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ROTEM and vitro reversal of warfarin with APCC

Kornhall, Ludvig ; Wikander, Daniel ; Strandberg, Karin LU ; Berntorp, Erik LU and Schott, Ulf LU (2019) In Journal of Cardiovascular Medicine and Cardiology 6(1). p.6-11
Abstract
Background: Warfarin-treated patients with a prolonged Prothrombin Time (PT) can have a normal rotational thromboelastometry (ROTEM) clotting time (CT). A previous in vitro study found that activated prothrombin complex concentrates (APCC) could reverse an albumin-induced coagulopathy monitored with ROTEM, but that prothrombin complex concentrates (PCC) could not. The aim of this study was to investigate the ability of ROTEM to monitor the in vitro reversal of warfarin-induced coagulopathy using APCC and to define an APCC dose response.

Method: During the routine control of PT in 27 patients treated with warfarin, one extra 4.5 ml test tube of citrated whole blood was retrieved. Two concentrations of tissue factor ROTEM tissue... (More)
Background: Warfarin-treated patients with a prolonged Prothrombin Time (PT) can have a normal rotational thromboelastometry (ROTEM) clotting time (CT). A previous in vitro study found that activated prothrombin complex concentrates (APCC) could reverse an albumin-induced coagulopathy monitored with ROTEM, but that prothrombin complex concentrates (PCC) could not. The aim of this study was to investigate the ability of ROTEM to monitor the in vitro reversal of warfarin-induced coagulopathy using APCC and to define an APCC dose response.

Method: During the routine control of PT in 27 patients treated with warfarin, one extra 4.5 ml test tube of citrated whole blood was retrieved. Two concentrations of tissue factor ROTEM tissue factor (TF) activating reagents were used: a standard ROTEM ExTEM and a diluted 1:19000 concentration. The effects of two separate doses of APCC added in vitro corresponding to in vivo doses of 50 IE or 100 IE/kg were then studied on the ROTEM.

Results: The ROTEM EXTEM CT was prolonged beyond the upper normal range of 68 s in patients with PT >3.0, with a correlation coefficient of 0.88 to PT. ROTEM with the ExTEM reagent alongside high and low doses of APCC resulted in a significant shortening of median CT, both compared to baseline (100 s) and after low (65 s) and high doses (57 s). This was most evident in patients with PT >2.0. ROTEM signals of clot propagation to clot formation time (CFT) and α angle had the reverse pattern. There was no effect on maximal clot strength with APCC. With the diluted TF no CT shortening was found with APCC.

