The underappreciated risk of thrombosis and bleeding in patients with myelofibrosis: a review

Abstract

Bleeding and thrombosis are long recognized complications of myelofibrosis (MF) and contribute significantly to its morbidity and mortality. However, so far, few studies have evaluated the frequency of these events, their characteristics, and their prognostic impact. Based on these studies, thrombotic events in MF are about as common as in essential thrombocytemia (ET) but less common than in polycythemia vera (PV), while bleeding events are relatively more common in MF than in ET or PV. The emergence of the concept of prefibrotic primary MF (PMF), which is associated with a higher frequency of thrombohemorrhagic complications than ET, and the growing evidence that prefibrotic PMF may also have a different thrombotic and bleeding risk profiles than fibrotic (overt) PMF, have emphasized the need for a reappraisal of the risk of thrombosis and hemorrhage in patients with MF. In this review, we discuss the frequency of thrombosis and bleeding in patients with MF, including prefibrotic PMF and their established and potential risk factors.

Association between myelofibrosis and thromboembolism: A population‐based retrospective cohort study

“…Moreover, we were able to examine a large number of potential thrombosis risk factors, whereas most of the previous studies had evaluated only a limited number of variables that included demographic variables, blood test, and cardiovascular risk factors. 4 Yet, this study has some limitations; first, we have not assessed the association with JAK2 mutation, because data were missing in a large number of patients. Second, despite the adjustment for propensity score, some residual confounding might still exist.…”

“…In addition, in this study we have a concurrent comparative control group with individual detailed data on outcome and other covariates, hence allowing us to control for confounders and perform an internally valid comparison within the same cohort, whereas most of the previous studies included only patients with myelofibrosis without a comparative group or used historic data, with adjustment confined to age. Moreover, we were able to examine a large number of potential thrombosis risk factors, whereas most of the previous studies had evaluated only a limited number of variables that included demographic variables, blood test, and cardiovascular risk factors . Yet, this study has some limitations; first, we have not assessed the association with JAK2 mutation, because data were missing in a large number of patients.…”

“…However, the evidence is scarce with respect to PMF and remains incompletely understood, stemming at least in part from the rarity of PMF in comparison to PV and ET. In addition, because of the worse outcome of PMF compared to other MPNs, the focus was on major determinants of mortality including malnutrition, cytopenias, infections, and leukemic transformation …”

“…In addition, because of the worse outcome of PMF compared to other MPNs, the focus was on major determinants of mortality including malnutrition, cytopenias, infections, and leukemic transformation. 4 Only a few studies have specifically addressed the issue of thrombosis in patients with PMF. [5][6][7][8] In addition, most often these studies focused on the identification of risk factors for thromboembolism, and the characteristics and distribution of thromboembolic events, and in most cases have not made a distinction between venous thrombosis and arterial thrombosis.…”

Ruxolitinib in the treatment of patients with myelofibrosis — questions and answers

“…This affects 10-30% of patients before and 10-20% after MPN diagnosis [34]. Thromboembolic disease is most common in patients with PV and less common in patients with essential thrombocytopaenia (ET) and MF [35]. Risk factors associated with an increased risk of venous and arterial embolisms are: prior history of thromboembolic disease, presence of JAK2 V617F mutation, and leukocytosis over 15 G/l [36].…”