CALR mutation analysis is not indicated in patients with splanchnic vein thrombosis without evidence of a myeloproliferative neoplasm: a micro-review

Stephen E. Langabeer

St. James’s Hospital, Dublin, Ireland

The recent discovery of exon 9 insertion and/or deletion mutations of the CALR gene in up to 80% of JAK2- and MPL-unmutated essential thrombocythemia and primary myelofibrosis patients compels the incorporation of CALR mutational analysis into the molecular diagnostic algorithm for these myeloproliferative neoplasms (MPN). MPN are a major cause of splanchnic vein thrombosis (SVT) which encompasses Budd-Chiari syndrome, portal and mesenteric vein thrombosis. Up to 40% of SVT patients are diagnosed with an overt or latent MPN [1]. While the MPN-associated JAK2 V617F mutation is consistently reported in cohorts of SVT patients, several studies have investigated the role of CALR mutation analysis for MPN diagnosis in the presence of SVT with some debate existing [2-10]. Here, all reports published to date are summarized (Table 1). Briefly, of 944 patients studied only eight (0.8%) had evidence of a CALR mutation and of whom seven already had a previous diagnosis of an MPN.


Table 1 Summary of studies investigating CALR mutation status in splanchnic vein thrombosis

MPN patients with CALR mutations have a significantly lower overall risk of thrombosis than their counterparts harboring the JAK2 V617F and this is clearly the case with respect to SVT. While CALR mutated MPN patients may develop SVT, summarizing those published studies to date, routine investigation for these mutations appears not to be indicated in the diagnostic algorithm for SVT where no clinical or hematological features of an MPN are present.


1. De Stefano V, Qi X, Betti S, Rossi E. Splanchnic vein thrombosis and myeloproliferative neoplasms: molecular-driven diagnosis and long-term treatment. Thromb Haemost 2016; 115:240-249.

2. Turon F, Cervantes F, Colomer D, Baiges A, Hernández-Gea V, Garcia-Pagán JC. Role of calreticulin mutations in the aetiological diagnosis of splanchnic vein thrombosis. Hepatology 2015; 62:72-74.

3. Haslam K, Langabeer SE. Incidence of CALR mutations in patients with splanchnic vein thrombosis. Br J Haematol 2015; 168:459-460.

4. Iurlo A, Cattaneo D, Gianelli U, Fermo E, Augello C, Cortelezzi A. Molecular analyses in the diagnosis of myeloproliferative neoplasm-related splanchnic vein thrombosis. Ann Hematol 2015; 94:881-882.

5. Roques M, Park JH, Minello A, Bastie JN, Girodon F. Detection of CALR mutation in the diagnosis of splanchnic vein thrombosis. Br J Haematol 2015; 169:601-603.

6. Castro N, Rapado I, Ayala R, Martinez-Lopez J. CALR mutations should not be studied in splanchnic vein thrombosis. Br J Haematol 2015; 170:588-589.

7. Plompen EP, Valk PJ, Chu I, et al. Somatic calreticulin mutations in patients with Budd-Chiari syndrome and portal vein thrombosis. Haematologica 2015; 100:e226-e228.

8. Colaizzo D, Amitrano L, Guardascione MA, et al. Clinical utility of screening for CALR exon 9 mutations in patients with splanchnic venous thrombosis. Thromb Haemost 2015; 113:1381-1382.

9. Sekhar M, Patch D, Austen B, Howard J, Hart S. Calreticulin mutations and their importance in splanchnic vein thrombosis. Br J Haematol 2015 2016; 174:158-160.

10. Zhang P, Ma H, Min Q, Zu M, Lu Z. CALR mutations in Chinese Budd-Chiari patients. Eur J Gastroenterol Hepatol 2016; 28:361-362.

Conflict of Interest: None