Inpatient Outcomes and Rates of Venous Thromboembolism and Gastrointestinal Bleeding in Patients with Hepatocellular Carcinoma: Results from Nationwide Inpatient Sample Database 2007-2016

Background: Patients with hepatocellular carcinoma (HCC) are at an increased risk for developing venous thromboembolism (VTE)- mainly portal venous thrombosis (PVT). Malignancy and liver cirrhosis ( 80%-90% of HCC cases are related to cirrhosis) are conditions that can perturb the hemostatic balance towards a prothrombotic state. Also, these patients with HCC are at high risk for gastrointestinal bleeding (GIB), making thromboprophylaxis and anticoagulation a treatment challenge. Additional information regarding the outcomes and severity of both VTE and GIB in patients with HCC would be useful to guide clinical decision-making Aim: To determine the rates, inpatient mortality, length of stay (LOS) and hospital cost of VTE and GIB-related admissions in patients with hepatocellular carcinoma. Method: We used ICD-9-CM and ICD-10-CM codes to identify hospitalizations from 2007 to 2016 that included HCC with primary discharge diagnoses of GIB or VTE. Linear trends in the rate of GIB and VTE, as well as in-hospital mortality, LOS, and inflation-adjusted hospital cost (in 2016 US dollars), were evaluated using Daniel's test; piecewise slopes were used as needed. All analyses accounted for the NIS sampling design with updated hospital trend weights used as appropriate. SAS v. 9.4 was used for all analyses. Results: Between 2007 and 2016, we identified 6,527,871 hospitalizations with HCC and a primary discharge diagnosis of GIB (3,517,059; 53.9%) or VTE (3,010,812; 46.1%). From 2007 to 2010, a decreasing trend was observed in the rate of GIB diagnoses (55.5% to 51.6%, ptrend < .001), whereas an increasing trend was observed for VTE diagnoses (44.5% to 48.4%, ptrend < .001). By contrast, from 2010 to 2016, an increasing trend was observed in GIB (51.6% to 55.2%, ptrend < .001), whereas a decreasing trend was observed in VTE (48.4% to 44.8%, ptrend < .001). For in-hospital mortality, a decreasing trend was observed for GIB (2.3% to 1.9%, ptrend < .001), whereas a decreasing trend was observed in VTE until 2012 (1.8% to 1.5%, ptrend < .001), after which no trend was indicated (1.5% to 1.6%, ptrend = .337). Although decreasing trends in LOS were observed for GIB (3.4 days to 3.2 days, ptrend < .001) and VTE (4.3 days to 3.3 days, ptrend < .001), increasing trends were observed for inflation-adjusted hospital cost for both GIB ($6,996 to $7,707, ptrend < .001) and VTE ($7,283 to $7,584, ptrend = .048). Conclusion: In this NIS cohort of hospitalized patients with HCC, GIB was more frequently observed than VTE. Trends observed in the rates of GIB and VTE went in opposite directions. In general decreasing trends were observed in in-hospital mortality and LOS for both VTE and GIB. By contrast, increasing trends were observed in the hospital cost for both diagnoses. Clinicians should balance benefits against risks when deciding VTE prophylaxis and treatment in patients with HCC. Future studies are needed to determine the ideal agent and specific dosages to treat HCC-associated VTE. Disclosures No relevant conflicts of interest to declare.

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Circulating Microparticles and Risk of Venous Thromboembolism.

Blood ◽

10.1182/blood.v114.22.3987.3987 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3987-3987

Author(s):

Paolo Bucciarelli ◽

Emanuele Previtali ◽

Ida Martinelli ◽

Andrea Artoni ◽

Serena M Passamonti ◽

...

