PMID- 18690358
OWN - NLM
STAT- MEDLINE
DCOM- 20081008
LR  - 20181201
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 100
IP  - 2
DP  - 2008 Aug
TI  - Thrombin generation assays are superior to traditional tests in assessing 
      anticoagulation reversal in vitro.
PG  - 350-5
AB  - Even though new anticoagulants are being devised with the notion that they do not 
      require regular monitoring, when bleeding occurs, it is important to have an 
      antidote and a reliable test to confirm whether the anticoagulant effects are 
      persisting. We examined the effects of five heparinoids, unfractionated heparin 
      (UFH), tinzaparin, enoxaparin, danaparoid and fondaparinux on the traditional 
      APTT and anti-Xa assays as well as on the calibrated automated thrombogram (CAT). 
      We also studied the ability of protamine sulphate (PS), NovoSeven, FEIBA and FFP 
      to reverse maximum anticoagulation induced by the different heparinoids. The CAT 
      was the only test to detect the coagulopathy of all the anticoagulants. PS 
      produced complete reversal of UFH, and this could be monitored with all three 
      tests. Tinzaparin can also be completely neutralised in vitro with high doses of 
      PS, but the maximum enoxaparin reversal achieved with PS is only approximately 
      60%. Fondaparinux does not significantly affect the APTT and PS has no 
      significant effect on its reversal. Only NovoSeven was able to correct the 
      fondaparinux induced CAT abnormalities whilst having no effect on the anti-Xa 
      level. None of the reversal agents was very effective in danaparoid spiked plasma 
      but NovoSeven, at high dose, increased the ETP by 40% and reduced the anti-Xa 
      level from 0.93 to 0.78 IU/ml. We conclude that the CAT is superior to the 
      traditional coagulation tests in that it not only detects the coagulopathy of all 
      the heparinoids but can be also be used to monitor their reversal.
FAU - Gatt, Alex
AU  - Gatt A
AD  - Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, 
      Sheffield, UK.
FAU - van Veen, Joost J
AU  - van Veen JJ
FAU - Woolley, Anita M
AU  - Woolley AM
FAU - Kitchen, Steve
AU  - Kitchen S
FAU - Cooper, Peter
AU  - Cooper P
FAU - Makris, Michael
AU  - Makris M
LA  - eng
GR  - British Heart Foundation/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Anticoagulants)
RN  - 0 (Blood Coagulation Factors)
RN  - 0 (Enoxaparin)
RN  - 0 (Heparin Antagonists)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Polysaccharides)
RN  - 0 (Protamines)
RN  - 0 (Recombinant Proteins)
RN  - 24967-94-0 (Dermatan Sulfate)
RN  - 7UQ7X4Y489 (Tinzaparin)
RN  - 9005-49-6 (Heparin)
RN  - 9007-28-7 (Chondroitin Sulfates)
RN  - 9050-30-0 (Heparitin Sulfate)
RN  - AC71R787OV (recombinant FVIIa)
RN  - BI6GY4U9CW (danaparoid)
RN  - CS849DUN3M (anti-inhibitor coagulant complex)
RN  - EC 3.4.21.21 (Factor VIIa)
RN  - EC 3.4.21.5 (Thrombin)
RN  - EC 3.4.21.6 (Factor Xa)
RN  - J177FOW5JL (Fondaparinux)
SB  - IM
CIN - Thromb Haemost. 2008 Aug;100(2):179-80. PMID: 18690334
MH  - Anticoagulants/*pharmacology
MH  - Blood Coagulation Factors/pharmacology
MH  - Blood Coagulation Tests/*methods
MH  - Chondroitin Sulfates/pharmacology
MH  - Dermatan Sulfate/pharmacology
MH  - Drug Interactions
MH  - Drug Monitoring/*methods
MH  - Enoxaparin/pharmacology
MH  - Factor VIIa/pharmacology
MH  - Factor Xa/metabolism
MH  - Fondaparinux
MH  - Heparin/pharmacology
MH  - Heparin Antagonists/*pharmacology
MH  - Heparin, Low-Molecular-Weight/pharmacology
MH  - Heparitin Sulfate/pharmacology
MH  - Humans
MH  - In Vitro Techniques
MH  - Partial Thromboplastin Time
MH  - Polysaccharides/pharmacology
MH  - Protamines/*pharmacology
MH  - Recombinant Proteins/pharmacology
MH  - Thrombin/biosynthesis/*metabolism
MH  - Tinzaparin
EDAT- 2008/08/12 09:00
MHDA- 2008/10/09 09:00
CRDT- 2008/08/12 09:00
PHST- 2008/08/12 09:00 [pubmed]
PHST- 2008/10/09 09:00 [medline]
PHST- 2008/08/12 09:00 [entrez]
AID - 08080350 [pii]
PST - ppublish
SO  - Thromb Haemost. 2008 Aug;100(2):350-5.