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Kalkan S, Ozan Gürsoy M, Güner A, Gürsoy S, Kalçık M, Geçkinli BB, Delil K, Ateş EA, Erdogan EG, Canbek S, Bayam E, Aykan AÇ, Aytürk M, Gündüz S, Özkan M. Assessment of Genetic Variants Linked to Susceptibility to Mechanical Prosthetic Valve Thrombosis. Am J Cardiol 2025; 234:22-29. [PMID: 39454698 DOI: 10.1016/j.amjcard.2024.10.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Revised: 09/15/2024] [Accepted: 10/10/2024] [Indexed: 10/28/2024]
Abstract
Prosthetic valve thrombosis (PVT) is a critical and life-threatening condition driven by multifactorial etiologies, including genetic predispositions. The study was designed as a single-center retrospective manner. Echocardiographic features and genetic test including factor II/prothrombin (G20210A), factor V Leiden (G1691A), factor V R2 (A4070G), apolipoprotein (Apo) B-100 (G10708A), ApoE (C112R), ApoE (R158C), methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, factor XIII G103T (V34L), β-fibrinogen (455G>A), PAI-1 4G/5G, and HPA-1 GPIIIa (T196C) genotyping variations were assessed. We performed genetic tests on 175 patients with PVT (biologically women [n = 124, 70.9%], with a mean age of 49.8 ± 13.1 years) and 101 patients (biologically women [n = 57, 56.4%], with a mean age of 54.7 ± 13.6 years) without thrombus formation. The thrombosis group was significantly younger compared with controls (p = 0.004). The percentage of patients with mechanical aortic valves was significantly lower in the thrombosis group compared with controls (22.3% vs 34.7%, p = 0.025). A significant difference was observed between the thrombosis and control groups regarding the genotype ratios of factor II/prothrombin (G20210A) (heterozygous, 6.8% vs 1%, p = 0.043) and HPA-1 GPIIIa (T196C) (homozygous mutant, 7.8% vs 0%, p = 0.034). In addition, there was a significant association of heterozygous MTHFR (A1298C) variation with obstructive thrombosis compared with nonobstructive thrombosis (46.9% vs 29.2%, p = 0.046). In conclusion, this is the first study to report a potential association between genetic variants, including HPA-1 GPIIIa (T196C), factor II/prothrombin (G20210A), MTHFR (A1298C), and PVT, necessitating extensive further research and additional clinical consideration.
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Affiliation(s)
- Semih Kalkan
- Department of Cardiology, Basaksehir Cam Sakura City Hospital, Istanbul, Türkiye.
| | - M Ozan Gürsoy
- Department of Cardiology, Health Scıences Unıversıty İzmir Tepecik Educatıon and Research Hospital, Izmir, Türkiye
| | - Ahmet Güner
- Department of Cardiology, Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Türkiye
| | - Semra Gürsoy
- Division of Pediatric Genetics, Department of Pediatrics, Dokuz Eylül University Faculty of Medicine, İzmir, Türkiye
| | - Macit Kalçık
- Department of Cardiology, Faculty of Medicine, Hitit University, Çorum, Türkiye
| | - Bilge Bilgen Geçkinli
- Department of Medical Genetics, Marmara University School of Medicine, Istanbul, Türkiye
| | - Kenan Delil
- Department of Medical Genetics, Marmara University School of Medicine, Istanbul, Türkiye
| | - Esra Arslan Ateş
- Department of Medical Genetics, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istanbul, Türkiye
| | | | - Sezin Canbek
- Department of Medical Genetics, Umraniye Training and Research Hospital, Istanbul, Türkiye
| | - Emrah Bayam
- Department of Cardiology, Koşuyolu Kartal Heart Training and Research Hospital, Istanbul, Türkiye
| | - A Çağrı Aykan
- Department Cardiology, Kahramanmaras Sütcü Imam University Faculty of Medicine, Kahramanmaras, Türkiye
| | - Mehmet Aytürk
- Department of Cardiology, Koşuyolu Kartal Heart Training and Research Hospital, Istanbul, Türkiye
| | - Sabahattin Gündüz
- Department of Cardiology, Faculty of Medicine, Bahcesehir University, Istanbul, Türkiye
| | - Mehmet Özkan
- Department of Cardiology, Koşuyolu Kartal Heart Training and Research Hospital, Istanbul, Türkiye; Division of Health Sciences, Ardahan University, Ardahan, Türkiye
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Rachapudi SS, Charoenkijkajorn C, Pakravan M, Lee AG. Prothrombin 20210A mutation in acute posterior cerebral artery infarction and branch retinal vein occlusion. CANADIAN JOURNAL OF OPHTHALMOLOGY 2023; 58:e259-e262. [PMID: 37545047 DOI: 10.1016/j.jcjo.2023.07.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 06/10/2023] [Accepted: 07/21/2023] [Indexed: 08/08/2023]
Affiliation(s)
| | | | | | - Andrew G Lee
- University of Texas Medical Branch, Galveston, TX; Blanton Eye Institute, Houston Methodist Hospital, Houston, TX; Weill Cornell Medicine, New York, NY; University of Texas MD Anderson Cancer Center, Houston, TX; Texas A&M College of Medicine, Bryan, TX; University of Iowa Hospitals and Clinics, Iowa City, IA.
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Abstract
Background and Objective Thrombophilia is a term used to define the conditions creating a tendency toward thrombosis. Factor V Leiden (FVL) is the most frequently observed genetic risk factor, and its frequency varies among societies and ethnicities. In this study, our aim is to identify the frequency of FVL mutation in patients with thrombosis, the frequency of FVL mutation for each thrombosis disease, whether there is any difference in the geographical distribution of FVL mutation in the Turkish population, correlation with age and gender, and correlation with arterial and venous thrombosis. Methods This is an observational case–control and retrospective study. Cases with the FVL mutation examination with clinical provisional diagnosis of arterial and/or venous thrombosis delivered and with the thrombosis proven by radiological visualization methods and laboratory examinations have been planned to be considered and assessed as cases with thrombosis. Results A total of 67 patients with thrombosis and 22 patients without thrombosis have been included within the study. Twenty-six of the cases with thrombosis were from the Black Sea region, 21 were from Eastern Anatolia, 12 were from Central Anatolia, 5 were from Marmara, and 3 were from Southeastern Anatolia. Eleven of the cases without thrombosis were from the Black Sea region, 1 was from Eastern Anatolia, 5 were from Central Anatolia, 2 were from Marmara, 1 was from Southeastern Anatolia, and 2 were from the Aegean region. The significance was resulted from the identification of thrombosis prevalence rate as significantly high in the Eastern Anatolian region. Discussion FVL mutation frequency is quite common in our country, and there are significant differences particularly in terms of regional distribution. Furthermore, FVL mutation is solely not the risk factor for thrombosis, and other coexisting genetic and acquired risk factors are substantial causes for the development of thrombosis.
