PMID- 20230412
OWN - NLM
STAT- MEDLINE
DCOM- 20100709
LR  - 20141120
IS  - 1365-2141 (Electronic)
IS  - 0007-1048 (Linking)
VI  - 149
IP  - 4
DP  - 2010 May
TI  - Monitoring heparin anticoagulation in the acute phase response.
PG  - 613-9
LID - 10.1111/j.1365-2141.2010.08129.x [doi]
AB  - The anticoagulant effect of unfractionated heparin (UFH) is monitored using the 
      activated partial thromboplastin time (APTT). An APTT of 1.5-2.5 times the 
      control is usually taken as the therapeutic range and assumed to reflect an 
      anti-activated factor X (anti-Xa) level of 0.35-0.7 u/ml. However, in some cases, 
      despite administration of sufficient heparin to achieve a therapeutic anti-Xa 
      assay level, the APTT remains sub-therapeutic. This 'apparent heparin resistance' 
      is commonly due to high levels of factor VIII (FVIII). In these situations, the 
      anti-Xa is usually preferred for monitoring in order to avoid, what might be, 
      dangerously high levels of heparin. We hypothesized that at high FVIII levels, 
      the heparin resistance encountered may be genuine rather than apparent and that 
      higher doses of heparin may indeed be needed for an equivalent anticoagulant 
      effect. The relationship between heparin level, APTT and anticoagulant effect at 
      different FVIII concentrations was determined using thrombelastography and the 
      thrombin generation assay. Thromboelastographic and thrombin generation 
      parameters concurred with APTT, demonstrating a genuine heparin resistance in the 
      presence of high FVIII levels. This suggests that APTT may be a more accurate 
      measure of anticoagulant effect in vivo than anti-Xa.
FAU - Uprichard, James
AU  - Uprichard J
AD  - Department of Haematology, Imperial College, and Hammersmith Hospital, London, 
      UK. j.uprichard@imperial.ac.uk
FAU - Manning, Richard A
AU  - Manning RA
FAU - Laffan, Michael A
AU  - Laffan MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100311
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Anticoagulants)
RN  - 0 (Factor Xa Inhibitors)
RN  - 9001-27-8 (Factor VIII)
RN  - 9005-49-6 (Heparin)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
MH  - Acute-Phase Reaction/*blood
MH  - Anticoagulants/*administration & dosage/therapeutic use
MH  - Blood Coagulation Tests/methods
MH  - Dose-Response Relationship, Drug
MH  - Drug Monitoring/*methods
MH  - Drug Resistance
MH  - Factor VIII/metabolism
MH  - Factor Xa Inhibitors
MH  - Heparin/*administration & dosage/therapeutic use
MH  - Humans
MH  - Male
MH  - Partial Thromboplastin Time
MH  - Thrombelastography/methods
MH  - Thrombin/biosynthesis
EDAT- 2010/03/17 06:00
MHDA- 2010/07/10 06:00
CRDT- 2010/03/17 06:00
PHST- 2010/03/17 06:00 [entrez]
PHST- 2010/03/17 06:00 [pubmed]
PHST- 2010/07/10 06:00 [medline]
AID - BJH8129 [pii]
AID - 10.1111/j.1365-2141.2010.08129.x [doi]
PST - ppublish
SO  - Br J Haematol. 2010 May;149(4):613-9. doi: 10.1111/j.1365-2141.2010.08129.x. Epub 
      2010 Mar 11.