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 ◽  
...  

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

2020 ◽  
Vol 30 (4) ◽  
pp. 491-497 ◽  
Author(s):  
Julia Rose Salinaro ◽  
Kourtnie McQuillen ◽  
Megan Stemple ◽  
Robert Boccaccio ◽  
Jessie Ehrisman ◽  
...  

ObjectivesNeoadjuvant chemotherapy may be considered for women with epithelial ovarian cancer who have poor performance status or a disease burden not amenable to primary cytoreductive surgery. Overlap exists between indications for neoadjuvant chemotherapy and known risk factors for venous thromboembolism, including impaired mobility, increasing age, and advanced malignancy. The objective of this study was to determine the rate of venous thromboembolism among women receiving neoadjuvant chemotherapy for epithelial ovarian cancer.MethodsA multi-institutional, observational study of patients receiving neoadjuvant chemotherapy for primary epithelial ovarian, fallopian tube, or peritoneal cancer was conducted. Primary outcome was rate of venous thromboembolism during neoadjuvant chemotherapy. Secondary outcomes included rates of venous thromboembolism at other stages of treatment (diagnosis, following interval debulking surgery, during adjuvant chemotherapy, or during treatment for recurrence) and associations between occurrence of venous thromboembolism during neoadjuvant chemotherapy, subject characteristics, and interval debulking outcomes. Venous thromboembolism was defined as deep vein thrombosis in the upper or lower extremities or in association with peripherally inserted central catheters or ports, pulmonary embolism, or concurrent deep vein thrombosis and pulmonary embolism. Both symptomatic and asymptomatic venous thromboembolism were reported.ResultsA total of 230 patients receiving neoadjuvant chemotherapy were included; 63 (27%) patients overall experienced a venous thromboembolism. The primary outcome of venous thromboembolism during neoadjuvant chemotherapy occurred in 16 (7.7%) patients. Of the remaining venous thromboembolism events, 22 were at diagnosis (9.6%), six post-operatively (3%), five during adjuvant chemotherapy (3%), and 14 during treatment for recurrence (12%). Patients experiencing a venous thromboembolism during neoadjuvant chemotherapy had a longer mean time to interval debulking and were less likely to undergo optimal cytoreduction (50% vs 80.2%, p=0.02).ConclusionsPatients with advanced ovarian cancer are at high risk for venous thromboembolism while receiving neoadjuvant chemotherapy. Consideration of thromboprophylaxis may be warranted.


2017 ◽  
Author(s):  
Guillermo A. Escobar ◽  
Peter K. Henke ◽  
Thomas W. Wakefield

Deep vein thrombosis (DVT) and pulmonary embolism (PE) comprise venous thromboembolism (VTE). Together, they comprise a serious health problem as there are over 275,000 new VTE cases per year in the United States, resulting in a prevalence of one to two per 1,000 individuals, with some studies suggesting that the incidence may even be double that. This review covers assessment of a VTE event, initial evaluation of a patient suspected of having VTE, medical history, clinical presentation of VTE, physical examination, laboratory evaluation, imaging, prophylaxis against perioperative VTE, indications for immediate intervention (threat to life or limb), indications for urgent intervention, and management of nonemergent VTE. Figures show a modified Caprini score questionnaire used at the University of Michigan to determine individual risk of VTE and the indicated prophylaxis regimen; Wells criteria for DVT and PE; phlegmasia cerulea dolens secondary to acute left iliofemoral DVT after thigh trauma; compression duplex ultrasonography of lower extremity veins; computed tomographic angiogram of the chest demonstrating a thrombus in the pulmonary artery, with extension into the right main pulmonary; management of PE according to Wells criteria findings; management of PE with right heart strain in cases of massive or submassive PE; treatment of DVT according to clinical scenario; a lower extremity venogram of a patient with May-Thurner syndrome and its subsequent endovascular treatment; and various examples of retrievable vena cava filters (not drawn to scale). Tables list initial clinical assessment for VTE, clinical scenarios possibly benefiting from prolonged anticoagulation after VTE, indications for laboratory investigation of secondary thrombophilia, venous thromboembolic risk accorded to hypercoagulable states, and Pulmonary Embolism Rule-out Criteria Score to avoid the need for D-dimer in patients suspected of having PE.   This review contains 11 highly rendered figures, 5 tables, and 167 references. Key words: anticoagulation; deep vein thrombosis; postthrombotic syndrome; pulmonary embolism; recurrent venous thromboembolism; thrombophilia; venous thromboembolism; PE; VTE; DVT 


