Increased Frequency of Thromboses Among Patients with Philadelphia (Ph) Negative Myeloproliferative Neoplasms in New Mexico: The Role of Prothrombotic Risk Factors

Introduction Thromboses are a common complication in patients with myeloproliferative neoplasms (MPN) and are reported to occur at a rate of 15- 20% at sea level. In the MPN-Thromboses spectrum which includes both arterial and venous thrombosis, cardiovascular disease (CVD) is noted to be the most common thrombotic event. JAK2 V617F is reported to be the most common driver mutation in MPNs and is associated with increased risk of thromboses. CALR and MPL are other mutations whose contribution to the thrombotic phenotype is not known. Chronic hypoxia from living in moderate or high altitude is reported to be an independent prothrombotic risk factor. The average elevation of New Mexico is 5,700 feet (1,740 meters) above sea level. The goal of this study is to evaluate the frequency of thromboses and prothrombotic risk factors in patients with MPN in patients in this distinct population. Methods We reviewed 134 patients, who were diagnosed with MPN in University of New Mexico Comprehensive Cancer Center between 2001 to 2019. A retrospective chart review was conducted to identify demographics, clinical and molecular risk factors for both arterial and venous thromboses. The mutation analyses for Janus Kinase 2 (JAK2), myeloproliferative leukemia (MPL) gene and calreticulin (CALR) gene were performed by polymerase chain reaction (PCR). Contingency table and logistic regression methods were applied to analyze and compare the distribution of the prothrombotic risk factors between the patients with and without thrombosis. Results In this study, 62 patients (47%) were diagnosed with ET, 47 patients (35%) with PV, and 22 patients (17%) with primary myelofibrosis (PMF). Seventy-five patients (56%) were females. Mean age at diagnosis was 62 years. 102 patients (77%) were living in the Albuquerque metropolitan area with an average elevation of 5312 feet above sea level and others were in areas with an elevation of 6000 feet or higher in New Mexico. Forty-four patients (33%) experienced either arterial (29) or venous thromboses (11) or both (4). A significant percentage (70.4%) of thrombotic events were either ischemic stroke or myocardial infarction. The patients with thromboses were predominantly males (21/36, 57%) while most patients without thromboses were females (56/90, 62%) with p=0.003. Twenty-one (53%) patients with thromboses had ET; however, a higher proportion of patients with PV (20/47, 42.5%) developed thromboses compared to ET or PMF (32.2% and 9% respectively). Also, a significant number of patients (32/44, 76%) with thromboses have JAK2 mutations while only 4 patients (9%) have CALR gene mutation. Although not statistically significant, CALR mutation was associated with lesser thrombotic events than other MPN patients. In univariate logistic regression analysis, PV and ET were significantly associated with increased thrombotic events. Patients with PV showed a 7.7-fold increase and patients with ET have a 5.1-fold increase in odds for thrombosis compared to patients with PMF (p=0.0365). Female gender was associated with decreased thrombotic risk with an odds ratio of 0.46 (p=0.0387). There was no significant difference between patients with and without thromboses, regarding other clinical characteristics such as age, previous aspirin use, leukocytosis, diabetes, hypertension, hyperlipidemia, obesity, and smoking. Conclusion An increased frequency of thromboses was observed among patients with Ph negative MPN in New Mexico which is significantly higher than previously reported studies. This strongly suggests the role of mild to moderate hypoxia as a contributing prothrombotic risk factor for MPN. The role of chronic hypoxia and its influence in thrombotic events in MPN need to be further evaluated in prospective studies. The decreased risk of thrombosis in females and patients harboring CALR mutations compared to other common mutations was consistent with other published studies. JAK2 mutation was not associated with an increased risk of thrombosis. Other genetic factors in this population were not evaluated in this study. Disclosures Arana Yi: Jazz Pharmaceuticals: Other: Advisory Board.