Keyword(s):

Body Mass Index ◽

Venous Thromboembolism ◽

Body Mass ◽

Plasma Levels ◽

Conflicts Of Interest ◽

Factor V Leiden ◽

Control Group ◽

Dependent Manner ◽

Healthy Controls ◽

Increased Risk

Abstract Abstract 3987 Poster Board III-923 Background Microparticles (MPs) are circulating, submicroscopic fragments (<1 μm of diameter) of membrane-bound cytoplasm that shed from the surface of an activated or apoptotic cell and play a role in coagulation, inflammation, cell remodelling and proliferation. There is increasing evidence that MPs are involved in thrombosis, but whether or not they are an independent risk factor for venous thromboembolism (VTE) is not established. Aim of the study To investigate the association between high plasma levels of MPs and risk of VTE Patients and Methods In a case-control study, 186 patients with a first episode of VTE (deep venous thrombosis and/or pulmonary embolism) and 418 healthy controls were included. MPs were analyzed by flow cytometry with a gate defined by a 1 μm beads and using APC-Annexin V together with FITC anti-CD41 or FITC anti-CD142 antibodies in order to identify platelet MPs (MP-Plts) and MPs exposing tissue factor (MP-TF), respectively. MPs levels were expressed as number/μL. Results Patients had significantly higher median plasma levels of both MPs-Plts and MPs-TF than controls [1942 vs 1519 (p<0.0001) and 579 vs 454 (p<0.0001)]. Higher median levels of MP-Plts and MP-TF were found in 41 patients who underwent blood sampling within 6 months from VTE than in those sampled later [2114 vs 1694 (p=0.086) and 652 vs 543 (p=0.120)]. Sex, age, body mass index and factor VIII plasma levels had no influence on MPs levels, as well as the use of oral contraceptives (this latter evaluated only in controls). In the whole study population, carriership of thrombophilia (antithrombin, protein C or protein S deficiency, factor V Leiden, prothrombin G20210A, antiphospholipid antibodies, hyperhomocysteinemia or combined abnormalities) had higher levels of MP-Plts and MP-TF than non-carriers [1907 vs 1565 (p=0.002) and 532 vs 468 (p=0.011)]. The odds ratio (OR) for VTE, adjusted for sex, age, body mass index and thrombophilia was 2.5-fold higher in individuals with MPs plasma levels >95th percentile of the control group (3633/μL for MPs-Plts and 1113/μL for MPs-TF) than in those with MPs levels ≤95th percentile [for MPs-Plts: OR=2.59 (95%CI 1.23 – 5.45); for MPs-TF: OR=2.38 (1.15 – 4.92)]. The risk increased in a dose-dependent manner for both MPs-Plts and MPs-TF, particularly above the 75th percentile of the distribution in controls. The exclusion of patients whose MPs levels were measured within 6 months from VTE (in order to avoid the possible effect of the acute phase on MPs measurements), did not change the results [adjusted OR: 2.63 (1.18 – 5.89) for MPs-Plts and 2.36 (1.10 – 5.19) for MPs-TF]. The Table shows the relative risks of VTE associated with the presence or absence of high MPs levels and thrombophilia. Individuals with MPs >95th percentile or thrombophilia alone had a 2 to 3-fold increased risk of VTE, whereas those with both MPs-Plts >95th percentile and thrombophilia had a 9-fold increased risk of VTE. This synergistic effect was confirmed also for MPs-TF and remained after the exclusion of patients whose blood sample was collected within 6 months from VTE [OR 7.72 (1.68-35.4) for MP-Plts and 8.14 (2.08-31.8) for MP-TF]. Conclusions Plasma levels of MPs are significantly higher in patients with VTE than in healthy controls. MPs levels >95th percentile are associated with a 2.5-fold increased risk of VTE. There is a synergistic interaction between high levels of MPs and thrombophilia on VTE risk. Disclosures: No relevant conflicts of interest to declare.

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Statins and Venous Thromboembolism In Lung Cancer

Blood ◽

10.1182/blood.v116.21.5122.5122 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5122-5122

Author(s):

Moh'd Khushman ◽

Abdel-ghanie Abu-samra ◽

Shatha Farhan ◽

Gordon Jacobsen ◽

Amr Hanbali ◽

...

