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antithrombin deficiency

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https://www.readbyqxmd.com/read/29458015/sulfenamide-and-sulfonamide-derivatives-of-metformin-can-exert-anti-coagulant-and-pro-fibrinolytic-properties
#1
Magdalena Markowicz-Piasecka, Kristiina M Huttunen, Łukasz Mateusiak, Elżbieta Mikiciuk-Olasik, Joanna Sikora
Type 2 diabetes mellitus (T2DM) is characterised not only by hyperglycaemia and insulin resistance but also an impaired balance between the processes of coagulation and fibrinolysis. The aim of this study was to examine the effects of metformin, a widely-used oral anti-diabetic drug, phenformin and eight sulfenamide and sulfonamide derivatives of metformin on several haemostasis parameters. Thrombin Time (TT) tests were performed according to the available commercial method. The activity of factor X was conducted based on deficient plasma factor X...
February 16, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29452444/risk-of-venous-thrombosis-in-antithrombin-deficiency-a-systematic-review-and-bayesian-meta-analysis
#2
F Nanne Croles, Jaime Borjas-Howard, Kazem Nasserinejad, Frank W G Leebeek, Karina Meijer
Antithrombin deficiency is a strong risk factor for venous thromboembolism (VTE), but the absolute risk of the first and recurrent VTE is unclear. The objective of this paper is to establish the absolute risks of the first and recurrent VTE and mortality in individuals with antithrombin deficiency. The databases Embase, Medline Ovid, Web of Science, the Cochrane Library, and Google Scholar were systematically searched for case-control and cohort studies. Bayesian random-effects meta-analysis was used to calculate odds ratios (ORs), absolute risks, and probabilities of ORs being above thresholds...
February 16, 2018: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/29402471/direct-oral-anticoagulant-use-in-patients-with-thrombophilia-antiphospholipid-syndrome-or-venous-thrombosis-of-unusual-sites-a-narrative-review
#3
REVIEW
Laurent Bertoletti, Ygal Benhamou, Yannick Béjot, Sylvestre Marechaux, Saida Cheggour, Boris Aleil, Nicolas Lellouche, Jean-Guillaume Dillinger, Aurélien Delluc
Direct oral anticoagulants (DOACs) are indicated in the treatment and prevention of venous thromboembolism (VTE). However, the use of DOACs in unusual VTE, including cerebral venous thrombosis (CVT) and splanchnic venous thrombosis (SVT), and in patients with biological thrombophilia including minor thrombophilia (Factor V Leiden and prothrombin G20210A), major innate thrombophilia (protein C and S deficiency, and antithrombin) and major acquired thrombophilia (antiphospholipid syndrome [APS]), remains controversial due to the paucity of available data...
February 2, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29399079/rivaroxaban-for-the-treatment-of-venous-thromboembolism-in-patients-with-nephrotic-syndrome-and-low-at-iii-a-pilot-study
#4
Lihua Zhang, Haitao Zhang, Jiong Zhang, Hong Tian, Ju Liang, Zhihong Liu
The anticoagulation effect of heparin requires adequate serum antithrombin (AT)-III levels. Rivaroxaban, however, exhibits its anticoagulation effects independent of AT-III. The aim of the present study was to evaluate the efficacy and safety of rivaroxaban as a treatment for venous thromboembolism in patients with AT-III deficiency due to nephrotic syndrome. Patients with nephrotic syndrome and low serum concentration and functional activity of AT-III and venous thromboembolism were randomly assigned to the rivaroxaban group (n=8) and low weight molecular heparin group (n=8)...
January 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29378360/activated-factor-x-based-versus-thrombin-based-antithrombin-testing-in-thrombophilia-workup-in-the-doac-era
#5
Heiko Rühl, Sara Reda, Jens Müller, Johannes Oldenburg, Bernd Pötzsch
Antithrombin (AT) activity tests are used for diagnosing hereditary AT deficiency, a main genetic determinant of thrombophilia. They are either based on inhibition of thrombin (FIIa) or activated factor X (FXa). FXa-based assays have been suggested to be preferable to FIIa-based assays due to their higher sensitivity for certain AT deficiency causing mutations. To assess the performance of these two methods in a real-world scenario, 745 consecutively collected samples from patients referred to our institute during a 3-month period for thrombophilia testing were analysed...
