Evaluation of thrombin generation in classical Philadelphianegative myeloproliferative neoplasms / Evaluarea generării trombinei în neoplasmele mieloproliferative Philadelphia- negative

Introduction: Patients with Philadelphia-negative chronic myeloproliferative neoplasms (Ph-MPN), polycytemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF), are prone to develop thrombotic events. We aimed to investigate the coagulation status in their plasma using thrombin generation assay (TGA), a functional global assay, on Ceveron® Alpha.

Materials and methods: The samples were collected from 89 consecutive Ph-negative MPN patients and from 78 controls into K2EDTA and CTAD tubes for blood cell counts, TGA and coagulation screening tests. Thrombin generation was analysed in platelet-poor plasma using Technothrombin® TGA assay kit.

Results: We found a significantly increased peak thrombin generation (p=0.049) and velocity index (VI) (p=0.012) in patients in comparison with controls, especially in ET patients, and a significantly higher values for peak thrombin (p=0.043) and VI (p=0.042) in patients receiving anagrelide in comparison with those treated with hydroxyurea. We also noticed an inverse correlation between the length of cytoreductive therapy and TGA parameters, (peak thrombin R=-0.25, p=0.018, AUC R=-0.257, p=0.015, and VI R=-0.21, p=0.048).

Conclusion: Our results suggest that Ph-MPN patients, and especially those with ET, are predisposed to thrombotic events due to their higher peak thrombin and VI values and their risk may decreases as treatment is longer. Patients treated with hydroxyurea generate less thrombin and could be less prone to develop thrombotic events in comparison with those treated with anagrelide.