scholarly journals The Study of Thrombosis in JAK2V617F Mutated Myeloproliferative Neoplasms

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1149-1149
Author(s):  
Jie Bai ◽  
Yuhui Zhang ◽  
Yingshao Wang ◽  
Guangshuai Teng ◽  
Yan Wang ◽  
...  

Introduction: Thrombosis is the most important risk factor affecting event-free survival and overall survival (OS) of patients with myeloproliferative neoplasms (MPNs). To explore the risk factors of thrombosis in patients with JAK2V617F-mutated MPN, a cohort of 1537 Chinese patients with JAK2V617F-mutated MPN was retrospectively analyzed for clinical characteristics, laboratory characteristics, cytogenetics, thromboembolism, disease progression and OS. Methods: The qualitative data were compared by the Chi-square test or Fisher's test, and continuous variables were compared with the Mann-Whitney U test or Kruskal-Wallis test. The Kaplan-Meier method and multivariate Cox analysis were used to study the risk factors of thrombosis in patients with JAK2V617F-mutated MPN. Results: Among the 1537 MPN patients, 931, 468 and 138 had polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), respectively. The median follow-up time was 7 years (range 1-47), and 12.8% of patients (197/1537) died during this period. A total of 16.8% (259/1399) of PV and ET patients had secondary myelofibrosis, and 2.5% (38/1537) of patients developed acute myeloid leukemia (AML). Thrombosis events occurred in 43.9% (675/1537) of patients, among which 91.4%(617/675) were arterial thrombosis and 16.6% (112/675) were venous thrombosis. The number of thrombosis events in PV, ET and PMF patients was 439 (47.2%), 197 (42.1%) and 39 (28.2%), respectively. The multivariate analysis indicated that age≥60 years old (P=0.003, HR=1.76, 95% CI[1.214, 2.552]), HCT≥48% (P=0.022, HR=1.635, 95% CI[1.073, 2.492]), at least one cardiovascular risk factor (P=0.024, HR=1.559, 95% CI[1.061,2.291]), a history of thrombosis (P<0.0001, HR=2.313, 95% CI[1.573,3.401]), and JAK2V617Fallele burden (V617F%) ≥50% (P=0.003, HR=1.804, 95% CI [1.221, 2.665]) are risk factors for thrombosis in JAK2V617F-mutated MPN. According to the results of the multivariate analysis, a risk model of thrombosis was established and comprised low-risk (0 points), intermediate-risk (1 points) and high-risk (≥2 points) groups, among which the incidence of thrombosis was 9.1%, 33.7% and 72.9%, respectively. Conclusions: The Chinese thrombosis risk model of JAK2V617F-mutated MPN established in this study suggests that elderly patients with a history of thrombosis should reduce V617F%, control HCT to less than 48% and mitigate cardiovascular risk factors, all of which are necessary measures to prevent thrombosis in patients with JAK2V617F-mutated MPN. Disclosures No relevant conflicts of interest to declare.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3369-3369
Author(s):  
Augusto B. Federici ◽  
Maria C Carraro ◽  
Antonella Lattuada ◽  
Chiara Vanelli ◽  
Veronica Sciumbata ◽  
...  

