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1
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Wang Z, Wu H. The Association of Prothrombin Gene G20210A Mutation with Recurrent Venous Thromboembolism: Evidence from a Meta-Analysis. Ann Vasc Surg 2025; 110:295-305. [PMID: 39096951 DOI: 10.1016/j.avsg.2024.06.044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 06/23/2024] [Accepted: 06/27/2024] [Indexed: 08/05/2024]
Abstract
OBJECTIVES The prothrombin (PT) G20210A mutation is one of the most prevalent genetic variations associated with an increased susceptibility to the first episode of venous thromboembolism (VTE). However, it remains uncertain whether this inherited thrombophilic abnormality also poses a risk for recurrent VTE. This meta-analysis aimed to assess the relation of PT G20210A mutation to the risk of recurrent VTE. METHODS PubMed and Scopus were systematically searched for pertinent prospective studies. Relative risks (RR) and 95% confidence intervals (CI) were used to test the association. Sixteen studies, with 16,174 participants, were included. RESULTS Carriers of the G20210 A mutation were at increased risk of recurrent VTE (RR = 1.60, 95% CI = 1.20-2.14) compared to noncarriers; the increased risk was observed in heterozygotes (GA versus GG) (RR = 1.79, 95% CI = 1.24-2.57), but not in GA/AA mutation. CONCLUSIONS This association was found to be significant in the long term (≥5 years of follow-up), but not in the short term (<5 years of follow-up).
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Affiliation(s)
- Zaiqing Wang
- Department of Cardiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, China
| | - Han Wu
- Department of General Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, China.
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2
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Emmerich J, Zuily S, Gouin-Thibault I, Morange PE, Couturaud F, Huisman M. Impact of thrombophilia on venous thromboembolism management. Presse Med 2024; 53:104247. [PMID: 39244017 DOI: 10.1016/j.lpm.2024.104247] [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] [Indexed: 09/09/2024] Open
Abstract
Hypercoagulable states, also called thrombophilia, can either be congenital or acquired. Congenital thrombophilia, associated mainly with venous thrombosis, is either secondary to coagulation-inhibitor deficiencies, i.e., antithrombin, protein C and Protein S, or gain of function mutations, i.e., factor V Leiden and prothrombin G20210A mutations. Despite the relative frequency of these two mutations, they have not been associated with venous thrombosis recurrence. Most prevalent thrombophilia have a limited impact and usually does not change indications for duration of antithrombotic treatment or prophylaxis compared to decisions based on clinical factors. However, rare inherited thrombophilia such as antithrombin deficiency could justify a long-term anticoagulation. The main acquired thrombophilia, the Antiphospholipid syndrome (APS), is associated with both arterial and venous thrombosis. Its impact on patient management is significant: choice of the anticoagulant (DOAC vs. warfarin), duration of anticoagulation, screening of any organ involvement and systemic autoimmune disease, introduction of immunosuppressive therapy.
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Affiliation(s)
- Joseph Emmerich
- Department of Vascular Medicine, Paris Saint-Joseph Hospital Group, University of Paris, 75014 Paris, France; INSERM CRESS UMR 1153, F-75005 Paris, France; FCRIN INNOVTE network, Saint-Etienne, France.