Keyword(s):

Lung Cancer ◽

Venous Thromboembolism ◽

Cancer Patients ◽

Conflicts Of Interest ◽

Statistical Significance ◽

Lipid Lowering ◽

Coagulation Cascade ◽

Controlled Study ◽

Increased Risk ◽

Statin Use

Abstract Abstract 5122 Background: Dyslipidemia plays a major role in the pathophysiology of atherosclerosis which may also contributed to an increased risk of and thromboembolism from the injury of the vascular endothelium and its activation of platelets, thereafter, the coagulation cascade. It has been well-established that the use of statins in patients with dyslipidemia reduces cardiovascular events and mortality, therefore, improves survival. In addition to a cholesterol-lowering effect, statins exhibit antithrombotic and anti-inflammatory properties that may confer a protective benefit to an increased risk of thromboembolism in cancer patients. Several case-controlled studies reported that cancer patients receiving long-term statins, but not other non-statin lipid lowering treatment, had a lower incidence of venous thromboembolism. Methods: To investigate any protective benefit from statin use in lung cancer patients, we have conducted this retrospective, case-controlled study. Total of 1548 patients with lung cancer were included from the tumor registery at Henry Ford Health System, Detroit, Michigan, between January 1999 and December 2004. The data were extracted from available electronic medical records of these patients. Statistical analyses were performed and stratified for statin users versus non statin users. Results: Out of 1,548 patients, 315 patients (average age was 68, range 46–90) were statin users at the time of their lung cancer diagnosis. The remaining 1233 patients (average age was 65.9, range 29–94) were non- statin users. After stratifying for statin use, 25 of the 315 statin users developed DVT/PE (7.9%), while 100 of the 1233 non-statin users developed DVT/PE (8.1%). This potential benefit from statin use can also be better visualized from comparing the development of DVT/PE between the statin and non-statin groups in a Kaplan-Meier curve for the probability of freedom from DVT/PE across time. Though statistical significance was not reached (log-rank p-value = 0.377), a trend towards a slightly decreased incidence of DVT/PE onset in the patients who receiving statin as the lipid-lowering agent has been observed. Conclusion: Based on our preliminary data, statin use in patients with lung cancer has demonstrated a weak but favorable protective effect on the development of a venous thromboembolism. The nature as a retrospective study and not well-balanced two group of patients (e.g., the average age of statin users were 2 years older than the non-statin users) may limit our results from reaching statistical significance. In addition, some of the patients who had no clear documentation of their home medications had also been categorized as non-statin users in our study. The results from our final data analysis will be presented. Disclosures: No relevant conflicts of interest to declare.

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Influence Of Antithrombin Deficiency On Symptomatic Recurrent Venous Thromboembolism (VTE) In Children: A Multicenter Cohort Study

Blood ◽

10.1182/blood.v122.21.3619.3619 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3619-3619

Author(s):

Gili Kenet ◽

Verena Limperger ◽

Neil A Goldenberg ◽

Christine Heller ◽

Susanne Holzhauer ◽

...

Keyword(s):

Multivariate Analysis ◽

Venous Thromboembolism ◽

Pediatric Patients ◽

Cox Regression ◽

Conflicts Of Interest ◽

Antithrombin Deficiency ◽

Increased Risk ◽

Recurrent Venous Thromboembolism ◽

At Deficiency ◽

Recurrent Vte

Abstract Objective To determine the importance of antithrombin [AT] deficiency as risk factor or predictor for fatal/non-fatal recurrent venous thromboembolism (VTE) in children. Methods In the present cohort of 874 consecutively enrolled pediatric patients with VTE aged newborn to <18 years the rate of VTE recurrence and the time to recurrence in relation to AT-deficiency [confirmed by underlying gene mutations; type 1 deficiency n=17; type 2 deficiency n=3], age and sex was determined. Twenty of 874 patients [2.4%] suffered from AT-deficiency. From the same cohort 150 VTE children carrying the heterozygous F5 G1691A mutation [F5: 17.7%] served as controls. Patients were prospectively followed for a median of 84 months. Data were pooled across participating sites to increase power and to enhance the generalisability of the data. Incidence rates were given as events per 1000 person-years. Results Of the 170 children enrolled 26 [AT n=9; F5 n=17] had recurrent VTE at a median of 15 months [95%CI: 12-36] following VTE onset: two of nine [AT] and two of 17 [F5] children suffered recurrent VTE while on anticoagulation with warfarin. The overall incidence rate of recurrence was 61.5 in patients with AT-deficiency compared to 23.5 for pediatric F5 carriers [p=0.02]. The recurrent-free survival probability is shown in the figure [logrank p-value: p=0.001]. When comparing AT patients and F5 children multivariate analysis [Cox regression] adjusted for age, sex and duration of anticoagulation treatment showed that AT deficiency [HR/95%CI: 4.1/1.8-9.4] significantly influenced the hazard for recurrent VTE. Conclusions Based on multivariate analysis, the presence of AT deficiency was associated with an increased risk of VTE recurrence. AT-deficiency in pediatric patients should be identified at VTE onset and the possible influence of intensified treatment protocols on recurrence should be studied in future prospective international studies. Condensed abstract To determine the relative importance of antithrombin deficiency or factor V (FV) mutations as risk factors for fatal/non-fatal recurrence in pediatric thromboembolism (VTE). Antithrombin deficiency influenced the hazard for recurrent VTE. Disclosures: No relevant conflicts of interest to declare.