Conclusion: A clear dose response of APCC added in vitro to correct the effects of warfarin on ROTEM EXTEM CT was verified. ROTEM CT should be tested with non-activated PCC for in vivo reversal of warfarin in patients along with verification of a normalised PT. Further studies are needed to verify if a ROTEM CT in the lower normal range of <57-65 s, as found in our in vitro APCC-spiked warfarin blood, is safe for invasive procedures. (Less)
Abstract (Swedish)
Background: Warfarin-treated patients with a prolonged Prothrombin Time (PT) can have a normal
rotational thromboelastometry (ROTEM) clotting time (CT). A previous in vitro study found that activated
prothrombin complex concentrates (APCC) could reverse an albumin-induced coagulopathy monitored
with ROTEM, but that prothrombin complex concentrates (PCC) could not. The aim of this study was to
investigate the ability of ROTEM to monitor the in vitro reversal of warfarin-induced coagulopathy using
APCC and to defi ne an APCC dose response.
Method: During the routine control of PT in 27 patients treated with warfarin, one extra 4.5 ml test
tube of citrated whole blood was retrieved. Two concentrations of tissue... (More)
Background: Warfarin-treated patients with a prolonged Prothrombin Time (PT) can have a normal
rotational thromboelastometry (ROTEM) clotting time (CT). A previous in vitro study found that activated
prothrombin complex concentrates (APCC) could reverse an albumin-induced coagulopathy monitored
with ROTEM, but that prothrombin complex concentrates (PCC) could not. The aim of this study was to
investigate the ability of ROTEM to monitor the in vitro reversal of warfarin-induced coagulopathy using
APCC and to defi ne an APCC dose response.
Method: During the routine control of PT in 27 patients treated with warfarin, one extra 4.5 ml test
tube of citrated whole blood was retrieved. Two concentrations of tissue factor ROTEM tissue factor
(TF) activating reagents were used: a standard ROTEM ExTEM and a diluted 1:19000 concentration. The
effects of two separate doses of APCC added in vitro corresponding to in vivo doses of 50 IE or 100 IE/kg
were then studied on the ROTEM.
Results: The ROTEM EXTEM CT was prolonged beyond the upper normal range of 68 s in patients
with PT >3.0, with a correlation coeffi cient of 0.88 to PT. ROTEM with the ExTEM reagent alongside high
and low doses of APCC resulted in a signifi cant shortening of median CT, both compared to baseline (100
s) and after low (65 s) and high doses (57 s). This was most evident in patients with PT >2.0. ROTEM
signals of clot propagation to clot formation time (CFT) and α angle had the reverse pattern. There was no
effect on maximal clot strength with APCC. With the diluted TF no CT shortening was found with APCC.
Conclusion: A clear dose response of APCC added in vitro to correct the effects of warfarin on ROTEM
EXTEM CT was verifi ed. ROTEM CT should be tested with non-activated PCC for in vivo reversal of warfarin
in patients along with verifi cation of a normalised PT. Further studies are needed to verify if a ROTEM
CT in the lower normal range of <57-65 s, as found in our in vitro APCC-spiked warfarin blood, is safe for
invasive procedures. (Less)
Please use this url to cite or link to this publication:
author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Cardiovascular Medicine and Cardiology
volume
6
issue
1
pages
6 - 11
publisher
Peertechz
ISSN
2455-2976
DOI
10.17352/2455-2976.000081
language
English
LU publication?
yes
id
443134ff-8c62-431b-b2f7-8d216818113c
date added to LUP
2019-05-21 11:52:15
date last changed
2019-05-21 13:39:38
@article{443134ff-8c62-431b-b2f7-8d216818113c,
  abstract     = {{Background: Warfarin-treated patients with a prolonged Prothrombin Time (PT) can have a normal rotational thromboelastometry (ROTEM) clotting time (CT). A previous in vitro study found that activated prothrombin complex concentrates (APCC) could reverse an albumin-induced coagulopathy monitored with ROTEM, but that prothrombin complex concentrates (PCC) could not. The aim of this study was to investigate the ability of ROTEM to monitor the in vitro reversal of warfarin-induced coagulopathy using APCC and to define an APCC dose response.<br>
<br>
Method: During the routine control of PT in 27 patients treated with warfarin, one extra 4.5 ml test tube of citrated whole blood was retrieved. Two concentrations of tissue factor ROTEM tissue factor (TF) activating reagents were used: a standard ROTEM ExTEM and a diluted 1:19000 concentration. The effects of two separate doses of APCC added in vitro corresponding to in vivo doses of 50 IE or 100 IE/kg were then studied on the ROTEM.<br>
<br>
Results: The ROTEM EXTEM CT was prolonged beyond the upper normal range of 68 s in patients with PT &gt;3.0, with a correlation coefficient of 0.88 to PT. ROTEM with the ExTEM reagent alongside high and low doses of APCC resulted in a significant shortening of median CT, both compared to baseline (100 s) and after low (65 s) and high doses (57 s). This was most evident in patients with PT &gt;2.0. ROTEM signals of clot propagation to clot formation time (CFT) and α angle had the reverse pattern. There was no effect on maximal clot strength with APCC. With the diluted TF no CT shortening was found with APCC.<br>
<br>
Conclusion: A clear dose response of APCC added in vitro to correct the effects of warfarin on ROTEM EXTEM CT was verified. ROTEM CT should be tested with non-activated PCC for in vivo reversal of warfarin in patients along with verification of a normalised PT. Further studies are needed to verify if a ROTEM CT in the lower normal range of &lt;57-65 s, as found in our in vitro APCC-spiked warfarin blood, is safe for invasive procedures.}},
  author       = {{Kornhall, Ludvig and Wikander, Daniel and Strandberg, Karin and Berntorp, Erik and Schott, Ulf}},
  issn         = {{2455-2976}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{1}},
  pages        = {{6--11}},
  publisher    = {{Peertechz}},
  series       = {{Journal of Cardiovascular Medicine and Cardiology}},
  title        = {{ROTEM and vitro reversal of warfarin with APCC}},
  url          = {{https://lup.lub.lu.se/search/files/64650608/JCMC_6_181.pdf}},
  doi          = {{10.17352/2455-2976.000081}},
  volume       = {{6}},
  year         = {{2019}},
}