Actual): 164

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33604
    • CHU Bordeaux
  • Dijon, France, 21033
    • CHU de Dijon
  • Le Chesnay, France, 78150
    • CH de Versailles
  • Lille, France, 59037
    • CHU de Lille
  • Paris, France, 75010
    • APHP, CHU Lariboisière
  • Paris, France, 75743
    • APHP, HOPITAL Necker enfants malades
  • Rennes, France, 35000
    • Rennes University Hospital
  • Vandœuvre-lès-Nancy, France, 54500
    • Chu de Nancy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Any hospitalized patient receiving UFH in the intensive, cardiac surgery and medicine departments

Description

Inclusion Criteria:

• Patients over the age of 18;
• Hospitalized patients to receive UFH;
• No patient opposition.

Patients will be divided into four groups:

• Group 1: patients with cardiac surgery with CBP. Blood samples in the operating room, 5 to 10 minutes after neutralization of heparin by protamine.
• Group 2: patients who had cardiac surgery with CBP, between day 1 and day 5 after surgery.
• Group 3: hospitalized patients in intensive care unit, including patients on extracorporeal life support (ECLS).

Group 4: patients hospitalized in a medical non-intensive care ward..

Exclusion Criteria:

• pregnant or lactating women;
• adults subject to legal protection (safeguarding of justice, guardianship, guardianship), persons deprived of their liberty.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1; patients with cardiac surgery with CBP. Blood samples in the operating room, 5 to 10 minutes after neutralization of heparin by protamine	Biological: measurement of anti-Xa activities; The measurement of anti-Xa activities will be carried out on frozen-defrosted plasma citrate and CTAD with 4 reagents; STA-Liquid anti-Xa (STAGO) (not containing dextran); Biophen Heparin LRT (Hyphen) (reactive containing dextran); Berichrom (Siemens) with dextran; Berichrom (Siemens) without dextran The dosage of platelet factor 4 and of the beta-TG will be carried out on frozen-defrosted plasma with the asserachrom PF4 and Asserachrom beta-TG (Diagnostica Stago) kits.; Other Names: dosage of platelet factor 4 and of the beta-TG
Group 2; patients who had cardiac surgery with CBP, between day 1 and day 5 after surgery.	Biological: measurement of anti-Xa activities; The measurement of anti-Xa activities will be carried out on frozen-defrosted plasma citrate and CTAD with 4 reagents; STA-Liquid anti-Xa (STAGO) (not containing dextran); Biophen Heparin LRT (Hyphen) (reactive containing dextran); Berichrom (Siemens) with dextran; Berichrom (Siemens) without dextran The dosage of platelet factor 4 and of the beta-TG will be carried out on frozen-defrosted plasma with the asserachrom PF4 and Asserachrom beta-TG (Diagnostica Stago) kits.; Other Names: dosage of platelet factor 4 and of the beta-TG
Group 3; hospitalized patients in intensive care unit, including patients on extracorporeal life support (ECLS).	Biological: measurement of anti-Xa activities; The measurement of anti-Xa activities will be carried out on frozen-defrosted plasma citrate and CTAD with 4 reagents; STA-Liquid anti-Xa (STAGO) (not containing dextran); Biophen Heparin LRT (Hyphen) (reactive containing dextran); Berichrom (Siemens) with dextran; Berichrom (Siemens) without dextran The dosage of platelet factor 4 and of the beta-TG will be carried out on frozen-defrosted plasma with the asserachrom PF4 and Asserachrom beta-TG (Diagnostica Stago) kits.; Other Names: dosage of platelet factor 4 and of the beta-TG
Group 4; patients hospitalized in a medical non-intensive care ward.	Biological: measurement of anti-Xa activities; The measurement of anti-Xa activities will be carried out on frozen-defrosted plasma citrate and CTAD with 4 reagents; STA-Liquid anti-Xa (STAGO) (not containing dextran); Biophen Heparin LRT (Hyphen) (reactive containing dextran); Berichrom (Siemens) with dextran; Berichrom (Siemens) without dextran The dosage of platelet factor 4 and of the beta-TG will be carried out on frozen-defrosted plasma with the asserachrom PF4 and Asserachrom beta-TG (Diagnostica Stago) kits.; Other Names: dosage of platelet factor 4 and of the beta-TG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the effect of different reagents containing or not dextran sulphate, on the measurement of anti-Xa for different groups of patients	Measure of anti-Xa activity in CTAD plasma	5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To define factors that influence the results of the biological test "anti-Xa" activity :type of anticoagulant (CTAD or citrate) .	Measure of anti-Xa activity	5 days
To define factors that influence the results of the biological test "anti-Xa" activity :concentration of platelet factor 4 (PF4) and beta-TG present in plasma	Measure of anti-Xa activity	5 days
To define factors that influence the results of the biological test "anti-Xa" activity :Patient characteristics including age and sex and if available, creatinine clearance, antithrombin, fibrinogen, platelet count	Measure of anti-Xa activity	5 days
To define factors that influence the results of the biological test "anti-Xa" activity :The indication of treatment	Measure of anti-Xa activity	5 days

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Investigators: Principal Investigator: Isabelle Gouin, Rennes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2020
• Primary Completion (Actual): January 16, 2021
• Study Completion (Actual): January 16, 2021

Study Registration Dates

• First Submitted: January 5, 2021
• First Submitted That Met QC Criteria: January 5, 2021
• First Posted (Actual): January 8, 2021

Study Record Updates

• Last Update Posted (Actual): February 9, 2021
• Last Update Submitted That Met QC Criteria: February 8, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: dextran sulphate; anti-Xa activity
• Additional Relevant MeSH Terms: Coagulants; Platelet Factor 4
• Other Study ID Numbers: 35RC19_3001_DEXHEP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No