Linked Life Data

19002040

Source:http://linkedlifedata.com/resource/pubmed/id/19002040

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2008-11-12
pubmed:abstractText
Supraphysiological concentrations of recombinant activated factor VII (rVIIa, NovoSeven) are used to control bleeding in hemophilia. Current experimental evidence suggests that rVIIa may increase thrombin generation via two pathways: one being tissue factor (TF)-dependent and another being activated platelet-dependent. Contribution of TF to the rVIIa action may justify different administration profiles of rVIIa. In the present study, thrombin and fibrin generation and spatial clot formation assays in platelet-free hemophilia A and normal plasma were used to investigate this contribution. By varying the concentration of TF and the way it becomes available to plasma, we obtained the following results. Activation of clotting with less than 5 pmol/l of TF facilitates thrombin and fibrin generation at low, but not at supraphysiological rVIIa concentrations. Activation with more than 13 pmol/l of TF saturates thrombin and fibrin generation kinetics, making it insensitive to rVIIa. rVIIa minimally modulates clot growth on the surface of TF-expressing fibroblasts. On the contrary, rVIIa produces spontaneous clot formation in nonflowing platelet-free plasma far away from fibroblasts via plasma lipid particles. Therefore, both the concentration and the distribution of TF determine relevance of a particular experimental system for the studies of rVIIa action. The results indicate that 300-1600 nmol/l (megadoses) of rVIIa may deliver coagulation outside of the TF-rich areas of blood vessel damage via the platelet-derived microparticles. Therefore, rate and extent of platelet-derived microparticles generation might be important with regard to rVIIa treatment safety.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1473-5733
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
743-55
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Mechanisms of action of recombinant activated factor VII in the context of tissue factor concentration and distribution.
pubmed:affiliation
National Research Center for Hematology, Moscow, Russia. ovanesov@gmail.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't