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Post-Bariatric Abdominoplasty: Analysis of 406 Cases With Focus on Risk Factors and Complications

Aesthetic Surgery Journal ◽

10.1093/asj/sjaa067 ◽

2020 ◽

Vol 41 (1) ◽

pp. 59-71 ◽

Cited By ~ 3

Author(s):

Torsten Schlosshauer ◽

Marcus Kiehlmann ◽

Diana Jung ◽

Robert Sader ◽

Ulrich M Rieger

Keyword(s):

Risk Factors ◽

Wound Healing ◽

Surgical Technique ◽

Significant Risk ◽

Level Of Evidence ◽

Increased Risk ◽

Potential Risk Factors ◽

Wound Healing Problems ◽

Bariatric Patients

Abstract Background Post-bariatric patients present a surgical challenge within abdominoplasty because of residual obesity and major comorbidities. In this study, we analyzed complications following abdominoplasty in post-bariatric patients and evaluated potential risk factors associated with these complications. Objectives The authors sought to determine the complications and risk factors following abdominoplasty in post-bariatric patients. Methods A retrospective study of patients who underwent abdominoplasty was performed from January 2009 to December 2018 at our institution. Variables analyzed were sex, age, body mass index (BMI), smoking, surgical technique, operative time, resection weight, drain output, and complications. Results A total of 406 patients were included in this study (320 female and 86 male) with a mean age of 44.4 years and a BMI of 30.6 kg/m2. Abdominoplasty techniques consisted of traditional (64.3%), fleur-de-lis technique (27.3%), and panniculectomy without umbilical displacement (8.4%). Overall complications recorded were 41.9%, the majority of these being wound-healing problems (32%). Minor and major complications were found in 29.1% and 12.8% of patients, respectively. A BMI value of ≥30 kg/m2 was associated with an increased risk for wound-healing problems (P = 0.001). The frequency of total complications was significantly related to age (P = 0.007), BMI (P = 0.004), and resection weight (P = 0.001). Abdominoplasty technique tended to influence total complications. Conclusions This study demonstrates in a fairly large sample of post-bariatric patients (n = 406) that abdominoplasty alone can be performed safely, with an acceptable complication rate. Age, BMI, and resection weight are shown to be significant risk factors for total complications. The role of surgical technique needs to be evaluated further. Level of Evidence: 4

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The Susceptibility of Healthy People to COVID-19 Infection and the Role of ACE2

Journal of Iranian Medical Council ◽

10.18502/jimc.v4i3.7212 ◽

2021 ◽

Author(s):

Mehdi Kushkestani ◽

Mohsen Parvani ◽

Bakhtyar Tartibian ◽

Rasoul Eslami

Keyword(s):

Risk Factors ◽

Cost Effective ◽

Normal Subjects ◽

Definitive Treatment ◽

Activity Levels ◽

Cost Effective Approach ◽

Increased Risk ◽

Physical Activity Levels ◽

Ace2 Gene

The COVID-19 virus has caused many deaths of people worldwide since the pandemic began. However, no definitive treatment for this infection has been discovered so far. It has been shown that comorbidities such as diabetes, hypertension and cardiovascular diseases are associated with an increased risk of SARS-COV-2 infection. Interestingly, SARS-COV-2, like SARS-COV, uses the ACE2 gene to enter the host cell. Also, changes or imbalance in ACE2.ACE can affect SARS-COV-2 susceptibility, related outcomes and mortality. Regarding the crucial role of ACE2 protein in COVID-19 infection, the effect of different factors such as age, BMI, physical activity levels, nutritional status, altitude, as well as blood group was assessed on the level of this protein. Further, to our knowledge, no study has been conducted to examine factors that increase or decrease the risk of COVID-19 and its related severity and outcome in normal subjects emphasizing the pivotal role of ACE2. Therefore, the primary purpose of this study was to investigate the involved mechanisms of ACE2 protein and other risk factors causing infection in different situations and finally, to introduce a safe, accurate, and cost-effective approach to prevent SARS-COV-2 infection and hard clinical outcomes in normal subjects.

