PMID- 30660948
OWN - NLM
STAT- MEDLINE
DCOM- 20190910
LR  - 20190910
IS  - 1879-2472 (Electronic)
IS  - 0049-3848 (Linking)
VI  - 175
DP  - 2019 Mar
TI  - Monitoring of heparins in antithrombin-deficient patients.
PG  - 8-12
LID - S0049-3848(19)30015-5 [pii]
LID - 10.1016/j.thromres.2019.01.007 [doi]
AB  - INTRODUCTION: Heparins exert their anticoagulant effect through activation of 
      antithrombin. Whether antithrombin deficiency leads to clinically relevantly 
      reduced anti-Xa activity of heparins is unknown. We investigated the relation 
      between antithrombin deficiency and anti-Xa activity measurements of plasma 
      samples spiked with unfractionated heparin (UFH) or low-molecular-weight heparin 
      (LMWH). MATERIALS AND METHODS: Plasma samples from 34 antithrombin-deficient 
      subjects and 17 family controls were spiked with UFH and LMWH (nadroparin) aimed 
      to correspond with an anti-Xa activity of 0.8 IU/mL. Antithrombin, beta-antithrombin 
      and anti-Xa activities were measured. RESULTS: Mean anti-Xa activity with LWMH 
      was 0.55 IU/mL (0.30-0.74) (recovery 69%, 38-93%) in antithrombin-deficient 
      subjects and 0.82 (0.71-0.89) IU/mL in controls (recovery 103%, 89-111%). 
      Expected anti-Xa measurements after LMWH spiking were found in 17/17 
      non-deficient subjects and in 8/34 antithrombin-deficient subjects. Anti-Xa 
      measurements in the expected range (0.6-1.0 IU/mL) after UFH spiking were found 
      in 17/17 non-deficient subjects and in 1/22 antithrombin-deficient subjects. 
      Antithrombin activity correlated with anti-Xa activity of UFH (R = 0.77) and LMWH 
      (R = 0.66). Mixing studies of pooled normal plasma and antithrombin-deficient 
      plasma showed that anti-Xa recovery was linearly reduced with antithrombin 
      activity decreasing below 100%. CONCLUSIONS: Reduced antithrombin activity causes 
      significantly reduced anti-Xa levels. Standard LWMH- or UFH-doses are likely to 
      lead to under treatment in antithrombin-deficient individuals.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Croles, Frederik Nanne
AU  - Croles FN
AD  - Department of Hematology, Erasmus University Medical Center, Rotterdam, The 
      Netherlands; Department of Haematology, University of Groningen, University 
      Medical Centre Groningen, Groningen, The Netherlands. Electronic address: 
      f.croles@erasmusmc.nl.
FAU - Lukens, Michael V
AU  - Lukens MV
AD  - Department of Laboratory Medicine, University of Groningen, University Medical 
      Centre Groningen, Groningen, The Netherlands.
FAU - Mulder, Rene
AU  - Mulder R
AD  - Department of Laboratory Medicine, University of Groningen, University Medical 
      Centre Groningen, Groningen, The Netherlands.
FAU - de Maat, Moniek P M
AU  - de Maat MPM
AD  - Department of Hematology, Erasmus University Medical Center, Rotterdam, The 
      Netherlands.
FAU - Mulder, Andre B
AU  - Mulder AB
AD  - Department of Laboratory Medicine, University of Groningen, University Medical 
      Centre Groningen, Groningen, The Netherlands.
FAU - Meijer, Karina
AU  - Meijer K
AD  - Department of Haematology, University of Groningen, University Medical Centre 
      Groningen, Groningen, The Netherlands.
LA  - eng
PT  - Journal Article
DEP - 20190115
PL  - United States
TA  - Thromb Res
JT  - Thrombosis research
JID - 0326377
RN  - 0 (Heparin, Low-Molecular-Weight)
SB  - IM
MH  - Antithrombin III Deficiency/*drug therapy
MH  - Cross-Sectional Studies
MH  - Female
MH  - Heparin, Low-Molecular-Weight/blood/pharmacology/*therapeutic use
MH  - Humans
MH  - Male
MH  - Retrospective Studies
OTO - NOTNLM
OT  - Anti-Xa measurements
OT  - Antithrombin III deficiency
OT  - Heparin
OT  - Low-molecular-weight heparin
OT  - SERPINC1 gene
EDAT- 2019/01/21 06:00
MHDA- 2019/09/11 06:00
CRDT- 2019/01/21 06:00
PHST- 2018/08/30 00:00 [received]
PHST- 2018/11/22 00:00 [revised]
PHST- 2019/01/14 00:00 [accepted]
PHST- 2019/01/21 06:00 [pubmed]
PHST- 2019/09/11 06:00 [medline]
PHST- 2019/01/21 06:00 [entrez]
AID - S0049-3848(19)30015-5 [pii]
AID - 10.1016/j.thromres.2019.01.007 [doi]
PST - ppublish
SO  - Thromb Res. 2019 Mar;175:8-12. doi: 10.1016/j.thromres.2019.01.007. Epub 2019 Jan 
      15.