Elevated factor VIII in hereditary haemorrhagic telangiectasia (HHT): Association with venous thromboembolism
Elevated factor VIII in hereditary haemorrhagic telangiectasia (HHT): Association with venous thromboembolism
复制标题
遗传性出血性毛细血管扩张症 (HHT) 中因子 VIII 升高：与静脉血栓栓塞的相关性
作者：
C. Shovlin;L. Sulaiman;F. Govani;J. Jackson;M. Begbie
遗传性出血性毛细血管扩张症（HHT）引起慢性鼻和胃肠道出血。血栓原药物通常用于严重出血。血栓风险尚未明确。为了确定HHT患者的血栓形成前变量，并评估其潜在的功能意义，一项基于elisa的试点研究比较了健康HHT患者与年龄/性别匹配的非HHT对照组的血浆蛋白，并在309个连续HHT患者中进行了全面研究。在初步研究中，与非HHT对照组相比，HHT组的因子VIII （FVIII）和血管性血友病因子抗原浓度升高（p<0.0013, Mann- Whitney）。服务实验室测量证实125名hht患者中FVIII:Ag含量高，近期无疾病、干预或静脉血栓栓塞。FVIII：随着年龄的增长，Ag水平升高。Logistic回归也提示hht相关性肺动静脉畸形（AVMs）与年龄无关。未发现FVIII:Ag与急性期反应、弥散性血管内凝血、ABO血型、肺动脉压或HHT出血标志物之间存在关联。FVIII:Ag升高与活化的部分凝血活素时间（aptt）缩短有关，VTE:VTE影响20/309 (6.5%)hht患者，中位年龄为61（36-71）岁。在pavm相关脑脓肿发生后的几个月内，4例VTE发生在因子v Leiden杂合子中。与VTE相关性最强的是距VTE 10-132个月的对数转换FVIII:Ag（优势比2.41,95%可信区间1.254,4.612,p=0.008）。经FVIII:Ag调整后，年龄对静脉血栓栓塞风险没有额外的影响。总之，HHT相关的FVIII:Ag水平升高可能影响HHT患者的血栓形成风险。个体化的风险-收益考虑可能有助于HHT的管理。
Summary Hereditary haemorrhagic telangiectasia (HHT) causes chronic nasal and gastrointestinal haemorrhage. Prothrombotic agents are commonly used for severe haemorrhage. Thrombotic risks have not been defined. In order to identify prothrombotic variables in HHT patients, and assess their potential functional significance, a pilot ELISA-based study comparing plasma proteins in healthy individuals with HHT to age/sex-matched non-HHT controls was validated in a full study of 309 consecutive HHTaffected individuals. In the pilot study, factor VIII (FVIII) and von Willebrand factor antigen concentrations were elevated in the HHT group compared to non-HHT controls (p<0.0013, Mann- Whitney). Service laboratory measurements confirmed high FVIII:Ag in 125 HHT-affected individuals with no recent illhealth, intervention or venous thromboemboli. FVIII:Ag levels increased with age. Logistic regression also suggested an age-independent association with HHT-associated pulmonary arteriovenous malformations (AVMs). No association was demonstrated between FVIII:Ag and acute phase response, disseminated intravascular coagulation, ABO group, pulmonary artery pressure, or markers of HHT haemorrhage. Elevated FVIII:Ag were associated with shortened activated partial thromboplastin times (APTTs), andVTE:VTE affected 20/309 (6.5%) HHT-affected individuals, at median age 61(36–71) years. Four VTE occurred in factorV Leiden heterozygotes in the months following PAVM-associated brain abscess. The strongest association with VTE was with log-transformed FVIII:Ag measured 10–132 months from VTE (odds ratio 2.41, 95% confidence intervals 1.254, 4.612, p=0.008). Age made no additional contribution to VTE risk once adjusted for FVIII:Ag. In conclusion, HHT-related elevation of FVIII:Ag levels may influence thrombotic risk in HHT. Individualised risk-benefit considerations may be helpful in HHT management.
DOI：
10.32388/wtlzrr
发表时间：
2020-02
期刊：
Zhonghua yi xue za zhi = Chinese medical journal; Free China ed
影响因子：
--
作者：
Ya-Fen Peng;Liang‐Kung Chen;Y. Chou;F. Chang;Shinn-Jang Hwang
通讯作者：
Ya-Fen Peng;Liang‐Kung Chen;Y. Chou;F. Chang;Shinn-Jang Hwang
影响因子：
6.5
作者：
BRAVERMAN, IM;KEH, A;JACOBSON, BS
通讯作者：
JACOBSON, BS