| | - Stéphane Zuily
- FCRIN INNOVTE network, Saint-Etienne, France; Vascular Medicine Division, Université de Lorraine, CHRU-Nancy, Rare Vascular and Systemic Autoimmune Diseases Regional Referral Center, France; Inserm, UMR 1116 DCAC, F-54000 Nancy, France
| | - Isabelle Gouin-Thibault
- Vascular Medicine Division, Université de Lorraine, CHRU-Nancy, Rare Vascular and Systemic Autoimmune Diseases Regional Referral Center, France; Department of Laboratory Hematology, Pontchaillou University Hospital of Rennes, Rennes, France; Institut de Recherche en Santé, Environnement et Travail (IRSET)-Institut National de la Santé et de la Recherche Médicale (INSERM)-1085, University of Rennes, Rennes, France
| | - Pierre-Emmanuel Morange
- Vascular Medicine Division, Université de Lorraine, CHRU-Nancy, Rare Vascular and Systemic Autoimmune Diseases Regional Referral Center, France; Aix-Marseille University, INSERM, INRAE, Centre de Recherche en CardioVasculaire et Nutrition, Laboratory of Haematology, CRB Assistance Publique - Hôpitaux de Marseille, Marseille, France
| | - Francis Couturaud
- Vascular Medicine Division, Université de Lorraine, CHRU-Nancy, Rare Vascular and Systemic Autoimmune Diseases Regional Referral Center, France; CHU Brest, Département de Médecine Interne et Pneumologie, Brest, France; Univ_Brest, INSERM U1304-GETBO, CIC INSERM 1412, F29609 Brest, France
| | - Menno Huisman
- Department of Medicine - Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands
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Dunster JL, Wright JR, Samani NJ, Goodall AH. A System-Wide Investigation and Stratification of the Hemostatic Proteome in Premature Myocardial Infarction. Front Cardiovasc Med 2022; 9:919394. [PMID: 35845083 PMCID: PMC9281867 DOI: 10.3389/fcvm.2022.919394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 05/26/2022] [Indexed: 11/13/2022] Open
Abstract
Introduction Advancing understanding of key factors that determine the magnitude of the hemostatic response may facilitate the identification of individuals at risk of generating an occlusive thrombus as a result of an atherothrombotic event such as an acute Myocardial Infarction (MI). While fibrinogen levels are a recognized risk factor for MI, the association of thrombotic risk with other coagulation proteins is inconsistent. This is likely due to the complex balance of pro- and anticoagulant factors in any individual. Methods We compared measured levels of pro- and anticoagulant proteins in plasma from 162 patients who suffered an MI at an early age (MI <50 y) and 186 age- and gender-matched healthy controls with no history of CAD. We then used the measurements from these individuals as inputs for an established mathematical model to investigate how small variations in hemostatic factors affect the overall amplitude of the hemostatic response and to identify differential key drivers of the hemostatic response in male and female patients and controls. Results Plasma from the MI patients contained significantly higher levels of Tissue Factor (P = 0.007), the components of the tenase (FIX and FVIII; P < 0.0001 for both) and the prothrombinase complexes (FX; P = 0.003), and lower levels of Tissue Factor Pathway Inhibitor (TFPI; P = 0.033) than controls. The mathematical model, which generates time-dependent predictions describing the depletion, activation, and interaction of the main procoagulant factors and inhibitors, identified different patterns of hemostatic response between MI patients and controls, and additionally, between males and females. Whereas, in males, TF, FVIII, FIX, and the inhibitor TFPI contribute to the differences seen between case and controls, and in females, FII, FVIII, and FIX had the greatest influence on the generation of thrombin. We additionally show that further donor stratification may be possible according to the predicted donor response to anticoagulant therapy. Conclusions We suggest that modeling could be of value in enhancing our prediction of risk of premature MI, recurrent risk, and therapeutic efficacy.
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Affiliation(s)
- Joanne L. Dunster
- School of Biological Sciences, Institute for Cardiovascular and Metabolic Research, Reading, United Kingdom
| | - Joy R. Wright
- Department of Cardiovascular Sciences, University of Leicester & NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom
| | - Nilesh J. Samani
- Department of Cardiovascular Sciences, University of Leicester & NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom
| | - Alison H. Goodall
- Department of Cardiovascular Sciences, University of Leicester & NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom
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4
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Gaddh M, Rosovsky RP. Venous Thromboembolism: Genetics and Thrombophilias. Semin Respir Crit Care Med 2021; 42:271-283. [PMID: 33694139 DOI: 10.1055/s-0041-1723937] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Venous thromboembolism (VTE) is a major cause of morbidity and mortality throughout the world. Up to one half of patients who present with VTE will have an underlying thrombophilic defect. This knowledge has led to a widespread practice of testing for such defects in patients who develop VTE. However, identifying a hereditary thrombophilia by itself does not necessarily change outcomes or dictate therapy. Furthermore, family history of VTE by itself can increase an asymptomatic person's VTE risk several-fold, independent of detecting a known inherited thrombophilia. In this article, we will describe the current validated hereditary thrombophilias including their history, prevalence, and association with VTE. With a focus on evaluating both risks and benefits of testing, we will also explore the controversies of why, who, and when to test as well as discuss contemporary societal guidelines. Lastly, we will share how these tests have been integrated into clinical practice and how to best utilize them in the future.
