scholarly journals Prevalence of theJAK2V617F mutation in patients with unprovoked venous thromboembolism of common sites and without overt myeloproliferative neoplasms

2009 ◽  
Vol 144 (6) ◽  
pp. 965-967 ◽  
Author(s):  
Tommaso Za ◽  
Alessia Fiorini ◽  
Elena Rossi ◽  
Angela Ciminello ◽  
Patrizia Chiusolo ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Myeloproliferative Neoplasms

Thrombotic Complications in Ph'-Negative Myeloproliferative Neoplasms - 10-Year Experience of A Medical Center in Asian Area

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5171-5171
Author(s):  
Yi-Sheng Chou ◽  
Ri-Dong Bai ◽  
Chung-Jen Teng ◽  
Ying-Chung Hong ◽  
Chun-Yu Liu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Risk Factor ◽  
Venous Thromboembolism ◽  
Myeloproliferative Neoplasms ◽  
Vein Thrombosis ◽  
Bone Marrow Cellularity ◽  
Reticulin Fiber ◽  
Thrombotic Complications ◽  
Marrow Cellularity

Abstract Abstract 5171 Although thrombotic complications are common in myeloproliferative neoplasms (MPN), the pertinent risk factors are not well characterized. This study aims to explore the general characteristics of MPN patients, focusing on risk factors for developing thrombotic complications. Thrombotic events were defined as relevant to the MPN if they occurred after the diagnosis of MPN or around the time of diagnosis. Results Totally 361 patients were collected, including 135 (37%) cases of polycythemia vera (PV), 167 (46%) cases of essential thrombocythemia (ET) and 59 (16%) cases of primary myelofibrosis (PMF). The positive rates of JAK2V617F mutation were 90%, 65%, and 75% for PV, ET and PMF, respectively (PV vs. ET, p<0.001). PV was associated with higher incidence of transformation to myelofibrosis compared with ET (9% vs. 3%, p=0.027) and also higher level of white blood cell count (WBC) (mean 15018/ul, 95% confidence interval (CI):13655–16381/ul; PV vs. ET, p=0.005; PV vs. PMF, p=0.001 ), higher bone marrow cellularity (bone marrow cellularity more than 60%: PV,89%; ET,70%; PV vs. ET, p=0.026; PMF,76%), and more frequent hypertension (PV, 50%; ET, 43%; PMF 19%; PV vs PMF, p<0.001; ET vs. PMF, p=0.001). ET was associated lower incidence of coagulopathy with prolonged INR in prothrombin time (ET, 19%; PV, 36%; PV vs. ET, p=0.001; PMF, 44%; ET vs. PMF, p=0.001). PMF was associated with higher incidence of leukemia transformation(PMF,15%; PV,3.7%; ET, 2.4%; PV vs. PMF, p=0.012; ET vs. PMF, p=0.001), higher incidence of coagulopathy with prolonged aPTT (PMF,51%; PV,37%;ET, 30%; ET vs. PMF, p=0.012), increased reticulin fiber(moderate increased reticulin fiber: MF,92%; PV,44%; PV vs. PMF, p<0.001; ET, 48%;ET vs. PMF,p<0.001) and splenomegaly (mean 17.3cm, 95% CI:15.8–18.4cm, p<0.001). Venous thromboembolism occurred in 6.4% of these MPN patients with incidence of 7.4%, 6.6% and 3.4% in patients of PV, ET and PMF, respectively. Arterial thrombosis developed in 20% of these MPN patients with incidence of 28%, 17%, and 10% in patients of PV, ET and PMF, respectively. (Table1) Majority of venous thromboembolism presented as deep vein thrombosis (DVT) /pulmonary embolism (PE) and portal or splenic vein thrombosis with an incidence of 1.7/1.1% and 2.2%, respectively. The most common arterial thrombotic events was ischemic stroke, followed in order by ischemic heart disease, peripheral artery occlusive disease (PAOD), and ischemic bowel disease with an incidence of 14%, 9%, 3.0% and 1.1%, respectively. (Table1) The probability of thrombosis-free survival in these 361 patients was 85%, 78% and 70% at 1, 3 and 10 year, respectively (Figure 1). In terms of arterial and venous thromembolism altogether, univariate risk factor analysis revealed several risk factors including a positive JAK2V617F, diagnosis of PV, WBC more than 16000/ul, hemoglobin level higher than 16 mg/dl, albumin level less than 4.0 g/dl, LDH higher than 250U/L, congestive heart failure(CHF),hypertension(HTN) and diabetes mellitus. With multivariate analysis, however, only WBC more than 16000/ul (Odds ratio: 3.556,95% CI:1.287–9.822,p=0.014) remained as the most significant risk factors for thromoboembolism. Conclusions Arterial thromboses are quite common in patients of MPN, especially PV. In these MPN patients, the risk of venous thrombosis including thrombosis at unusual sites is also markedly increased. The most important risk factor predisposing to vascular thrombosis (vein and artery) is WBC more than 16000/ul. Our results provide informative clinical data for management of Asian patients with MPN and facilitate further study of these disorders in this area. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Trends and Inpatient Outcomes of Venous Thromboembolism-Related Admissions in Patients with Philadelphia-Negative Myeloproliferative Neoplasms