February 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29377625/mild-antithrombin-deficiency-and-risk-of-recurrent-venous-thromboembolism-results-from-the-mega-follow-up-study
#6
Juraj Sokol, Jasmijn F Timp, Saskia le Cessie, Astrid van Hylckama-Vlieg, Frits R Rosendaal, Peter Kubisz, Suzanne Cannegieter, Willem M Lijfering
BACKGROUND: Mild antithrombin deficiency (previously defined as antithrombin activity below 70% or 80%) has been associated with a 2.4-3.5-fold increased risk of recurrent venous thromboembolism (VTE). This finding may have implications for duration of antithrombotic therapy in VTE patients with mild antithrombin deficiency. OBJECTIVES: To externally validate whether mild antithrombin deficiency is a risk. factor for recurrent VTE. METHODS: In a population based cohort study, patients with a first VTE (n=2357) were stratified according to percentile cut-off antithrombin levels (<5th [<87%], 5-10th [87-92%], >10th percentile [>92%]) and functional antithrombin levels (<70%, 70-80%, >80%)...
January 28, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29369598/a-case-of-hereditary-thrombophilia-in-a-chinese-han-patient-with-both-antithrombin-deficiency-and-factor-v-leiden-a-case-report-and-literature-review
#7
(no author information available yet)
Hereditary thrombophilia is a blood coagulation disorder that increases the risk of venous thromboembolism, due to several genetic risk factors. Factor V Leiden(FVL) is the most common contributing factor to thrombophilia in the Caucasian population but very rare in Asian population and concurrent occurrence of antithrombin(AT) deficiency and FVL in Chinese Han population is even more rare. We report the case of a 22-year-old female who experienced recurrent intracranial venous thromboses, furthermore, color Doppler ultrasound showed multiple extracranial thromboses...
December 25, 2017: Neuro Endocrinology Letters
https://www.readbyqxmd.com/read/29353463/protective-effect-of-a-newly-developed-fucose-deficient-recombinant-antithrombin-against-histone-induced-endothelial-damage
#8
Toshiaki Iba, Tatsuhiko Hirota, Koichi Sato, Isao Nagaoka
Antithrombin is expected to modulate both prothrombotic and proinflammatory reactions in sepsis; vascular endothelium is the primary target. In the present study, we sought to evaluate the protective effects of a newly developed fucose-deficient recombinant antithrombin. Endothelial cells were treated in vitro with histone H4 to induce cellular damage. Low to high doses of either plasma-derived antithrombin or recombinant thrombomodulin were used as treatment interventions. Morphological change, apoptotic rate, cell viability, cell injury, and syndecan-4 level in the medium were evaluated...
January 20, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29296762/whole-exome-sequencing-in-evaluation-of-patients-with-venous-thromboembolism
#9
Eun-Ju Lee, Daniel J Dykas, Andrew D Leavitt, Rodney M Camire, Eduard Ebberink, Pablo García de Frutos, Kavitha Gnanasambandan, Sean X Gu, James A Huntington, Steven R Lentz, Koen Mertens, Christopher R Parish, Alireza R Rezaie, Peter P Sayeski, Caroline Cromwell, Noffar Bar, Stephanie Halene, Natalia Neparidze, Terri L Parker, Adrienne J Burns, Anne Dumont, Xiaopan Yao, Cassius Iyad Ochoa Chaar, Jean M Connors, Allen E Bale, Alfred Ian Lee
Genetics play a significant role in venous thromboembolism (VTE), yet current clinical laboratory-based testing identifies a known heritable thrombophilia (factor V Leiden, prothrombin gene mutation G20210A, or a deficiency of protein C, protein S, or antithrombin) in only a minority of VTE patients. We hypothesized that a substantial number of VTE patients could have lesser-known thrombophilia mutations. To test this hypothesis, we performed whole-exome sequencing (WES) in 64 patients with VTE, focusing our analysis on a novel 55-gene extended thrombophilia panel that we compiled...
July 11, 2017: Blood Advances
https://www.readbyqxmd.com/read/29238798/association-between-hypercoagulable-conditions-and-calciphylaxis-in-patients-with-renal-disease-a-case-control-study
#10
Allison S Dobry, Lauren N Ko, Jessica St John, J Mark Sloan, Sagar Nigwekar, Daniela Kroshinsky
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...
