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[PMID]: 29238798
[Au] Autor:Dobry AS; Ko LN; St John J; Sloan JM; Nigwekar S; Kroshinsky D
[Ad] Address:Department of Dermatology, Massachusetts General Hospital, and Harvard Medical School, Boston.
[Ti] Title:Association Between Hypercoagulable Conditions and Calciphylaxis in Patients With Renal Disease: A Case-Control Study.
[So] Source:JAMA Dermatol;154(2):182-187, 2018 Feb 01.
[Is] ISSN:2168-6084
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Importance: Calciphylaxis is a rare skin disease with high morbidity and mortality that frequently affects patients with renal disease. Hypercoagulable conditions are frequently observed in both patients with calciphylaxis and those with chronic kidney disease (CKD), complicating our understanding of which hypercoagulable conditions are specific to calciphylaxis. Objective: To identify hypercoagulable conditions that are risk factors for developing calciphylaxis while controlling for CKD. Design, Setting, and Participants: This was a case-control study, comparing the hypercoagulability status of patients with calciphylaxis and with renal disease with that of a matched control population at 2 large urban academic hospitals in Boston, Massachusetts. Retrospective medical record review of laboratory values was performed to identify patients with hypercoagulable conditions. Case and control patients were further stratified based on both severity of CKD and warfarin. Patients with a dermatologic diagnosis of calciphylaxis between 2006 and 2014 and concomitant CKD were included as cases (n = 38). Three controls (n = 114) per case patient with CKD were included, and were matched by age, sex, and race. Main Outcomes and Measures: The rate of various hypercoagulable states (ie, antithrombin III [ATIII] deficiency, protein C and S deficiency, factor V Leiden mutation, prothrombin gene mutation [G20210A], elevated factor VIII level, lupus anticoagulant, anti-IgG or IgM cardiolipin antibodies, heparin-induced thrombocytopenia antibodies, and elevation of homocysteine) in patients with calciphylaxis compared with their matched controls. Results: Of the calciphylaxis cohort, 28 (58%) were female and 18 (55%) were non-Hispanic white. Among all patients, lupus anticoagulant (13 [48%] positive in cases vs 1 [5%] in controls; P = .001), protein C deficiency (9 [50%] vs 1 [8%]; P = .02), and combined thrombophilias (18 [62%] vs 10 [31%]; P = .02) were found to be significantly associated with calciphylaxis. In a subanalysis of patients with stage 5 CKD, only lupus anticoagulant (12 [53%] vs 9 [0%]; P = .01) and combined thrombophilia (15 [63%] vs 1 [8%]; P = .004) remained significantly associated with calciphylaxis. In a separate subanalysis of warfarin-unexposed patients, only lupus anticoagulant (7 [50%] vs 1 [6%]; P = .01) and protein C deficiency (5 [46%] vs 10 [0%]; P = .04) remained significantly associated with calciphylaxis. Conclusions and Relevance: Presence of lupus anticoagulant and combined thrombophilias are risk factors for the development of calciphylaxis in patients with late-stage renal disease. Clinicians should be aware of these associations in patients with impaired kidney function and may consider increased screening and appropriate anticoagulation treatment to reduce the risk of calciphylaxis development.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180216
[Lr] Last revision date:180216
[St] Status:In-Data-Review
[do] DOI:10.1001/jamadermatol.2017.4920

  2 / 2139 MEDLINE  
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[PMID]: 29040284
[Au] Autor:Lee SY; Kim EK; Kim MS; Shin SH; Chang H; Jang SY; Kim HJ; Kim DK
[Ad] Address:Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
[Ti] Title:The prevalence and clinical manifestation of hereditary thrombophilia in Korean patients with unprovoked venous thromboembolisms.
