Prevalence, Genetic Background, and Clinical Phenotype of Congenital Thrombophilia in Chronic Thromboembolic Pulmonary Hypertension

Tian Yu Lian; Jian Zhou Liu; Fan Guo; Yu Ping Zhou; Tao Wu; Hui Wang; Jing Yi Li; Xin Xin Yan; Fu Hua Peng; Kai Sun; Xi Qi Xu; Zhi Yan Han; Xin Jiang; Duolao Wang; Qi Miao; Zhi Cheng Jing

doi:10.1016/j.jacasi.2022.02.010

Prevalence, Genetic Background, and Clinical Phenotype of Congenital Thrombophilia in Chronic Thromboembolic Pulmonary Hypertension

Tian Yu Lian
, Jian Zhou Liu
, Fan Guo
, Yu Ping Zhou
, Tao Wu
, Hui Wang
, Jing Yi Li
, Xin Xin Yan
, Fu Hua Peng
, Kai Sun
, Xi Qi Xu
, Zhi Yan Han
, Xin Jiang
, Duolao Wang
, Qi Miao
, Zhi Cheng Jing

Clinical Sciences

Chinese Academy of Medical Sciences

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

Abstract

Background

The role of congenital thrombophilia in chronic thromboembolic pulmonary hypertension (CTEPH) remains unresolved.

Objectives

The purpose of this study was to investigate the prevalence, genetic background, and clinical phenotype of congenital thrombophilia in CTEPH.

Methods

In total, 367 patients with CTEPH from May 2013 to December 2020 were consecutively enrolled in this cross-sectional study in FuWai Hospital and Peking Union Medical College Hospital in China. The primary outcome was the occurrence of congenital thrombophilia diagnosed through tests for congenital anticoagulants activity (including protein C, protein S, and antithrombin III), factor V Leiden and prothrombin G20210A sequence variants. Next-generation sequencing was conducted for patients with congenital thrombophilia. Clinical phenotype was compared between patients with and without thrombophilia.

Results

A total of 36 (9.8%; 95% CI: 6.8%-12.9%) patients were diagnosed as congenital thrombophilia, including 13 protein C deficiency (3.5%; 95% CI: 1.6%-5.4%), 19 protein S deficiency (5.2%; 95% CI: 2.9%-7.5%), and 4 antithrombin III deficiency (1.1%; 95% CI: 0%-2.2%). No factor V Leiden or prothrombin G20210A sequence variants were identified. Genotype for patients with thrombophilia revealed that 10 (76.9%) protein C deficiency patients were PROC sequence variant carriers, 4 (21.1%) protein S deficiency were PROS1 sequence variant carriers, and 2 (50.0%) antithrombin III deficiency were SERPINC1 sequence variant carriers. In the logistic regression model, male sex (OR: 3.24; 95% CI: 1.43-7.31) and proximal lesion in pulmonary arteries (OR: 4.10; 95% CI: 1.91-8.85) had significant differences between the congenital thrombophilia and nonthrombophilia group in CTEPH patients.

Conclusions

Congenital thrombophilia was not rare. Male sex and proximal lesion in pulmonary arteries might be the specific clinical phenotype for CTEPH patients with congenital thrombophilia.

Original language	English
Pages (from-to)	247-255
Number of pages	9
Journal	JACC: Asia
Volume	2
Issue number	3
Early online date	17 May 2022
DOIs	https://doi.org/10.1016/j.jacasi.2022.02.010
Publication status	Published - 17 May 2022

Keywords

antithrombin III deficiency
chronic thromboembolic pulmonary hypertension
congenital thrombophilia
genotype
protein C deficiency
protein S deficiency

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10.1016/j.jacasi.2022.02.010Licence: CC BY-NC-ND

1-s2Final published version, 423 KBLicence: CC BY-NC-ND

Cite this

Lian, T. Y., Liu, J. Z., Guo, F., Zhou, Y. P., Wu, T., Wang, H., Li, J. Y., Yan, X. X., Peng, F. H., Sun, K., Xu, X. Q., Han, Z. Y., Jiang, X., Wang, D., Miao, Q., & Jing, Z. C. (2022). Prevalence, Genetic Background, and Clinical Phenotype of Congenital Thrombophilia in Chronic Thromboembolic Pulmonary Hypertension. JACC: Asia, 2(3), 247-255. https://doi.org/10.1016/j.jacasi.2022.02.010