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Affiliation(s)
- Manila Gaddh
- Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia
| | - Rachel P Rosovsky
- Division of Hematology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
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5
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Xiang J, Yang J, Chen L, Chen Q, Yang H, Sun C, Zhou Q, Peng Z. Reinterpretation of common pathogenic variants in ClinVar revealed a high proportion of downgrades. Sci Rep 2020; 10:331. [PMID: 31942019 PMCID: PMC6962394 DOI: 10.1038/s41598-019-57335-5] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Accepted: 12/28/2019] [Indexed: 11/24/2022] Open
Abstract
High-frequency disease-causing alleles exist, but their number is rather small. This study aimed to interpret and reclassify common pathogenic (P) and likely pathogenic (LP) variants in ClinVar and to identify indicators linked with reclassification. We analyzed P/LP variants without conflicting interpretations in ClinVar. Only variants with an allele frequency exceeding 0.5% in at least one ancestry in gnomAD were included. Variants were manually interpreted according to the guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Of 326 variants retrieved, 217 variants in 173 genes were selected for curation. Overall, 87 (40%) variants were downgraded to benign, likely benign or variant of uncertain significance. Five variants (2%) were found to be more likely to be risk factors. Most of the reclassifications were of variants with a low rank, an older classification, a higher allele frequency, or which were collected through methods other than clinical testing. ClinVar provides a universal platform for users who intend to share the classification variants, resulting in the improved concordance of variant interpretation. P/LP variants with a high allele frequency should be used with caution. Ongoing improvements would further improve the practicability of ClinVar database.
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Affiliation(s)
- Jiale Xiang
- BGI Genomics, BGI-Shenzhen, Shenzhen, 518083, China
| | - Jiyun Yang
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China.,Sichuan Provincial Key Laboratory for Human Disease Gene Study, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, 610072, China
| | - Lisha Chen
- BGI Genomics, BGI-Shenzhen, Shenzhen, 518083, China.,BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, 518083, China
| | - Qiang Chen
- Department of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Haiyan Yang
- BGI College, Zhengzhou University, Zhengzhou, 45000, China
| | - Chengcheng Sun
- School of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China
| | - Qing Zhou
- The MOE Key Laboratory of Biosystems Homeostasis & Protection, Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China
| | - Zhiyu Peng
- BGI Genomics, BGI-Shenzhen, Shenzhen, 518083, China.
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Acute Unilateral Renal Infarction in the Setting of an Inherited Thrombophilia and Atrial Septal Defect. Case Rep Hematol 2017; 2017:3159363. [PMID: 28928995 PMCID: PMC5591998 DOI: 10.1155/2017/3159363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Accepted: 07/31/2017] [Indexed: 11/21/2022] Open
Abstract
We present a case of renal infarction in a 43-year-old female with history of stroke at age 14. She was found to be heterozygous for the prothrombin G20210A gene mutation. Loop monitoring revealed no atrial fibrillation. Transthoracic and transesophageal echocardiograms showed no thrombus. However, there was a small shunt due to an atrial septal defect (ASD). She was treated with warfarin and had device closure of her ASD. This was a suspected case of paradoxical embolism through an ASD leading to renal infarction.
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Palareti G. Optimal long-term pharmacological treatment of patients with venous thromboembolism that was unprovoked or associated with weak risk factors. Expert Rev Hematol 2017; 10:921-931. [PMID: 28803491 DOI: 10.1080/17474086.2017.1366851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Unprovoked venous thromboembolism (VTE) tend to recur. Many factors, patient- or event-related, influence the individual risk of recurrence. After initial and long-term (usually for 3-6 months) anticoagulant therapy, extended anticoagulation has been recommended in patients at high risk of recurrence, provided they do not have a high risk of bleeding. Areas covered: The effect of different risk factors on the risk of recurrence is discussed, as well as risk factors for bleeding. The estimation of individual balance between these two risks is crucial to decide which can be the best treatment duration in single patients. The use of direct oral anticoagulants, with likely less risk of bleeding, may influence the balance. D-dimer assessment during and after anticoagulation is stopped is also commented for its role to help identifying the individual risk of recurrence. Expert commentary: All patients with a first VTE should be reconsidered after the initial 3-6 months of treatment. Anticoagulation can then be stopped or continued in relation to low or very high risk of recurrence, respectively. Serial D-dimer assessment during the first 2 or 3 months after anticoagulation is stopped is useful in patients with uncertain risk evaluation (especially after unprovoked events).
