scholarly journals Deciphering the individual contribution of absolute neutrophil and monocyte counts to thrombosis risk in polycythemia vera and essential thrombocythemia

2021 ◽  
Author(s):  
Faiqa Farrukh ◽  
Paola Guglielmelli ◽  
Giuseppe G. Loscocco ◽  
Animesh Pardanani ◽  
Curtis A. Hanson ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Individual Contribution ◽  
Thrombosis Risk ◽  
The Individual

scholarly journals Thrombotic, inflammatory, and HIF-regulated genes and thrombosis risk in polycythemia vera and essential thrombocythemia

2020 ◽  
Vol 4 (6) ◽  
pp. 1115-1130 ◽  
Author(s):  
Radhika Gangaraju ◽  
Jihyun Song ◽  
Soo Jin Kim ◽  
Tsewang Tashi ◽  
Brandi N. Reeves ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Quantitative Polymerase Chain Reaction ◽  
Hypoxia Inducible Factor ◽  
Chain Reaction ◽  
Thrombosis Risk ◽  
Inflammatory State ◽  
History Of ◽  
Gene Transcripts ◽  
Polymerase Chain

Abstract Thrombosis is a major cause of morbidity and mortality in polycythemia vera (PV) and essential thrombocythemia (ET). The pathophysiology of thrombosis in these disorders remains unclear, and we hypothesized that upregulation of thrombotic, inflammatory, and hypoxia-inducible factor (HIF)–regulated genes may play a role in it. We performed unbiased RNA sequencing in granulocytes and platelets of PV patients and found differential expression of several thrombotic, inflammatory, and HIF-regulated genes. The expression of many of these genes positively correlated with JAK2 expression and JAK2V617F allelic burden. We then validated these findings by quantitative polymerase chain reaction analyses of selected gene transcripts in a larger number of PV and ET granulocytes and platelets (58 patients) and in 28 controls, and we compared these findings in patients with and without thrombosis. The study included 29 females and 29 males; of these, 28 had a history of thrombosis. We found that transcripts of several selected genes were upregulated in patients with PV or ET compared with controls. In granulocytes, the expression levels of F3, SELP, VEGFA, and SLC2A1 were significantly higher in patients with a history of thrombosis compared with those who did not have thrombosis. Patients with a history of thrombosis have significantly higher expression of IL1RAP (P < .05) in platelets compared with those without thrombosis. Our study confirms the presence of a thrombo-inflammatory state and augmented HIF activity in PV and ET and its role in thrombosis. These data may provide the background for targeted therapies in PV and ET.

Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera or essential thrombocythemia

Blood ◽  
2007 ◽  
Vol 110 (3) ◽  
pp. 840-846 ◽  
Author(s):  
Alessandro M. Vannucchi ◽  
Elisabetta Antonioli ◽  
Paola Guglielmelli ◽  
Alessandro Rambaldi ◽  
Giovanni Barosi ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Cardiovascular Events ◽  
Leukocyte Count ◽  
Wild Type ◽  
Major Cardiovascular Events ◽  
Thrombosis Risk ◽  
Secondary Myelofibrosis ◽  
To Receive ◽  
Retrospective Multicenter Study

Abstract JAK2 617V>F mutation occurs in a homozygous state in 25% to 30% of patients with polycythemia vera (PV) and 2% to 4% with essential thrombocythemia (ET). Whether homozygosity associates with distinct clinical phenotypes is still under debate. This retrospective multicenter study considered 118 JAK2 617V>F homozygous patients (104 PV, 14 ET) whose clinical characteristics were compared with those of 587 heterozygous and 257 wild-type patients. Irrespective of their clinical diagnosis, homozygous patients were older, displayed a higher leukocyte count and hematocrit value at diagnosis, and presented larger spleen volume. Aquagenic pruritus was significantly more common among homozygous PV patients. JAK2 617V>F homozygosity associated with more frequent evolution into secondary myelofibrosis in both PV and ET. After adjustment for sex, age, leukocyte count, and previous thrombosis in a multivariate analysis, homozygous ET patients displayed a significantly higher risk of cardiovascular events (hazard ratio [HR] 3.97, 95% confidence interval [CI] 1.34–11.7; P = .013) than wild-type (HR = 1.0) or heterozygous patients (HR = 1.49). No significant association of JAK2 617V>F homozygosity with thrombosis risk was observed in PV. Finally, JAK2 617V>F homozygous patients were more likely to receive chemotherapy for control of disease. We conclude that JAK2 617V>F homozygosity identifies PV or ET patients with a more symptomatic myeloproliferative disorder and is associated with a higher risk of major cardiovascular events in patients with ET.

