Increased platelet and leukocyte activation as contributing mechanisms for thrombosis in essential thrombocythemia and correlation with the JAK2 mutational status.
OBJECTIVE
The mechanisms accounting for the increased risk of thrombosis in patients with essential thrombocythemia (ET) are not well known. The aim of the present study was to ascertain the role of platelet and leukocyte activation in the thrombosis of ET.


METHODS
The activation status of platelets and leukocytes was assessed by flow cytometry studies in 49 patients with ET (22 with previous thrombosis and 27 without a history of thrombosis) and in a group of age- and sex-matched healthy individuals. The assessment included platelet P-selectin expression (measured both at baseline and after stimulation with ADP, thrombin, arachidonic acid (AA), and collagen), platelet-neutrophil and platelet-monocyte complexes, determination of CD11b in the neutrophils and monocytes, and expression of tissue factor in the monocytes (mTF). The JAK2 V617F mutation was studied and correlated with platelet and leukocyte activation.


RESULTS
As compared with controls, ET patients had significantly higher values of baseline P-selectin and thrombin- and AA-induced platelet P-selectin expression, as well as higher platelet-neutrophil and platelet-monocyte complexes, neutrophil CD11b expression and baseline mTF expression. Platelet P-selectin, monocyte CD11b, and lipopolysaccharide-induced mTF expression was significantly higher in ET patients with a history of thrombosis than in patients without thrombosis. Patients with the JAK2 V617F mutation or thrombosis showed higher baseline and AA-induced platelet P-selectin expression than did those without thrombosis.


CONCLUSIONS
These results would support a role for platelet and monocyte activation in the thrombosis of ET. In these patients, the presence of the JAK2 V617F mutation is associated with higher platelet activation.
Arellano-Rodrigo
Eduardo
E
Hematology Department, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain.
Alvarez-Larrán
Alberto
A
Reverter
Juan Carlos
JC
Villamor
Neus
N
Colomer
Dolors
D
Cervantes
Francisco
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D053614:Janus Kinase 2; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D015539:Platelet Activation / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000150:complications*; D013927:Thrombosis / Q000209:etiology*
D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2