Abstract Abstract 3369 Background: Patients with Ph-negative Myeloproliferative Neoplasms (MPN) such as Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) can be exposed during the course of these MPN to thrombotic and bleeding complications, with increased morbidity and mortality. Age, previous history of thrombosis, increased White Blood Cell (WBC) and Jak2 allele burden have been proposed as risk factors for Venous (VTE) and Arterial (ATE) thromboses while bleeding has been previously associated with abnormalities of the von Willebrand factor (VWF). Aims: To investigate any significant role of ADAMTS-13 and VWF activities in the thrombotic and bleeding complications observed in a small but well characterized cohort of MPN patients. Patients and Methods: 88 consecutive patients were diagnosed at the Hematology and Transfusion Medicine Division, L.SACCO University Hospital of Milan, according to WHO criteria. Patients signed an informed consent to participate in this clinical study with a protocol approved by local IRB and they showed MPN type (%), mean age (range), gender M/F and Jak2 positivity (%) as follows: PV[n=42 (48%), 68 (36–86), 18/24; 85.7%]; ET [n=34 (38%), 66 (30–93), 10/24, 61.7%]; PMF [n=12 (14%), 67 (37–88), 7/5, 58%]. Thrombotic and bleeding episodes were recorded and managed from the time of diagnosis and associated with the use of aspirin (ASA) and of other MPN therapies. Among additional lab parameters, plasmatic ADAMTS-13 and VWF activities were also measured at enrolment as endothelial/platelet marker. These activities were assayed with Technozym ADAMTS-13 activity (Technoclone GmbH, Austria), Innovance VWF-GPIb activity (Siemens AG, Germany) and HemosIL-VWF antigen (Instrumentation Laboratory, USA). Multimeric analyses were also tested using very sensitive intermediate SDS-agarose gel electrophoresis. Statistical analyses were performed by SPSS-17.2. Results: 59/88 (67%) patients did not show any thrombotic or bleeding complications during the 6-year follow-up. In these cases mean (range) values of VWF:GPIb and VWF:Ag were 104 (29–202) and 133 (52–288) U/dL while ADAMTS-13 was 102 (63–143). 20/88 (23%) cases showed at least one thrombotic event (13ATE/7VTE): AMI (6), STROKE (6), TIA (2), PE (1), DVT (7). Patients with thromboses showed relatively higher values VWF:GPIb and lower ADAMTS-13 and this was confirmed in multivariate analysis especially for ET [VWF:GPIb=135 (61–237) U/dL, p=0.004 and ADAMTS-13=89(62–134), p=0.009]. Major bleeding episodes mainly mucosal (5 gastrointestinal, 3 post-surgery, 1 severe menorrhagia) requiring blood transfusions or hysterectomy were observed in 9/88 (10%) patients. At the multivariate analysis, major bleedings were significantly associated with lower VWF:GPIb [68 (25–111) U/dL, p=0.022), lower VWF:Ag [93 (35–146) U/dL, p=0.016] and to the ASA intake (p=0.006). Most of these bleeders showed also a relative loss of the highest molecular weight multimers. Conclusions: Based on these observations, we confirm that thrombotic events in MPN may certainly have multiple risk factors: however, lower ADAMTS-13 and higher VWF activities might play a role as additional risk factors especially in ET. Conversely, lower levels of VWF with loss of the largest multimers are important risk factors for bleeding in MPN especially in patients treated with ASA. Disclosures: No relevant conflicts of interest to declare.


2017 ◽  
Vol 5 (2) ◽  
pp. 64-68
Author(s):  
Raj Krishna Dangol ◽  
Bibek Koju ◽  
Priya Lanjekar ◽  
Chandrashekhar Pulipati

Introduction: Detection of cardiovascular risk in young age is important to motivate them to modify life styles and seek health care early to lower the chances of acquiring cardiovascular disease in later age. This study was done to assess cardiovascular risk factors among first year medical students. Methods: A cross-sectional study was conducted throughout September and October 2017 in which all first year medical students from a medical college were assessed for the presence of cardiovascular risk factors. Participants’ demography, family history of illness, anthropometric measurements, and blood reports of lipid profile and fasting glucose were acquired. Data were analyzed with Statistical Package for Social Sciences (SPSS-21). Result: There were 99 participants; 55 males and 44 females. One or more risk factors were present in 87 (87.9%) participants. Moreover, 67.7% (n = 67) participants had more than one risk factors. Low HDL-cholesterol was the most common (n = 55, 55.6%) risk factor followed by elevated triacylglycerol (n = 47, 47.5%) and family history of hypertension (n = 45, 45.5%). There was no significant difference in presence of various risk factors between genders. Conclusion: There was higher prevalence of cardiovascular risk factors among first year medical students. Majority of them had more than one risk factors. Low HDL-cholesterol was the most common risk factor. The risk factors were comparable in males and females.