TH Open ◽  
2019 ◽  
Vol 03 (03) ◽  
pp. e203-e209 ◽  
Author(s):  
Vatsala Katiyar ◽  
Alok Uprety ◽  
Andres Mendez-Hernandez ◽  
Harry E. Fuentes ◽  
Xavier A. Andrade ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Hospital Mortality ◽  
Myeloproliferative Neoplasms ◽  
Significant Risk ◽  
Primary Myelofibrosis ◽  
Assessment Tools ◽  
Chi Square ◽  
Inpatient Outcomes ◽  
Risk Patients ◽  
Over Time

Background Patients with Philadelphia-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (MF), have a significant risk of venous thromboembolism (VTE). We aim to determine the trends in annual rates of VTE-related admissions, associated cost, length of stay (LOS), and in-hospital mortality in patients with MPN. Methods We identified patients with PV, ET, and MF from the Nationwide Inpatient Sample (NIS) database from 2006 to 2014 using ICD-9CM coding. Hospitalizations where VTE was among the top-three diagnoses were considered VTE-related. We compared in-hospital outcomes between VTE and non-VTE hospitalizations using chi-square and Mann–Whitney U-test and used linear regression for trend analysis. Results We identified 1,046,666 admissions with a diagnosis of MPN. Patients were predominantly white (65.6%), females (52.7%), with a median age of 66 years (range: 18–108). The predominant MPN was ET (54%). There was no difference in in-hospital mortality between groups (VTE: 3.4% vs. non-VTE: 3.2%; p = 0.12); however, VTE admissions had a longer LOS (median: 6 vs. 5 days; p < 0.01) and higher cost (median: VTE US$32,239 vs. 28,403; p ≤ 0.01).The annual rate of VTE admissions decreased over time (2006: 3.94% vs. 2014: 2.43%; p ≤ 0.01), compared with non-VTE–related admissions. Conclusion In our study, VTE-related admissions had similar in-hospital mortality as compared with non-VTE–related admissions. The rates of hospitalizations due to VTE have decreased over time but are associated with a higher cost and LOS. Newer risk assessment tools may assist in preventing VTE in high-risk patients and optimizing resource utilization.

scholarly journals Thrombocytosis in COVID-19 patients without myeloproliferative neoplasms is associated with better prognosis but higher rate of venous thromboembolism

2021 ◽  
Vol 11 (11) ◽  
Author(s):  
Marko Lucijanic ◽  
Ivan Krecak ◽  
Ena Soric ◽  
Martina Sedinic ◽  
Anica Sabljic ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Myeloproliferative Neoplasms

scholarly journals A systematic review of antithrombotic treatment of venous thromboembolism in patients with myeloproliferative neoplasms

2021 ◽  
Vol 5 (1) ◽  
pp. 113-121
Author(s):  
Eva N. Hamulyák ◽  
Joost G. Daams ◽  
Frank W. G. Leebeek ◽  
Bart J. Biemond ◽  
Peter A. W. te Boekhorst ◽  
...  
Keyword(s):  
Systematic Review ◽  
Venous Thromboembolism ◽  
Observational Studies ◽  
Randomized Trials ◽  
Myeloproliferative Neoplasms ◽  
Recurrence Risk ◽  
Antithrombotic Treatment ◽  
Statistical Heterogeneity ◽  
History Of ◽  
Recurrent Vte

