Factor V east Texas variant causes bleeding in a three-generation family.
Factor V east Texas variant causes bleeding in a three-generation family.
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DOI：
10.1111/jth.15612
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Mast AE
中科院分区：
文献类型：
--
作者：
Peterson JA;Gupta S;Martinez ND;Hardesty B;Maroney SA;Mast AE
The factor V east Texas bleeding disorder (FVETBD) is caused by increased plasma tissue factor pathway inhibitor-α (TFPIα) concentration. The underlying cause is a variant in F5 causing alternative splicing within exon 13 and producing FV-short, which tightly binds the C-terminus of TFPIα, prolonging its circulatory half-life. To diagnose a family presenting with variable bleeding and laboratory phenotypes. Samples were obtained from 17 family members for F5 exon 13 sequencing. Plasma/platelet TFPI and platelet FV were measured by ELISA and/or Western blot. Plasma thrombin generation potential was evaluated using calibrated automated thrombography. The FVET variant was identified in all family members with bleeding symptoms and associated with elevated plasma TFPIα (4.5- to 13.4-fold) and total TFPI (2- to 3-fold). However, TFPIα and FV-short were not elevated in platelets. TF-initiated thrombin generation in patient plasma was diminished but was restored by a monoclonal anti-TFPI antibody or factor VIIa. TFPIα localized within vascular extracellular matrix in an oral lesion biopsy from an affected family member. FVETBD was diagnosed in an extended family. The variant was autosomal dominant and highly penetrant. Elevated plasma TFPIα, rather than platelet TFPIα, was likely the primary cause of bleeding. Plasma FV-short did not deplete TFPIα from extracellular matrix. In vitro thrombin generation was restored with an anti-TFPI antibody or factor VIIa suggesting effective therapies may be available. Increased awareness of, and testing for, bleeding disorders associated with F5 exon 13 variants and elevated plasma TFPI are needed.
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影响因子：
6.7
作者：
Maroney SA;Peterson JA;Zwifelhofer W;Martinez ND;Yan K;Bercovitz RS;Woods RK;Mast AE
通讯作者：
Mast AE
影响因子：
20.3
作者：
Cunha, Marisa L. R.;Bakhtiari, Kamran;Middeldorp, Saskia
通讯作者：
Middeldorp, Saskia
影响因子：
4.6
作者：
Kwak H;Lee S;Jo S;Kwon YE;Kang H;Choi G;Jung ME;Kwak MJ;Kim S;Oh BH;Kim DS;Hwang SH
通讯作者：
Hwang SH
影响因子：
20.3
作者：
Kuang, SQ;Hasham, S;Milewicz, DM
通讯作者：
Milewicz, DM
DOI：
10.1111/j.1538-7836.2009.03454.x
发表时间：
2009-07
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Maroney SA;Ferrel JP;Pan S;White TA;Simari RD;McVey JH;Mast AE
通讯作者：
Mast AE