2021 ◽  
Vol 8 ◽  
Author(s):  
Fan Yang ◽  
Junwei Tian ◽  
Linyi Peng ◽  
Li Zhang ◽  
Jia Liu ◽  
...  

Objectives: This study aims to describe clinical characteristics and outcome of thrombotic microangiopathy (TMA) in Chinese patients with systemic lupus erythematosus (SLE), and investigate the risk factors.Methods: We conducted a retrospective single-center cohort and enrolled patients of TMA associated with SLE between January 2015 and December 2018. Demographic characteristics, clinical features, laboratory profiles, therapeutic strategies, and outcomes were collected. The risk factors of TMA in patients with SLE for mortality using multivariate analysis were estimated.Results: A total of 119 patients with a diagnosis of TMA were enrolled within the study period in our center, and SLE was found in 72 (60.5%) patients. The mean age was 29.2 ± 10.1 and 65 (92.3%) were women. Only 15 patients were found with definite causes, the other 57 cases remained with unclear reasons. Sixty-two patients got improved, while 10 patients died after treatment (mortality rate: 13.9%). Compared with the survival group, the deceased group had a higher prevalence of neuropsychiatric manifestations, infection with two or more sites, increased levels of C-reaction protein (CRP) and D-Dimer, and decreased platelet count. Multivariate analysis showed that the decrease of platelet count is the independent risk factor for in-hospital mortality for TMA in patients with SLE. The receiver operating characteristic (ROC) curve analysis displayed that a cutoff value of &lt;18 × 109/L for platelet count could significantly increase the risk of death.Conclusions: Thrombotic microangiopathy often occurs in patients with active SLE with high mortality (13.9%), and thrombocytopenia, especially when the platelet count is lower than 18 × 109/L, is the risk factor for death.


2006 ◽  
Vol 96 (11) ◽  
pp. 578-583 ◽  
Author(s):  
Irit Aberbach ◽  
Liliana Schliamser ◽  
Zeev Blumenfeld ◽  
Benjamin Brenner ◽  
Galit Sarig

SummaryThe risk of thrombosis in women increases significantly during treatment with hormonal therapy (HT). The aim of this study was to evaluate ProC Global assay in women with a history of venous thromboembolism (VTE) while using HT. Protein C activation time normalized ratio (PCAT-NR) levels were significantly lower in 32 women with a history ofVTE while using HT (0.72 ± 0.1) compared with 56 healthy controls without HT, matched by age at blood sampling (0.99 ± 0.2) and 40 healthy controls with HT, matched by age and HT at VTE event (0.94 ± 0.2) (P<0.001 for both). PCAT-NR lower than the cut-off level of 0.8 was found in 23/32 (72%) patients compared with 5/56 (9%) age-matched controls (OR=26, 95%CI: 7-106, P<0.001) and 9/40 (22.5%) of HT-matched controls (OR=9, 95%CI: 2.7-30, P<0.001). Any thrombophilic risk factor was found in 20/32 (62.5%) of patients compared with 12/56 (21.4%) of agematched controls (OR=6, 95%CI: 2.1-10, P<0.001) and 12/40 (30%) of HT-matched controls (OR=4, 95%CI: 1.3-11.8, P=0.006).Out of the variables that are risk factors of VTE as age, HT or thrombophilic risk factor, ProC Global assay was found in the multivariate analysis - logistic regression, as the parameter that was the most associated with patient group [Exp(B)=15.8, 95% CI: 4.2-59.0, P<0.001]. In conclusion, abnormal PCAT-NR is associated with VTE in women using HT. ProC Global assay may potentially serve asa diagnostic tool for evaluating the risk of VTE in women prior to administration of HT.


