Selective testing for calreticulin gene mutations in patients with splanchnic vein thrombosis: A prospective cohort study
| Autor: | Emmanuelle de Raucourt, Johanne Poisson, Nicole Casadevall, Pierre-Emmanuel Rautou, Francisco Cervantes, Kamal Zekrini, Fanny Turon, Odile Goria, Dominique-Charles Valla, Christophe Marzac, Florence Lorre, Juan Carlos García-Pagán, Christophe Bureau, Bruno Cassinat, Annalisa Andreoli, Dolors Colomer, François Durand, Jean-Jacques Kiladjian, Aurélie Plessier |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male medicine.medical_specialty Gastroenterology 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases Internal medicine medicine Humans Prospective Studies Prospective cohort study Myeloproliferative neoplasm Genetic testing Venous Thrombosis Myeloproliferative Disorders Hepatology biology medicine.diagnostic_test business.industry Janus Kinase 2 Middle Aged medicine.disease Portal vein thrombosis Splanchnic vein thrombosis 030220 oncology & carcinogenesis Mutation Immunology Cohort biology.protein Budd–Chiari syndrome Female 030211 gastroenterology & hepatology Calreticulin business |
| Zdroj: | Journal of Hepatology. 67:501-507 |
| ISSN: | 0168-8278 |
| DOI: | 10.1016/j.jhep.2017.04.021 |
| Popis: | Background and Aims Myeloproliferative neoplasms (MPN) are the leading cause of splanchnic vein thrombosis (SVT). Janus kinase 2 gene ( JAK2 ) V617F mutations are found in 80 to 90% of patients with SVT and MPN. Mutations of the calreticulin ( CALR ) gene have also been reported. However, as their prevalence ranges from 0 to 2%, the utility of routine testing is questionable. This study aimed to identify a group of patients with SVT at high risk of harboring CALR mutations and thus requiring this genetic testing. Methods CALR , JAK2 V617F and thrombopoietin receptor gene ( MPL ) mutations were analysed in a test cohort that included 312 patients with SVT. Criteria to identify patients at high risk of CALR mutations in this test cohort was used and evaluated in a validation cohort that included 209 patients with SVT. Results In the test cohort, 59 patients had JAK2 V617F , five had CALR and none had MPL mutations. Patients with CALR mutations had higher spleen height and platelet count than patients without these mutations. All patients with CALR mutations had a spleen height ⩾16cm and platelet count >200×10 9 /L. These criteria had a positive predictive value of 56% (5/9) and a negative predictive value of 100% (0/233) for the identification of CALR mutations. In the validation cohort, these criteria had a positive predictive value of 33% (2/6) and a negative predictive value of 99% (1/96). Conclusion CALR mutations should be tested in patients with SVT, a spleen height ⩾16cm, platelet count >200×10 9 /L, and no JAK2 V617F . This strategy avoids 96% of unnecessary CALR mutations testing. Lay summary: Mutations of the CALR gene are detected in 0 to 2% of patients with SVT, thus the utility of systematic CALR mutation testing to diagnose MPN is questionable. This study demonstrates that CALR mutations testing can be restricted to patients with SVT, a spleen height ⩾16cm, a platelet count >200×10 9 /L, and no JAK2 V617F . This strategy avoids 96% of unnecessary CALR mutations testing. |
| Databáze: | OpenAIRE |
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