Linked Life Data

2936571

Source:http://linkedlifedata.com/resource/pubmed/id/2936571

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1986-4-18
pubmed:abstractText
Conventionally, heparin has been evaluated for its anticoagulant effect by various nonspecific, poorly standardized coagulant methods such as the U.S. Pharmacopeial and other global (APTT) tests. However, these assays are relatively insensitive to heparin fractions and fragments, and give varying with the newer modes of heparin administration. It has become necessary, therefore, to develop other methods able to detect a proper therapeutic/prophylactic level and to evaluate a standard potency for these agents. Newer amidolytic assays utilizing synthetic substrates provide for specific anti-factor Xa or anti-factor IIa evaluation. Although these factors are believed to reflect the antithrombotic effect of heparin and its fractions/fragments, conclusive clinical studies are not available at this time. Interactions with non-AT-III-mediated pathways, the contact, kallikrein-kinin, and fibrinolytic system, other coagulant factors, endothelium, and eicosanoid system all can contribute to the overall antithrombotic response of heparin. Some of these actions are not measurable by current in vitro test methods. Amidolytic, immunochemical, and physical assays using various activators to generate endogenous factor Xa, as well as assays for the detection of metabolic or release products of each of these systems, may be more relevant to in vivo conditions. Specific low molecular weight markers such as fibrinopeptide A, which provide the earliest detection of hemostatic activation, can be measured directly, or an in vitro system can be developed to quantitate the relative generation of these markers. These methods can then be modified to assay the in vitro potency of heparin preparations. With proper consideration of reagent specificity and concentration, molecular interactions, reaction time and temperature, ionic type and concentration, reliable accurate methods for a true in vitro representation of in vivo events may be developed. Clinical assays must measure an endogenous response to therapy and not merely an absolute circulating level of drug. However, a standardized pure enzyme system may be ideal to evaluate the potency of these agents. The development of heparin derivatives necessitates a reassessment of currently practiced laboratory technology. Furthermore, well-defined biochemical methods are required for a standardized evaluation of potency and clinical monitoring of these agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1040-8363
pubmed:author
pubmed:issnType
Print
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
361-89
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1986
pubmed:articleTitle
In vitro evaluation of heparin fractions: old vs. new methods.
pubmed:publicationType
Journal Article, Review