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CC BY 4.0 · TH Open 2021; 05(03): e338-e342
DOI: 10.1055/s-0041-1733856
Original Article

Is Hematopoietic Clonality of Indetermined Potential a Risk Factor for Pulmonary Embolism?

S. Soudet    *
1   Department of Vascular Medicine, CHU Amiens Picardie, Amiens, France
2   EA 7516 CHIMERE, Université Picardie Jules Verne, Amiens, France
,
G. Jedraszak‡   *
3   Department of Genetic, CHU Amiens Picardie, Amiens, France
4   EA 4666 HEMATIM, Université Picardie Jules Verne, Amiens, France
,
O. Evrard
3   Department of Genetic, CHU Amiens Picardie, Amiens, France
4   EA 4666 HEMATIM, Université Picardie Jules Verne, Amiens, France
,
J.P. Marolleau
3   Department of Genetic, CHU Amiens Picardie, Amiens, France
4   EA 4666 HEMATIM, Université Picardie Jules Verne, Amiens, France
,
L. Garcon
3   Department of Genetic, CHU Amiens Picardie, Amiens, France
4   EA 4666 HEMATIM, Université Picardie Jules Verne, Amiens, France
,
M.A. Sevestre Pietri
1   Department of Vascular Medicine, CHU Amiens Picardie, Amiens, France
2   EA 7516 CHIMERE, Université Picardie Jules Verne, Amiens, France
› Author Affiliations Funding This research was supported by grants from: The French Society of Vascular Medicine (SFMV) and The Groupement de Recherche Inter-Régional en Recheche Clinique Nord Ouest, France.
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Abstract

Background Unprovoked pulmonary embolism (uPE) is a severe and frequent condition. Identification of new risk factors is mandatory to identify patients that would benefit from a long-term treatment. Clonal hematopoiesis of indeterminate potential (CHIP) is defined by the acquisition of somatic mutations that drive clonal expansion in the absence of cytopenia. Its prevalence is estimated of 5% in the population above 65 years. Since inflammation and endothelial dysfunction may share a pathophysiological pathway(1), we hypothesized that CHIP, may be a risk factor for uPE.

Methods We conducted a pilot retrospective observational study. Patients with iPE between 18 to 65 years old were included. PE was considered as unprovoked, when no transient nor persistant risk factor was present and when thrombophilia testing was negative. We excluded documented atherosclerosis, personal or familial history of VTE and presence of cytopenias. CHIP proportion in uPE patients were analyzed using next generation sequencing of the coding sequence of a custom panel composed by DNMT3A, ASXL1, SF3B1, TET2 and TP 53.

Results Upon 61 patients with uPE consecutively included, a total of 19 somatic mutations were found in 12 patients (20%) IC95% [10 - 20]. 15 mutations were found in DNMT3A gene, 3 in ASXL1 and one in TET2. There was no diference in terms of age, PE location, DVT presence and risk stratification in CHIP carriers and non carriers.

Conclusion We report for the first time, the presence of high rates of CHIP in patients presenting with uPE. Thus, CHIP may be a new risk factor for VTE. These results need to be confirmed in an ongoing prospective case-control study including more patients and using a more diverse gene panel to better determine CHIP incidence in uPE.

Keywords

gene mutations - pulmonary embolism - venous thrombosis

Disclosures

None.


Contributions

SS contribute to the conception of the research and wrote the manuscript.


SS, GJ and EO performed genetic analyses.


LG, JPM and MAS contributed to the conception of the research and revised the manuscript.


* Equally contributors.




Publication History

Received: 11 February 2021

Accepted: 01 July 2021

Article published online:
17 August 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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