Selective testing for calreticulin gene mutations in patients with splanchnic vein thrombosis: A prospective cohort study.
J Hepatol
; 67(3): 501-507, 2017 09.
Article
em En
| MEDLINE
| ID: mdl-28483676
ABSTRACT
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, JAK2V617F 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 JAK2V617F, 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 >200×109/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 >200×109/L, and no JAK2V617F. This strategy avoids 96% of unnecessary CALR mutations testing. Laysummary:
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 >200×109/L, and no JAK2V617F. This strategy avoids 96% of unnecessary CALR mutations testing.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trombose Venosa
/
Calreticulina
/
Mutação
Tipo de estudo:
Etiology_studies
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Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article