[So] Source:PLoS One;12(10):e0185785, 2017.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Hereditary thrombophilia (HT) is a genetic predisposition to thrombosis. Asian mutation spectrum of HT is different from Western ones. We investigated the incidence and clinical characteristics of HT in Korean patients with unprovoked venous thromboembolism (VTE). METHODS: Among 369 consecutive patients with thromboembolic event who underwent thrombophilia tests, we enrolled 222 patients diagnosed with unprovoked VTE. The presence of HT was confirmed by DNA sequencing of the genes that cause deficits in natural anticoagulants (NAs). Median follow-up duration was 40±38 months. RESULTS: Among the 222 patients with unprovoked VTE, 66 (29.7%) demonstrated decreased NA level, and 33 (14.9%) were finally confirmed to have HT in a genetic molecular test. Antithrombin III deficiency (6.3%) was most frequently detected, followed by protein C deficiency (5.4%), protein S deficiency (1.8%), and dysplasminogenemia (1.4%). The HT group was significantly younger (37 [32-50] vs. 52 [43-65] years; P < 0.001) and had a higher proportion of male (69.7% vs. 47%; P = 0.013), more previous VTE events (57.6% vs. 31.7%; P = 0.004), and a greater family history of VTE (43.8% vs. 1.9%; P < 0.001) than the non-HT group. Age <45 years and a family history of VTE were independent predictors for unprovoked VTE with HT (odds ratio, 9.435 [2.45-36.35]; P = 0.001 and 92.667 [14.95-574.29]; P < 0.001). CONCLUSIONS: About 15% of patients with unprovoked VTE had HT. A positive family history of VTE and age <45 years were independent predictors for unprovoked VTE caused by HT.
[Mh] MeSH terms primary: Antithrombin III Deficiency/physiopathology
Conjunctivitis/physiopathology
Plasminogen/deficiency
Protein C Deficiency/physiopathology
Protein S Deficiency/physiopathology
Skin Diseases, Genetic/physiopathology
Thrombophilia/physiopathology
Venous Thromboembolism/physiopathology
[Mh] MeSH terms secundary: Adult
Aged
Antithrombin III/genetics
Antithrombin III Deficiency/complications
Antithrombin III Deficiency/diagnosis
Antithrombin III Deficiency/genetics
Conjunctivitis/complications
Conjunctivitis/diagnosis
Conjunctivitis/genetics
Female
Gene Expression
Humans
Male
Middle Aged
Plasminogen/genetics
Protein C/genetics
Protein C Deficiency/complications
Protein C Deficiency/diagnosis
Protein C Deficiency/genetics
Protein S/genetics
Protein S Deficiency/complications
Protein S Deficiency/diagnosis
Protein S Deficiency/genetics
Republic of Korea
Retrospective Studies
Sequence Analysis, DNA
Skin Diseases, Genetic/complications
Skin Diseases, Genetic/diagnosis
Skin Diseases, Genetic/genetics
Thrombophilia/diagnosis
Thrombophilia/etiology
Thrombophilia/genetics
Venous Thromboembolism/diagnosis
Venous Thromboembolism/etiology
Venous Thromboembolism/genetics
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Protein C); 0 (Protein S); 9000-94-6 (Antithrombin III); 9001-91-6 (Plasminogen)
[Em] Entry month:1710
[Cu] Class update date: 171031
[Lr] Last revision date:171031
[Js] Journal subset:IM
[Da] Date of entry for processing:171018
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185785

  3 / 2139 MEDLINE  
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[PMID]: 28877605
[Au] Autor:El-Menyar A; Asim M; Al-Thani H
[Ad] Address:1 Clinical Research, Trauma Surgery Section, Hamad General Hospital, Doha, Qatar.
[Ti] Title:Obesity Paradox in Patients With Deep Venous Thrombosis.
[So] Source:Clin Appl Thromb Hemost;:1076029617727858, 2017 Jan 01.
[Is] ISSN:1938-2723
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:We aimed to investigate the association between obesity and deep venous thrombosis (DVT) in a country with a high prevalence of obesity. This is a retrospective cohort study of patients who presented with DVT between 2008 and 2012. Data were analyzed and compared based on body mass index (BMI), and patients were classified into normal (<25), overweight (≥25 to <30), obese I (30 to <35), obese II (35 to <40), and obese III (≥40). Among 662 patients with DVT, 28% were overweight and 49% were obese. The mean age was 50.3 (16.5) years, and 51% were females. Diabetes mellitus and prior venous thromboembolism were significantly higher among obese patients. History of malignancy was more common in nonobese patients. Protein S and antithrombin III deficiency and hyperhomocysteinemia were more prevalent among morbid obese patients. Also, obese patients had higher incidence of thrombosis in the distal veins ( P = .03). Warfarin use and long-term therapy were more frequent in obese than nonobese. Postthrombotic syndrome was comparable in obese and nonobese groups. Recurrent DVT was higher in obese I ( P < .01), whereas mortality rates were greater in nonobese groups ( P = .001). Malignancy, diabetes mellitus, and common femoral vein involvement were predictors of mortality, whereas BMI ≥30 was the predictor of survival. Cox regression models showed that after adjusting for age, sex, pulmonary embolism, and duration of warfarin treatment, BMI ≥40 had better survival (hazard ratio: 0.177, 95% confidence interval: 0.045-0.691, P = .013). There is a significant association between obesity and DVT. Obese patients have characteristic risk factors and better survival. This obesity paradox needs further studies to assess its clinical and pharmacotherapeutic implications.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1709
[Cu] Class update date: 170907
[Lr] Last revision date:170907
[St] Status:Publisher
[do] DOI:10.1177/1076029617727858

  4 / 2139 MEDLINE  
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[PMID]: 28866705
[Au] Autor:Wan Ab Rahman WS; Abdullah WZ; Hassan MN; Hussin A; Zulkafli Z; Haron J
[Ad] Address:Universiti Sains Malaysia, School of Dental Sciences, 16150 Kubang Kerian, Kelantan, Malaysia. suriana@usm.my.