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Goren Sahin D, Bayraktutar BN, Yıldız Taş A, Akay OM, Ozkaya A, Yalcin Ö, Sahin A. Can Rotational Thromboelastometry be a New Predictive Tool for Retinal Vein Occlusion Development? Curr Eye Res 2018; 44:406-412. [PMID: 30512971 DOI: 10.1080/02713683.2018.1554152] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
PURPOSE To evaluate clotting dynamics by a new tool called rotational tromboelastometry (ROTEM) in retinal vein occlusion. MATERIALS AND METHODS Thirty-six patients who were diagnosed with retinal vein occlusion and 43 age and sex matched healthy controls were included in this study. Diabetes and use of anticoagulant therapy were exclusion criteria. All study participants underwent detailed ophthalmologic and systemic medical examination, including blood pressure measurement, hemoglobin-hematocrit levels, platelet count, coagulation parameters including prothrombin time, activated partial thromboplastin time, fibrinogen levels, and D-dimer levels. Peripheral blood samples were collected and analyzed with ROTEM Coagulation Analyzer (Tem International, Munich, Germany). RESULTS The RVO patients and controls did not differ with respect to age, sex, hemoglobin, hematocrit, platelet numbers, prothrombin time, activated partial thromboplastin time, fibrinogen levels, D-dimer levels, and glucose levels. When extrinsic thromboelastometry results were analyzed, RVO patients showed a significantly decreased clotting time (76.5 ± 15.0 vs. 95.0 ± 21 s, respectively; p = 0.01) and clot formation time (83.3 ± 22 vs. 99.7 ± 24s; p = 0.01) as compared with healthy controls. Other ROTEM parameters did now show any difference between two groups. CONCLUSION Patients with retinal vein occlusion showed faster clotting time and shorter clotting formation time as compared with healthy controls. ROTEM detects the altered clotting dynamics and may be a useful tool to elucidate the disease pathophysiology. Further studies are needed to investigate if it can be used as a screening test for individuals who are under risk to develop RVO or as a first step test to evaluate hypercoagulable state in RVO.
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Affiliation(s)
- Deniz Goren Sahin
- a Department of Hematology , Istanbul Bilim University Medical School , Istanbul , Turkey
| | - Betül N Bayraktutar
- b Department of Ophthalmology , Koç University Medical School , Istanbul , Turkey
| | - Ayşe Yıldız Taş
- b Department of Ophthalmology , Koç University Medical School , Istanbul , Turkey
| | - Olga Meltem Akay
- c Department of Hematology , Koç University Hospital , Istanbul , Turkey
| | - Abdullah Ozkaya
- d Department of Ophthalmology , Istanbul Beyoglu Eye Education and Research Hospital , Istanbul , Turkey
| | - Özlem Yalcin
- e Department of Physiology , Koç University Medical School , Istanbul , Turkey
| | - Afsun Sahin
- b Department of Ophthalmology , Koç University Medical School , Istanbul , Turkey
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Genetics of myocardial infarction: The role of thrombosis-associated genes. A review article. Meta Gene 2017. [DOI: 10.1016/j.mgene.2017.03.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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Spontaneously developed paraplegia in a patient with Factor V Leiden mutation. Spinal Cord Ser Cases 2017; 2:15039. [PMID: 28053741 DOI: 10.1038/scsandc.2015.39] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Revised: 10/30/2015] [Accepted: 12/09/2015] [Indexed: 11/09/2022] Open
Abstract
Factor V Leiden (FVL) mutation is the one-point mutation in G1691A in the tenth exon of the gene for Factor V, caused by the substitution of glutamine for arginine at codon 506. We present here a patient with a mutation of the Factor V gene and taking anticoagulant therapy, who became paraplegic following surgery for dural hematoma and spontaneous spinal intramedullary hematoma. His physical examination revealed T5 ASIA A, complete paraplegia. Our case is important in the literature, as being the first case with spinal intramedullary hematoma that developed due to anticoagulant use.
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Coagulation, thrombophilia and patency of arteriovenous fistula in children undergoing haemodialysis compared with healthy volunteers: a prospective analysis. Blood Coagul Fibrinolysis 2016; 27:190-8. [PMID: 26829282 DOI: 10.1097/mbc.0000000000000417] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
UNLABELLED This study aimed to assess whether markers of coagulation, fibrinolysis or thrombophilia are increased in children on haemodialysis compared with controls and whether measurement of any of these factors could help to identify patients at an increased risk of arteriovenous fistula (AVF) occlusion. Blood samples were taken from 55 children immediately before a session of haemodialysis and from 20 healthy volunteers. Thrombin-antithrombin (TAT), D-dimer, plasmin-antiplasmin (PAP) and anticardiolipin immunoglobulin G (ACA-Ig G) were measured by ELISA. Factor V Leiden mutation (G1691A) was determined by gene polymorphism [restriction fragment length polymorphism (RFLP)]. Determination of the patency of the AVF was prospectively followed up for a minimum of 4 years or until the AVF was nonfunctioning. Fifty-five patients were studied with a median follow-up of 659 days (range 30-1670 days). A significant increase was found in the levels of D-dimer, PAP and ACA-Ig G in haemodialysis patients with thrombosed and nonthrombosed native AVFs vs. CONTROLS There was a significant difference between both chronic haemodialysis patients with thrombosed and nonthrombosed native AVF with regard to ACA-IgG levels. At 1 year follow-up, primary patency was 61.4% (27 patients). In multivariate analysis, D-dimer was inversely associated with secondary patency.Thrombophilia may predispose children with end stage renal disease to access failure. The promising finding is that in children on haemodialysis, D-dimer levels were increased and inversely correlated with secondary patency. Further evaluation is required into the possible role of D-dimer as a biomarker of AVF occlusion.