Abstract Patients with myeloproliferative neoplasms (MPNs), polycythemia vera, essential thrombocythemia, and primary myelofibrosis, have an increased risk of thrombosis. Risk of recurrent thrombosis can be reduced with antithrombotic therapy and/or cytoreduction, but the optimal long-term management in patients with MPN with a history of venous thromboembolism (VTE) is unknown, and clinical practice is heterogeneous. We performed a systematic review and meta-analysis of randomized trials and observational studies evaluating anticoagulant and/or antiplatelet therapy, with or without cytoreduction, in MPN patients with a history of VTE. A total of 5675 unique citations were screened for eligibility. No randomized trials were identified. Ten observational studies involving 1295 patients with MPN were included in the analysis. Overall, 23% had an arterial or recurrent venous thrombotic event on follow-up. The recurrence risk was lowest for patients on oral anticoagulation plus cytoreduction (16%); 55 of 313 (18%) with vitamin K antagonists (VKA) and 5 of 63 (8%) with direct oral anticoagulants (DOACs). In 746 analyzed patients, the risk of recurrent VTE ranged up to 33% (median 13%) and was low in 63 DOAC plus cytoreduction-treated patients (3.2%). All types of antithrombotic treatments were associated with a lower risk of recurrent VTE when combined with cytoreduction. Most studies had a high risk of bias, whereas clinical and statistical heterogeneity led to inconsistent and imprecise findings. In summary, evidence on the optimal antithrombotic treatment of VTE in patients with MPN is based on observational studies only with low certainty for all strategies. Our data suggest that a combination of anticoagulation and cytoreduction may provide the lowest recurrence risk.

scholarly journals AB0825 JAK2 (V617F) MUTATION AND ASSOCIATION TO IMMUNE MEDIATED DISEASES. STUDY OF 130 PATIENTS FROM A SINGLE UNIVERSITY HOSPITAL

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1436.2-1437
Author(s):  
C. Álvarez-Reguera ◽  
L. Sanchez-Bilbao ◽  
A. Batlle-López ◽  
S. Fernández López ◽  
M. Á. González-Gay ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Myeloproliferative Neoplasms ◽  
Primary Myelofibrosis ◽  
Vein Thrombosis ◽  
Immune Mediated ◽  
V617f Mutation ◽  
Deep Vein

Background:Janus Kinases (JAK) are tirosin-kinases that can promote cytokine production in immune and hematopoietic cells. The JAK-2 (V617F) mutation is the most frequently detected mutation in myeloproliferative neoplasms (MPN) which include essential thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (PMF) and undifferenciated MPN. JAK-2 (V617F) mutation displays a pro-inflammatory phenotype that may be associated to a higher risk of immune mediated diseases (IMID), thromboembolic complications or other cancers (1-3).Objectives:To evaluate the presence of a) IMID (rheumatic and non-rheumatic), b) cancer and, c) Deep vein thrombosis/ Venous thromboembolism (DVT/VTE) events in a cohort of patients with a positive JAK-2 (V617F) mutation.Methods:We studied all the patients diagnosed with a positive JAK-2 (V16F) mutation in a single University Hospital between January, 2004 and December, 2019.Results:The study included 130 patients (73 men/57 women; mean age, 70.1±14.5 years). They were diagnosed of ET (n=64, 49.2%), PV 46 (35.4%), undifferentiated MPN (n=12, 9.2%) and PMF (n=8, 6.1%). Of these patients, 54 (41.5 %) (44 non rheumatic and 10 rheumatic) were diagnosed with at least one IMID, 46 (35.4%) with other cancer different of MPN and 36 (27.7%) with DVT/VTE events. (Table 1/Figure 1).Conclusion:Due to its prevalence and potential complications, IMID should be taken into consideration when a patient is diagnosed with a positive JAK-2 (V617F) mutation.References:[1]Perner F, et al. Cells. 2019;8:854.[2]Xu Q, et al. Clin Rheumatol. 2020 Jul 16.[3]Hasselbalch HC, et al. 2020; 23;17(1):248.Table 1.Associated diseases in 130 patients with JAK2 (V617F) mutation. Data are n (%)Myeloproliferative neoplasms (MPN)130 (100) Essential thrombocythemia (ET)64 (49.2) Polycythemia vera (PV)46 (35.4) Undifferentiated MPN12 (9.2) Primary myelofibrosis (PMF)8 (6.5)Non-rheumatic IMID44 (33.8) Diabetes mellitus22 (50) Asthma10 (22.7) Psoriasis6 (13.6) Crohn disease2 (4.5) Autoimmune thyroiditis2 (4.5)Rheumatic IMID10 (7.7) Rheumatoid arthritis4 (40) Polymyalgia rheumatica3 (30) Sjögren disease1 (10) Antiphospholipid syndrome1 (10) Adult-onset Still’s disease1 (10)Malignancies different of MPN44 (33.8) Solid tumours // Hematologic malignancies // Skin cancer22 (50) // 13 (29.5) // 9 (20.4)Deep vein thrombosis/Venous thromboembolism (DVT/VTE) events35 (26.9)Figure 1.Associated diseases accordingly to the subtype of Myeloproliferative neoplasm. Data are n.ABBREVIATIONS: DVT/VTE: Deep vein thrombosis/ Venous thromboembolism. ET: Essential Thrombocythemia, IMID: Immune Mediated Diseases, PV: Polycythemia Vera; MPN: Myeloproliferative Neoplasms; PMF: Primary myelofibrosis; UMPN: Undifferenciated myeloproliferative neoplasms.Disclosure of Interests:Carmen Álvarez-Reguera: None declared, Lara Sanchez-Bilbao: None declared, Ana Batlle-López: None declared, Sara Fernández López: None declared, Miguel Á. González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi and MSD., Grant/research support from: Abbvie, MSD, Janssen and Roche, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD., Grant/research support from: Abbvie, MSD and Roche