[Ti] Title:Familial antithrombin III deficiency in a Malay patient with massive thrombosis.
[So] Source:Malays J Pathol;39(2):197-200, 2017 Aug.
[Is] ISSN:0126-8635
[Cp] Country of publication:Malaysia
[La] Language:eng
[Ab] Abstract:Patients with low antithrombin III (AT III) has increased risk for arteriovenous thromboembolic (TE) disease. We report a 28-year-old Malay lady who presented with spontaneous right calf pain and swelling of one week duration. She was on oral contraceptive pills and had a history of travelling for a long distance prior to the presentation. Her brother who was diagnosed with AT III deficiency had arterial thrombosis at a young age. She was diagnosed as having right popliteal vein thrombosis by ultrasound and treated with subcutaneous fondaparinux. While on treatment, she developed massive bilateral pulmonary embolism (PE). Thrombophilia study showed reduced AT III activity (38µl/dl) and normal results for protein C, protein S, activated protein C resistance and lupus anticoagulant assays. This patient has heterozygous AT III deficiency added with significant acquired factors responsible for the TE events. Those with AT III deficiency may have resistance to heparin therapy and require higher doses of heparin.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1709
[Cu] Class update date: 171116
[Lr] Last revision date:171116
[St] Status:In-Process

  5 / 2139 MEDLINE  
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[PMID]: 28865216
[Au] Autor:Zarczynska K; Baumgartner W; Sobiech P
[Ad] Address:.
[Ti] Title:Coagulology, biochemical profile and muscle pathology in calves diagnosed with nutritional muscular dystrophy.
[So] Source:Pol J Vet Sci;20(2):387-394, 2017 Mar 01.
[Is] ISSN:1505-1773
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:The aim of this study was to explain the correlations between selenium deficiency, hemostatic and biochemical disorders, and the progression of pathological changes in calves diagnosed with nutritional muscular dystrophy (NMD). The study was performed on 20 calves with supplementation of 8 ml selenium and vitamin E preparation and 20 calves with symptoms of NMD. Blood was sampled from calves aged 5, 12 and 19 days. On day 19, samples of the biceps femoris muscle were collected from 6 animals in each group for histopathological analysis. The following blood parameters were determined: PLT, PT, TT, APTT, fibrinogen and D-dimer concentrations, antithrombin III activity, glucose, selenium and vitamin E concentrations, activity of CK, LDH and GSH-Px. Muscle sections were stained with H&E and HBFP. Platelet counts were significantly lower in calves with symptoms of NMD. No significant differences in coagulation parameters were observed between the groups. Sick calves were diagnosed with hyperglycemia and elevation of CK and LDH activity. Selenium and vitamin E concentrations in the blood serum were significantly lower in the experimental group together with significant drop in GSH-Px activity. Changes characteristic of Zenker's necrosis were observed in a muscle of the sick animals. To our best knowledge this is the first study in which the attempt was made to explain the relationship between selenium deficiency and changes in the coagulation system in ruminants.