December 13, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/29236713/sirt3-deficiency-does-not-affect-venous-thrombosis-or-netosis-despite-mild-elevation-of-intracellular-ros-in-platelets-and-neutrophils-in-mice
#11
Hideki Hayashi, Deya Cherpokova, Kimberly Martinod, Thilo Witsch, Siu Ling Wong, Maureen Gallant, Stephen M Cifuni, Leonard P Guarente, Denisa D Wagner
Inflammation is a common denominator in chronic diseases of aging. Yet, how inflammation fuels these diseases remains unknown. Neutrophils are the primary leukocytes involved in the early phase of innate immunity and inflammation. As part of their anti-microbial defense, neutrophils form extracellular traps (NETs) by releasing decondensed chromatin lined with cytotoxic proteins. NETs have been shown to induce tissue injury and thrombosis. Here, we demonstrated that Sirt3, a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, an enzyme linked to human longevity, was expressed in mouse neutrophils and platelets...
2017: PloS One
https://www.readbyqxmd.com/read/29153735/clinical-and-laboratory-characteristics-of-antithrombin-deficiencies-a-large-cohort-study-from-a-single-diagnostic-center
#12
Réka Gindele, Anna Selmeczi, Zsolt Oláh, Péter Ilonczai, György Pfliegler, Erzsébet Marján, László Nemes, Ágnes Nagy, Hajna Losonczy, Gorana Mitic, Mirjana Kovac, Gábor Balogh, István Komáromi, Ágota Schlammadinger, Katalin Rázsó, Zoltán Boda, László Muszbek, Zsuzsanna Bereczky
INTRODUCTION: Inherited antithrombin (AT) deficiency is a heterogeneous disease. Due to low prevalence, only a few studies are available concerning genotype-phenotype associations. The aim was to describe the clinical, laboratory and genetic characteristics of AT deficiency in a large cohort including children and to add further laboratory data on the different sensitivity of functional AT assays. PATIENTS AND METHODS: Non-related AT deficient patients (n=156) and their family members (total n=246) were recruited...
October 31, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/29150108/economy-class-syndrome-what-is-it-and-who-are-the-individuals-at-risk
#13
Luci Maria SantAna Dusse, Marcos Vinícius Ferreira Silva, Letícia Gonçalves Freitas, Milena Soriano Marcolino, Maria das Graças Carvalho
The term 'economy class syndrome' refers to the occurrence of thrombotic events during long-haul flights that mainly occur in passengers in the economy class of the aircraft. This syndrome results from several factors related to the aircraft cabin (immobilization, hypobaric hypoxia and low humidity) and the passenger (body mass index, thrombophilia, oral contraceptives or hormone replacement therapy, cancer), acting together to predispose to excessive blood coagulation, which can result in venous thromboembolism...
October 2017: Revista Brasileira de Hematologia e Hemoterapia
https://www.readbyqxmd.com/read/29137435/recurrent-mutations-in-a-serpinc1-hotspot-associate-with-venous-thrombosis-without-apparent-antithrombin-deficiency
#14
Wei Zeng, Bei Hu, Liang Tang, Yan-Yan You, Mara Toderici, Maria Eugenia de la Morena-Barrio, Javier Corral, Yu Hu
Despite the essential anticoagulant function of antithrombin and the high risk of thrombosis associated with its deficiency, the prevalence of antithrombin deficiency among patients with venous thromboembolism (VTE) is very low. However, increasing evidence suggests that antithrombin deficiency may be underestimated. The analysis of SERPINC1, the gene encoding antithrombin, in 1,304 consecutive Chinese VTE patients and 1,334 healthy controls revealed a hotspot involving residues 294 and 295 that severely increases the risk of VTE...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29074563/pregnancy-thrombophilia-and-the-risk-of-a-first-venous-thrombosis-systematic-review-and-bayesian-meta-analysis
#15
REVIEW
F Nanne Croles, Kazem Nasserinejad, Johannes J Duvekot, Marieke Jha Kruip, Karina Meijer, Frank Wg Leebeek
Objective To provide evidence to support updated guidelines for the management of pregnant women with hereditary thrombophilia in order to reduce the risk of a first venous thromboembolism (VTE) in pregnancy.Design Systematic review and bayesian meta-analysis.Data sources Embase, Medline, Web of Science, Cochrane Library, and Google Scholar from inception through 14 November 2016.Review methods Observational studies that reported on pregnancies without the use of anticoagulants and the outcome of first VTE for women with thrombophilia were eligible for inclusion...