@article{b24b315104da4760a211e995f069dcc5,

title = "Prevalence, Genetic Background, and Clinical Phenotype of Congenital Thrombophilia in Chronic Thromboembolic Pulmonary Hypertension",

abstract = "BackgroundThe role of congenital thrombophilia in chronic thromboembolic pulmonary hypertension (CTEPH) remains unresolved.ObjectivesThe purpose of this study was to investigate the prevalence, genetic background, and clinical phenotype of congenital thrombophilia in CTEPH.MethodsIn total, 367 patients with CTEPH from May 2013 to December 2020 were consecutively enrolled in this cross-sectional study in FuWai Hospital and Peking Union Medical College Hospital in China. The primary outcome was the occurrence of congenital thrombophilia diagnosed through tests for congenital anticoagulants activity (including protein C, protein S, and antithrombin III), factor V Leiden and prothrombin G20210A sequence variants. Next-generation sequencing was conducted for patients with congenital thrombophilia. Clinical phenotype was compared between patients with and without thrombophilia.ResultsA total of 36 (9.8\%; 95\% CI: 6.8\%-12.9\%) patients were diagnosed as congenital thrombophilia, including 13 protein C deficiency (3.5\%; 95\% CI: 1.6\%-5.4\%), 19 protein S deficiency (5.2\%; 95\% CI: 2.9\%-7.5\%), and 4 antithrombin III deficiency (1.1\%; 95\% CI: 0\%-2.2\%). No factor V Leiden or prothrombin G20210A sequence variants were identified. Genotype for patients with thrombophilia revealed that 10 (76.9\%) protein C deficiency patients were PROC sequence variant carriers, 4 (21.1\%) protein S deficiency were PROS1 sequence variant carriers, and 2 (50.0\%) antithrombin III deficiency were SERPINC1 sequence variant carriers. In the logistic regression model, male sex (OR: 3.24; 95\% CI: 1.43-7.31) and proximal lesion in pulmonary arteries (OR: 4.10; 95\% CI: 1.91-8.85) had significant differences between the congenital thrombophilia and nonthrombophilia group in CTEPH patients.ConclusionsCongenital thrombophilia was not rare. Male sex and proximal lesion in pulmonary arteries might be the specific clinical phenotype for CTEPH patients with congenital thrombophilia.",

keywords = "antithrombin III deficiency, chronic thromboembolic pulmonary hypertension, congenital thrombophilia, genotype, protein C deficiency, protein S deficiency",

author = "Lian, \{Tian Yu\} and Liu, \{Jian Zhou\} and Fan Guo and Zhou, \{Yu Ping\} and Tao Wu and Hui Wang and Li, \{Jing Yi\} and Yan, \{Xin Xin\} and Peng, \{Fu Hua\} and Kai Sun and Xu, \{Xi Qi\} and Han, \{Zhi Yan\} and Xin Jiang and Duolao Wang and Qi Miao and Jing, \{Zhi Cheng\}",

year = "2022",

month = may,

day = "17",

doi = "10.1016/j.jacasi.2022.02.010",

language = "English",

volume = "2",

pages = "247--255",

journal = "JACC: Asia",

issn = "2772-3747",

publisher = "Elsevier Inc.",

number = "3",

}

TY - JOUR

T1 - Prevalence, Genetic Background, and Clinical Phenotype of Congenital Thrombophilia in Chronic Thromboembolic Pulmonary Hypertension