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-14
Author(s):  
Guillaume Roberge ◽  
Philip S. Wells

Background. Patients with end stage renal disease on dialysis are at higher risk of major bleeding and recurrent thrombosis and as such, treatment of acute venous thromboembolism (VTE) is challenging. Ideally, treatment would avoid inpatient admission as for most other patients with acute VTE. DOACs represent the easiest option but there are concerns over bioaccumulation increasing bleeding risk. Despite the absence of a standardized therapeutic range, anti-Xa trough level is measured to monitor potential DOACs bioaccumulation and thus, used for safety surveillance. Methods. We describe a case of a 51 yo female, 36 kg, on chronic hemodialysis with a provoked acute upper extremity deep vein thrombosis. Due to a lack of subcutaneous fat and calciphylaxis we were reluctant to use low molecular weight heparin and warfarin. She was treated with apixaban 2,5 mg twice daily for 6 weeks. Over 4 weeks, the apixaban anti-Xa trough levels were measured on dialysis days 12 hours after the morning dose. Results. The anti-Xa trough levels ranged from 58 to 84 ng/mL, similar to what is expected in patients with normal kidney function. There were no adverse events in the 3 months after anticoagulation initiation. Conclusion. We saw no evidence of bioaccumulation. This indicates a potential role for apixaban low doses in acute venous thromboembolism for patients on dialysis. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: The use of Apixaban for treatment of acute venous thromboembolism in patient on dialysis has not been approved.


2020 ◽  
Author(s):  
Aziz S

Background: Venous Thromboembolism (VTE) is a clinical disorder characterized by the pathological occurrence of single or many thrombi developing mainly in the deep veins of the lower limbs and pulmonary veins but also other parts of the venous circulation, albeit less. A frequently occurring venous thrombosis is a deep vein thrombosis (DVT), which is the presence of thrombus in deep veins of the lower extremity. Once this clot fragment is swept off (embolism), it moves along with the venous blood and flows to the pulmonary vessels, where it may result in a clinically significant disorder called pulmonary thromboembolism (PTE). Thrombosis occurring in the superficial veins would only cause discomfort but generally with insignificant consequences. Aim: This study aimed to assess patterns and risk factors of venous thromboembolism (VTE) among patients in the Aseer region. Methodology: A record-based descriptive analysis (retrospective) was used in this study. The clinical study targeted the patients with venous thromboembolism (VTE including PE & DVT) either admitted with the diagnosis or complicated during the hospitalization period in Aseer Central Hospital during the period from January 2010 to June 2019. Data extracted using pre-structured data collection sheet. The extracted data were patients' bio-demographic data, VTE related data, treatment received and relevant complications of treatment, and patient’s follow-up history. Results: The study included total of 207 patients with thromboembolism. The age of patients was between 15 - 100 years old with the average age being 57.3+12.9 years. Approximately 58% of the patients were female. Deep vein thrombosis (DVT) was recorded in 60.4% of the cases and 27.5% of them were diagnosed with pulmonary embolism (PE) while 12.1% had both PE and DVT. Exact of 59.6% of cases with PE had immobilization history for 24 to 72 hours as compared to 31.2% of DVT and 44% of patients with mixed thromboembolism. DM was recorded among 14% of PE cases and 21.6% of DVT. Warfarin with Enoxaparin was the most frequently given treatment in total (23.2%). Heparin followed by Warfarin was the second most common treatment. Conclusions and recommendation: The study revealed that VTE was commonly reported especially DVT and PE among the recorded cases and it was bilateral in a considerable number of cases. Immobilization with chronic disease and morbid obesity was noted as the most significant predictor for VTE.


TH Open ◽  
2019 ◽  
Vol 03 (02) ◽  
pp. e171-e179 ◽  
Author(s):  
Nils Skajaa ◽  
Erzsébet Horváth-Puhó ◽  
Kasper Adelborg ◽  
Paolo Prandoni ◽  
Kenneth J. Rothman ◽  
...  