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NLP Methods for Extraction of Symptoms from Unstructured Data for Use in Prognostic COVID-19 Analytic Models

Journal of Artificial Intelligence Research ◽

10.1613/jair.1.12631 ◽

2021 ◽

Vol 72 ◽

pp. 429-474

Author(s):

Greg M. Silverman ◽

Himanshu S. Sahoo ◽

Nicholas E. Ingraham ◽

Monica Lupei ◽

Michael A. Puskarich ◽

...

Keyword(s):

Hospital Mortality ◽

Clinical Decision Making ◽

Quality Care ◽

Vital Signs ◽

Clinical Decision ◽

Prognostic Models ◽

P Value ◽

Rule Based ◽

Presenting Symptoms ◽

Increased Risk

Statistical modeling of outcomes based on a patient's presenting symptoms (symptomatology) can help deliver high quality care and allocate essential resources, which is especially important during the COVID-19 pandemic. Patient symptoms are typically found in unstructured notes, and thus not readily available for clinical decision making. In an attempt to fill this gap, this study compared two methods for symptom extraction from Emergency Department (ED) admission notes. Both methods utilized a lexicon derived by expanding The Center for Disease Control and Prevention's (CDC) Symptoms of Coronavirus list. The first method utilized a word2vec model to expand the lexicon using a dictionary mapping to the Uni ed Medical Language System (UMLS). The second method utilized the expanded lexicon as a rule-based gazetteer and the UMLS. These methods were evaluated against a manually annotated reference (f1-score of 0.87 for UMLS-based ensemble; and 0.85 for rule-based gazetteer with UMLS). Through analyses of associations of extracted symptoms used as features against various outcomes, salient risks among the population of COVID-19 patients, including increased risk of in-hospital mortality (OR 1.85, p-value < 0.001), were identified for patients presenting with dyspnea. Disparities between English and non-English speaking patients were also identified, the most salient being a concerning finding of opposing risk signals between fatigue and in-hospital mortality (non-English: OR 1.95, p-value = 0.02; English: OR 0.63, p-value = 0.01). While use of symptomatology for modeling of outcomes is not unique, unlike previous studies this study showed that models built using symptoms with the outcome of in-hospital mortality were not significantly different from models using data collected during an in-patient encounter (AUC of 0.9 with 95% CI of [0.88, 0.91] using only vital signs; AUC of 0.87 with 95% CI of [0.85, 0.88] using only symptoms). These findings indicate that prognostic models based on symptomatology could aid in extending COVID-19 patient care through telemedicine, replacing the need for in-person options. The methods presented in this study have potential for use in development of symptomatology-based models for other diseases, including for the study of Post-Acute Sequelae of COVID-19 (PASC).

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D-Dimer Levels and Risk of Recurrence Following Provoked Venous Thromboembolism: Findings from the Riete Registry

Blood ◽

10.1182/blood-2018-99-111190 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3810-3810

Author(s):

Martin Ellis ◽

Martin Mar ◽

Monreal Manuel ◽

Orly Hamburger-Avnery ◽

Alessandra Bura-Riviere ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Venous Thromboembolism ◽

