Thrombosis History and Relationship With Low Thrombocytosis, Leukocytosis, and Other Characteristics At Diagnosis In 977 Essential Thrombocythemia Patients A Multivariate Analysis Of The Registro Italiano Trombocitemie (RIT)
Authors: Gugliotta Luigi , Iurlo Alessandra , Tieghi Alessia , Gugliotta Gabriele , Candoni Anna , Rumi Elisa , Antonioli Elisabetta , Ricco Alessandra , Lunghi Monica , Scalzulli Rosario Potito , Scortechini Anna Rita , Codeluppi Katia , Martino Bruno , Dragani Alfredo , Patriarca Andrea , Martinelli Vincenzo , Battipaglia Giorgia , Randi Maria Luigia , Cosi Elisabetta , Liberati Anna Marina , Appolloni Viviana , Maschio Nilla , Mastrullo Lucia , Villa Maria Rosaria , Esposito Maria Rosaria , Cantore Nicola , Palmieri Fausto , Langella Maria , Rivellini Flavia , Mazzucconi Maria Gabriella , Santoro Cristina , De Biasi Ercole , Rago Angela , Polverelli Nicola , Spedini Pierangelo , Cacciola Emma , Cacciola Rossella R , Pierri Ivana , Mitsheunig Laura , Salvucci Marzia , Porretto Ferdinando , Piccin Andrea , Santoro Umberto , Gaidano Gianluca , Cimino Giuseppe , Lanza Francesco , Cortelezzi Agostino , Tagariello Giuseppe , Rupoli Serena , Specchia Giorgina , Passamonti Francesco , Vannucchi Alessandro M. , Pane Fabrizio , Vianelli Nicola , Miglio Rossella , Monari Paola 
Published: October 2019

Abstract

Background
In essential thrombocythemia (ET) patients, history of thrombosis and age over 60 y are validated risk factors for occurrence of thrombosis during the follow-up. Leukocytosis, JAK2 V617F mutation, cardiovascular (CV) general risk factors, and male gender are candidate risk factors for thrombosis. The thrombocytosis, a constitutive abnormality in ET, is associated with both thrombotic and hemorrhagic complications.

Aim
To evaluate in a large cohort of ET patients the potential relationship between the thrombosis history and the main clinical and biological characteristics at diagnosis, i.e. before any interference of cytoreductive treatment.

Methods
A cohort of ET patients (PVSG or WHO criteria) of the Registro Italiano Trombocitemie (RIT) was retrospectively analyzed through logistic regression models.

Results
A total of 977 patients, 387 males and 590 females, presented at diagnosis: median age 56 y (43% with age >60 y), median PLT count 783 x 109/L (33% with low thrombocytosis, <700 x 109/L), median WBC count 8.8 x 109/L (29% with leukocytosis, >10 x 109/L), median HCT 42.6% (high HCT: >47% in 24% of the males and >44% in 23% of the females), CV general risk factors in 69% of cases (one of smoking, hypercholesterolemia, hypertriglyceridemia, hypertension, diabetes, obesity, CV disease, familiarity for thrombosis), bone marrow fibrosis grade 0 in 67% of cases, JAK2 V617F mutation in 56% of the 399 tested patients.
The history of thrombosis (arterial in 74% of cases) was reported in 194 (19.9%) patients.
The history of thrombosis in univariate analysis was significantly related to: age >60 y (p 0.001), male gender (p 0.009), CV general risk factors (p 0.002), low thrombocytosis (p 0.000), leukocytosis (p 0.003), high HCT (p 0.004), and JAK2 V617F mutation (p 0.008). No relationship was found with bone marrow fibrosis.
In multivariate analysis a relationship was confirmed between thrombosis history and age >60 y (p 0.023), male gender (0.046), CV general risk factors (0.039), low thrombocytosis (p 0.004), leukocytosis (0.019), and JAK2 V617F mutation (p 0.033).
The rate of thrombosis history in the patients without both low thrombocytosis and leukocytosis (11%, 49/428) resulted significantly lower (p 0.0001) than in the patients with leukocytosis (24%, 54/224), the patients with low thrombocytosis (27%, 71/266), and the patients with both low thrombocytosis and leukocytosis (34%, 20/59).

Conclusion
In this cohort of ET patients the rate of thrombosis history in multivariate analysis is significantly related to various clinical and biological characteristics at diagnosis, including low thrombocytosis (PLT <700 x 109/L), leukocytosis (WBC >10 x 109/L), JAK2 V617F mutation, age >60 y, male gender, and CV general risk factors.

Acknowledgment
this study was partially supported by the GIMEMA Foundation (Promotor of the RIT) and by the AIL Foundation.

Disclosures:
Gugliotta: SHIRE Company: Honoraria, Membership on an entity’s Board of Directors or advisory committees.