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The major risks in essential thrombocythemia are thrombosis and hemorrhage. In this large, randomized trial, the patients given anagrelide plus aspirin had higher rates of arterial thrombosis and serious hemorrhage, whereas the hydroxyurea group had a higher rate of venous thromboembolism. The rate of transformation to myelofibrosis was higher in the anagrelide group. In this trial, patients given anagrelide plus aspirin had higher rates of arterial thrombosis and serious hemorrhage, whereas the hydroxyurea group had a higher rate of venous thromboembolism. The principal feature of essential thrombocythemia, a clonal hematologic stem-cell disorder, 1 – 4 is thrombosis, with arterial events being more common than venous events. Hemorrhage also occurs, particularly if the platelet count is very high. In the long term, some cases transform to myelofibrosis, myelodysplasia, or acute myeloid leukemia. Factors that increase the risk of thrombosis are an age of more than 60 years, prior thrombosis, and, to a lesser extent, cardiovascular risk factors. 5 – 7 The importance of the platelet count as a risk factor is unclear, but a reduction in platelet count reduces the frequency of thrombosis, and aspirin relieves . . .

Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms with variable risk of evolution into post-PV and post-ET myelofibrosis, from now on referred to as secondary myelofibrosis (SMF). No specific tools have been defined for risk stratification in SMF. To develop a prognostic model for predicting survival, we studied 685 JAK2, CALR , and MPL annotated patients with SMF. Median survival of the whole cohort was 9.3 years (95% CI: 8-not reached-NR-). Through penalized Cox regressions we identified negative predictors of survival and according to beta risk coefficients we assigned 2 points to hemoglobin level <11 g/dl, to circulating blasts ⩾3%, and to CALR -unmutated genotype, 1 point to platelet count <150 × 10 9 /l and to constitutional symptoms, and 0.15 points to any year of age. Myelofibrosis Secondary to PV and ET-Prognostic Model (MYSEC-PM) allocated SMF patients into four risk categories with different survival ( P <0.0001): low (median survival NR; 133 patients), intermediate-1 (9.3 years, 95% CI: 8.1-NR; 245 patients), intermediate-2 (4.4 years, 95% CI: 3.2–7.9; 126 patients), and high risk (2 years, 95% CI: 1.7–3.9; 75 patients). Finally, we found that the MYSEC-PM represents the most appropriate tool for SMF decision-making to be used in clinical and trial settings.

The authors identified calreticulin mutations in the majority of patients with essential thrombocythemia and myelofibrosis who did not have JAK2 mutations. The mutation alters calreticulin protein, and cells expressing the mutant protein are more responsive to growth factors. Philadelphia chromosome–negative myeloproliferative neoplasms include polycythemia vera, essential thrombocythemia, and primary myelofibrosis. 1 A unique gain-of-function mutation in the Janus kinase 2 gene ( JAK2 ) is found in about three quarters of patients in whom these disease entities have been diagnosed. 2 , 3 The valine-to-phenylalanine (V617F) alteration constitutively activates JAK2, resulting in increased phosphorylation of its substrates and leading to increased cytokine responsiveness of myeloid cells. The JAK2 V617F mutation is present in approximately 95% of patients with polycythemia vera and in 50 to 60% of those with essential thrombocythemia or primary myelofibrosis. 4 In addition, somatic mutations of JAK2 exon 12 . . .

Essential thrombocythemia is associated with increased risks of bleeding and thrombosis. Estimation of the risk of thrombosis is based on history of thrombosis, presence of the JAK2 V617F mutation, age, and cardiovascular risk. Treatment commonly involves low-dose aspirin; therapy is used in patients with high thrombotic risk.

Elevated levels of neutrophil extracellular traps (NETs) are associated with thrombotic risks, in particular, for patients with elevated platelet counts, such as those with essential thrombocythemia (ET). Here, the tendency for NETosis and neutrophil activity in such patients was assessed. A total of forty-one pediatric patients with elevated platelet counts diagnosed with ET (nine with CALR driver mutation, eleven with JAK2, thirteen triple-negative, and one dual-negative (TN)) or secondary thrombocytosis (five) were recruited. The tendency for NETosis was determined in a leucocyte-rich blood plasma smear using immunofluorescence staining with antibodies against myeloperoxidase and elastase. Activity of neutrophils was assessed ex vivo in parallel-plate flow chambers. The mean level of NETosis in healthy volunteers was 2.7-6.7% (95% CI). Among the ET patients, there was no statistically significant difference in NETosis level between those with mutations in CALR (19-43%), JAK2 (22-58%), and TN ones (6-27%). Patients with secondary thrombocytosis also had an elevated level of NETosis (8-66%). The velocity of neutrophil chemotaxis was significantly increased in all patients, in particular for those with mutations in CALR. These data reveal a major shift in the neutrophil activity in ET and suggest that the immunomorphological techniques presented here may allow reproducible and widely available characterization of neutrophil status.