scholarly journals Outcomes of Patients Receiving Direct Oral Anticoagulants for Myeloproliferative Neoplasm Associated Venous Thromboembolism

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4183-4183
Author(s):  
Andrew Doyle ◽  
Karen Breen ◽  
Donal P. McLornan ◽  
Deepti Radia ◽  
Beverley J. Hunt ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Sinus Thrombosis ◽  
Myeloproliferative Neoplasms ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Cerebral Venous Sinus Thrombosis ◽  
High Rate ◽  
Recurrence Rates

Introduction Myeloproliferative neoplasms (MPN) are associated with an increased rate of venous thromboembolism (VTE), which can be a major cause of morbidity and mortality especially in the more indolent diseases of polycythaemia rubra vera (PV) and essential thrombocythaemia (ET). Splanchnic vein thromboses are common in MPN and may have high recurrence rates between 15-20% over 10 years1. Traditionally, vitamin K antagonists (VKA) have been the mainstay of anticoagulation for MPN-associated VTE and recent data suggests a high rate of recurrent VTE on their discontinuation in MPN patients2. In the last 5 years, there has been a significant change to the use of direct oral anticoagulants (DOAC) in non-MPN associated VTE and limited data is available in the MPN setting due to the exclusion of malignancies from initial Phase III studies. Methods A retrospective review of patients treated at a single tertiary centre for MPN was performed. Clinical details were obtained from electronic clinical notes, imaging and prescriptions. Results A total of 102 patients were identified as having a MPN-associated VTE with 24 of these receiving DOACs. The median age at VTE was 48 years (range 27.4-92.2 years) with 10 males (41.7%), primary diagnosis: 10 PV, 5 ET, 7 myelofibrosis (MF) and 2 MPN/myelodysplasia overlap. 18 patients were JAK2 V617F positive, 1 pt had MPL mutation and 5 pts were triple negative. In total 29 thrombotic events were recorded - 10 splanchnic (34.4%), 10 pulmonary embolism (34.4%), 5 deep vein thrombosis (17.2%), 2 cerebral venous sinus thrombosis (6.9%), 1 superficial thrombophlebitis (3.4%). The median follow-up period was 2.2 years (range 0.7-7.5 years) with 16 patients initiated on DOAC (12 rivaroxaban and 4 apixaban) and 8 patients changed from VKA or heparin (3 rivaroxaban, 3 apixaban and 1 edoxaban). Two patients used more than one DOAC in this period. 21 patients were receiving long-term anticoagulation and 3 had defined courses of anticoagulation due to provocation. 21 patients were receiving cytoreductive agents or regular venesection along with anticoagulation. During the total follow-up period of patients receiving DOACs, amounting to 66 pt years, there were no VTE recurrences in 23 patients and indeterminate imaging for 1. There were no episodes of major bleeding but 2 patients (8.3%) had clinically relevant non-major bleeding both of which were taking aspirin in addition to DOAC. Conclusions These results suggest that there were very low/no recurrence rates of VTE and no major bleeding in patients with MPN-associated VTE who are receiving DOACs. These include heterogeneous sites of VTE including splanchnic vein thromboses and cerebral venous sinus thrombosis. Of note, cytoreductive measures were also used in a majority of these patients. We suggest that DOACs could be safely used in this group in appropriately selected patients with MPN. References: 1. Finazzi G, De Stefano V, Barbui T. Splanchnic vein thrombosis in myeloproliferative neoplasms: treatment algorithm. Blood Cancer J. 2018; 8(7): 64. 2. De Stefano V, Ruggeri M, Cervantes F et al. High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with vitamin K antagonists. Leukemia. 2016; 30(10): 2032-38. Table Disclosures McLornan: Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Novartis: Honoraria. Radia:Blueprint Medicines: Consultancy; Novartis: Consultancy, Speakers Bureau. Harrison:AOP: Honoraria; Promedior: Honoraria; Gilead: Speakers Bureau; Roche: Honoraria; Janssen: Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Sierra Oncology: Honoraria; CTI: Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; Shire: Speakers Bureau; Incyte: Speakers Bureau.

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