[Mh] MeSH terms primary: Blood Coagulation Disorders/veterinary
Cattle Diseases/blood
Muscle, Skeletal/pathology
Muscular Dystrophy, Animal/etiology
Nutrition Disorders/veterinary
Selenium/deficiency
[Mh] MeSH terms secundary: Animals
Blood Coagulation Disorders/etiology
Blood Coagulation Disorders/pathology
Cattle
Cattle Diseases/pathology
Glutathione Peroxidase/metabolism
Muscular Dystrophy, Animal/blood
Muscular Dystrophy, Animal/pathology
Nutrition Disorders/blood
Nutrition Disorders/etiology
Nutrition Disorders/pathology
Vitamin E/metabolism
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:1406-18-4 (Vitamin E); EC 1.11.1.9 (Glutathione Peroxidase); H6241UJ22B (Selenium)
[Em] Entry month:1711
[Cu] Class update date: 171106
[Lr] Last revision date:171106
[Js] Journal subset:IM
[Da] Date of entry for processing:170903
[St] Status:MEDLINE

  6 / 2139 MEDLINE  
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[PMID]: 28805957
[Au] Autor:Choi SW; Kim BB; Choi DH; Park G; Shin BC; Song H; Kim D; Kim DM
[Ad] Address:Department of Cardiology, Gwangju Veterans Hospital, Gwangju, Republic of Korea.
[Ti] Title:Stroke or left atrial thrombus prediction using antithrombin III and mean platelet volume in patients with nonvalvular atrial fibrillation.
[So] Source:Clin Cardiol;, 2017 Aug 14.
[Is] ISSN:1932-8737
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: CHADS (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke) and CHA DS -VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke, vascular disease, age 65 to 74 years, sex category) scores showed just moderate discrimination ability in predicting thromboembolic complications in patients with nonvalvular atrial fibrillation (AF). HYPOTHESIS: To determine the association of antithrombin III (AT-III) deficiency and mean platelet volume (MPV) with the development of stroke or left atrial (LA) thrombus in patients with AF. METHODS: AT-III and MPV were analyzed in 352 patients with AF. The primary endpoint was a composite of ischemic stroke event and incidental LA thrombus. RESULTS: There were 50 events (14.2%) during a mean 35.4 months of follow-up. A significantly higher stroke or LA thrombus rate was observed in the low-AT-III group (<70%) than that in the high-AT-III group (≥70%). A significantly higher stroke or LA thrombus rate was observed in the high-MPV group (≥7.0 fL) than that in the low-MPV group (<7.0 fL). AF patients with an MPV ≥7.0 fL and AT-III deficiency had higher stroke or LA thrombus risk than those without an MPV ≥7.0 fL and AT-III deficiency. In the Cox proportional hazard analysis, high MPV was found to be an independent predictor of stroke or LA thrombus risk (hazard ratio: 6.408; 95% confidence interval: 2.874-14.286). Although AT-III deficiency was not an independent predictor of stroke or LA thrombus risk, a trend was observed. CONCLUSIONS: High MPV and AT-III deficiency were predictive markers for stroke or LA thrombus. Their predictive power for stroke was independent of antiplatelet treatment, anticoagulation therapy, and a high CHA DS -VASc score in patients with AF.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1708
[Cu] Class update date: 170814
[Lr] Last revision date:170814
[St] Status:Publisher
[do] DOI:10.1002/clc.22759

  7 / 2139 MEDLINE  
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[PMID]: 28792912
[Au] Autor:Dluski D; Mierzynski R; Poniedzialek-Czajkowska E; Leszczynska-Gorzelak B
[Ad] Address:.
[Ti] Title:Adverse pregnancy outcomes and inherited thrombophilia.
[So] Source:J Perinat Med;, 2017 Aug 09.