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Association between Risk Factors for Vascular Dementia and Adiponectin

BioMed Research International ◽

10.1155/2014/261672 ◽

2014 ◽

Vol 2014 ◽

pp. 1-13 ◽

Cited By ~ 17

Author(s):

Juhyun Song ◽

Won Taek Lee ◽

Kyung Ah Park ◽

Jong Eun Lee

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Signal Transduction ◽

Vascular Dementia ◽

Case Control ◽

Case Control Studies ◽

Insulin Signal Transduction ◽

Increased Risk ◽

The Brain

Vascular dementia is caused by various factors, including increased age, diabetes, hypertension, atherosclerosis, and stroke. Adiponectin is an adipokine secreted by adipose tissue. Adiponectin is widely known as a regulating factor related to cardiovascular disease and diabetes. Adiponectin plasma levels decrease with age. Decreased adiponectin increases the risk of cardiovascular disease and diabetes. Adiponectin improves hypertension and atherosclerosis by acting as a vasodilator and antiatherogenic factor. Moreover, adiponectin is involved in cognitive dysfunction via modulation of insulin signal transduction in the brain. Case-control studies demonstrate the association between low adiponectin and increased risk of stroke, hypertension, and diabetes. This review summarizes the recent findings on the association between risk factors for vascular dementia and adiponectin. To emphasize this relationship, we will discuss the importance of research regarding the role of adiponectin in vascular dementia.

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The Power of Extracellular Vesicles in Myeloproliferative Neoplasms: “Crafting” a Microenvironment That Matters

Cells ◽

10.3390/cells10092316 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2316

Author(s):

Lucia Catani ◽

Michele Cavo ◽

Francesca Palandri

Keyword(s):

Extracellular Vesicles ◽

Immune Escape ◽

Myeloproliferative Neoplasms ◽

Cell Communication ◽

Bioactive Molecules ◽

Driver Genes ◽

Hematopoietic Stem ◽

Increased Risk ◽

Patients Experience

Myeloproliferative Neoplasms (MPN) are acquired clonal disorders of the hematopoietic stem cells and include Essential Thrombocythemia, Polycythemia Vera and Myelofibrosis. MPN are characterized by mutations in three driver genes (JAK2, CALR and MPL) and by a state of chronic inflammation. Notably, MPN patients experience increased risk of thrombosis, disease progression, second neoplasia and evolution to acute leukemia. Extracellular vesicles (EVs) are a heterogeneous population of microparticles with a role in cell-cell communication. The EV-mediated cross-talk occurs via the trafficking of bioactive molecules such as nucleic acids, proteins, metabolites and lipids. Growing interest is focused on EVs and their potential impact on the regulation of blood cancers. Overall, EVs have been suggested to orchestrate the complex interplay between tumor cells and the microenvironment with a pivotal role in “education” and “crafting” of the microenvironment by regulating angiogenesis, coagulation, immune escape and drug resistance of tumors. This review is focused on the role of EVs in MPN. Specifically, we will provide an overview of recent findings on the involvement of EVs in MPN pathogenesis and discuss opportunities for their potential application as diagnostic and prognostic biomarkers.

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Diagnostic Studies for Thrombophilia in Women on Hormonal Therapy and During Pregnancy, and in Children

Archives of Pathology & Laboratory Medicine ◽

10.5858/2002-126-1296-dsftiw ◽

2002 ◽

Vol 126 (11) ◽

pp. 1296-1303

Author(s):

Benjamin R. Brenner ◽

Ulrike Nowak-Göttl ◽

Andrea Kosch ◽

Marilyn Manco-Johnson ◽

Michael Laposata

Keyword(s):

