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Coagulation factor ...
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Vincent, Lisa M.
(author)
Coagulation factor V-A2440G causes east Texas bleeding disorder via TFPI alpha
- Article/chapterEnglish2013
Publisher, publication year, extent ...
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2013
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electronicrdacarrier
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LIBRIS-ID:oai:lup.lub.lu.se:dc904ca7-8ee4-4020-b68a-37394302eca4
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https://lup.lub.lu.se/record/4101982URI
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https://doi.org/10.1172/JCI69091DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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The autosomal dominantly inherited east Texas bleeding disorder is linked to an A2440G variant in exon 13 of the F5 gene. Affected individuals have normal levels of coagulation factor V (FV) activity, but demonstrate inhibition of global coagulation tests. We demonstrated that the A2440G mutation causes upregulation of an alternatively spliced F5 transcript that results in an in-frame deletion of 702 amino acids of the large activation fragment, the B domain. The approximately 250-kDa FV isoform (FV-short), which can be fully activated by thrombin, is present in all A2440G carriers' plasma (n = 16). FV-short inhibits coagulation through an indirect mechanism by forming a complex with tissue factor pathway inhibitor-alpha (TFPI alpha), resulting in an approximately 10-fold increase in plasma TFPI alpha, suggesting that the TFPI alpha:FV-short complexes are retained in circulation. The TFPI alpha:FV-short complexes efficiently inhibit thrombin generation of both intrinsic and extrinsic coagulation pathways. These data demonstrate that the east Texas bleeding disorder-associated F5(A2440G) leads to the formation of the TFPI alpha:FV-short complex, which inhibits activation and propagation of coagulation.
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Added entries (persons, corporate bodies, meetings, titles ...)
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Tran, SinhLund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups(Swepub:lu)klke-str
(author)
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Livaja Koshiar, RuzicaLund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups(Swepub:lu)med-rlv
(author)
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Bensend, Tracy A.
(author)
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Milewicz, Dianna M.
(author)
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Dahlbäck, BjörnLund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups(Swepub:lu)klke-bda
(author)
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Klinisk kemi, MalmöForskargrupper vid Lunds universitet
(creator_code:org_t)
Related titles
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In:Journal of Clinical Investigation123:9, s. 3777-37870021-9738
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