[Is] ISSN:1619-3997
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:AIM: (1) To evaluate the prevalence of inherited thrombophilia in pregnant women with adverse pregnancy outcomes: intrauterine growth retardation (IUGR), preeclampsia (PE) and placental abruption. (2) To assess the impact of inherited thrombophilia on the nature of obstetric complications. (3) To assess levels of protein S, protein C, antithrombin III and homocysteine in pregnant women with adverse pregnancy outcomes. SUBJECTS AND METHODS: The study comprised 162 pregnant women. The patients were divided into three test groups and one control group. In all 162 patients the following tests were completed: activated protein C resistance (APC-R), the level of free protein S, activity of protein C, antithrombin III and the level of homocysteine. The data were statistically analyzed via χ2 of independence or homogeneity test. RESULTS: In 32 of 162 patients participating in clinical research thrombophilia was diagnosed (10 patients with APC-R, 21 patients with protein S deficiency, one patient with hyperhomocysteinemia): seven patients belonged to the control group and 25 patients had diagnosed adverse pregnancy outcomes (P=0.04). In 32 patients with diagnosed thrombophilia, level of protein S was decreased (P=0.04). Protein S deficiency was diagnosed, when level of protein S was lower than 30% in the second trimester and lower than 24% in the third trimester. The incidence of activated protein C resistance caused by the mutation of factor V Leiden was in six patients (5.9%) with adverse pregnancy outcomes, and in four patients (6.6%) from the control group. Results were not statistically significant. No protein C deficiency was diagnosed (diagnosis: level<60%), but in 50% of patients with thrombophilia level of protein C was over the norm (P=0.02). The level of antithrombin III was often decreased in patients with preeclampsia - (32.4%), then in the other patients - (17.2%) (P=0.04), but no patient was diagnosed with antithrombin III deficiency (diagnosis: level<60%). CONCLUSIONS: Tests for thrombophilia should be carried out in women with adverse pregnancy outcomes in their history, who are planning pregnancy, to start anticoagulant prophylaxis. Our study supports the thesis that tests for thrombophilia should be carried out in women with a history of adverse pregnancy outcomes and who are planning a pregnancy to start anticoagulant prophylaxis.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1708
[Cu] Class update date: 170809
[Lr] Last revision date:170809
[St] Status:Publisher

  8 / 2139 MEDLINE  
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[PMID]: 28696344
[Au] Autor:Taylor BS; So-Armah K; Tate JP; Marconi VC; Koethe JR; Bedimo RJ; Butt AA; Gibert CL; Goetz MB; Rodriguez-Barradas MC; Womack JA; Gerschenson M; Lo Re V; Rimland D; Yin MT; Leaf D; Tracy RP; Justice AC; Freiberg MS
[Ad] Address:*Medical Service/Infectious Diseases, South Texas Veterans Health Care System, San Antonio, TX; Department of Medicine, UT Health San Antonio, San Antonio, TX;†Department of Medicine, Boston University School of Medicine, Boston, MA;‡Section of General Internal Medicine, VA Connecticut Healthcare System, West Haven, CT; Department of Internal Medicine, Yale University School of Medicine, New Haven, CT;§Medical Service, VA Medical Center, Atlanta, GA; Medical Service, Emory University School of Medicine, Atlanta, GA;‖Departments of Medicine and Biostatistics, Vanderbilt University School of Medicine, Nashville, TN;¶Department of Medicine, Infectious Diseases Section, VA North Texas Health Care System; UT Southwestern Medical Center, Dallas, TX;#Center for Health Equity Research and Promotion, VA Pittsburg Healthcare System, Pittsburgh, PA; Hamad Healthcare Quality Institute, Hamad Medical Corporation, Doha, Qatar; Department of Medicine, Weill Cornell Medical College, Doha, Qatar and New York, NY;**Medical Service/Infectious Diseases, VA Medical Center, Washington, DC; Department of Medicine, George Washington University Medical Center, Washington, DC;††Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA; David Geffen School of Medicine at UCLA, Los Angeles, CA;‡‡Infectious Diseases Section, Michael E. DeBakey VA Medical Center, Houston, TX; Infectious Diseases Section, Baylor College of Medicine, Houston, TX;§§VA Connecticut Healthcare System, West Haven, CT;‖‖Cell and Molecular Biology Department, John A. Burns School of Medicine, University of Hawaii- Manoa, Honolulu, HI;¶¶Philadelphia VA Medical Center, Philadelphia, PA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, VA;##Division of Infectious Diseases, Columbia University Medical Center, New York, NY;***Infectious Diseases Section, VA Greater Los Angeles Healthcare System, Los Angeles, CA; Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA;†††Departments of Pathology and Laboratory Medicine and Biochemistry, College of Medicine, University of Vermont, Burlington, VT; and‡‡‡Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN; Geriatric Research, Education, and Clinical Center, VA Tennessee Valley Healthcare System, Nashville, TN.
[Ti] Title:HIV and Obesity Comorbidity Increase Interleukin 6 but Not Soluble CD14 or D-Dimer.
[So] Source:J Acquir Immune Defic Syndr;75(5):500-508, 2017 Aug 15.