Background Many cardiovascular conditions exhibit seasonality in occurrence and mortality, but little is known about the seasonality of venous thromboembolism. Methods Using Danish registries, we identified all patients with deep vein thrombosis, pulmonary embolism, splanchnic vein thrombosis, cerebral vein thrombosis, and retinal vein thrombosis during 1977–2016. We tallied monthly deaths occurring within 90 days of the venous thromboembolism diagnosis. We estimated peak-to-trough ratios and timing of the peak of both diagnoses and deaths summed over all years of the study period. The departure from 1.0 of the peak-to-trough ratio measures the intensity of any seasonal pattern. Results We estimated a peak-to-trough ratio of 1.09 (95% confidence interval: 1.07–1.11) for deep vein thrombosis and 1.22 (1.19–1.24) for pulmonary embolism occurrence. The peak-to-trough ratios for splanchnic vein thrombosis, cerebral vein thrombosis, and retinal vein thrombosis occurrence were 1.10 (1.01–1.20), 1.19 (1.00–1.40), and 1.12 (1.07–1.17), respectively. The occurrence of all conditions peaked during winter or fall. In time trend analyses, the peak-to-trough ratio increased considerably for splanchnic vein thrombosis, cerebral vein thrombosis, and retinal vein thrombosis occurrence. In associated mortality, the peak-to-trough ratio for deep vein thrombosis was larger (1.15, 1.07–1.23) than that for pulmonary embolism (1.04, 1.01–1.08). Discussion Excess winter risks were modest, but more marked for pulmonary embolism occurrence than for deep vein thrombosis occurrence. The seasonal pattern intensified throughout the study period for splanchnic vein thrombosis, cerebral vein thrombosis, and retinal vein thrombosis. The winter peak in mortality following pulmonary embolism was smaller than that for deep vein thrombosis.


Hip & Pelvis ◽  
2014 ◽  
Vol 26 (2) ◽  
pp. 124 ◽  
Author(s):  
Yong Sik Lee ◽  
Byung Ho Seo ◽  
Soo Won Lee ◽  
Sung Hwan Kim ◽  
Byung Kil Ahn

2017 ◽  
Vol 22 (6) ◽  
pp. 518-524 ◽  
Author(s):  
Marco P Donadini ◽  
Francesco Dentali ◽  
Samuela Pegoraro ◽  
Fulvio Pomero ◽  
Chiara Brignone ◽  
...  

Isolated distal deep vein thrombosis (IDDVT) is a common clinical manifestation of venous thromboembolism (VTE). However, there are only scant and heterogeneous data available on the long-term risk of recurrent VTE after IDDVT, and the optimal therapeutic management remains uncertain. We carried out a retrospective cohort study of consecutive patients diagnosed with symptomatic IDDVT between 2004 and 2011, according to a predefined short-term treatment protocol (low molecular weight heparin (LMWH) for 4–6 weeks). The primary outcome was the occurrence of recurrent VTE. A total of 321 patients were enrolled. IDDVT was associated with a transient risk factor or cancer in 165 (51.4%) and 56 (17.4%) patients, respectively. LMWH was administered for 4–6 weeks to 280 patients (87.2%), who were included in the primary analysis. Overall, during a mean follow-up of 42.3 months, 42 patients (15%) developed recurrent VTE, which occurred as proximal DVT or PE in 21 cases. The recurrence rate of VTE per 100 patient-years was 3.5 in patients with transient risk factors, 7.2 in patients with unprovoked IDDVT, and 5.9 in patients with cancer ( p=0.018). At multivariable analysis, unprovoked IDDVT and previous VTE were significantly associated with recurrent VTE (HR 2.16, 95% CI 1.12–4.16 and HR 1.97, 95% CI 1.01–3.86, respectively). In conclusion, the long-term risk of recurrent VTE after IDDVT treated for 4–6 weeks is not negligible, in particular in patients with unprovoked IDDVT or cancer. Further studies are needed to clarify whether a longer, but definite treatment duration effectively prevents these recurrences.


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