Author(s):  
Tupitsyn V.V. ◽  
Bataev Kh.M. ◽  
Men’shikova A.N. ◽  
Godina Z.N.

Relevance. Information about the cardiovascular diseases risk factors (CVD RF) for in men with chronic lung inflam-matory pathology (CLID) is contradictory and requires clarification. Aim. To evaluate the peculiarities of CVD RF in men under 60 years of age with CLID in myocardial infarction (MI) to improve prevention. Material and methods. The study included men aged 19-60 years old with type I myocardial infarction. Patients are divided into two age-comparable groups: I - the study group, with CLID - 142 patients; II - control, without it - 424 patients. A comparative analysis of the frequency of observation of the main and additional cardiovascular risk fac-tors in groups was performed. Results. In patients of the study group, more often than in the control group we observed: hereditary burden of is-chemic heart disease (40.8 and 31.6%, respectively; p = 0.0461) and arterial hypertension (54.2 and 44.6%; p = 0.0461), frequent colds (24.6 and 12.0%; p = 0.0003), a history of extrasystoles (19.7 and 12.7%; p = 0.04); chronic foci of infections of internal organs (75.4 and 29.5%; p˂0.0001), non-ulcer lesions of the digestive system (26.1 and 14.6%; p = 0.007), smoking (95.1 and 66.3%; p˂0.0001), MI in winter (40.8 and 25.9%; p = 0.006). Less commonly were observed: oral cavity infections (9.2 and 23.6%; p˂0.0001); hypodynamia (74.5 and 82.5%; p = 0.0358), over-weight (44.4 and 55.2%; p = 0.0136), a subjective relationship between the worsening of the course of coronary heart disease and the season of the year (43.7 and 55.2%; p = 0.0173) and MI - in the autumn (14.1 and 21.9%; p = 0.006) period. Conclusions. The structure of CVD RF in men under 60 years of age with CLID with MI is characterized by the pre-dominance of smoking, non-ulcer pathology of the digestive system, frequent pro-student diseases, meteorological dependence, a history of cardiac arrhythmias and foci of internal organ infections. It is advisable to use the listed factors when planning preventive measures in such patients.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Birgit-Christiane Zyriax ◽  
Kira Dransfeld ◽  
Eberhard Windler

Abstract Background Assessment of cardiovascular risk by scores lacks sensitivity and leaves the majority of future cardiovascular patients unidentified particularly individuals at low cardiovascular risk. The present analysis investigates into the correlation of carotid intima–media thickness (CIMT) and cardiovascular risk factors and derived scores as to the potential of improved cardiovascular risk prediction by combining the two. Methods The Stress, Atherosclerosis and ECG Study (STRATEGY) is a cross-sectional study of selectively healthy 107 women and 106 men without diagnosed and treated cardiovascular risk factors evenly distributed between 30 and 70 years. CIMT was determined by evaluating B-mode ultrasonograms offline according to a standardized protocol. The unpaired t-test was used to compare normal-distributed continuous variables, the Chi-squared test for normal-distributed categorical variables and the Mann–Whitney U test for non-normal distributed continuous variables. The association between risk prediction scores and CIMT was calculated by the Spearman rank correlation coefficient. Pearson correlation coefficient was used for the correlation between cardiovascular risk factors and CIMT. A multiple linear regression analysis was executed for the association of cardiovascular risk factors and CIMT. Results Age, systolic blood pressure, fasting glucose, total, LDL- and non-HDL-cholesterol and waist circumference were significantly associated with CIMT (each P ≤ 0.03). The Framingham Risk Score, the Prospective Cardiovascular Münster Study Score and the European Society of Cardiology Score correlated significantly but only moderately with CIMT. The Framingham Risk Score considering BMI correlated most strongly and predicted 27% of the CIMT variance in men and 20% in women. Conclusion In individuals without overt cardiovascular risk factors and thus at low cardiovascular risk, CIMT and cardiovascular risk factors correlated only partially suggesting that combining CIMT and conventional risk factors or common derived scores may improve risk prediction in individuals at low cardiovascular risk. The clinical benefit as to cardiovascular events of such combined risk prediction needs to be explored in large prospective cohorts of still healthy low-risk volunteers. DRKS ID DRKS00015209 07/02/2019 retrospectively registered https://www.drks.de/drks_web/navigate.do?navigationId=resultsExt