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8
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Colucci G, Tsakiris DA. Thrombophilia Screening: Universal, Selected, or Neither? Clin Appl Thromb Hemost 2017; 23:893-899. [PMID: 28049358 DOI: 10.1177/1076029616683803] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
The utility of thrombophilia testing in clinical practice is still a matter of debate because studies have not shown a benefit in the reduction of recurrent venous thromboembolism (VTE) risk in patients with thrombosis, despite the clearly higher VTE risk for first thrombosis. Screening for thrombophilia is indicated in selected patients. Particularly in selected young patients, especially women of childbearing age, the knowledge of the genetic thrombophilic defect may help in specific situations to decrease the risk of VTE events. Avoidance of modifiable risk factors and/or prophylactic thromboembolic procedures may be evaluated in selected patients. A comprehensive workup including personal and familial history, clinical examination, and laboratory test results including hereditary thrombophilia remains helpful in assessing the cumulative risk and the management of this group of selected patients.
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Affiliation(s)
- Giuseppe Colucci
- 1 Service of Hematology, Clinica Luganese Moncucco, Lugano and synlab Suisse, Lucerne, Switzerland.,2 Diagnostic Hematology, Department of Hematology, University Hospital Basel, Basel, Switzerland
| | - Dimitrios A Tsakiris
- 2 Diagnostic Hematology, Department of Hematology, University Hospital Basel, Basel, Switzerland
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9
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10
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Hotoleanu C. Genetic Risk Factors in Venous Thromboembolism. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2016; 906:253-272. [PMID: 27638626 DOI: 10.1007/5584_2016_120] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Genetic risk factors predispose to thrombophilia and play the most important etiopathogenic role in venous thromboembolism (VTE) in people younger than 50 years old. At least one inherited risk factor could be found in about half of the cases with a first episode of idiopathic VTE.Roughly, genetic risk factors are classified into two main categories: loss of function mutations (such as deficiencies of antithrombin, protein C, protein S) and gain of function mutations, (such as prothrombin mutation G20210A, factor V Leiden). A revolutionary contribution to the genetic background of VTE was brought by the achievements of the genome-wide association studies which analyze the association of a huge number of polymorphisms in large sample size.Hereditary thrombophilia testing should be done only in selected cases. The detection of hereditary thrombophilia has impact on the management of the anticoagulation in children with purpura fulminans, pregnant women at risk of VTE and may be useful in the assessment of the risk for recurrent thrombosis in patients presenting an episode of VTE at a young age (<40 years) and in cases with positive family history regarding thrombosis.
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Affiliation(s)
- Cristina Hotoleanu
- Department 5, Iuliu Hatieganu University of Medicine and Pharmacy, 8, Victor Babes street, 400012, Cluj-Napoca, Romania.
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11
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Meyer MR, Witt DM, Delate T, Johnson SG, Fang M, Go A, Clark NP. Thrombophilia testing patterns amongst patients with acute venous thromboembolism. Thromb Res 2015; 136:1160-4. [PMID: 26477821 PMCID: PMC4727748 DOI: 10.1016/j.thromres.2015.10.019] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2015] [Revised: 09/08/2015] [Accepted: 10/09/2015] [Indexed: 11/30/2022]
Abstract
BACKGROUND Thrombophilia testing has limited value in determining the selection and duration of anticoagulation therapy for venous thromboembolism (VTE), yet is commonly performed. This study describes the patterns and appropriateness of thrombophilia testing in a large cohort of patients with acute VTE. MATERIALS AND METHODS This was a retrospective study of a random sample of patients with a validated diagnosis of acute VTE diagnosed between January 1, 2004 and December 31, 2010. Events were identified from administrative data and verified via manual review. Patients were grouped by thrombophilia testing status and compared on patient characteristics and thrombophilia testing results and appropriateness. RESULTS Of 1314 patients with validated VTE, 315 (24%) underwent thrombophilia testing, 62 (20%) of whom had ≥ 1 positive test. Tested patients were younger and more likely to have had a family history of VTE. Factor V Leiden (17%) and prothrombin G20210A mutation (4%) were the most commonly detected thrombophilias. Only 31 (10%) of tested patients met eligibility criteria for thrombophilia testing (i.e., at least one strong thrombophilic risk factor present) and were tested at least 90 days following unprovoked index VTE. CONCLUSIONS Thrombophilia is commonly evaluated in patients without a clear indication for testing and during times where results may be unreliable. Future studies are needed to assess interventions aimed at reducing inappropriate thrombophilia testing without adversely affecting patient outcomes.
