Linked Life Data

19689280

Source:http://linkedlifedata.com/resource/pubmed/id/19689280

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2009-8-19
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1875-533X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3028-40
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Structure-activity relationships of low molecular weight heparins expose to the risk of achieving inappropriate targets in patients with renal failure.
pubmed:affiliation
Department of Clinical and Experimental Medicine, International Research Centre Autoimmune Disease (IRCAD), Amedeo Avogadro University, Maggiore Hospital, Novara, Italy. strattanefro@hotmail.com
pubmed:publicationType
Journal Article, Review