Abstract Number: PB1139
Meeting: ISTH 2021 Congress
Theme: Venous Thromboembolism » Genetic Risk Factors of Thrombosis
Background: Idiopathic pulmonary embolism (iPE) is a severe and frequent condition accounting for half of pulmonary embolisms. Characterization of new risk factors is mandatory in order to identify patients that would benefit from a long-term treatment.
Aims: To evaluate if idiopathic pulmonary embolism is associated with the presence of clonal hematopoiesis of indetermined significance (CHIP).
Methods: We conducted a pilot retrospective monocentric observational study. Patients with iPE between 18 to 65 years old, after a first documented episode of PE were included. PE was considered non provoked, when no transient nor persistant risk factor was present and when extensive thrombophilia testing was negative. Patients with documented atherosclerosis, previous VTE, familial history of VTE, presence of cytopenias, presence of any driven mutation of myeloproliferative neoplasms were excluded. CHIP proportion in iPE patients were analyzed using next generation sequencing of the coding sequence of a custom panel composed by DNMT3A, ASXL1, SF3B1, TET2 and TP 53. Presence of CHIP was considered with a variation allelic fraction higher than 1%.
Results: Upon 61 patients with iPE consecutively included, a total of 19 somatic mutations were found in 12 patients (20 %). 15 mutations were found in DNMT3A gene, 3 in ASXL1 and one in TET2. No mutation in SF3B1 nor TP53 genes were identified. There was no difference in terms of age, PE location, DVT presence and risk stratification in CHIP carriers and non carriers. Median follow-up was 2 years.
|
CHIP carriers |
CHIP non carriers |
p |
Median age, IQR, y |
59.5 [56.25 – 65] |
54 [46 – 58] |
0.08 |
Sex ratio, % |
16 |
12 |
0.64 |
PE location (proximal), % |
33 |
45 |
0.54 |
DVT proportion, % |
42 |
47 |
0.66 |
Median hematocrit, IQR, % |
0.42 [39.5 – 43.5] |
0.43 [38 – 44.3] |
0.61 |
Median platelet numeration, IQR, 109/L |
214 [175 – 246] |
207 [176 – 298] |
0.55 |
Median WBC, IQR, 109/L |
6.5 [5.7 – 8] |
5 [3.5 – 7] |
0.46 |
Conclusions: We report, for the first time, an association between idiopathic pulmonary embolism and CHIP, that may become a new risk factor of VTE. CHIP-induced inflammation of vascular endothelium, well documented for TET2 mutation, leading to atherosclerosis and potentially clinical iPE, may represent the missing link between arterial and venous thrombosis. These results need to be confirmed in a prospective study including.
To cite this abstract in AMA style:
Soudet S, Jedraszak G, Evrard O, Garcon L, Marolleau JP, MAS. Is Hematopoietic Clonality of Indetermined Potential a Risk Factor for Pulmonary Embolism? [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/is-hematopoietic-clonality-of-indetermined-potential-a-risk-factor-for-pulmonary-embolism/. Accessed March 21, 2024.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/is-hematopoietic-clonality-of-indetermined-potential-a-risk-factor-for-pulmonary-embolism/