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Affiliation(s)
- Melissa R Meyer
- Kaiser Permanente Colorado, Pharmacy Department, Aurora, CO, United States
| | - Daniel M Witt
- Kaiser Permanente Colorado, Pharmacy Department, Aurora, CO, United States; University of Utah College of Pharmacy, Department of Pharmacotherapy, Salt Lake City, UT, United States
| | - Thomas Delate
- Kaiser Permanente Colorado, Pharmacy Department, Aurora, CO, United States; University of Colorado Denver Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, United States
| | - Samuel G Johnson
- Kaiser Permanente Colorado, Pharmacy Department, Aurora, CO, United States; University of Colorado Denver Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, United States
| | - Margaret Fang
- University of California San Francisco, Division of Hospital Medicine, San Francisco, CA, United States
| | - Alan Go
- Kaiser Permanente Northern California, Division of Research, Oakland, CA, United States; Stanford University School of Medicine, Department of Health Research and Policy, Stanford, CA, United States
| | - Nathan P Clark
- Kaiser Permanente Colorado, Pharmacy Department, Aurora, CO, United States; University of Colorado Denver Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, United States.
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Sepúlveda C, Palomo I, Fuentes E. Primary and secondary haemostasis changes related to aging. Mech Ageing Dev 2015; 150:46-54. [PMID: 26296601 DOI: 10.1016/j.mad.2015.08.006] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2015] [Revised: 08/02/2015] [Accepted: 08/11/2015] [Indexed: 12/17/2022]
Abstract
Life expectancy has increased in many countries as a result the world's population is aging. The projections indicate that the proportion of the elderly in a few decades will increase significantly. Aging carries with it a series of physiological changes; one of them is an imbalance in the hemostatic system. Thus the levels or activity of various proteins involved, such as most coagulation factors, natural anticoagulants and the fibrinolytic system are altered so that the hemostatic balance leans toward thrombosis. Also, platelet activity suggests a state of abnormal activation (P-selectin, beta thromboglobulin and platelet factor). In this review we will systematically examine the alterations in the hemostatic components that occur during aging. Therefore, understanding these hemostatic changes could contribute to developing strategies for the proper management of health in old age.
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Affiliation(s)
- Cesar Sepúlveda
- Department of Clinical Biochemistry and Immunohaematology, Faculty of Health Sciences, Interdisciplinary Excellence Research Program on Healthy Aging (PIEI-ES), Universidad de Talca, Talca, Chile
| | - Iván Palomo
- Department of Clinical Biochemistry and Immunohaematology, Faculty of Health Sciences, Interdisciplinary Excellence Research Program on Healthy Aging (PIEI-ES), Universidad de Talca, Talca, Chile; Centro de Estudios en Alimentos Procesados (CEAP), CONICYT- Regional, Gore Maule R09I2001, Chile.
| | - Eduardo Fuentes
- Department of Clinical Biochemistry and Immunohaematology, Faculty of Health Sciences, Interdisciplinary Excellence Research Program on Healthy Aging (PIEI-ES), Universidad de Talca, Talca, Chile; Centro de Estudios en Alimentos Procesados (CEAP), CONICYT- Regional, Gore Maule R09I2001, Chile.