Platelet activation and inhibition in polycythemia vera and essential thrombocythemia

Blood ◽  
2013 ◽  
Vol 121 (10) ◽  
pp. 1701-1711 ◽  
Author(s):  
Carlo Patrono ◽  
Bianca Rocca ◽  
Valerio De Stefano
Keyword(s):  
Polycythemia Vera ◽  
Antiplatelet Therapy ◽  
Platelet Activation ◽  
Essential Thrombocythemia ◽  
Low Dose ◽  
Treatment Guidelines ◽  
Bleeding Complications ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
The Individual

Abstract Persistently enhanced platelet activation has been characterized in polycythemia vera (PV) and essential thrombocythemia (ET) and shown to contribute to a higher risk of both arterial and venous thrombotic complications. The incidence of major bleeding complications is also somewhat higher in PV and ET than in the general population. Although its efficacy and safety was assessed in just 1 relatively small trial in PV, low-dose aspirin is currently recommended in practically all PV and ET patients. Although for most patients with a thrombosis history the benefit/risk profile of antiplatelet therapy is likely to be favorable, in those with no such history this balance will depend critically on the level of thrombotic and hemorrhagic risks of the individual patient. Recent evidence for a chemopreventive effect of low-dose aspirin may tilt the balance of benefits and harm in favor of using aspirin more broadly, but the potential for additional benefits needs regulatory scrutiny and novel treatment guidelines. A clear pharmacodynamic rationale and analytical tools are available for a personalized approach to antiplatelet therapy in ET, and an improved regimen of low-dose aspirin therapy should be tested in a properly sized randomized trial.

Use of pegylated interferon in young patients with polycythemia vera and essential thrombocythemia

2020 ◽  
Author(s):  
Nicole Kucine ◽  
Shayla Bergmann ◽  
Spencer Krichevsky ◽  
Devin Jones ◽  
Michael Rytting ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Young Patients ◽  
Pegylated Interferon

scholarly journals Lower response to BNT162b2 vaccine in patients with myelofibrosis compared to polycythemia vera and essential thrombocythemia

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Fulvia Pimpinelli ◽  
Francesco Marchesi ◽  
Giulia Piaggio ◽  
Diana Giannarelli ◽  
Elena Papa ◽  
...  
Keyword(s):  
Prospective Study ◽  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Active Treatment ◽  
Myeloproliferative Neoplasm ◽  
Large Prospective Study ◽  
Lower Response ◽  
Ongoing Treatment ◽  
Vaccine Immunogenicity

AbstractIn a population of 42 Philadelphia negative myeloproliferative neoplasm patients, all on systemic active treatment, the likelihood of responding to anti-SARS-CoV-2 BNT162b2 vaccine at 2 weeks after the second dose was significantly lower in the ten patients with myelofibrosis compared to the 32 with essential thrombocythemia (n = 17) and polycythemia vera (n = 15) grouped together, both in terms of neutralizing anti-SARS-CoV-2 IgG titers and seroprotection rates (32.47 AU/mL vs 217.97 AU/mL, p = 0.003 and 60% vs 93.8%, p = 0.021, respectively). Ruxolitinib, which was the ongoing treatment in five patients with myelofibrosis and three with polycythemia vera, may be implicated in reducing vaccine immunogenicity (p = 0.076), though large prospective study is needed to address this issue.

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