AU - Lian, Tian Yu

AU - Liu, Jian Zhou

AU - Guo, Fan

AU - Zhou, Yu Ping

AU - Wu, Tao

AU - Wang, Hui

AU - Li, Jing Yi

AU - Yan, Xin Xin

AU - Peng, Fu Hua

AU - Sun, Kai

AU - Xu, Xi Qi

AU - Han, Zhi Yan

AU - Jiang, Xin

AU - Wang, Duolao

AU - Miao, Qi

AU - Jing, Zhi Cheng

PY - 2022/5/17

Y1 - 2022/5/17

N2 - BackgroundThe role of congenital thrombophilia in chronic thromboembolic pulmonary hypertension (CTEPH) remains unresolved.ObjectivesThe purpose of this study was to investigate the prevalence, genetic background, and clinical phenotype of congenital thrombophilia in CTEPH.MethodsIn total, 367 patients with CTEPH from May 2013 to December 2020 were consecutively enrolled in this cross-sectional study in FuWai Hospital and Peking Union Medical College Hospital in China. The primary outcome was the occurrence of congenital thrombophilia diagnosed through tests for congenital anticoagulants activity (including protein C, protein S, and antithrombin III), factor V Leiden and prothrombin G20210A sequence variants. Next-generation sequencing was conducted for patients with congenital thrombophilia. Clinical phenotype was compared between patients with and without thrombophilia.ResultsA total of 36 (9.8%; 95% CI: 6.8%-12.9%) patients were diagnosed as congenital thrombophilia, including 13 protein C deficiency (3.5%; 95% CI: 1.6%-5.4%), 19 protein S deficiency (5.2%; 95% CI: 2.9%-7.5%), and 4 antithrombin III deficiency (1.1%; 95% CI: 0%-2.2%). No factor V Leiden or prothrombin G20210A sequence variants were identified. Genotype for patients with thrombophilia revealed that 10 (76.9%) protein C deficiency patients were PROC sequence variant carriers, 4 (21.1%) protein S deficiency were PROS1 sequence variant carriers, and 2 (50.0%) antithrombin III deficiency were SERPINC1 sequence variant carriers. In the logistic regression model, male sex (OR: 3.24; 95% CI: 1.43-7.31) and proximal lesion in pulmonary arteries (OR: 4.10; 95% CI: 1.91-8.85) had significant differences between the congenital thrombophilia and nonthrombophilia group in CTEPH patients.ConclusionsCongenital thrombophilia was not rare. Male sex and proximal lesion in pulmonary arteries might be the specific clinical phenotype for CTEPH patients with congenital thrombophilia.

AB - BackgroundThe role of congenital thrombophilia in chronic thromboembolic pulmonary hypertension (CTEPH) remains unresolved.ObjectivesThe purpose of this study was to investigate the prevalence, genetic background, and clinical phenotype of congenital thrombophilia in CTEPH.MethodsIn total, 367 patients with CTEPH from May 2013 to December 2020 were consecutively enrolled in this cross-sectional study in FuWai Hospital and Peking Union Medical College Hospital in China. The primary outcome was the occurrence of congenital thrombophilia diagnosed through tests for congenital anticoagulants activity (including protein C, protein S, and antithrombin III), factor V Leiden and prothrombin G20210A sequence variants. Next-generation sequencing was conducted for patients with congenital thrombophilia. Clinical phenotype was compared between patients with and without thrombophilia.ResultsA total of 36 (9.8%; 95% CI: 6.8%-12.9%) patients were diagnosed as congenital thrombophilia, including 13 protein C deficiency (3.5%; 95% CI: 1.6%-5.4%), 19 protein S deficiency (5.2%; 95% CI: 2.9%-7.5%), and 4 antithrombin III deficiency (1.1%; 95% CI: 0%-2.2%). No factor V Leiden or prothrombin G20210A sequence variants were identified. Genotype for patients with thrombophilia revealed that 10 (76.9%) protein C deficiency patients were PROC sequence variant carriers, 4 (21.1%) protein S deficiency were PROS1 sequence variant carriers, and 2 (50.0%) antithrombin III deficiency were SERPINC1 sequence variant carriers. In the logistic regression model, male sex (OR: 3.24; 95% CI: 1.43-7.31) and proximal lesion in pulmonary arteries (OR: 4.10; 95% CI: 1.91-8.85) had significant differences between the congenital thrombophilia and nonthrombophilia group in CTEPH patients.ConclusionsCongenital thrombophilia was not rare. Male sex and proximal lesion in pulmonary arteries might be the specific clinical phenotype for CTEPH patients with congenital thrombophilia.

KW - antithrombin III deficiency

KW - chronic thromboembolic pulmonary hypertension

KW - congenital thrombophilia

KW - genotype

KW - protein C deficiency

KW - protein S deficiency

U2 - 10.1016/j.jacasi.2022.02.010

DO - 10.1016/j.jacasi.2022.02.010

M3 - Article

SN - 2772-3747

VL - 2

SP - 247

EP - 255

JO - JACC: Asia

JF - JACC: Asia

IS - 3

ER -

Prevalence, Genetic Background, and Clinical Phenotype of Congenital Thrombophilia in Chronic Thromboembolic Pulmonary Hypertension

Abstract

Keywords

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