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Kalkanli S, Ayyildiz O, Tiftik N, Batun S, Isikdogan A, Ince H, Tekes S, Muftuoglu E. Factor V Leiden Mutation in Venous Thrombosis in Southeast Turkey. Angiology 2016; 57:193-6. [PMID: 16518527 DOI: 10.1177/000331970605700209] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Venous thrombosis (VT) is a common disease, with an annual incidence in the general population of approximately 1 per 1,000. Factor V Leiden mutation (G1691A) (FVL) is the most common risk factor in venous thrombosis. The prevalence of FVL for thrombosis varies greatly in different regions of the world. FVL mutation has been identified both by conventional method and fluorescence resonance energy transfer (FRET) with the LightCycler. Sixty-one patients with VT, different in age and sex, were consecutively entered into this study to assess the prevalence of FVL in VT in southeast Turkey. FVL mutation was found in 24.6% (15/61). Fourteen individuals were heterozygous and 1 homozygous, a rate of 22.9% and 1.6%, respectively. In conclusion, the authors suggest that FVL mutation is common in patients with venous thrombosis in southeast Turkey.
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Affiliation(s)
- Sevgi Kalkanli
- Department of Medical Genetic-Biology, University of Dicle, Diyarbakir, Turkey.
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Moussaoui S, Saussoy P, Ambroise J, Defour JP, Zouitene R, Sifi K, Abadi N. Genetic Risk Factors of Venous Thromboembolism in the East Algerian Population. Clin Appl Thromb Hemost 2016; 23:105-115. [DOI: 10.1177/1076029615600789] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
Many genetic risk factors have been identified for causing venous thromboembolism (VTE). Most of them affect the function of natural anticoagulant pathways, particularly the protein C system, although recent studies suggest a role of components of the hematopoietic pathway in the etiology of venous thrombosis. In this case–control study, we aimed to determine the frequency of prothrombin G20210A and factor V Leiden (FVL) G1691A polymorphisms and protein C, protein S, and antithrombin III deficiencies in the East Algerian population and to investigate whether these genetic factors are associated with VTE. On the other hand, our study tends to evaluate the status of JAK2V617F and calreticulin (CALR) mutations among these cases. The participants consisted of 121 cases with VTE and 146 healthy controls. Polymorphisms of FVL G1691A and prothrombin G20210A were genotyped by polymerase chain reaction (PCR) restriction fragment length polymorphism. JAK2-V617F and calreticulin mutations were analyzed by quantitative PCR and PCR followed by capillary electrophoresis sequencing, respectively. Protein C, protein S, and antithrombin levels were determined and then hereditary deficiencies were identified. Of all cases and controls, none was a carrier of the antithrombin III deficiency, prothrombin gene G20210A, and CALR mutations. Only 1 case reported having a positive JAK2 mutation (mutant allele burden was 15%). The FVL mutation (GA/AA) was found in 14 (11.6%) cases and 2 (1.4%) controls and it was significantly different between both the groups ( P = .001). Deficiencies of protein S and protein C were detected in 17 (18.8%) cases. The univariate analysis resulted in a significant impact of FVL (odds ratio [OR] = 9.4, 95% confidence interval [CI] = 2.1-42.3; P = .003) and of protein S deficiency (OR = 16.9, 95% CI =2.1-132.8, P = .007) on the VTE status. Both factors stayed significant after adjustment for sex and age. The OR of the protein C deficiency was slightly elevated (OR = 6.4, 95% CI = 0.7-55.5), but it did not reach the level of statistical significance ( P = .091), and it was therefore not considered as a risk factor. In conclusion, coagulant factor V gene G1691A mutation and protein S deficiency constitute important genetic risk factors in patients with VTE in Eastern Algeria. The somatic mutation of JAK2 V617F and CALR mutations are less frequent causes of VTE, thus routine testing for these mutations is not recommended.
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Affiliation(s)
- S. Moussaoui
- Laboratoire de recherche en biologie et génétique moléculaire, CHU Dr Benbadis rue Bensghir-Abdelwahed 25000, Constantine, Algeria
- Laboratoire de biochimie, CHU Dr Benbadis rue Bensghir-Abdelwahed 25000, Constantine, Algeria
| | - P. Saussoy
- Laboratoire de biologie moléculaire, cliniques Saint Luc, Université Catholique de Louvain (UCL), Brussels, Belgium
| | - J. Ambroise
- Centres des Technologies Moléculaires Appliquées (CTMA), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCL), Brussels, Belgium
| | - J. P. Defour
- Cliniques Universitaires Saint Luc, Ludwig Institute for Cancer Research, de Duve Institute, Université catholique de Louvain, Brussels, Belgium
| | - R. Zouitene
- Laboratoire d’hémobiologie, hôpital militaire régional universitaire de Constantine, Algeria
| | - K. Sifi
- Laboratoire de recherche en biologie et génétique moléculaire, CHU Dr Benbadis rue Bensghir-Abdelwahed 25000, Constantine, Algeria
- Laboratoire de biochimie, CHU Dr Benbadis rue Bensghir-Abdelwahed 25000, Constantine, Algeria
| | - N. Abadi
- Laboratoire de recherche en biologie et génétique moléculaire, CHU Dr Benbadis rue Bensghir-Abdelwahed 25000, Constantine, Algeria
- Laboratoire de biochimie, CHU Dr Benbadis rue Bensghir-Abdelwahed 25000, Constantine, Algeria
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Dölek B, Eraslan S, Eroğlu S, Kesim BE, Ulutin T, Yalçiner A, Laleli YR, Gözükirmizi N. Molecular Analysis of Factor V Leiden, Factor V Hong Kong, Factor II G20210A, Methylenetetrahydrofolate Reductase C677T, and A1298C Mutations Related to Turkish Thrombosis Patients. Clin Appl Thromb Hemost 2016; 13:435-8. [PMID: 17911197 DOI: 10.1177/1076029607303341] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Inherited gene disorders related to the hemostatic system have been documented as risk factors for thrombosis. The roles of factor V Hong Kong (FV Hong Kong), factor V Leiden (FV Leiden), factor II G20210A (FII G20210A), methylenetetrahydrofolate reductase (MTHFR) C677T, and MTHFR A1298C mutations in Turkish patients with thrombosis (270 patients) compared with healthy controls (114 subjects) were evaluated. Polymerase chain reaction—based restriction enzyme analysis was carried out to screen these mutations, and single-strand conformation analysis was established to identify variations using the primers selected for restriction enzyme analysis studies. As a result, a significant relationship was determined among FV Leiden, FII G20210A, and thrombosis. The FV Hong Kong mutation was observed in only 2 patients with pulmonary vein thrombosis who are FV Leiden/FV Hong Kong compound heterozygous for FV gene. MTHFR C677T and A1298C were equally distributed in the patient group compared with the control group. All named mutations were also identified with single-strand conformation analysis, but a new variant/polymorphism during studies was not found. Because some inherited abnormalities are associated with thromboembolic disorders, determining the mutations and gene-to-gene interactions in patients with thrombosis history has a great impact on diagnosis and treatment of these diseases.