Risk Factors ◽

Clinical Practice ◽

Oral Contraceptive ◽

Medical Literature ◽

Data Extraction ◽

Data Sources ◽

Current Clinical Practice ◽

Extensive Review ◽

Prothrombotic Risk Factors

Abstract Objective.—To review the role of acquired and inherited prothrombotic risk factors that increase the risk of thrombosis in oral contraceptive users, during pregnancy, and in neonates, infants, and children; and to determine by the consensus opinion of recognized experts in the field which risk factors should be determined in which individuals at which time. Data Sources.—Review of the medical literature and current clinical practice by a panel of experts in the field of thrombophilia. Data Extraction and Synthesis.—The experts made an extensive review of the published literature and prepared a draft manuscript, which included preliminary recommendations. The draft manuscript was circulated to participants in the College of American Pathologists Conference XXXVI: Diagnostic Issues in Thrombophilia prior to the conference. The manuscript and recommendations were then presented at the conference for discussion. Recommendations were accepted if a consensus of the 26 experts attending the conference was reached. The results of the discussion were used to revise the manuscript into its final form. Conclusions.—This report reviews the options for testing for thrombophilic states in women using oral contraceptives, during pregnancy, and in neonates and children. General guidelines for testing in these clinical situations are provided, along with citation of the appropriate supporting literature.

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Abstract WP164: Role of Risk Factors in the Paradoxical Effect of Smoking on Peri-procedural Stroke in SAMMPRIS

Stroke ◽

10.1161/str.44.suppl_1.awp164 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Christine A Holmstedt ◽

Tanya N Turan ◽

Michael J Lynn ◽

Bethany F Lane ◽

Jean Montgomery ◽

...

Keyword(s):

Risk Factors ◽

Odds Ratio ◽

Multivariate Analyses ◽

Smoking Status ◽

Active Form ◽

Intracranial Stenosis ◽

Contributory Factor ◽

Increased Risk ◽

Never Smokers

Background: A previous SAMMPRIS analysis of patients randomized to stenting showed that peri-procedural ischemic infarcts were significantly associated with diabetes, basilar stenosis, age, and smoking status with never smokers having a higher risk (odds ratio = 8.8, p< 0.001). We sought to determine if this finding could be due to a higher burden of other risk factors in never smokers. Method: Baseline features in 213 patients undergoing stenting in SAMMPRIS were compared between never smokers vs. former and current smokers in univariate and multivariate analyses. Logistic regression was used to determine the effect of smoking on peri-procedural ischemic infarcts after adjusting for factors related to smoking. Data: Univariate results are shown in Table 1. Never smokers were significantly (P<0.05) more likely to be female, diabetic, hypertensive, and have another intracranial stenosis, but in multivariate analyses only hypertension and another intracranial stenosis remained significantly (P<0.05) associated with smoking status. In a multivariate model that incorporated hypertension and another intracranial stenosis along with smoking status, diabetes, basilar stenosis, and age, smoking status remained significant with an increased risk among patients who never smoked (odds ratio = 5.3, p = 0.005). Conclusion: While never smokers had significantly higher rates of some risk factors compared to active or previous smokers, these risk factors do not explain all the increased risk of early stroke in never smokers after stenting in SAMMPRIS. Another contributory factor may be that smoking accelerates the conversion of clopidogrel to its active form.

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Childhood trauma and being at-risk for psychosis are associated with higher peripheral endocannabinoids

Psychological Medicine ◽

10.1017/s0033291719001946 ◽

2019 ◽

Vol 50 (11) ◽

pp. 1862-1871 ◽

Cited By ~ 2

Author(s):

E. Appiah-Kusi ◽

R. Wilson ◽

M. Colizzi ◽

E. Foglia ◽

E. Klamerus ◽

...

Keyword(s):

