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ObjectiveTo further understand the factors that promote thrombosis in essential thrombocythemia （ET） that were not included in IPSET-thrombosis （International Prognostic Score of Thrombosis for ET）. MethodsA systematic evaluation was conducted on 292 studies by retrieving PubMed，Web of Science, and The Cochrane Library. The incidence and relative risk ratio （RR） of thrombosis in ET patients with different risk factors were calculated. The confidence levels for the outcome were analyzed in combination with RR values and recommendation scores (RS) to find the thrombotic risk factors in ET patients. ResultsOut of 9 risk factors that promoted ET thrombosis, there were 4 factors in IPSET-thrombosis, including history of thrombosis （35.0%, RR=3.30, 95% CI : 2.30-4.75）, JAK2V617F positive （21.0%, RR=2.28, 95%CI : 1.14-4.56）, age over 60 years old （ 22.4% , RR=1.95, 95%CI : 1.17-3.23） and cardiovascular risk factors （17.7%, RR =1.90, 95%CI : 1.08-3.35）. The remaining five risk factors, not listed in IPSET-thrombosis, included monoclonal type of ET based on X-chromosome inactivation pattern （XCIP, 30.6%, RR=4.49, 95% CI: 1.58-12.77）, high JAK2V617F burden （33.9%, RR=3.69, 95%CI: 1.70-7.99）, leukocytosis （18.7%, RR=3.05, 95%CI: 1.81-5.13）, MPL mutation （22.1%, RR=2.40, 95%CI: 1.08-5.33） and splenomegaly （25.6%, RR=1.76, 95%CI：1.29-2.40）. ConclusionAmong the risk factors promoting thrombosis in ET patients, five thrombotic risk factors not included in the IPSET-thrombosis have been identified.

Abnormal platelet activation can lead to thrombosis in essential thrombocythemia (ET) and thus impact patient prognosis. Platelet activation-associated proteins are key molecules for platelet activation. However, it is unclear which proteins are most closely associated with the disease's prognosis. To determine which platelet activation-related proteins can be employed as ET patient prognosis predictors, we used label-free quantification (LFQ) and parallel reaction monitoring (PRM) technology and first determined the serum proteomic expression levels and the differential proteins of ET patients. Then, based on the IPSET (International Prognostic Score for ET), the differential protein associated with the prognostic score was found. To investigate potential processes affecting prognosis, the connection of this protein with prognostic markers, such as thrombotic history, age, white blood cell count, coagulation factors, and inflammatory factors, were further examined. The levels of platelet activation-related proteins GPIbα, SELP, PF4, MMP1, and FLNA were significantly higher in ET patients, according to LFQ and PRM analyses (p < 0.01). Based on regression analysis of the IPSET prognostic score, it is suggested that the SELP level was positively correlated with the prognostic score and prognostic risk factor analysis (p < 0.05). Further regression analysis of SELP with coagulation factors showed that antithrombin (AT-III) was negatively correlated with SELP levels (p < 0.05). Further regression analysis of the inflammatory factors with AT-III and SELP revealed that IL-10, IL-12P70, and IL-31 were negatively correlated with AT-III and SELP (p < 0.01). Platelet activation pathway-related proteins are expressed more frequently in ET patients, and serum SELP may be a prognostic marker for these individuals by encouraging leukocyte increase and inflammatory factor expression and causing aberrant coagulation. [ABSTRACT FROM AUTHOR]

Thrombotic events are the most frequent manifestations of essential thrombocythemia (ET). The objective of this study is to determine the incidence of thrombosis at different sites on follow-up in patients with ET. We searched PubMed, Web of Science, and The Cochrane Library databases and calculated the incidence of thrombosis by pooling and analyzing the extracted data using a random-effects model. A total of 70 studies (N = 25,805) were included in the analysis. The total and annual incidences of arterial thrombosis on follow-up were 13.4% and 2.0%, respectively. The total and annual incidences of the different manifestations of arterial thrombosis were as follows: stroke (5.3% and 0.8%), transient ischemic attack (5.1% and 1.2%), myocardial infarction (2.4% and 0.5%), unstable angina (0.9% and 0.2%), and peripheral arterial thrombosis (2.0% and 0.2%), respectively. In contrast, the total and annual incidences of arterial thrombosis in JAK2-positive patients were 18.4% and 2.7%, respectively. The total and annual incidences of arterial thrombosis in JAK2-negative patients were 5.9% and 0.8%, respectively. The total and annual incidences of venous thrombosis were 5.5% and 0.7%, respectively, and the incidences of the different manifestations of venous thrombosis at different sites were as follows: peripheral venous thrombosis (2.9% and 0.5%), superficial venous thrombosis (1.8% and 0.7%), deep venous thrombosis (1.6% and 0.3%), abdominal venous thrombosis (0.8% and 0.1%), pulmonary embolism (0.3% and 0.1%), and cerebral venous thrombosis (0.2% and 0%), respectively. The total and annual incidences of venous thrombosis in JAK2-positive patients were 7.4% and 1.2%, respectively. The total and annual incidences of venous thrombosis in JAK2-negative patients were 1.6% and 0.4%, respectively. The incidence of arterial thrombosis was higher than that of venous thrombosis in patients with ET. Arterial thrombosis manifested with cerebral arterial thrombosis, followed by cardiac thrombosis. Venous thrombosis events were mainly peripheral and superficial venous thrombosis. JAK2-positive patients have a higher incidence of arterial and venous thromboses than JAK2-negative patients, the sequence of thrombsis sites was similar to that of the overall patients. [ABSTRACT FROM AUTHOR]

Thrombosis is a common complication of myeloproliferative neoplasm (MPN), and it is a major cause of disability and death. With the development of next-generation gene-sequencing technology, the relationship between non-driver mutations and thrombotic risk factors has also attracted considerable attention. To analyze the risk factors of thrombosis in patients with essential thrombocythemia (ET) and polycythemia vera (PV), we retrospectively analyzed the clinical data of 125 MPN patients (75 ET and 50 PV) and performed a multivariate analysis of the risk factors of thrombosis using a Cox proportional risk model. Among the 125 patients, 35 (28.0%) had thrombotic events, and the incidence of thrombotic events was 21.3% and 38.0% in ET and PV patients, respectively. In ET patients, the multivariate analysis showed that a TET2 mutation and history of remote thrombosis were independent risk factors for thrombosis in ET patients, with an HR of 4.1 (95% CI: 1.40–12.01; p = 0.01) for TET2 mutation and 6.89 (95% CI: 1.45–32.68; p = 0.015) for a history of remote thrombosis. In PV patients, the multivariate analysis presented the neutrophil-to-lymphocyte ratio (NLR) (HR: 4.77, 95% CI: 1.33–17.16; p = 0.017) and a history of remote thrombosis (HR: 1.67, 95% CI: 1.03–1.32; p = 0.014) as independent risk factors for thrombosis, with no significant change in the risk of thrombosis in patients with TET2 mutations. A further analysis of the clinical characteristics and coagulation occurring in ET patients with a TET2 mutation revealed that the values of age and D-dimer were significantly higher and antithrombin III was significantly lower in TET2-mutated ET patients compared to TET2-unmutated patients. In summary, TET2 mutation may be more valuable in predicting thrombosis in ET patients than in PV patients. ET patients with a TET2 mutation are older and present differences in coagulation compared to TET2-unmutated patients. [ABSTRACT FROM AUTHOR]