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13
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Thaler J, Pabinger I, Ay C. Anticoagulant Treatment of Deep Vein Thrombosis and Pulmonary Embolism: The Present State of the Art. Front Cardiovasc Med 2015; 2:30. [PMID: 26664901 PMCID: PMC4671349 DOI: 10.3389/fcvm.2015.00030] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2015] [Accepted: 06/26/2015] [Indexed: 12/19/2022] Open
Abstract
Venous thromboembolism (VTE), a disease entity comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a frequent and potentially life-threatening event. To date different agents are available for the effective treatment of acute VTE and the prevention of recurrence. For several years, the standard of care was the subcutaneous application of a low molecular weight heparin (LMWH) or fondaparinux, followed by a vitamin K antagonist (VKA). The so-called direct oral anticoagulants (DOAC) were introduced rather recently in clinical practice for the treatment of VTE. DOAC seem to have a favorable risk-benefit profile compared to VKA. Moreover, DOAC significantly simplify VTE treatment because they are administered in fixed doses and no routine monitoring is needed. Patients with objectively diagnosed DVT or PE should receive therapeutic anticoagulation for a minimum of 3 months. Whether a patient ought to receive extended treatment needs to be evaluated on an individual basis, depending mainly on risk factors determined by characteristics of the thrombotic event and patient-related factors. In specific patient groups (e.g., pregnant women, cancer patients, and elderly patients), treatment of VTE is more challenging than that in the general population and additional issues need to be considered in those patients. The aim of this review is to give an overview of the currently available treatment modalities of acute VTE and secondary prophylaxis. In particular, specific aspects regarding the initiation of VTE treatment, duration of anticoagulation, and specific patient groups will be discussed.
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Affiliation(s)
- Johannes Thaler
- Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna , Vienna , Austria
| | - Ingrid Pabinger
- Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna , Vienna , Austria
| | - Cihan Ay
- Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna , Vienna , Austria
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14
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Palareti G. How D-dimer assay can be useful in deciding the duration of anticoagulation after venous thromboembolism: a review. Expert Rev Hematol 2014; 8:79-88. [DOI: 10.1586/17474086.2015.975791] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Abstract
Although controversial, screening for thrombophilia has become common. Testing for antiphospholipid antibodies is indicated in order to guide treatment decisions if there is clinical suspicion for antiphospholipid syndrome. The utility of identifying other thrombophilias in symptomatic venous thromboembolism (VTE) is questionable, as the risk of recurrence does not appear to be increased by an appreciable degree with the most common disorders (heterozygosity for factor V Leiden or prothrombin mutation). Although recurrence appears to be increased in those with homozygous or multiple abnormalities and potentially deficiencies in natural anticoagulants, screening to detect these conditions is difficult to justify based on their rarity. The American College of Chest Physicians' current guidelines note the increased risk of recurrence with idiopathic, proximal events regardless of thrombophilia status. They suggest duration of anticoagulation therapy be based on location and provoking factors rather than whether or not the individual has a thrombophilia. Because routine prophylaxis in asymptomatic individuals with thrombophilia is not recommended, screening of asymptomatic family members is difficult to justify. Screening prior to prescribing combination oral contraceptives is not cost effective, may result in unwanted pregnancies, and may have little effect on the overall rate of VTE.
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Affiliation(s)
- Lori B Hornsby
- Department of Pharmacy Practice, Auburn University Harrison School of Pharmacy, Auburn, AL, USA Midtown Medical Center, Columbus, GA, USA
| | - Emily M Armstrong
- Department of Pharmacy Practice, Auburn University Harrison School of Pharmacy, Auburn, AL, USA Department of Internal Medicine, University of South Alabama, Mobile, AL, USA
| | - Jessica M Bellone
- Ambulatory Pharmacy Services, Froedtert and the Medical College of Wisconsin, Milwaukee, WI, USA
| | - Sarah Treadway
- Department of Pharmacy Practice, Auburn University Harrison School of Pharmacy, Auburn, AL, USA Department of Family Medicine, University of South Alabama, Mobile, AL, USA
| | - Haley M Phillippe
- Department of Pharmacy Practice, Auburn University Harrison School of Pharmacy, Auburn, AL, USA Family Medicine-Huntsville Campus, University of Alabama School of Medicine, Huntsville, AL, USA
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16
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Phillippe HM, Hornsby LB, Treadway S, Armstrong EM, Bellone JM. Inherited Thrombophilia. J Pharm Pract 2014; 27:227-33. [DOI: 10.1177/0897190014530390] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Thrombophilia alters normal hemostasis, shifting the balance in favor of thrombus formation. Inherited conditions include factor V Leiden (FVL), prothrombin G20210A mutation, deficiencies in natural anticoagulants (antithrombin [AT], protein C, and protein S), hyperhomocysteinemia, and elevations in clotting factors (factors VIII and XI). Although FVL and prothrombin mutation are common disorders, deficiencies in the natural anticoagulants are rare. The risk of initial thrombosis conferred by inherited thrombophilia varies with the highest risk in those homozygous for either FVL or prothrombin mutation, or with AT deficiency. In the nonpregnant patient, the presence of a thrombophilia does not affect treatment of an acute event. Although vitamin B supplementation has been shown to decrease the levels of homocysteine, the treatment has failed to show a benefit in thrombus prevention and is therefore not recommended.