Anticoagulant Therapy ◽

Conflicts Of Interest ◽

Hazard Ratio ◽

Increased Risk ◽

Risk Patients ◽

Recurrent Vte ◽

D Dimer

Abstract Background. Patients with venous thromboembolism (VTE) secondary to transient risk factors or cancer may develop VTE recurrences after discontinuing anticoagulant therapy. Identifying at-risk patients could help to guide the ideal duration of anticoagulant therapy in these patients. Methods. We used the RIETE database to assess the prognostic value of d-dimer testing after discontinuing anticoagulation to identify patients at increased risk for recurrences. The proportion of patients with raised d-dimer levels was determined and the hazard ratio (HR) for VTE recurrences compared to those with normal levels was calculated. Univariate and multivariate analyses of factors associated with VTE recurrence were performed. Results. 3 606 patients were identified in the database in April 2018: 2 590 had VTE after a transient risk factor and 1016 had a cancer. D-dimer levels were measured after discontinuing anticoagulation in 1 732 (67%) patients with transient risk factors and 732 (72%) patients with cancer-associated VTE and these patients formed the cohort in which recurrent VTE rate was calculated. D-dimers and were elevated in 551 (31.8%) of patients with a transient risk factor and were normal in 1181 (68.2%). In the cancer-associated group, d-dimers were elevated in 398 (54.3%) and normal in 334 (45.7%) patients. The adjusted hazard ratio for recurrent VTE was: 2.32 (95%CI: 1.55-3.49) in patients with transient risk factors and 2.23 (95%CI: 1.50-3.39) in those with cancer. Conclusions. Patients with raised d-dimer levels after discontinuing anticoagulant therapy for provoked or cancer-associated VTE are at increased risk for recurrent VTE and death. Future studies could target these patients for extended anticoagulation. Disclosures No relevant conflicts of interest to declare.

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Association Between Low Blood Pressure and Clinical Outcomes in Patients With Acute Ischemic Stroke

Stroke ◽

10.1161/strokeaha.119.027336 ◽

2020 ◽

Vol 51 (1) ◽

pp. 338-341

Author(s):

Merelijne A. Verschoof ◽

Adrien E. Groot ◽

Jan-Dirk Vermeij ◽

Willeke F. Westendorp ◽

Sophie A. van den Berg ◽

...

Keyword(s):

Heart Failure ◽

Blood Pressure ◽

Ischemic Stroke ◽

Gastrointestinal Bleeding ◽

Hospital Mortality ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Odds Ratio ◽

Increased Risk ◽

Low Blood Pressure

Background and Purpose— Low blood pressure is uncommon in patients with acute ischemic stroke (AIS). We assessed the association between baseline low blood pressure and outcomes in patients with AIS. Methods— Post hoc analysis of the PASS (Preventive Antibiotics in Stroke Study). We compared patients with AIS and low (<10th percentile) baseline systolic blood pressure (SBP) to patients with normal SBP (≥10th percentile <185 mm Hg). The first SBP measured at the Emergency Department was used. Outcomes included in-hospital mortality, major complications <7 days of stroke onset, and functional outcome at 90 days (modified Rankin scale score). We used regression analysis to calculate (common) odds ratios and adjusted for predefined prognostic factors. Results— Two thousand one hundred twenty-four out of 2538 patients had AIS. The cutoff for low SBP was 130 mm Hg (n=212; range, 70–129 mm Hg). One thousand four hundred forty patients had a normal SBP (range, 130–184 mm Hg). Low SBP was associated with an increased risk of in-hospital mortality (8.0% versus 4.2%; adjusted odds ratio [aOR], 1.58; 95% CI, 1.13–2.21) and complications (16.0% versus 6.5%; aOR, 2.56; 95% CI, 1.60–4.10). Specifically, heart failure (2.4% versus 0.1%; aOR, 17.85; 95% CI, 3.36–94.86), gastrointestinal bleeding (1.9% versus 0.1%; aOR, 26.04; 95% CI, 2.83–239.30), and sepsis (3.3% versus 0.5%; aOR, 5.53; 95% CI, 1.84–16.67) were more common in patients with low SBP. Functional outcome at 90 days did not differ (shift towards worse outcome: adjusted common odds ratio, 1.24; 95% CI, 0.95–1.61). Conclusions— Whether it is cause or consequence, low SBP at presentation in patients with AIS was associated with an increased risk of in-hospital mortality and complications, specifically heart failure, gastrointestinal bleeding, and sepsis. Clinicians should be vigilant for potentially treatable complications. Clinical Trial Registration— URL: https://www.controlled-trials.com . Unique identifier: ISRCTN66140176.

