Publication Only: Myeloproliferative neoplasms - Biology & translational research
Essential Thrombocythemia (ET) is characterized by hypercoagulability and increased risk of arterial and venous thrombosis. The thromboelastometry profile by ROTEM, a point of care system for assessment of global coagulation in whole blood, has never been investigated in these patients, who have abnormalities in blood cell counts. This approach is attractive in that the test reflects the activity of both soluble and cellular components of hemostasis. Furthermore, the test is rapid, does not require blood sample centrifugation and may be useful in prospective studies of thrombotic risk assessment in ET patients.
To evaluate the global clotting process in ET patients by thromboelastometry with ROTEM and establish whether and to what extent elevated platelet count and mutational status affect the global hemostasis evaluation.
Analysis was performed in 52 ET patients using INTEM and EXTEM reagents, to evaluate the intrinsic and extrinsic pathway, respectively. Maximum clot firmness (MCF, [mm]), which reflects the maximum tensile strength of the thrombus, clotting formation time (CFT [sec]), namely the time that clot takes to increase from 2 mm to 20 mm above baseline, and clotting time (CT [sec]), the time to clot initiation, were recorded. Patient thrombotic risk was classified as, i.e.: very low risk (age≤60 yrs, no thrombosis history, JAK2/MPL−), low risk (age≤60 yrs, no thrombosis history, JAK2/MPL+), intermediate risk (age > 60 yrs, no thrombosis history, JAK2/MPL−), and high risk (thrombosis history or age >60 yrs with JAK2/MPL+).
ROTEM analysis with both EXTEM and INTEM reagents showed that ET patients had a hypercoagulable profile, characterized by significant (p < 0.01) short CFT and high MCF values compared to healthy subjects. None of the ROTEM parameters per se correlated with classes of thrombotic risk. However, a strong correlation (p < 0.01) was present between platelet count and CFT or MCF (both with EXTEM and INTEM reagents). Therefore, the parameters were adjusted for platelet count. After adjustment, corrected CFT (cCFT) significantly correlated with the patient thrombotic risk category (p < 0.05). Furthermore, corrected MCF (cMCF) was significantly increased in JAK2V617F+/MPL+ compared to CalR+ subjects (p < 0.01).
This study confirms the occurrence of a hypercoagulable state in ET patients and shows that ROTEM parameters are significantly influenced by platelet count. Correction of CFT and MCF values allows a better understanding of global coagulation of ET patients and may potentially better reflect the thrombotic risk in these patients.