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Affiliation(s)
- Bilgen Dölek
- Department of Molecular Biology and Genetics, Istanbul University, Istanbul, Turkey.
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Sayinalp N, Haznedaroğlu IC, Aksu S, Büyükaşik Y, Göker H, Parlak H, Ozcebe OI, Kirazli S, Dündar SV, Gürgey A. The Predictability of Factor V Leiden (FV:Q506) Gene Mutation via Clotting-Based Diagnosis of Activated Protein C Resistance. Clin Appl Thromb Hemost 2016; 10:265-70. [PMID: 15247984 DOI: 10.1177/107602960401000309] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
After the discovery of activated protein C resistance (APCR) due to factor V Leiden mutation and the causal relationship of the phenomenon with clinical thromboembolism, a wide variety of functional clotting-based assays were developed for testing of APCR in relation to the specific DNA-based analysis of FV:Q506 Leiden. The aim of this study is to assess a clotting-based APCR assay using procoagulant crotalidae snake venom with respect to the sensitivity, specificity, and predictability for the presence of the factor V Leiden mutation. APCR testing and factor V DNA analyses have been performed concurrently on 319 patient specimens. APCR values of the patients with homozygous factor V Leiden mutation (70.4±13.5 s) were significantly lower (p<0.001) in comparison to the subjects with the heterozygous mutation (87.6±13.4 s). The assay is highly sensitive (98.7%) and specific (91.9%) for the screening of factor V Leiden mutation. The sensitivity and specificity of the APCR testing reached to 100% below the cut-off value of 120 s among the patients with homozygous factor V Leiden mutation. Therefore, this method could help the desired effective optimal screening strategy for the laboratory search of hereditary thrombophilia focusing on the diagnosis of APCR due to FV:Q506.
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Affiliation(s)
- N Sayinalp
- Hacettepe University Medical School, Department of Hematology, Ankara, Turkey.
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Schockman S, Glueck CJ, Hutchins RK, Patel J, Shah P, Wang P. Diagnostic ramifications of ocular vascular occlusion as a first thrombotic event associated with factor V Leiden and prothrombin gene heterozygosity. Clin Ophthalmol 2015; 9:591-600. [PMID: 25897198 PMCID: PMC4396423 DOI: 10.2147/opth.s80714] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
AIM This study aimed to assess the diagnostic ramifications of vascular occlusion of the ocular vein and artery as a first thrombotic event associated with factor V Leiden (FVL) and/or prothrombin gene (PTG) heterozygosity. METHODS Patients with ocular vein (n=191) and artery (n=74) occlusion, free of cardioembolic etiologies, were sequentially referred from vitreoretinal specialists for measurement of thrombophilia-hypofibrinolysis and compared to 110 healthy normal controls. RESULTS Of the 265 patients, 29 (11%; 17 women, 12 men) of all referred ocular vascular occlusion (OVO) cases were found to be heterozygous for FVL and/or PTG, including 16 with FVL, 12 with PTG, and 1 with both. Of the 29 cases, 16 had central retinal vein occlusion (CRVO), 2 branch retinal vein occlusion (BRVO), 5 nonarteritic anterior ischemic optic neuropathy (NA-AION), 3 retinal artery occlusion (RAO), 2 amaurosis fugax (AF), and 1 had both CRVO and RAO. Of the 16 FVL cases, 15 (94%) had OVO as a first thrombotic event without prior deep venous thrombosis (DVT) or pulmonary embolism (PE); 6 (38%) also had other thrombotic events, including recurrent miscarriage, osteonecrosis, ischemic stroke, and/or ischemic colitis; and 5 (31%) had immediate family members with previous venous thromboembolism (VTE). Of the 12 PTG cases, 9 (75%) had OVO as a first thrombotic event, 5 (42%) experienced VTE other than DVT or PE, and 6 (50%) had immediate family members with VTE. In one patient with both FVL and PTG, DVT occurred before BRVO. Of the 17 women with FVL and/or PTG mutations, 7 (41%) experienced ≥1 miscarriage, 6 (35%) were on estrogen therapy, and 1 (6%) was on clomiphene. CONCLUSION Of the 265 patients with OVO, 29 (11%) had FVL and/or PTG, and 83% of these 29 cases presented with OVO as their first thrombotic event. By diagnosing thrombophilia as an etiology for OVO, the ophthalmologist opens a window to family screening and preventive therapy.