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Venous Thromboembolism in Hospitalized Patients with Multiple Myeloma: A Nationwide Analysis

Blood ◽

10.1182/blood-2018-99-116101 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3596-3596

Author(s):

Kahee A Mohammed ◽

Kristen M Sanfilippo

Keyword(s):

Multiple Myeloma ◽

Venous Thromboembolism ◽

Hospital Mortality ◽

Hospitalized Patients ◽

Major Surgery ◽

Hospital Level ◽

Prolonged Hospitalization ◽

Increased Risk ◽

The Impact ◽

Hospital Characteristics

Abstract Background: The burden of multiple myeloma has increased in last 30 years, both in US and globally. Patients with multiple myeloma are at increased risk of developing venous thromboembolism (VTE) resulting in significant morbidity and mortality. This study aimed to (1) determine patient and hospital characteristics associated with VTE, (2) assess the impact of VTE on in-hospital mortality and prolonged hospitalization, and (3) examine trends in the rates of VTE and VTE-associated in-hospital mortality and prolonged hospitalization in patients with multiple myeloma. Methods: A retrospective analysis of Nationwide Inpatient Sample, 2008 - 2014, was conducted. International Classification of Diseases-9-Clinical Modification codes were used to identify hospitalized patients (aged ≥ 18 years) with multiple myeloma. Trends in the prevalence of VTE and VTE-associated in-hospital mortality and prolonged hospitalization rates were assessed using the Cochrane-Armitage test. Weighted, multilevel hierarchical logistic regression using generalized linear mixed models with generalized estimated equations were used to examine the association between patient and hospital characteristics and study outcomes Results: Among 136,652 hospitalized patients with multiple myeloma, 4.2% were diagnosed with VTE. Although statistically insignificant, a slight increase in VTE rates were observed from 2008 to 2014 (3.9% to 4.4%) (p 0.18). In adjusted multilevel hierarchical regression, we found higher odds of VTE in male gender (odds ratio [OR] = 1.08, 95% Confidence Interval [CI] = 1.02 - 1.14), Black race (OR = 1.11, 95% CI = 1.03 - 1.19), those who had a major surgery (OR = 1.73, 95% CI = 1.62 - 1.85), and higher Elixhauser comorbidity index (OR = 3.73, 95% CI = 2.66 - 5.23). Hospital level correlates of VTE included: admission to teaching vs. non-teaching (OR = 1.07, 95% CI = 1.01 - 1.13), and admission to medium vs. small sized hospitals (OR = 1.11, 95% CI = 1.01 - 1.23), while lower odds of VTE were noted among patients admitted to hospitals located in Northeast (OR = 0.91, 95% CI = 0.84 - 0.98) vs. South. Patients diagnosed with vs. without VTE had higher odds of in-hospital mortality (OR = 1.36, 95% CI = 1.22 - 1.51) and prolonged hospital stay (OR = 1.65, 95% CI = 1.55 - 1.75). A statistically significant trend for decreasing VTE associated mortality (10.0% to 5.3%) (p <.001) and prolonged hospitalization (32.1% to 28.2%) (p <.001) rates were observed across study years. Conclusions: During the study period, there has been an increase in rate of VTE among patients with multiple myeloma. Patients with multiple myeloma and VTE had a high risk of in-hospital mortality compared to those without VTE; however, rates of VTE-associated in-hospital mortality and prolongation of hospitalization have decreased over time. Hospital level characteristics were significantly associated with VTE. These findings might reflect changing detection guidelines and better management of VTE in cancer patients. Lastly, patient level characteristics independently predict the occurrence of VTE. Given the higher in-hospital mortality associated with patients with VTE and multiple myeloma, there is a need for prospective studies to identify effective strategies to prevent VTE in this patient population and improve outcomes. Disclosures Sanfilippo: Bristol-Myers Squibb: Speakers Bureau.

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Hematocrit and Incidence of Venous Thromboembolism

Blood ◽

10.1182/blood-2019-124126 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1142-1142

Author(s):

Mary Cushman ◽

Wendy Wang ◽

Romil Parikh ◽

Pamela L Lutsey ◽

Joan D Beckman ◽

...

