Young platelet millionaires with essential thrombocythemia

Abstract

The platelet count threshold for World Health Organization classification system-compliant diagnosis of essential thrombocythemia (ET) is ≥450 × 10 9 /L. 1 Extreme thrombocytosis (ExT), on the other hand, is arbitrarily defined by platelet count of ≥1000 × 10 9 /L and occurs in approximately 22% of patients with ET, at time of diagnosis. 2 Note, ExT is most frequent in the context of young patients with ET with incidence rates of 44%/29%/29% in patients aged ≤40, 41-60, and > 60 years respectively. 3 The presence of ExT in ET has been shown to confer a lower risk for arterial thrombosis 4 ; additionally, its association with hemorrhage has been linked to aspirin use. 5 Nevertheless, ExT often poses a therapeutic dilemma with low-risk young ET patients in terms of the need for cytoreductive therapy, stemming from an unsubstantiated concern for a heightened thrombotic risk, or to ameliorate bleeding tendency and microvascular symptoms. In light of inadequate published literature on ExT in ET, we compiled this report specifically focusing on young patients. Our main objectives were to (a) characterize the clinical phenotype of "young" platelet millionaires with ET via comparison with their counterparts without ExT and (b) assess long term outlook in terms of thrombosis, myelofibrotic/leukemic transformation and overall survival. Study patients were retrospectively recruited from the Mayo Clinic myeloproliferative neoplasms (MPN) database which is maintained under an institutional review board approved protocol and included 3023 MPN patients evaluated over five decades (1967 through 2017). 2 Of 1070 adult patients with ET; 192 (18%) were aged below 40 years. Major arterial thrombosis included myocardial infarction, angina, cerebrovascular accidents, transient ischemic attack, peripheral arterial thrombosis, aortic thrombosis, mesenteric artery thrombosis, and central retinal thrombosis. Major venous thrombosis included deep venous thrombosis, pulmonary embolism, portal/ splenic/mesenteric/hepatic vein thrombosis, and cerebral sinus thrombosis. Bleeding events that required red cell transfusions were

Polycythemia vera and essential thrombocythemia of intermediate-age: A real-life, multicenter analysis of first-line treatment approach

“…In a study evaluating a young ET group (age 18-39 years), among 192 patients (12% in the high-risk group), as many as 107 (55%) received CTR. 16 Similar results were obtained from the analysis of an entire population of young low-risk ET patients (age 18-59 years), where cytoreduction was started in 170 (51%) of patients. 17 In a recent real-world study focused on young patients with a diagnosis of MPN, a total of 444 patients (median age of diagnosis 20.4 years, range 2-25 years) from multiple European centers were evaluated.…”

“…Findings similar to those presented in this study have been observed for young patients with ET, with 1 study highlighting that cytoreduction is given willingly in patients with ExT1000, despite a comparable distribution of CV risk factors and lower incidence of AT. 16 Recently, Abu-Zeinah et al presented a database analysis of 40,333 MPN patients followed between 2001-2017. The authors confirmed higher mortality in young PV and ET patients in comparison to the healthy population of the same age.…”

Survival expectation after thrombosis and overt-myelofibrosis in essential thrombocythemia and prefibrotic myelofibrosis: a multistate model approach

“…Whether the reduction of vascular complications may impact survival remains to be demonstrated in appropriate prospective studies. Furthermore, we found two additional independent predictors of mortality in thrombosis-mediated transition, namely platelet count >1000 × 10 9 /L (HR = 5.74, 95% CI = 1.79–18.40, p = 0.003), in line with a previous observation [ 13 ], and the incident arterial vs. venous thrombosis (HR = 4.43, 95% CI = 1.04–18.91, p = 0.044).…”

“…Alessandra Carobbio 1 , Alessandro Maria Vannucchi 2 , Elisa Rumi 3,4 , Valerio De Stefano 5,6 , Alessandro Rambaldi 7,8 , Giuseppe Carli 9 , Maria Luigia Randi 10 , Heinz Gisslinger 11 , Francesco Passamonti 12 , Juergen Thiele 13 , Naseema Gangat 14 , Ayalew Tefferi 14 and Tiziano Barbui Hematology and Bone Marrow Transplant Unit, ASST Papa Giovanni XXIII, Bergamo, Italy. 8 Department of Oncology and Hematology, University of Milan, Milan, Italy.…”

Extreme thrombocytosis in low‐risk essential thrombocythemia: Retrospective review of vascular events and treatment strategies

“…The current study complements our recent report on 192 young patients (age <40 years) with ET where ExT was associated with CALR mutation, lower likelihood of presentation with thrombosis and shortened overall and leukemia-free survival. 9 In both the current and the aforementioned study, 9…”