PMID- 15701143
OWN - NLM
STAT- MEDLINE
DCOM- 20050527
LR  - 20181201
IS  - 0014-2972 (Print)
IS  - 0014-2972 (Linking)
VI  - 35 Suppl 1
DP  - 2005 Mar
TI  - From heparins to factor Xa inhibitors and beyond.
PG  - 12-20
AB  - Despite some disadvantages, unfractionated heparin (UFH) and oral anticoagulants 
      have been the only anticoagulants for prophylaxis and therapy of thromboembolic 
      disorders for several decades. Based on the increasing knowledge of the structure 
      and pharmacology of heparin, low molecular weight heparins (LMWH) have been 
      developed in the 1980s. Compared to UFH, their advantages are mainly based on 
      their reduced nonspecific binding to proteins and cells resulting in improved 
      pharmacokinetics. In 1991, LMWH were declared as the most efficient prophylaxis 
      in high-risk patients. Although the use of LMWH is increasing and they are today 
      also applied for therapy and in other indications like acute coronary syndrome, 
      they are considered not optimal concerning efficacy and safety. With the approval 
      of fondaparinux for the prevention of venous thromboembolic disease in high-risk 
      orthopedic patients, there might be a paradigm shift in the field of 
      anticoagulants. Fondaparinux, a synthetic, chemically defined pentasaccharide, is 
      the first selective inhibitor of factor Xa. By its highly specific binding to 
      antithrombin, it selectively inhibits factor Xa and consequently prevents 
      thrombin generation. In contrast to UFH and LMWH, it does not bind to any other 
      cells and other proteins than antithrombin. This leads to a favourable linear 
      pharmacokinetic profile, allowing once-daily subcutaneous application of a fixed 
      dose without monitoring in thromboembolism prophylaxis. In addition to the 
      evaluation of fondaparinux for further indications, chemical modifications of 
      this pentasaccharide such as the long-acting idraparinux are currently under 
      investigation.
FAU - Alban, S
AU  - Alban S
AD  - Christian-Albrechts-University of Kiel, Germany. salban@pharmazie.uni-kiel.de
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Eur J Clin Invest
JT  - European journal of clinical investigation
JID - 0245331
RN  - 0 (Anticoagulants)
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Oligosaccharides)
RN  - 0 (Polysaccharides)
RN  - 0 (SanOrg 123781)
RN  - 6ADD3H8MFZ (idraparinux)
RN  - 9005-49-6 (Heparin)
RN  - J177FOW5JL (Fondaparinux)
SB  - IM
MH  - Anticoagulants/*therapeutic use
MH  - *Factor Xa Inhibitors
MH  - Fondaparinux
MH  - Heparin/*therapeutic use
MH  - Heparin, Low-Molecular-Weight/therapeutic use
MH  - Humans
MH  - Oligosaccharides/therapeutic use
MH  - Polysaccharides/pharmacokinetics/therapeutic use
RF  - 48
EDAT- 2005/02/11 09:00
MHDA- 2005/05/28 09:00
CRDT- 2005/02/11 09:00
PHST- 2005/02/11 09:00 [pubmed]
PHST- 2005/05/28 09:00 [medline]
PHST- 2005/02/11 09:00 [entrez]
AID - ECI1452 [pii]
AID - 10.1111/j.0960-135X.2005.01452.x [doi]
PST - ppublish
SO  - Eur J Clin Invest. 2005 Mar;35 Suppl 1:12-20. doi: 
      10.1111/j.0960-135X.2005.01452.x.