Mutations of calreticulin (CALR) are associated with lower risk for thrombotic events in patients with essential thrombocythemia (ET). These findings, from a multicenter retrospective study, were published in the European Journal of Haematology.

In patients with ET, higher levels of platelets, lower hemoglobin levels, and fewer thrombotic complications, with a two-fold reduced risk of thrombosis, are characteristics of a driver mutation in the CALR gene. In this study, researchers sought to determine the impact of CALR mutation type on thrombotic risk.

Medical records from 983 patients treated at 11 hospitals in Spain and 4 in Poland since 2000 were assessed for major thrombotic events 2 years prior to and a median 7.6 years after an ET diagnosis and for CALR and Janus kinase 2 (JAK2) V617F mutations.

Continue Reading

Patients were aged median 54 years, 36.2% were men, 64.8% had JAK2V617F mutation, and 27.6% had CALR mutation (53.3% type 1; 36.4% type 2; 10.3% other).

Among mutation-carrying patients (n=909), 15.8% had 1 or more thrombotic events 2 years prior to ET diagnosis (5.9%) or during the follow-up (10.5%). Thrombotic events were elevated among JAK2V617F carriers (incidence rate [IR], 29.2; 95% CI, 24.9-34.0 per 1000 person-years [py]) compared with CALR mutation carriers (IR, 13.0; 95% CI, 9.5-17.5 per 1000 py; P =.0001).

Compared with CALR-type 1, risk for first thrombotic events at 10 years was higher among JAK2V617F carriers (relative risk [RR], 2.65; 95% CI, 1.19-5.87; P =.016). Thrombosis-free survival at 10 years was 77.5% among JAK2V617F, 84.4% among CALR-type 1, and 91.6% among CALR-type 2 carriers (P =.002).

CALR-type 2 mutations were associated with significantly lower thrombotic event risk (odds ratio [OR], 0.45; 95% CI, 0.19-0.90; P =.04).

This study was limited by missing data on anti-aggregation or anticoagulation therapies, which may have altered thrombotic event risk.

These data suggested patients with CALR mutations, especially type 2, were at decreased risk for thrombotic events.


Pérez Encinas MM, Sobas M, Gómez-Casares MT, et al. The risk of thrombosis in essential thrombocythemia is associated with the type of CALR mutation: a multicentre collaborative study. Eur J Haematol. 2020;00:1-9. doi:10.1111/ejh.13561