PMID- 19689280
OWN - NLM
STAT- MEDLINE
DCOM- 20091106
LR  - 20190823
IS  - 1875-533X (Electronic)
IS  - 0929-8673 (Linking)
VI  - 16
IP  - 23
DP  - 2009
TI  - Structure-activity relationships of low molecular weight heparins expose to the 
      risk of achieving inappropriate targets in patients with renal failure.
PG  - 3028-40
AB  - Heparins are used in "therapeutic doses" for systemic anticoagulation to treat 
      patients who have confirmed venous thromboembolism, or in "prophylactic doses 
      "for the prevention of venous thromboembolism: they are generally lower doses and 
      are employed once a day. Structure-function relationships are strongly influenced 
      by the chain length of the molecules. In fact, unfractionated heparin (UFH) binds 
      to ATIII lysine site leading to a conformational change of the ATIII arginine 
      reactive centre able to create a covalent binding to the active centre serine of 
      thrombin in a ternary complex formation composed by heparin, ATIII and thrombin. 
      On the other side, low molecular weight heparins (LMWHs) are too short to be able 
      to form this ternary complex, and mainly exert their anticoagulant effect by 
      binding the factor Xa, always via ATIII. Lastly, the short unique 
      pentasaccharidic sequence which is crucial for heparin's activity and has been 
      recently synthesized as Fondaparinux, only acts via the formation of the high 
      affinity ternary complex with ATIII-factor Xa. Due to their structure-function 
      relationships, LMWHs cannot be monitored by conventional coagulation test used 
      for monitoring UFH and need more specific anti-factor Xa activity determinations, 
      but monitoring has been considered unnecessary in the general population due to a 
      predictable dose/effect ratio. However, a disturbing rise of bleeding 
      complications in patients with renal failure treated with LMWH has been published 
      in the last years, that is explained by the accumulation of LMWHs in this 
      setting, due the consequences of structure-metabolisms relationships of the small 
      members of the heparin's family. In this context, physicians are often left to a 
      "best guess" method of empiric dose adjustment, which is at risk of achieving 
      inappropriate targets, with a percentage of values above and below target of 51% 
      and 34%, respectively, depending on LMWHs dosage, body mass index and renal 
      function. Without anti-Xa activity monitoring, the quality of care delivered in 
      the setting of renal failure is poor, as over-prophylaxis can result in 
      potentially dangerous anticoagulation, while under-prophylaxis can result in 
      life-threatening thrombosis.
FAU - Stratta, Piero
AU  - Stratta P
AD  - Department of Clinical and Experimental Medicine, International Research Centre 
      Autoimmune Disease (IRCAD), Amedeo Avogadro University, Maggiore Hospital, 
      Novara, Italy. strattanefro@hotmail.com
FAU - Karvela, Eirini
AU  - Karvela E
FAU - Canavese, Caterina
AU  - Canavese C
FAU - Quaglia, Marco
AU  - Quaglia M
FAU - Lazzarich, Elisa
AU  - Lazzarich E
FAU - Fenoglio, Roberta
AU  - Fenoglio R
FAU - Pergolini, Patrizia
AU  - Pergolini P
FAU - Bellomo, Giorgio
AU  - Bellomo G
FAU - Cena, Tiziana
AU  - Cena T
FAU - Magnani, Corrado
AU  - Magnani C
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Curr Med Chem
JT  - Current medicinal chemistry
JID - 9440157
RN  - 0 (Anticoagulants)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 9000-94-6 (Antithrombin III)
RN  - 9001-28-9 (Factor IX)
RN  - 9005-49-6 (Heparin)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
MH  - Anticoagulants/*chemistry/*therapeutic use
MH  - Antithrombin III/metabolism
MH  - Factor IX/metabolism
MH  - Heparin/chemistry
MH  - Heparin, Low-Molecular-Weight/*chemistry/*therapeutic use
MH  - Humans
MH  - Renal Insufficiency/*complications/mortality
MH  - Risk
MH  - Structure-Activity Relationship
MH  - Thrombin/metabolism
RF  - 92
EDAT- 2009/08/20 09:00
MHDA- 2009/11/07 06:00
CRDT- 2009/08/20 09:00
PHST- 2009/08/20 09:00 [entrez]
PHST- 2009/08/20 09:00 [pubmed]
PHST- 2009/11/07 06:00 [medline]
AID - 10.2174/092986709788803105 [doi]
PST - ppublish
SO  - Curr Med Chem. 2009;16(23):3028-40. doi: 10.2174/092986709788803105.