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Affiliation(s)
- Samantha Schockman
- Internal Medicine Residency Program, The Jewish Hospital-Mercy Health, Cincinnati, Ohio, USA
| | - Charles J Glueck
- Cholesterol, Metabolism, and Thrombosis Center, The Jewish Hospital-Mercy Health, Cincinnati, Ohio, USA ; Mercy Health Physicians, Mercy Health, Cincinnati, Ohio, USA
| | - Robert K Hutchins
- Department of Ophthalmology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA ; Cincinnati Eye Institute, Cincinnati, Ohio, USA
| | - Jaykumar Patel
- Cholesterol, Metabolism, and Thrombosis Center, The Jewish Hospital-Mercy Health, Cincinnati, Ohio, USA
| | - Parth Shah
- Cholesterol, Metabolism, and Thrombosis Center, The Jewish Hospital-Mercy Health, Cincinnati, Ohio, USA
| | - Ping Wang
- Cholesterol, Metabolism, and Thrombosis Center, The Jewish Hospital-Mercy Health, Cincinnati, Ohio, USA
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Epidemiology of Prothrombin G20210A Mutation in the Mediterranean Region. Mediterr J Hematol Infect Dis 2011; 3:e2011054. [PMID: 22220251 PMCID: PMC3248331 DOI: 10.4084/mjhid.2011.054] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2011] [Accepted: 10/07/2011] [Indexed: 11/08/2022] Open
Abstract
There are many genetic and acquired risk factors that are known to cause venous thromboembolic disorders (VTE). One of these is the Prothrombin G20210A mutation, which has been identified in 1996. Prothrombin G20210A mutation causes higher levels of the clotting factor prothrombin in the blood of carriers, which creates a higher tendency towards blood clotting (hypercoagulability), and therefore the carriers become at higher risk of developing VTE. High prevalence of Prothrombin G20210A mutation was reported in Caucasian populations, but the prevalence was almost absent in non-Caucasians. That was most obvious in countries of South Europe and the Mediterranean region. This review article discusses Prothrombin G20210A mutation, how it causes VTE, the origin of the mutation, and its distribution worldwide with special concentration on the Mediterranean area.
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Epidemiology of activated protein C resistance and factor v leiden mutation in the mediterranean region. Mediterr J Hematol Infect Dis 2011; 3:e2011037. [PMID: 22224194 PMCID: PMC3251907 DOI: 10.4084/mjhid.2011.037] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2011] [Accepted: 08/17/2011] [Indexed: 02/06/2023] Open
Abstract
Venous thromboembolic disorders (VTE) are serious disorders with high morbidity and mortality rates. Many genetic and acquired risk factors were identified to cause VTE. The most common genetic risk factor is Factor V Leiden mutation (FVL). FVL was found in high percentage of populations of Caucasian origin but was almost absent in non-Caucasians. It was also reported in populations living in North Africa and the Middle East. This review article briefly explains FVL and how it causes VTE, the distribution of FVL worldwide, and then it elaborates on the epidemiology of FVL in the Mediterranean Region and how this brought speculations that FVL might have originated in the Eastern Mediterranean area.
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Eroglu A, Sertkaya D, Akar N. The Role of Factor V Leiden in Adult Patients With Venous Thromboembolism: A Meta-Analysis of Published Studies from Turkey. Clin Appl Thromb Hemost 2011; 18:40-4. [DOI: 10.1177/1076029611412369] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Factor V Leiden (FVL) is the most common inherited risk factor for venous thromboembolism (VTE). The frequency of FVL in patients with VTE has been reported from different parts of Turkey. A meta-analysis was performed to estimate the risk of VTE associated with FVL in Turkish population. Published studies were retrieved from Pubmed and Science Citation Index/Expanded. We selected studies comparing the prevalence of FVL in patients with VTE with controls. The analysis was performed by the software comprehensive meta-analysis. The analysis consisted of 10 studies including 1202 patients with VTE and 1283 controls. The pooled frequency of FVL was significantly higher in patients with VTE (22.8%) than controls (7.6%). The pooled odds ratio (OR) was 3.4 (95% confidence interval [CI], 2.6-4.5). The study showed homogeneity ( Q value, 9.955). No publication bias was observed in any comparison model. Our meta-analysis showed an association of FVL with VTE in Turkey.
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Affiliation(s)
- Aydan Eroglu
- General Surgery, Ankara University Medical School, Ankara, Turkey
| | - Durdu Sertkaya
- Faculty of Science, Statistics Section, Hacettepe University, Beytepe/Ankara, Turkey
| | - Nejat Akar
- Pediatrics, TOBB-ETU University Hospital
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16
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Association of deep venous thrombosis with prothrombotic gene polymorphism identified in lung cancer cases. Mol Biol Rep 2010; 38:2395-400. [DOI: 10.1007/s11033-010-0373-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2010] [Accepted: 11/04/2010] [Indexed: 11/26/2022]
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17
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Kupeli E, Verdi H, Simsek A, Atac FB, Eyuboglu FO. Genetic Mutations in Turkish Population With Pulmonary Embolism and Deep Venous Thrombosis. Clin Appl Thromb Hemost 2010; 17:E87-94. [PMID: 21078611 DOI: 10.1177/1076029610385224] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Venous thromboembolism (VTE) is a universal health hazard. Inherited and acquired risk factors increase the risk of VTE. We evaluated the relationship between factor V (G1691A, A1090G, and A1299G), prothrombin (PT G20210A), methylenetetrahydrofolate reductase (MTHFR C677T) mutations, plasminogen activator inhibitor 1 (PAI-1 -675) polymorphism, and VTE in Turkish population. In all, 80 patients with VTE and 104 controls were included. Heterozygous factor V Leiden (FVL) mutation was significantly higher among patients ( P = .04) with allele frequency of 6.3% ( P = .01). Heterozygous PT G20210A mutation was also significantly higher among patients ( P = .001) with allele frequency of 6.9% ( P = .003). MTHFR 677TT genotype was significantly higher in patients ( P = .009) with allele frequency of 23.8% ( P = .005). No significant difference was found in FV A1090G and FV A1299G mutation rate as well as PAI-1 genotypes and their allele frequencies ( P > .05). Thus, frequencies of FV G1691A, PT G20210A, and MTHFR C677T mutations are higher in patients with VTE. FV A1090G, FV A1299G mutations, and PAI-1 gene polymorphisms may not be a risk factor for VTE in Turkish population.