Keyword(s):

Body Mass Index ◽

Venous Thromboembolism ◽

Confidence Interval ◽

Body Mass ◽

Complete Blood Count ◽

Conflicts Of Interest ◽

Reference Group ◽

Smoking Status ◽

Population Sample ◽

Increased Risk

Background. Polycythemia vera patients with high hematocrit have increased risk of venous thromboembolism (VTE). We tested whether high hematocrit in the general population is also associated with elevated VTE risk. Methods. The prospective Atherosclerosis Risk in Communities (ARIC) Study performed a complete blood count in 13,891 adults aged 45-64 at baseline in 1987-89. We identified and validated incident hospitalized VTEs through 2015, with provoked VTE defined as occurring within 90 days of surgery, trauma, immobilization or with cancer. We performed proportional hazards regression analyses using race-sex specific categorization of hematocrit percentiles (i.e., <5, 5-24.9, 25-74.9, 75-94.9, and 95-100 percentiles, with the 25-74.9th percentile serving as the reference group). Results. At baseline, higher hematocrit was associated with smoking prevalence, greater pack years smoked, higher body-mass index and higher prevalence of diabetes. With 26 years median follow-up, 800 participants had incident deep vein thrombosis of the leg and/or pulmonary embolism. The figure shows a J-shaped association of hematocrit with VTE incidence. The VTE incidence at the highest level of hematocrit was approximately double that at the mid level. Low hematocrit also was associated with elevated VTE incidence but the confidence interval overlapped 1. The Table shows modeling results. Accounting for other risk factors, the risk of overall VTE was elevated 72% for participants above the 95th percentile of hematocrit compared with the reference. Specifically, hazard ratios (95% confidence interval) of incident VTE were 1.27 (0.91,1.76), 1.06 (0.87,1.28), 1 (reference), 1.17 (0.98, 1.40) and 1.72 (1.30, 2.27) across the five hematocrit percentiles, adjusted for age, race, sex, body mass index, and other potential confounding variables including smoking status and pack-years. The association of high hematocrit with VTE was limited to provoked VTE, with little evidence for unprovoked VTE. Results were similar for hemoglobin (not shown). Discussion. High hematocrit and hemoglobin in a general middle-aged population sample were associated with increased long-term risk of VTE, particularly provoked VTE. The reasons for this pattern require further study. Disclosures No relevant conflicts of interest to declare.

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Elevated Levels of IL-6 and IL-8 Are Associated with An Increased Risk of Venous Thromboembolism – a Case Control Study.

Blood ◽

10.1182/blood.v114.22.2975.2975 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2975-2975

Author(s):

Marinez F Matos ◽

Dayse M Lourenço ◽

Cristina M Orikaza ◽

Maria A E Noguti ◽

Vânia M Morelli

Keyword(s):

