PMID- 34582127
OWN - NLM
STAT- MEDLINE
DCOM- 20220204
LR  - 20220204
IS  - 1751-553X (Electronic)
IS  - 1751-5521 (Linking)
VI  - 44
IP  - 1
DP  - 2022 Feb
TI  - Study of in vitro thrombin generation after neutralization of heparin.
PG  - 168-176
LID - 10.1111/ijlh.13703 [doi]
AB  - INTRODUCTION: Thrombin generation (TG) documents hypercoagulability. TG in 
      platelet-poor plasma is exquisitely sensitive to heparins, which thus must be 
      neutralized before testing. Heparinase and hexadimethrine bromide (polybrene) 
      have been used for that purpose, but their effects per se on TG have been poorly 
      studied so far. METHODS: (i) TG was studied in commercial normal pooled plasma 
      (NPP; CryoCheck((R)) , Cryopep) in absence or presence of neutralizing agents. (ii) 
      NPP was spiked with increasing concentrations of unfractionated heparin (UFH; up 
      to 1.0 IU/mL) or low-molecular-weight heparin (LMWH; enoxaparin up to 1.2 IU/mL) 
      and TG studied after incubation of heparinase (Hepzyme((R)) ; 15 minutes) or 
      polybrene (0.025 mg/mL; 10 minutes). RESULTS: (i) With ThromboScreen reagent to 
      initiate TG, addition of heparinase was associated with increased peak, whereas 
      polybrene caused lengthening of lag time and time to peak, compared with 
      nonsupplemented NPP. (ii) With polybrene, TG was completely restored over the 
      whole range of UFH and LMWH studied. By contrast, heparinase failed to fully 
      restore TG in presence of UFH concentrations >/=0.8 IU/mL or LMWH concentrations 
      >/=1.0 IU/mL. Those effects were matched with detectable tiny residual amounts of 
      non-neutralized heparin (as assessed with an anti-Xa assay) and were less 
      pronounced with a higher picomolar concentration of tissue factor (DrugScreen 
      reagent). CONCLUSION: Polybrene fully restored TG of heparinized plasma at the 
      expense of an alteration of TG, pointing to the need to use adapted reference 
      ranges. Heparinase failed to do so in presence of high concentrations of both 
      heparins.
CI  - (c) 2021 John Wiley & Sons Ltd.
FAU - Hardy, Michael
AU  - Hardy M
AUID- ORCID: 0000-0001-6701-9417
AD  - Universite catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis 
      Center (NTHC), Hematology Laboratory, Yvoir, Belgium.
AD  - Universite catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis 
      Center (NTHC), Anesthesiology Department, Yvoir, Belgium.
FAU - Douxfils, Jonathan
AU  - Douxfils J
AUID- ORCID: 0000-0002-7644-5298
AD  - Pharmacy Department, Namur Thrombosis and Hemostasis Center (NTHC), University of 
      Namur, Namur, Belgium.
AD  - Qualiblood s.a., Namur, Belgium.
FAU - Morimont, Laure
AU  - Morimont L
AUID- ORCID: 0000-0001-9195-304X
AD  - Pharmacy Department, Namur Thrombosis and Hemostasis Center (NTHC), University of 
      Namur, Namur, Belgium.
AD  - Qualiblood s.a., Namur, Belgium.
FAU - Didembourg, Marie
AU  - Didembourg M
AUID- ORCID: 0000-0002-9170-0314
AD  - Pharmacy Department, Namur Thrombosis and Hemostasis Center (NTHC), University of 
      Namur, Namur, Belgium.
FAU - Carlo, Audrey
AU  - Carlo A
AUID- ORCID: 0000-0002-2954-965X
AD  - Diagnostica Stago, Asnieres-sur-Seine, France.
FAU - de Maistre, Emmanuel
AU  - de Maistre E
AD  - CHU de Dijon, Service d'Hematologie biologique, Dijon, France.
FAU - Lecompte, Thomas
AU  - Lecompte T
AD  - Division of Angiology and Hemostasis - Geneva Platelet Group, Departements of 
      Medecine, Universite de Geneve et Hopitaux Universitaires de Geneve, Geneva, 
      Switzerland.
FAU - Mullier, Francois
AU  - Mullier F
AUID- ORCID: 0000-0001-6947-6099
AD  - Universite catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis 
      Center (NTHC), Hematology Laboratory, Yvoir, Belgium.
LA  - eng
GR  - Fondation Mont-Godinne/
PT  - Journal Article
DEP - 20210928
PL  - England
TA  - Int J Lab Hematol
JT  - International journal of laboratory hematology
JID - 101300213
RN  - 0 (Heparin Antagonists)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 4C905MSK4W (Hexadimethrine Bromide)
RN  - 9005-49-6 (Heparin)
RN  - EC 3.4.21.5 (Thrombin)
RN  - EC 4.2.2.7 (Heparin Lyase)
SB  - IM
MH  - *Blood Coagulation
MH  - Blood Coagulation Tests/*methods/*standards
MH  - *Heparin/adverse effects
MH  - Heparin Antagonists
MH  - Heparin Lyase
MH  - Heparin, Low-Molecular-Weight
MH  - Hexadimethrine Bromide
MH  - Humans
MH  - Neutralization Tests
MH  - *Thrombin
OTO - NOTNLM
OT  - heparin
OT  - heparin lyase
OT  - hexadimethrine bromide
OT  - thrombin generation
EDAT- 2021/09/29 06:00
MHDA- 2022/02/05 06:00
CRDT- 2021/09/28 12:35
PHST- 2021/09/01 00:00 [revised]
PHST- 2021/06/10 00:00 [received]
PHST- 2021/09/03 00:00 [accepted]
PHST- 2021/09/29 06:00 [pubmed]
PHST- 2022/02/05 06:00 [medline]
PHST- 2021/09/28 12:35 [entrez]
AID - 10.1111/ijlh.13703 [doi]
PST - ppublish
SO  - Int J Lab Hematol. 2022 Feb;44(1):168-176. doi: 10.1111/ijlh.13703. Epub 2021 Sep 
      28.