Parameters from global hemostasis assays are not able to consistently predict hypercoagulability events in patients with myeloproliferative neoplasms (MPNs) including primary myelofibrosis, according to a systematic literature review published in Seminars in Thrombosis and Hemostasis

“Further prospective longitudinal studies are needed to validate these biomarker tools so that thrombotic potential could be utilized as a primary endpoint of such studies,” the authors of the review wrote.

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Global hemostasis assays have been proposed as biomarkers to evaluate the thrombotic risk and hypercoagulability among patients with MPNs. 

Here, a team of researchers led by Craig M. Kessler, MD, from the Division of Hematology-Oncology at Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital in Washington DC conducted a systematic review of the literature to explore the association between the results of thrombin generation assays, rotational thromboelastometry, and thromboelastography and thrombotic events as well as treatment strategies in MPNs. 

The team analyzed 32 cross-sectional studies, which included 1608 patients with MPNs including primary myelofibrosis and 1062 controls.

Of these 32 studies, 13 reported arterial or venous thrombosis. The overall thrombosis rate was 13.8%.

Twenty-seven studies used the thrombin generation assay, but there was great heterogeneity in plasma preparation and the trigger reagents used. In spite of this, there was a trend toward higher peaks in patients with MPNs than in control individuals. 

Moreover, the endogenous thrombin potential was higher among patients with essential thrombocythemia, a type of MPN, than controls. 

The researchers also reported an overall trend towards a lower endogenous thrombin potential between patients with polycythemia vera and those with primary myelofibrosis compared to controls. 

When they compared patients with primary myelofibrosis who were Janus kinase 2 (JAK2) positive with those who were JAK2 negative, the researchers observed no differences in endogenous thrombin potential. Similarly, there was no substantial difference in endogenous thrombin potential between patients with primary myelofibrosis who had a prior history of thrombotic events and those who did not or between patients who had been treated with different strategies. 

There were 3 studies that used rotational thromboelastometry and 3 that used thromboelastography. The rotational thromboelastometry studies showed a trend toward reduced clot formation times and greater maximum clot firmness in patients with all types of MPNs compared to controls, whereas the thromboelastography studies generated mixed results.

“We conclude that the ability of parameters from global hemostasis assays to predict for hypercoagulability events in MPN patients is inconsistent and inconclusive,” the researchers wrote.

MPNs include a group of diseases comprising polycythemia vera, essential thrombocythemia, and primary myelofibrosis.

Reference

Tiu A, Chiasakul T, Kessler CM. The pitfalls of global hemostasis assays in myeloproliferative neoplasms and future challenges. Semin Thromb Hemost. Published online April 17, 2023. doi:10.1055/s-0043-57010