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Affiliation(s)
- Elif Kupeli
- Department of Pulmonary Diseases, Baskent University School of Medicine, Ankara, Turkey
| | - Hasibe Verdi
- Medical Biology, Baskent University School of Medicine, Ankara, Turkey
| | - Abdullah Simsek
- Department of Pulmonary Diseases, Baskent University School of Medicine, Ankara, Turkey
| | - Fatma Belgin Atac
- Medical Biology, Baskent University School of Medicine, Ankara, Turkey
| | - Fusun Oner Eyuboglu
- Department of Pulmonary Diseases, Baskent University School of Medicine, Ankara, Turkey
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18
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Hwang S, Kim DY, Kim M, Chon YE, Lee HJ, Park YN, Park JY, Ahn SH, Han KH, Chon CY. [Deficiencies in proteins C and S in a patient with idiopathic portal hypertension accompanied by portal vein thrombosis]. THE KOREAN JOURNAL OF HEPATOLOGY 2010; 16:176-81. [PMID: 20606502 DOI: 10.3350/kjhep.2010.16.2.176] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Portal vein thrombosis (PVT) is an uncommon cause of presinusoidal portal hypertension. Among various hepatoportal disorders, noncirrhotic portal hypertension conditions such as idiopathic portal hypertension (IPH) are considered to have a close relation with PVT. PVT is known to have several predisposing conditions, including infection, malignancies, and coagulation disorders. There is growing interest and recognition that deficiencies in proteins C and S are associated with a hypercoagulable state. These deficiencies are regarded as key factors of systemic hypercoagulability and recurrent venous thromboembolism. We report the case of a 19-year-old male diagnosed as IPH with PVT and combined deficiencies in proteins C and S.
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Affiliation(s)
- Sena Hwang
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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19
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Natural anticoagulant protein levels in Turkish patients with inflammatory bowel disease. Blood Coagul Fibrinolysis 2010; 21:118-21. [DOI: 10.1097/mbc.0b013e328335d025] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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20
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Bayraktar Y, Harmanci O, Büyükasik Y, Shorbagi AI, Sungur AH, Boylu CA, Gürgey A, Balkanci F. JAK2V617F mutation in patients with portal vein thrombosis. Dig Dis Sci 2008; 53:2778-83. [PMID: 18343999 DOI: 10.1007/s10620-008-0225-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2007] [Accepted: 02/19/2008] [Indexed: 02/02/2023]
Abstract
In a retrospective cohort, we investigated the presence of the JAK2V617F mutation in chronic non-cirrhotic portal vein thrombosis (PVT) patients, irrespective of the presence or absence of myeloproliferative diseases (MPDs). We identified 25 patients in whom thrombophilia workup was completed. The diagnoses of MPDs were made according to the World Health Organization (WHO) criteria. JAK2V617F mutation analysis was performed by allele-specific polymerase chain reaction (PCR). There were 9 male and 16 female patients. Prior to JAK2V617F analysis, there were one or more thrombophilic risk factors in 19 patients (76%). The JAK2V617F mutation analysis revealed the presence of this mutation (all in the heterozygote state) in six patients (24%; two male, four female). Five of the six cases with prior clinical diagnosis of MPDs were found to have wild-type JAK2. We found that the addition of JAK2V617F analysis into the thrombophilia workup in patients with chronic PVT contributes to a 4% increase in the diagnosis of thrombophilic conditions.
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Affiliation(s)
- Yusuf Bayraktar
- Department of Gastroenterology, Hacettepe University Faculty of Medicine, 06100, Sihhiye, Ankara, Turkey.
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21
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Genc G, Atay NE, Kepenekli E, Yarali N. May thrombosis be a cause of congenital extremity absence? Indian J Pediatr 2007; 74:497-9. [PMID: 17526965 DOI: 10.1007/s12098-007-0086-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Congenital extremity anomalies have many modes of presentation. Interruption of vascular supply with thrombophily is a rare cause of congenital extremity absence. Here it is presented a 7 mth old male with absence of the left lower extremity. Laboratory tests revealed Factor V Leiden and Prothrombin G20210A heterozygote mutation and that was as the cause of extremity absence. At the patients with congenital extremity absences, it is not imprudent to explore a possible thrombophilic mutation along with other known etiologic factors.
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Affiliation(s)
- Gurkan Genc
- Department of Pediatrics, Dr. Sami Ulus Children's Hospital, Ankara, Turkey.
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22
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Harmanci O, Ersoy O, Gurgey A, Buyukasik Y, Gedikoglu G, Balkanci F, Sivri B, Bayraktar Y. The etiologic distribution of thrombophilic factors in chronic portal vein thrombosis. J Clin Gastroenterol 2007; 41:521-7. [PMID: 17450038 DOI: 10.1097/01.mcg.0000225635.52780.47] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
GOALS We aimed to prospectively investigate the full etiologic contributors to portal vein thrombosis. BACKGROUND Portal vein thrombosis in the absence of liver disease is a rare cause of portal hypertension with a different clinical course and management strategy. The etiologic distribution of this interesting clinical picture is important as far as diagnostic and management issues are concerned. STUDY After the application of exclusion criteria, 59 patients were included in the study who had normal liver functions, normal liver histology and studied the thrombophilia factors of both acquired factors and congenital factors like protein C, protein S, antithrombin levels with the mutations. RESULTS In all, 23.7% of the patients were found to have acquired thrombophilia factors like myeloproliferative disorders and cyst hydatid disease, whereas 22.1% of the patient population was found to harbor no identifiable cause of thrombophilia, which we termed as idiopathic. One or more causes of thrombophilia were identified in 46 patients. There were 27 patients with protein C deficiency, 18 patients with protein S deficiency. The antithrombin deficiency was found in 17 patients. The factor V Leiden mutation was found in 7 patients. There was 1 patient with homozygote mutation, whereas the remaining 6 patients were heterozygotes. There were 3 patients with prothrombin mutation who were heterozygote for this mutation. CONCLUSIONS Complete investigation of thrombophilia is crucial to delineate the outline of thrombophilic risk factors to estimate the rethrombosis risk and for further management concerns.
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Affiliation(s)
- Ozgur Harmanci
- Department of Gastroenterology, Hacettepe University Faculty of Medicine, 06100 Sihhiye, Ankara, Turkey.
