Thrombin Generation In Patients with Essential Thrombocythemia Treated with Anagrelide
Authors: Zawilska Krystyna M , Skubiszak Agnieszka , Kurosz Jolanta M , Jaworski Jerzy 
Published: October 2019

Abstract
Abstract 5050

Introduction:
Thrombosis may be serious and life threatening in patients with essential thrombocythemia (ET). Bleeding is usually from the gastrointestinal tract, and is, in most cases, generally associated with a platelet count greater than 1 million/μL. The mechanism by which thrombocythemia produces hemorrhage or thrombosis is not well defined. Several defects have been described, including a decrease in platelet aggregation or hyperaggregation, a decrease in von Willebrand ristocetin cofactor activity and high molecular weight von Willebrand factor multimers. Some reports show patients with an acquired deficiency of antithrombin, protein C, and acquired APC resistance, probably due to a reduction in free protein S levels. More recently the presence of JAK2V617F mutation and baseline leukocyte (WBC) count have been considered as independent predictors of major thrombosis in ET.

Aim of the study:
To assess the thrombin generation by the calibrated automated thrombogram method in plasma from ET patients treated with anagrelide. This assay reflects the net results of the procoagulant and anticoagulant forces operating in plasma. The area under the thrombin generation curve (also known as the endogenous thrombin potential (ETP) is a good overall indicator of prothrombotic and hemorrhagic tendency. It could be hypothezised, that platelet-lowering treatment could diminish haemostasis disturbances in ET.

Material and methods:
The study group consisted of ten ET patients (4 males and 6 females; age range, 24–70 years), diagnosed according to the Polycythemia Vera Study Group criteria. All patients have been treated with anagrelide for mean 4 years (range 1 – 7 years), without antiplatelet drugs. At the time of enrollment their mean platelet number was 344 000/μL (210 000 – 535 000), WBC count 8 600/μL (3 300 – 9 800), and hematocrit 38 (33-47). One patient had a history of splenic vein thrombosis, another had a gastrointestinal bleeding before the start of treatment. Four ET patients (40%) were positive for the JAK2V617F. Ten healthy subjects (4 males and 6 females; age range, 30–70 years) without history of thrombohemorrhagic events, acted as a control group. Thrombin generation (TG) was determined by calibrated automated thrombography (Technothrombin TGA-Technoclone). Thrombin generation curves were described in terms of lag time, peak height, time to peak, slope and ETP. Whole blood thromboelastometry with TEM-ROTEM delta - Pentapharm GmbH has been performed as well.

Results:
Thrombin generation (ETP) in platelet free plasma was significantly increased in patients with ET (2235 ± 376 nM/min) in comparison with controls (1631 ± 257 nM/min; p=0,0082), the TG lag time, peak, time to peak and slope were also abnormal. Patients with ET showed markedly increased values of INTEM coagulation time-CT, clot formation time-CFT and increased maximum clot firmness, when compared to results of the control group (Table). There were no differences in the EXTEM values.

Conclusion:
Our results suggest that patients with essential thrombocythemia, in spite of a long-lasting anagrelide treatment, still exhibit an increased thrombin generation as well as formation of a clot with an increased firmness.

Disclosures:
No relevant conflicts of interest to declare.