October 26, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/29071478/gene-analysis-of-inherited-antithrombin-deficiency-and-functional-analysis-of-abnormal-antithrombin-protein-n87d
#16
Sayaka Kamijima, Akiko Sekiya, Mao Takata, Haruka Nakano, Morika Murakami, Tomonori Nakazato, Hidesaku Asakura, Eriko Morishita
Inherited antithrombin (AT) deficiency is one of the most clinically significant forms of congenital thrombophilia and follows an autosomal dominant mode of inheritance. We analyzed SERPINC1 in a patient who developed deep-vein thrombosis and low AT activity during pregnancy, and identified a novel missense mutation c.259A>G (p.Asn87Asp; N87D). Surprisingly, analysis of the parents' DNA showed that they did not possess this mutant, and thus, it may have been due to a de novo mutation. We also expressed this mutant AT protein in COS-1 cells and compared its intracellular localization and intracellular and extracellular antigen levels with that of wild-type AT...
October 25, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29063359/heparin-coumarin-protein-c-antithrombin-fibrinolysis-and-other-clotting-related-resistances-old-and-new-concepts-in-blood-coagulation
#17
REVIEW
A Girolami, E Cosi, S Ferrari, B Girolami
The concept of resistance in blood coagulation has become important. In the past it was limited to the resistance shown by some patients to heparin, coumarin or aspirin. Subsequently, it was demonstrated that a mutation in a single clotting factor, FV, showed resistance to activated protein C. Since activated protein C is supposed to downregulate aFV and aFVIII, their persistence in the circulation gives origin to a hypercoagulable state. Recently antithrombin resistance has been defined. Several prothrombin abnormalities (dysprothrombinemias) have been shown to be resistant to the action of antithrombin...
October 23, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/29040284/the-prevalence-and-clinical-manifestation-of-hereditary-thrombophilia-in-korean-patients-with-unprovoked-venous-thromboembolisms
#18
Su Yeon Lee, Eun Kyoug Kim, Min Sun Kim, Sun Hye Shin, Haseong Chang, Shin Yi Jang, Hee-Jin Kim, Duk-Kyung Kim
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)...
2017: PloS One
https://www.readbyqxmd.com/read/28978853/idiopathic-thrombosis
#19
Hiroko Tsuda
Idiopathic thrombosis involves a group of inherited thrombophilia predisposed to severe thrombosis of early onset and associated with an adverse outcome due to recurrence, and therefore, requires long-term anticoagulation therapy. The causative factors of a predisposition to thrombosis include immobility, dehydration, infection, surgery, injury, cancer, pregnancy, and estrogen use. The inherited deficiencies of antithrombin (AT), protein C (PC), and protein S (PS) are specified as "Specific Pediatric Chronic Diseases...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28961453/in-vitro-exploration-of-latent-prothrombin-mutants-conveying-antithrombin-resistance
#20
Shogo Tamura, Moe Murata-Kawakami, Yuki Takagi, Sachiko Suzuki, Akira Katsumi, Akira Takagi, Tetsuhito Kojima
INTRODUCTION: Antithrombin resistance (ATR) prothrombinemia is an inherited thrombophilic disorder caused by missense mutations in prothrombin gene (F2) at Arg596 of the sodium-binding region. Previously, prothrombin mutants Yukuhashi (Arg596Leu), Belgrade (Arg596Gln), and Padua 2 (Arg596Trp) were reported as ATR-prothrombins possessing a risk of familial venous thrombosis. To identify additional F2 mutations causing the ATR-phenotype, we investigated the coagulant properties of recombinant prothrombins mutated at amino acid residues within the sodium-binding region by single nucleotide substitutions (Thr540, Arg541, Glu592, and Lys599)...
September 20, 2017: Thrombosis Research
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