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23
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Karagulle E, Turk E, Gokturk HS, Yildirim E, Moray G. Prothrombin 20210 G/A Defect as a Cause of Mesenteric Venous Infarction: Report of a Case. Surg Today 2007; 37:251-3. [PMID: 17342369 DOI: 10.1007/s00595-006-3381-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2006] [Accepted: 08/10/2006] [Indexed: 11/30/2022]
Abstract
A 50-year-old man with abdominal pain, nausea, and vomiting presented at our emergency department. Physical examination revealed diffuse abdominal tenderness and absent bowel sounds. Computed tomography showed partial portal vein thrombosis extending to the right portal vein and the superior mesenteric vein, perfusion defects in the liver, and nonopacified intestinal segment after contrast injection. An emergency laparotomy was performed. The wall of the distal jejunum was edematous, congested, and a 10-cm jejunal segment was necrotic. A partial intestinal resection and a primary anastomosis were performed. Screening for thrombophilia revealed a heterozygote 20210 G/A mutation of the prothrombin gene. Anticoagulation was initiated. Computed tomography 45 days after surgery showed a complete dissolution of the thrombi and cavernous transformation in the main portal vein. His subsequent clinical course was uneventful. Mesenteric venous thrombosis which causes an intestinal infarction is rare, and also difficult to diagnose. However, a prothrombin 20210 defect should be considered in the differential diagnosis of patients with unexplained thrombosis.
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Affiliation(s)
- Erdal Karagulle
- Department of General Surgery, Baskent University, Hocacihan mah. Saray caddesi No:1, Selcuklu, Konya 42080, Turkey
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24
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Yurekli BPS, Aksoy DY, Aybar M, Egesel T, Gurgey A, Hascelik G, Kirazli S, Haznedaroglu IC, Arslan S. The search for a common thrombophilic state during the active state of inflammatory bowel disease. J Clin Gastroenterol 2006; 40:809-813. [PMID: 17016137 DOI: 10.1097/01.mcg.0000225603.33481.56] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The clinical course of inflammatory bowel disease (IBD) is frequently associated with thromboembolic complications. The aim of this study was to investigate common thrombophilic markers in Turkish patients with active IBD. Twenty-seven consecutive patients with IBD who were followed-up at the Hacettepe University Hospital were recruited. All the patients were in the active disease state. International normalized ratio, activated partial thromboplastin time, lupus anticoagulant, anticardiolipin IgG, IgM antibodies, protein C, protein S, antithrombin-III, factor V, and factor II mutation of all the IBD patients and of a sex-matched and age-matched control group of non-IBD patients were measured. International normalized ratio, activated partial thromboplastin time, protein C, protein S, lupus anticoagulant, anticardiolipin IgG and IgM, and Proteins C and S mutations were comparable between the 2 groups, but antithrombin-III was significantly lower in the IBD group compared with healthy control group (P<0.0001). As a conclusion, it is reasonable to assume that there may be a subpopulation of the patients with IBD, in whom thrombophilic abnormalities might be important for either disease manifestation or for thrombotic complications. Those hemostatic abnormalities could be either inherited or secondary to the ongoing disease process. Routine screening for the common markers of thrombophilia does not seem to be warranted unless simultaneous arterial and venous thrombosis, major organ thrombosis, strong family history of thrombophilia, unusual and recurrent thrombosis resistant to standard anticoagulant therapy are present. Further studies are definitely required to clarify these complicated associations.
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25
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Harmanci O, Buyukasik Y, Kirazli S, Balkanci F, Bayraktar Y. Does endothelium agree with the concept of idiopathic hepatic vessel thrombosis. World J Gastroenterol 2006; 12:1273-7. [PMID: 16534884 PMCID: PMC4124442 DOI: 10.3748/wjg.v12.i8.1273] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the major steps of thrombogenesis and to identify the differences in these steps between idiopathic patient group and control group.
METHODS: Fibrinogenesis was studied by measuring the activated factor VII, total and free levels of tissue factor pathway inhibitor (TFPI). The fibrinolysis step was investigated by determining the global fibrinolytic capacity. The endothelial function was assessed by measuring the levels of soluble adhesion molecules, namely soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1) and soluble E-selectin molecule. The exclusion criteria from “idiopathic” patient group were abdominal surgery, pregnancy, use of oral contraceptives, anti-phospholipid syndrome, Behçet’s disease, cancer, myeloproliferative diseases. The congenital factors like mutations of factor-V Leiden and prothrombin, deficiencies of proteins C and S, antithrombin, hyperhomocysteinemia and hyperfibrinogenemia were ruled out. The total number of patients was reduced from 96 to 9 (7 with portal vein thrombosis, 2 Budd Chiari syndrome) by exclusion criteria.
RESULTS: The levels of adhesion molecules sICAM-1, sVCAM-1, free TFPI levels and global fibrinolytic capacity were significantly different (P < 0.05) in the patient group indicating an endothelial dysfunction and a lower fibrinolytic activity.
CONCLUSION: These results show that this patient group should be tested by means of endothelial dysfunction and managed differently.
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Affiliation(s)
- Ozgur Harmanci
- Department of Gastroenterology, Hacettepe University Faculty of Medicine, 06100 Sihhiye, Ankara, Turkey.
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26
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Koshy A, Jeyakumari M. Prothrombin G20210A gene variant is not associated with idiopathic portal vein thrombosis in an area endemic for portal vein thrombosis. Ann Hematol 2005; 85:126-8. [PMID: 16283309 DOI: 10.1007/s00277-005-0020-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2005] [Accepted: 09/19/2005] [Indexed: 02/07/2023]
Abstract
Prothrombin G20210A gene variant has been found in 0-23% of patients with portal vein thrombosis (PVT). This wide variation makes it difficult to assess the importance of prothrombin G20210A gene variant as a predisposing factor for PVT. In this study from South India, none of the patients with idiopathic PVT (0/38) or any of the controls (0/46) had prothrombin G20210A gene variant. Prothrombin G20210A gene variant does not contribute to the development of PVT in India.
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Affiliation(s)
- Abraham Koshy
- Department of Gastroenterology, Institute of Population Health and Clinical Research, St John's Medical College Hospital, Bangalore, India.
