PB0318 - Laboratory response to unfractionated heparin at low antithrombin levels: an in-vitro study

Sunday, June 23, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Co-Author(s)

PG

Pierre Gueret

MD-PhD
Laboratory of Hematology, Pontchaillou University Hospital, Rennes, France
Rennes, Bretagne, France
AM

Alexandre Mansour

MD-PhD
Department of Anesthesia and Critical Care, Pontchaillou University Hospital, IRSET-INSERM-1085, Univ Rennes, France
Rennes, Bretagne, France
AP

Adeline Pontis

MD
Laboratory of Hematology, Pontchaillou University Hospital of Rennes, IRSET-INSERM-1085, Univ Rennes, France.
Rennes, Bretagne, France
MG

Maelle Gallin

Pharm D
Laboratory of Hematology, Pontchaillou University Hospital of Rennes, France
Rennes, Bretagne, France
LM

Laure Maucorps

MD
Laboratory of Hematology, Pontchaillou University Hospital of Rennes, France
Rennes, Bretagne, France
FN

Fabienne Nedelec-Gac

Pharm D
Laboratory of Hematology, Pontchaillou University Hospital of Rennes, France
Rennes, Bretagne, France
TL

Thomas Lecompte

MD-PhD
University of Namur, Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), Namur, Belgium; Vascular medicine department University Hospital of Nancy, University of Lorraine, Nancy; University Hospital of Dijon Bourgogne; Pontchaillou University Hospital of Rennes, France
Rennes, Bretagne, France

Presenting Author(s)

Isabelle Gouin Thibault

PhD - PharmD
Laboratoire d'Hématology, Pontchaillou University Hospital of Rennes, IRSET-INSERM-1085, Univ Rennes, France.
Rennes, Bretagne, France

Background: Unfractionated heparin (UFH) use is nowadays mainly restricted to critically ill and fragile patients, who often encounter both reduced response to heparin and acquired AT deficiency, leading to consider AT administration. However, the relationship between AT plasma levels and anticoagulant effects of UFH, is not well established. Whether there is a minimum level of AT to achieve therapeutic anticoagulation (threshold) is often assumed but not supported by solid data.

Aims: The aim of this in-vitro study was to determine the relationship between AT plasma levels and anticoagulant effects of UFH.

Methods: Increasing amounts of purified AT (Aclotine® - from 0 to 110 IU/dL, final concentration checked with STA®-Stachrom ATIII (Stago)), and UFH (Héparine Choay® - from 0 to 0.85 IU/mL) were spiked into AT immuno-depleted plasma; CRYOcheck® Pooled Normal Plasma (PNP) was also studied, both plasmas were from Cryopep®.
Laboratory tests: STA®-Liquid Anti-Xa (Stago, no dextran), BIOPHEN™ Heparin LRT (Hyphen Biophen, with dextran), STA-PTT Automate® (Stago), Actin® FS Activated PTT (Siemens) on a STAR MAX® 3 analyzer; “Calibrated Automated Thrombogram” (CAT) using PPP-reagent HIGH® (Stago).

Results: Despite the known differences between the two anti-Xa assays regarding sensitivity to UFH, for both assays, there was a strong positive relationship between anti-Xa levels and AT values without threshold. Anti-Xa levels were detectable (> 0.1 IU/mL) and within the therapeutic range (> 0.3 IU/mL) with the lowest AT levels in presence of the highest UFH concentrations (Figure 1). Similar results were found with both APTT reagents.
Regarding CAT, inhibition of Endogenous Thrombin Potential (ETP) (Figure 2) and of Peak Height (PH) was found, with increasing UFH concentrations, irrespective of AT levels. However the lower the AT, the greater thrombin generation.

Conclusion(s): The results suggest that in case of a reduced response to heparin in patients with low AT, increasing doses of UFH could overcome acquired AT deficiency.