2011
DOI: 10.1111/j.1538-7836.2011.04223.x
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Abstract: Summary.  Background and objectives: Platelet binding and activity play important roles in the efficacy of factor VIIa (FVIIa) as a bypassing agent for hemophilia treatment. An analog of FVIIa with increased tissue factor (TF)‐independent activity, NN1731, has been produced by introducing three amino acid changes in the protease domain. NN1731 has a conformation similar to TF‐bound FVIIa, even in the absence of TF. This results in much greater intrinsic proteolytic activity, but similar activity in the presenc… Show more

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Cited by 24 publications
(28 citation statements)
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References 30 publications
(34 reference statements)
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“…Finally, in vitro studies have shown that recombinant FVIIa preferentially binds to procoagulant platelets (34,35), and similar preferential binding to COAT platelets has been described for vatreptacog alfa, a novel recombinant FVIIa variant (36). Taking these data into account, the individual level of COAT platelets might be an important component for explaining the difference in hemostatic response to these drugs.…”
Section: Discussionmentioning
confidence: 70%
“…Finally, in vitro studies have shown that recombinant FVIIa preferentially binds to procoagulant platelets (34,35), and similar preferential binding to COAT platelets has been described for vatreptacog alfa, a novel recombinant FVIIa variant (36). Taking these data into account, the individual level of COAT platelets might be an important component for explaining the difference in hemostatic response to these drugs.…”
Section: Discussionmentioning
confidence: 70%
“…9,10 This mode of action is supported by the greater clinical efficacy of an analog of rhFVIIa with enhanced TF-independent activity and platelet-binding sites. [11][12][13] Additional evidence was recently provided by the hemostatic capacity in a hemophilia mouse injury model of a chimeric mouse FVIIa (mFVIIa) molecule harboring the g-carboxyglutamic acid (Gla) domain of mouse FIX that does not bind mouse TF (mTF).…”
Section: Introductionmentioning
confidence: 99%
“…on May 12, 2018. by guest www.bloodjournal.org From such molecules reportedly increase catalytic activity on platelets, [42][43][44][45] whereas some may increase TF-dependent activity, 46 and yet others have been found to prolong the lifetime in the circulation. 47,48 Each of these changes can potentially alter the therapeutic window of TF-and phospholipid-dependent actions of rFVIIa, leading to drastically different efficacy and safety profiles.…”
Section: Discussionmentioning
confidence: 99%