The current retrospective study evaluated clinical, genetic, and prognostic correlates of increased absolute basophil (ABC) and eosinophil (AEC) counts in polycythemia vera (PV; N  = 475) and essential thrombocythemia (ET; N  = 658). Median (range) ABC and AEC were 0.1 (0-3.2) and 0.3 (0-6.5) x 10 9 /L in PV and 0.07 (0-0.8) and 0.2 (0-1.4) x 10 9 /L in ET. In PV, ABC ≥ 0.1 × 10⁹/L was associated with palpable splenomegaly and increased AEC, leukocyte count, and platelet count while AEC ≥ 0.5 × 10⁹/L was associated with increased ABC and leukocyte count. In ET, ABC ≥ 0.1 × 10⁹/L was associated with increased AEC, leukocyte count, platelet count, and cardiovascular risk factors while AEC ≥ 0.5 × 10⁹/L correlated with ABC and increased leukocyte count; genetic associations were seen only in ET and included ABC ≥ 0.1 × 10⁹/L with triple-negative driver mutation status ( p  = 0.03). In PV, AEC did not correlate with overall (OS), leukemia-free (LFS), myelofibrosis-free (MFFS), arterial thrombosis-free (ATFS), or venous thrombosis-free (VTFS) survival; by contrast, ABC ≥ 0.1 × 10⁹/L was associated with longer ATFS ( p  = 0.03) while ABC ≥ 0.3 × 10⁹/L was associated with inferior LFS ( p  < 0.01) and MFFS ( p  < 0.01); the associations with LFS and MFFS were sustained during multivariable analysis. In ET, both ABC ≥ 0.1 × 10⁹/L and AEC ≥ 0.5 × 10⁹/L were independently associated with inferior OS but impact on LFS, MFFS, ATFS, or VTFS was not apparent. The results from the current study warrant additional studies to clarify the potential association between basophilia in PV and disease transformation into acute myeloid leukemia and myelofibrosis.

The impact of calreticulin ( CALR ) mutations on long-term survival in essential thrombocythemia (ET) was examined in 299 patients whose diagnosis predated 2006. Mutational frequencies were 53% for Janus kinase 2 ( JAK2 ), 32% for CALR and 3% for MPL ; the remaining 12% were ‘triple-negative’. We confirmed the association of mutant CALR (vs JAK2 V617F) with younger age ( P =0.002), male sex ( P =0.01), higher platelet count (0.0004), lower hemoglobin ( P <0.0001), lower leukocyte count (0.02) and lower incidence of recurrent thrombosis (0.04). Triple-negative patients were also younger than their JAK2 -mutated counterparts ( P =0.003) and displayed lower hemoglobin ( P =0.003), lower leukocyte count (<0.0001) and lower thrombotic events ( P =0.02). Median follow-up time was 12.7 years and 47% of the patients were followed until death. Survival was the longest for triple-negative and shortest for MPL-mutated patients. Median survival was 19 years for JAK2 and 20 years for CALR-mutated cases ( P =0.32); the corresponding figures for patients of age ⩽65 years were 26 and 32 years ( P =0.56). The two mutational categories were also similar for leukemic ( P =0.28) and fibrotic ( P =0.28) progression rates. The current study is uniquely characterized by its very long follow-up period and provides accurate estimates of long-term survival in ET and complements current information on mutation-specific phenotype and prognosis.

The paucity of essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (pre-PMF) in individuals younger than 18 years highlights several unresolved issues in diagnosis, clinical outcomes, and treatment strategies. To address these knowledge gaps, we analyzed a large bidirectional cohort consisting of childhood and adolescent ET (CAA-ET, n = 156) and pre-PMF (CAA-preMF, n = 13), as well as adult ET (n = 349). We introduced immunophenotypic abnormalities as novel clonal markers in CAA-ET and CAA-preMF, establishing a comprehensive method for clonal marker detection that integrated driver and non-driver mutations, positive endogenous erythroid colony formation, immunophenotypic abnormalities, and chromosomal aberrations. Next-generation sequencing revealed distinct mutational profiles between CAA-ET and adult ET, along with different age-related trends in the distribution of driver mutations. Venous thrombosis was more prevalent in CAA-ET, with JAK2 V617F emerging as a potential risk factor (P = 0.018). Immunophenotypic abnormalities were identified as risk factors for disease progression (P = 0.027). Significant differences between expected and actual treatment practices were identified. Compared to CAA-ET, CAA-preMF demonstrated poorer progression-free survival (P < 0.001) and faster disease progression (P = 0.019). This study provides a critical foundation for refining diagnostic, prognostic, and therapeutic approaches for CAA-ET and CAA-preMF.

Lemierre’s syndrome (LS) represents a rare yet potentially life-threatening systemic infection, characterized by thrombophlebitis of the internal jugular vein and abscess formation in distant organs. It typically follows episodes of tonsillitis or other infections of the oropharyngeal region. Pulmonary complications, including septic pulmonary emboli, are common. Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN) sometimes associated with the JAK2V617F mutation, which predisposes patients to thrombotic events. A 66-year-old male with JAK2V617F-positive ET presented with severe pulsatile pain radiating from the right temporal region to the occipital area following a recent dental infection. Although pain management was administered, the pain continued to persist. Computed tomography of the chest revealed multiple subpleural nodules, raising suspicion for septic pulmonary emboli. Further investigation with gadolinium-enhanced magnetic resonance imaging identified a thrombus extending from the right sigmoid sinus into the internal jugular vein, consistent with cerebral venous thrombosis. The patient was diagnosed with　LS, complicated by septic thrombosis. Blood cultures yielded alpha-hemolytic streptococcus. Empirical antimicrobial therapy combined with anticoagulation was initiated, resulting in a gradual improvement of symptoms, including the resolution of fever and pain. Follow-up imaging confirmed the resolution of both the infection and thrombosis. This is the first reported case of LS in a patient with JAK2V617F-positive ET. The coexistence of LS and JAK2V617F-positive MPN highlights the potential interplay between proinflammatory and prothrombotic conditions associated with the JAK2V617F mutation.