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Test your knowledge! Take our quick quiz before and after you read this article to find out if you improved your knowledge. Results help us to improve content and continually provide open-access education.
Question 1 of 1
Patients with calreticulin (CALR) and Janus kinase 2 (JAK2) mutations have been shown to have different risks of developing thrombosis. Which of the following statements is true about mutation profile and thrombotic risk?
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Thrombosis is one of the main complications experienced by patients diagnosed with essential thrombocythemia (ET) and confers significant morbidity and mortality.1 While it is well known that the presence of the Janus kinase 2 (JAK2)V617F mutation is an important risk factor for thrombosis, there is increasing evidence to suggest that other mutations, especially those involving calreticulin (CALR), may also increase thrombotic risk.1
As JAK2V617F and CALR mutations represent two distinct subtypes of ET, Neupane et al.1 performed a systematic review and meta-analysis in American Journal of Hematology, comparing the cumulative thrombotic risk between CALR1-, CALR2-, and JAK2V617F-mutated ET. Here, we summarize the key results.
For more information on the risk of thromboembolic complications in myeloproliferative neoplasms (MPN), check out this article and discussion from the MPN Hub Steering Committee published on the MPN Hub.
Figure 1. Pooled odds ratios for thrombotic risk across all selected studies*
*Adapted from Neupane, et al.1
After sensitivity analysis and the removal of studies with medium and high bias risk, the pooled odds ratios of thrombotic risk across the remaining eight studies are shown in Figure 2.
Figure 2. Pooled odds ratios of thrombotic risk across eight studies post sensitivity analysis*
*Adapted from Neupane, et al.1
Subgroup analysis of the site of thrombosis did not reveal any statistically significant results; however, there was lower venous thrombotic risk in patients with a CALR2 mutation vs a JAK2 mutation.
Results from this meta-analysis show that patients with either a CALR1 or CALR2 mutation have a lower thrombotic risk compared with patients with a JAK2 mutation and patients with a CALR1 mutation have a higher risk of thrombosis vs patients with a CALR2 mutation. The pathophysiology underlying this difference remains unknown; however, it has been suggested that CALR2 reduces activation of the thrombopoietin receptor and adenosine diphosphate-induced platelet activation due to its lower net positive charge.
Limitations of this analysis include variations in population sizes, study designs, and follow-up periods. While further investigation is needed, the analysis highlights the potential and need for individual management strategies based on specific mutational profiles.
References
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