[Is] ISSN:1944-7884
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVES: Obesity prevalence among people living with HIV (HIV+) is rising. HIV and obesity are proinflammatory states, but their combined effect on inflammation (measured by interleukin 6, IL-6), altered coagulation (D-dimer), and monocyte activation (soluble CD14, sCD14) is unknown. We hypothesized inflammation increases when obesity and HIV infection co-occur. METHODS: The Veterans Aging Cohort Study survey cohort is a prospective, observational study of predominantly male HIV+ veterans and veterans uninfected with HIV; a subset provided blood samples. Inclusion criteria for this analysis were body mass index ≥ 18.5 kg/m and biomarker measurement. Dependent variables were IL-6, sCD14, and D-dimer quartiles. Obesity/HIV status was the primary predictor. Unadjusted and adjusted logistic regression models were constructed. RESULTS: Data were analyzed for 1477 HIV+ and 823 uninfected participants. Unadjusted median IL-6 levels were significantly higher and sCD14 levels significantly lower in obese/HIV+ compared with nonobese/uninfected (P <0.01 for both). In adjusted analyses, the odds ratio for increased IL-6 in obese/HIV+ patients was 1.76 (95% confidence interval: 1.18 to 2.47) compared with nonobese/uninfected, and obesity/HIV+ remained associated with lower odds of elevated sCD14. We did not detect a synergistic association of co-occurring HIV and obesity on IL-6 or sCD14 elevation. D-dimer levels did not differ significantly between body mass index/HIV status groups. CONCLUSIONS: HIV-obesity comorbidity is associated with elevated IL-6, decreases in sCD14, and no significant difference in D-dimer. These findings are clinically significant, as previous studies associated these biomarkers with mortality. Future studies should assess whether other biomarkers show similar trends and potential mechanisms for unanticipated sCD14 and D-dimer findings.
[Mh] MeSH terms primary: Fibrin Fibrinogen Degradation Products/analysis
HIV Infections/epidemiology
HIV Infections/immunology
Inflammation/immunology
Interleukin-6/blood
Lipopolysaccharide Receptors/blood
Obesity/epidemiology
Obesity/immunology
[Mh] MeSH terms secundary: Adult
Aging/blood
Aging/immunology
Biomarkers/blood
Comorbidity
Cross-Sectional Studies
Female
HIV Infections/blood
Humans
Inflammation/blood
Interleukin-6/immunology
Male
Middle Aged
Obesity/blood
Prospective Studies
United States/epidemiology
Veterans
[Pt] Publication type:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Name of substance:0 (Biomarkers); 0 (Fibrin Fibrinogen Degradation Products); 0 (IL6 protein, human); 0 (Interleukin-6); 0 (Lipopolysaccharide Receptors); 0 (fibrin fragment D)
[Em] Entry month:1708
[Cu] Class update date: 171116
[Lr] Last revision date:171116
[Js] Journal subset:IM; X
[Da] Date of entry for processing:170712
[St] Status:MEDLINE
[do] DOI:10.1097/QAI.0000000000001444

  9 / 2139 MEDLINE  
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[PMID]: 28691885
[Au] Autor:Pasi KJ; Rangarajan S; Georgiev P; Mant T; Creagh MD; Lissitchkov T; Bevan D; Austin S; Hay CR; Hegemann I; Kazmi R; Chowdary P; Gercheva-Kyuchukova L; Mamonov V; Timofeeva M; Soh CH; Garg P; Vaishnaw A; Akinc A; Sørensen B; Ragni MV
[Ad] Address:From the Royal London Haemophilia Centre, Barts and the London School of Medicine and Dentistry (K.J.P.), National Institute for Health Research (NIHR) Biomedical Research Centre (T.M.), Guy's and St. Thomas' NHS Foundation Trust, King's College London (D.B.), St. George's Healthcare NHS Trust Haemo
[Ti] Title:Targeting of Antithrombin in Hemophilia A or B with RNAi Therapy.
[So] Source:N Engl J Med;377(9):819-828, 2017 08 31.