Risk Factors ◽

At Risk ◽

Childhood Trauma ◽

Childhood Maltreatment ◽

Peripheral Blood ◽

Endocannabinoid System ◽

History Of Childhood ◽

Increased Risk ◽

History Of

AbstractBackgroundEvidence has been accumulating regarding alterations in components of the endocannabinoid system in patients with psychosis. Of all the putative risk factors associated with psychosis, being at clinical high-risk for psychosis (CHR) has the strongest association with the onset of psychosis, and exposure to childhood trauma has been linked to an increased risk of development of psychotic disorder. We aimed to investigate whether being at-risk for psychosis and exposure to childhood trauma were associated with altered endocannabinoid levels.MethodWe compared 33 CHR participants with 58 healthy controls (HC) and collected information about previous exposure to childhood trauma as well as plasma samples to analyse endocannabinoid levels.ResultsIndividuals with both CHR and experience of childhood trauma had higher N-palmitoylethanolamine (p < 0.001) and anandamide (p < 0.001) levels in peripheral blood compared to HC and those with no childhood trauma. There was also a significant correlation between N-palmitoylethanolamine levels and symptoms as well as childhood trauma.ConclusionsOur results suggest an association between CHR and/or childhood maltreatment and elevated endocannabinoid levels in peripheral blood, with a greater alteration in those with both CHR status and history of childhood maltreatment compared to those with either of those risks alone. Furthermore, endocannabinoid levels increased linearly with the number of risk factors and elevated endocannabinoid levels correlated with the severity of CHR symptoms and extent of childhood maltreatment. Further studies in larger cohorts, employing longitudinal designs are needed to confirm these findings and delineate the precise role of endocannabinoid alterations in the pathophysiology of psychosis.

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Venous Thrombosis: The Role of Genes, Environment, and Behavior

Hematology ◽

10.1182/asheducation.v2005.1.1.1 ◽

2005 ◽

Vol 2005 (1) ◽

pp. 1-12 ◽

Cited By ~ 5

Author(s):

Frits R. Rosendaal

Keyword(s):

Risk Factors ◽

Venous Thrombosis ◽

Protein S ◽

Behavioral Risk ◽

Antithrombin Deficiency ◽

Increased Risk ◽

Environment And Behavior ◽

And Behavior ◽

Subsequent Identification

Abstract Over the last decade we have witnessed an avalanche of newly identified risk factors for venous thrombosis. This has advanced our knowledge of its etiology, because more determinants have been described and because the underlying concepts have received a new and broader understanding. Venous thrombosis is a common multicausal disease occurring as the result of interacting genetic, environmental and behavioral risk factors. Some of these have been known since medieval times, such as the increased risk of thrombosis during immobilization in pregnancy and after childbirth (although retained milk of the breast-feeding mother was seen as the primary cause for the latter). Pregnancy and puerperium still cause thrombosis, as do exogenous hormones in oral contraceptives and hormonal replacement therapy. Furthermore, the immobilization in the puerperium of the old days translates directly to situations of immobilization in current times, such as prolonged travel in airplanes or excessive electronic gaming. While pedigrees with abundant thrombosis were observed in the early 1900s, the first cause of heritable thrombophilia (antithrombin deficiency) was discovered in 1965, with the subsequent identification of deficiencies of protein C and protein S in the early 1980s. These were uncommon and strong risk factors, whereas the more recently discovered genetic variants are common and weak, and cause disease only in the presence of other factors.

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How I treat rare venous thromboses

Blood ◽

10.1182/blood-2008-07-165969 ◽

2008 ◽

Vol 112 (13) ◽

pp. 4818-4823 ◽

Cited By ~ 37

Author(s):

Ida Martinelli ◽

Massimo Franchini ◽

Pier Mannuccio Mannucci

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Recent Progress ◽

Randomized Trials ◽

Lower Limbs ◽

Optimal Management ◽

Venous Diseases ◽

Acquired Thrombophilia ◽

Venous Thromboses

Abstract Venous thromboembolism may involve venous sites other than the lower limbs, such as cerebral, splanchnic, and upper limb veins. Although uncommon, these thromboses may be clinically severe and challenging for caregivers. In this review, the main pathogenic, clinical, and therapeutic features of thromboses in rare venous sites are discussed. Even though there was a lot of recent progress in understanding the mechanistic role of inherited and acquired thrombophilia and of the interactions between different risk factors, the optimal management of these patients is still unsettled, being currently based on the consensus of experts due to the lack of randomized trials. The implementation of large interdisciplinary registries is a necessary weapon to optimize the treatment of rare venous diseases.

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