2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098739
Author(s):  
Yuxia Cheng ◽  
Ping Zu ◽  
Jie Zhao ◽  
Lintao Shi ◽  
Hongyan Shi ◽  
...  

Objective To investigate the characteristics of diabetic foot ulcer (DFU) recurrence. Methods A total of 573 patients with DFUs were recruited and divided into an initial group (395 patients) and a recurrence group (178 patients). The factors related to recurrence were analyzed using multivariate regression. Results The recurrence group had longer diabetes duration (odds ratio [OR] 192; 95% confidence interval 120, 252 vs. 156; 96, 240); lower glycated hemoglobin levels (OR 8.1; 95% CI 6.8, 9.6 vs. 9.1; 7.4, 10.5), and higher rates than the initial group of amputation (37.5% vs. 2.0%), history of vascular intervention (21.3% vs. 3.9%), retinopathy (77.7% vs. 64.7%), callus (44.4% vs. 20.8%), foot deformity (51.2% vs. 24.6%), and outdoor sports shoe wearing (34.0% vs. 21.2%). Multiple factor logistic regression analysis showed that diabetes duration (OR 1.004), callus (OR 2.769), vascular intervention (OR 2.824) and amputation (OR 22.256) were independent risk factors for DFU recurrence. Conclusion Diabetes duration, callus, history of vascular intervention, and amputation were independent risk factors for recurrent DFUs in a cohort of Chinese patients with active DFU. The prevention and treatment of DFUs, especially callus treatment, foot care, and blood glucose control, should be improved in China.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Caro Codon ◽  
T Lopez-Fernandez ◽  
C Alvarez-Ortega ◽  
P Zamora Aunon ◽  
I Rodriguez Rodriguez ◽  
...  

Abstract Background The actual usefulness of CV risk factor assessment in the prognostic evaluation of cancer patients treated with cardiotoxic treatment remains largely unknown. Design Prospective multicenter study in patients scheduled to receive anticancer therapy related with moderate/high cardiotoxic risk. Methods A total of 1324 patients underwent follow-up in a dedicated cardio-oncology clinic from April 2012 to October 2017. Special care was given to the identification and control of CV risk factors. Clinical data, blood samples and echocardiographic parameters were prospectively collected according to protocol, at baseline before cancer therapy and then at 3 weeks, 3 months, 6 months, 1 year, 1.5 years and 2 years after initiation of cancer therapy. Results At baseline, 893 patients (67.4%) presented at least 1 risk factor, with a significant number of patients newly diagnosed during follow-up. Individual risk factors were not related with worse prognosis during a 2-year follow-up. However, a higher Systemic Coronary Risk Estimation (SCORE) was significantly associated with higher rates of severe cardiotoxicity and all-cause mortality [HR 1.79 (95% CI 1.16–2.76) for SCORE 5–9 and HR 4.90 (95% CI 2.44–9.82) for SCORE ≥10 when compared with patients with lower SCORE (0–4)]. Conclusions This large cohort of patients treated with a potentially cardiotoxic regimen showed a significant prevalence of CV risk factors at baseline and significant incidence during follow-up. Baseline cardiovascular risk assessment using SCORE predicted severe cardiotoxicity and all-cause mortality. Therefore, its use should be recommended in the evaluation of cancer patients. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was partially funded by the Fondo Investigaciones Sanitarias (Spain), Centro de Investigaciόn Biomédica en Red Cardiovascular CIBER-CV (Spain)


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