[Is] ISSN:1533-4406
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Current hemophilia treatment involves frequent intravenous infusions of clotting factors, which is associated with variable hemostatic protection, a high treatment burden, and a risk of the development of inhibitory alloantibodies. Fitusiran, an investigational RNA interference (RNAi) therapy that targets antithrombin (encoded by SERPINC1), is in development to address these and other limitations. METHODS: In this phase 1 dose-escalation study, we enrolled 4 healthy volunteers and 25 participants with moderate or severe hemophilia A or B who did not have inhibitory alloantibodies. Healthy volunteers received a single subcutaneous injection of fitusiran (at a dose of 0.03 mg per kilogram of body weight) or placebo. The participants with hemophilia received three injections of fitusiran administered either once weekly (at a dose of 0.015, 0.045, or 0.075 mg per kilogram) or once monthly (at a dose of 0.225, 0.45, 0.9, or 1.8 mg per kilogram or a fixed dose of 80 mg). The study objectives were to assess the pharmacokinetic and pharmacodynamic characteristics and safety of fitusiran. RESULTS: No thromboembolic events were observed during the study. The most common adverse events were mild injection-site reactions. Plasma levels of fitusiran increased in a dose-dependent manner and showed no accumulation with repeated administration. The monthly regimen induced a dose-dependent mean maximum antithrombin reduction of 70 to 89% from baseline. A reduction in the antithrombin level of more than 75% from baseline resulted in median peak thrombin values at the lower end of the range observed in healthy participants. CONCLUSIONS: Once-monthly subcutaneous administration of fitusiran resulted in dose-dependent lowering of the antithrombin level and increased thrombin generation in participants with hemophilia A or B who did not have inhibitory alloantibodies. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov number, NCT02035605 .).
[Mh] MeSH terms primary: Antithrombin III/antagonists & inhibitors
Hemophilia A/therapy
Hemophilia B/therapy
RNAi Therapeutics
[Mh] MeSH terms secundary: Adult
Antithrombins/blood
Dose-Response Relationship, Drug
Healthy Volunteers
Hemophilia A/blood
Hemophilia B/blood
Humans
Injections, Subcutaneous
Male
Middle Aged
Single-Blind Method
Thrombin/biosynthesis
Young Adult
[Pt] Publication type:CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Name of substance:0 (Antithrombins); 0 (SERPINC1 protein, human); 9000-94-6 (Antithrombin III); EC 3.4.21.5 (Thrombin)
[Em] Entry month:1709
[Cu] Class update date: 170912
[Lr] Last revision date:170912
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:170711
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMoa1616569

  10 / 2139 MEDLINE  
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[PMID]: 28670948
[Au] Autor:Carroll R; Rebarber A; Booker W; Fox N; Saltzman D; Lam-Rachlin J; Gupta S
[Ad] Address:a The Department of Obstetrics, Gynecology, and Reproductive Science , Icahn School of Medicine at Mount Sinai , New York , USA.
[Ti] Title:Double versus single thrombophilias during pregnancy.
[So] Source:J Matern Fetal Neonatal Med;:1-4, 2017 Jul 16.
[Is] ISSN:1476-4954
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:OBJECTIVE: The primary objective of this study was to evaluate whether women with double thrombophilias have a greater risk for obstetric complications as compared with women who have single thrombophilias. STUDY DESIGN: This is a retrospective cohort study of all patients in a single practice with a clinically significant inherited thrombophilia and treated with anticoagulation between 2005 and 2013. Thrombophilias evaluated include: factor V Leiden, prothrombin G20210A gene mutation, protein S deficiency, protein C deficiency, and antithrombin III deficiency. Double thrombophilia was defined as the presence of two thrombophilias or homozygosity for factor V Leiden or prothrombin Gene Mutation. Demographic and obstetrical outcome data were collected. Data on all patients with double thrombophilias who met inclusion criteria was reported. Data was then compared between the patients with double thrombophilias and single thrombophilias with singleton gestations. The data was analyzed with Pearson's chi-squared or Student's t-test as appropriate with p value <.05 used for significance. RESULTS: Eighteen patients with clinically significant double thrombophilias who met inclusion criteria were identified. Most patients delivered full term (88.9%) and appropriate for gestational age (77.8%) infants. One hundred thirty-two patients with single thrombophilias and 14 patients with double thrombophilias with singleton gestations were then compared. Demographic characteristics were not significantly different between the two groups. There were no significant differences in obstetrical outcomes between patients. CONCLUSIONS: There were no significant differences in obstetrical outcomes for patients with clinically significant double thrombophilias versus single thrombophilias when treated with anticoagulation.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1707
[Cu] Class update date: 171026
[Lr] Last revision date:171026
[St] Status:Publisher
[do] DOI:10.1080/14767058.2017.1349745


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