Venous Thromboembolism ◽

Prospective Studies ◽

Plasma Levels ◽

Conflicts Of Interest ◽

Limit Of Detection ◽

Case Control ◽

Control Group ◽

Case Control Studies ◽

Increased Risk ◽

The Impact

Abstract Abstract 2975 Poster Board II-953 Background: high levels of some cytokines have been associated with an increased risk of venous thromboembolism (VTE) in some case-control studies, but not in prospective studies. However, data regarding the impact of cytokines levels on the risk of VTE are still limited. The aim of this study was to investigate the association between the risk of VTE and plasma levels of interleukin (IL)-1β, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-αa and monocyte chemotactic protein (MCP)-1. Materials and Methods: we studied 122 patients (96 women, 79%), with a first objectively confirmed episode of VTE and with a median age of 39.5 years (range: 21-60). Exclusion criteria were malignancy, autoimmune diseases, antiphospholipid syndrome, chronic renal or liver disease and arterial thrombosis. Patients were seen at least 1 month after the discontinuation of the anticoagulant treatment and > 7 months after the event of VTE. Control group was comprised of 131 healthy subjects (105 women, 80%), with median age of 38 years (range: 18-66), recruited via the patients from the same geographic region and ethnic background. Controls were matched for age and sex. Plasma levels of cytokines were measured by commercial ELISA and a highly sensitive assay was used to measure IL-1β, IL-6 and IL-10 levels. Since a high percentage of samples of IL-1β (73%), IL-10 (62%) and TNF-αa (97%) was below the lower limit of detection (LLD) of the assay, levels of these cytokines were categorized as detectable (> LLD) and not detectable (< LLD). Elevated levels of IL-6 (> 2.15pg/mL), IL-8 (> 10.11pg/mL) and MCP-1 (> 84.11pg/mL) were defined by plasma concentration of these cytokines exceeding the 90th percentile of the distribution of the control population. Results: elevated levels of IL-6 were detected in 27% of the patients with VTE in comparison with 10% (by definition) of the controls [odds ratios (OR) = 3.4, 95% Confidence Interval (CI) 1.6 - 7.6]. Elevated levels of IL-8 were detected in 21% of the patients in comparison with 10% of the controls (OR = 2.5, 95%CI 1.1 - 5.6). The risk remained significant for IL-6 (OR = 2.8, 95%CI 1.2 - 6.5) and IL-8 (OR = 2.6, 95%CI 1.1 - 6.7) after adjustment for putative confounders (sex, age, body mass index, smoking and high levels of homocysteine and C-reactive protein). On the other hand, we found no significant association between VTE and elevated levels of MCP-1 (OR = 0.8, 95%CI 0.3 - 1.9) as well as detectable levels of IL-1β (OR = 0.9, 95%CI 0.5-1.6), IL-10 (OR = 1.3, 95%CI 0.8 - 2.2) and TNF-αa (OR = 6.7, 95%CI 0.8 - 56.7). In our study, patients were included at different time intervals after the VTE episode [median: 36 months (range: 7-87)]. No correlation was found between the time since the event of VTE and levels of IL-6 (rs = 0.06, P = 0.54) and IL-8 (rs= 0.07; P = 0.48). Conclusion: this study shows a significant impact of elevated levels of IL-6 and IL-8 on the risk of VTE in a relatively young population of patients. Interestingly, no association was found between the time since the event and the level of these cytokines. Taking into account the importance of the relationship between inflammation and VTE, more epidemiological data including prospective studies are required to elucidate the role of inflammation on the risk of VTE. This study was supported by FAPESP (2005/56799-0). Disclosures: No relevant conflicts of interest to declare.

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Prevalence of FACTOR IX-R338L (FACTOR IX PADUA) IN A COHORT of PATIENTS with Venous Thromboembolism and Mild Elevation of FACTOR IX LEVELS.

Blood ◽

10.1182/blood.v114.22.5057.5057 ◽

2009 ◽

Vol 114 (22) ◽

pp. 5057-5057

Author(s):

Bruna de Moraes Mazetto ◽

Fernanda A. Orsi ◽

Lúcia Helena Siqueira ◽

Erich Vinicius de Paula ◽

Tayana B Mello ◽

...

Keyword(s):

Venous Thromboembolism ◽

Molecular Mechanisms ◽

Conflicts Of Interest ◽

Recombinant Expression ◽

Coagulation Factor ◽

Factor Ix ◽

Control Group ◽

Increased Risk ◽

Pcr Rflp

Abstract Abstract 5057 Introduction Elevated plasma levels of blood coagulation factor IX (FIX) have been associated with increased risk of venous thromboembolism (VTE) in humans. However, the molecular mechanisms underlying elevated FIX have not been elucidated. Recently, a mutation in the FIX gene resulting in a FIX molecule with Arginine Leucine substitution at position 338 (FIX-R338L or Factor IX Padua) has been associated with very high levels of FIX (776%) in a patient with spontaneous VTE. Recombinant expression of FIX-R338L confirmed the gain-of-function mutation. Objective Here we evaluated the levels of FIX and the prevalence of Factor IX Padua in a cohort of patients with VTE followed at our center. The prevalence of FIX Padua was evaluated by using a PCR-RFLP strategy by which PCR with specific primers was followed by digestion with the enzyme TaqI. Results The prevalence of FIX Padua was evaluated in a population of 192 patients with spontaneous VTE (69 males and 123 females; median age 36-yo). A population of 192 healthy individuals matched for age, sex and ethnicity was used as a control group for the determination of FIX levels. Median FIX levels was 128.0% (61.0-207.0%) in patients with VTE. Twenty-nine patients presented FIX levels above the 90th percentile (160.2%). Factor IX Padua was not identified in any patients or controls, even in those with elevated FIX levels. Conclusion in the present study FIX Padua was not identified in any of our patients, indicating that this mutation is not associated with mild elevations of FIX levels frequently observed in patients with VTE. Disclosures No relevant conflicts of interest to declare.

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