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27
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Ağaoğlu N, Türkyilmaz S, Ovali E, Uçar F, Ağaoğlu C. Prevalence of Prothrombotic Abnormalities in Patients with Acute Mesenteric Ischemia. World J Surg 2005; 29:1135-8. [PMID: 16086214 DOI: 10.1007/s00268-005-7692-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Acute mesenteric ischemia (AMI) is a rare condition that may be associated with a variety of congenital prothrombotic disorders (PDs). The purpose of this study was to assess the prevalence of these disorders in 28 AMI patients compared with 103 healthy individuals from the northeastern region of Turkey. They were screened for protein C, antithrombin III, and protein S deficiencies; and gene analysis was performed using the polymerase chain reaction. A PD was revealed in 16 (57%) patients and 33 (32%) controls (p = 0.020). Factor V Leiden (FVL), prothrombin G20210A mutation, and TT677 homozygous mutation of methylenetetrahydrofolate reductase was detected in 10 (36%) patients versus 16 (15%) controls (p = 0.035), 3 (11%) patients versus 10 (9%) controls (p = 1.00), and 1 (3%) patient versus no controls, respectively. Consistent with caucasian ethnic groups, there was high prevalence of PDs, especially FVL; and these abnormalities might be a significant predisposing factor in the pathogenesis of AMI.
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Affiliation(s)
- Nazim Ağaoğlu
- Department of General Surgery, Karadeniz Technical University, Faculty of Medicine, Trabzon 61080, Turkey.
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28
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Aksoy MC, Aksoy DY, Haznedaroglu IC, Sayinalp N, Kirazli S, Alpaslan M. Enhanced tissue factor pathway inhibitor response as a defense mechanism against ongoing local microvascular events of Legg-Calve-Perthes disease. Pediatr Hematol Oncol 2005; 22:391-9. [PMID: 16020129 DOI: 10.1080/08880010590964273] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
The precise pathogenetic basis of Legg-Calve-Perthes disease (LCPD) is currently unknown. Hemostatic abnormalities, i.e., hypercoagulability and/or hypofibrinolysis, were proposed in the genesis of the LCPD. Deficiency of tissue factor pathway inhibitor (TFPI), a critical natural anticoagulant molecule, may lead to a prothrombotic state in a wide variety of conditions. The aim of this study is to assess the circulating TFPI pool in the LCPD. Group I consisted of 44 patients with LCPD and group II comprised 38 healthy children. Median (IQR) TPFI concentration was significantly higher in the group I (p < .0001). Enhanced TFPI response could be regarded as a compensatory defense mechanism against ongoing local microvascular events of occlusion and revascularization of LCPD. TFPI molecule may be an important link between the crossroads of the LCPD genesis and pathogenetic microvascular changes in the disease course. Further investigations are needed to shed light on the endothelial anticoagulant kinetics, the unique microvascular compromise, and the self-limiting nature of the disease.
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Affiliation(s)
- Mehmet Cemalettin Aksoy
- Department of Orthopaedics and Traumatology, Hacettepe University Medical School, Ankara, Turkey
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Abstract
OBJECTIVE To investigate the association of two common prothrombotic mutations, factor V G1691A (FV G1691A) and prothrombin G20210A (PT G20210A), in neonates with thrombosis. METHODS Twenty-six neonates with thrombosis were assessed with the spectrum of assays for thrombophilia, including the two DNA-based prothrombotic factors. RESULTS Eight patients (31%) had the FV G1691A mutation in heterozygous state. PT G20210A mutation was detected in four patients (15%). Overall, two common prothrombotic factors were detected in 12 neonates (46%) and an underlying disease or a triggering event in 18 neonates (69%). Thrombosis was considered to be idiopathic in five neonates (19%). CONCLUSIONS The pathogenesis of thrombosis in neonates is multi-factorial. Along with underlying diseases or triggering events, congenital prothrombotic factors (FV G1691A and PT G20210A) showed a trend toward a higher frequency in neonates with thrombosis. These data indicate that mutations associated with underlying disorders in neonates may contribute to the development of thromboembolic disease.
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Affiliation(s)
- Aytemiz Gurgey
- University of Hacettepe, Faculty of Medicine, Ankara, Turkey.
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30
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Gurgey A, Balta G, Boyvat A. Factor V Leiden mutation and PAI-1 gene 4G/5G genotype in thrombotic patients with Behcet's disease. Blood Coagul Fibrinolysis 2003; 14:121-4. [PMID: 12632020 DOI: 10.1097/00001721-200302000-00001] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Behcet's disease is a chronic systemic vasculitis with particular systemic features including thrombotic events. The present study was designed to analyse the role of the factor V Leiden and the prothrombin G20210A mutations and plasminogen activator inhibitor-1 4G/5G polymorphism on the thrombotic risk of patients with Behcet's disease. A total of 50 unrelated patients with Behcet's disease (34 male, 16 female) were the subjects of the study. Twenty-seven of 50 patients with a history of thrombosis comprised group 1, and 23 patients with no thrombosis comprised group 2. In group 1, nine of the 27 patients (33%) were found to have the factor V Leiden mutation (7.1% in healthy population), and the 4G/4G genotype was found in 23% of the patients (26% in control). No patient had the prothrombin G20210A mutation (2.2% in healthy control). In group 2, two patients (9%) had the factor V Leiden and one patient (4%) had the prothrombin G20210A mutations. The 4G/4G polymorphism was found in 30.5% of the patients. The differences in the frequencies of factor V Leiden mutation between group 1 and group 2 (odds ratio, 5.3; 95% confidence interval, 1.0-27.5) and between group 1 and the healthy population were statistically significant ( 0.05). No statistically significant association was found for the prothrombin G20210A mutation and the 4G/5G genotype between the two groups or between each group and the healthy population, indicating that the prothrombin G20210A mutation and the 4G/4G polymorphism do not play a role in the development of thrombosis in Behcet's disease. These data suggested that the factor V Leiden mutation might be a risk factor for the development of thrombosis in Behcet's disease patients.
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Affiliation(s)
- Aytemiz Gurgey
- Department of Pediatric Hematology, Hacettepe University Medical School, Ankara, Turkey.
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