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Affiliation(s)
- Haley M. Phillippe
- Department of Pharmacy Practice, Auburn University Harrison School of Pharmacy, Auburn, AL, USA
- Family Medicine-Huntsville Campus, University of Alabama School of Medicine, Huntsville, AL, USA
| | - Lori B. Hornsby
- Department of Pharmacy Practice, Auburn University Harrison School of Pharmacy, Auburn, AL, USA
- Midtown Medical Center, Columbus, GA, USA
| | - Sarah Treadway
- Department of Pharmacy Practice, Auburn University Harrison School of Pharmacy, Auburn, AL, USA
- Department of Family Medicine, University of South Alabama, Mobile, AL, USA
| | - Emily M. Armstrong
- Department of Pharmacy Practice, Auburn University Harrison School of Pharmacy, Auburn, AL, USA
- Department of Internal Medicine, University of South Alabama, Mobile, AL, USA
| | - Jessica M. Bellone
- Ambulatory Pharmacy Services, Froedtert and the Medical College of Wisconsin, Milwaukee, WI, USA
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17
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Silvey M, Carpenter SL. Inherited thrombophilia in children. Curr Probl Pediatr Adolesc Health Care 2013; 43:163-8. [PMID: 23890023 DOI: 10.1016/j.cppeds.2013.05.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2013] [Revised: 05/21/2013] [Accepted: 05/24/2013] [Indexed: 10/26/2022]
Abstract
Thrombosis in children has multiple etiologies, including inherited disorders such as factor V Leiden mutation, prothrombin 20210A mutation, and deficiencies in protein C, S, or antithrombin. Epidemiology of the disorders varies, as does the risk of thrombosis. Venous thromboembolism is the typical presentation. However, more severe anticoagulant protein deficiencies may present with purpura fulminans. Treatment of thrombosis is relatively uniform, regardless of the underlying genetic risk factor. In this article, we discuss the most well-studied inherited thrombophilias and the epidemiology, pathophysiology, and relative thrombotic risk of each. Treatment of thrombosis is also briefly reviewed.
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Affiliation(s)
- Michael Silvey
- Division of Pediatric Hematology/Oncology/BMT, Children's Mercy Hospitals and Clinics, Kansas City, MO, USA
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18
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Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e691S-e736S. [PMID: 22315276 PMCID: PMC3278054 DOI: 10.1378/chest.11-2300] [Citation(s) in RCA: 871] [Impact Index Per Article: 67.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/31/2011] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The use of anticoagulant therapy during pregnancy is challenging because of the potential for both fetal and maternal complications. This guideline focuses on the management of VTE and thrombophilia as well as the use of antithrombotic agents during pregnancy. METHODS The methods of this guideline follow the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. RESULTS We recommend low-molecular-weight heparin for the prevention and treatment of VTE in pregnant women instead of unfractionated heparin (Grade 1B). For pregnant women with acute VTE, we suggest that anticoagulants be continued for at least 6 weeks postpartum (for a minimum duration of therapy of 3 months) compared with shorter durations of treatment (Grade 2C). For women who fulfill the laboratory criteria for antiphospholipid antibody (APLA) syndrome and meet the clinical APLA criteria based on a history of three or more pregnancy losses, we recommend antepartum administration of prophylactic or intermediate-dose unfractionated heparin or prophylactic low-molecular-weight heparin combined with low-dose aspirin (75-100 mg/d) over no treatment (Grade 1B). For women with inherited thrombophilia and a history of pregnancy complications, we suggest not to use antithrombotic prophylaxis (Grade 2C). For women with two or more miscarriages but without APLA or thrombophilia, we recommend against antithrombotic prophylaxis (Grade 1B). CONCLUSIONS Most recommendations in this guideline are based on observational studies and extrapolation from other populations. There is an urgent need for appropriately designed studies in this population.
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Affiliation(s)
- Shannon M Bates
- Department of Medicine, McMaster University and Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada.
| | - Ian A Greer
- Faculty of Health and Life Sciences, University of Liverpool, Liverpool, England
| | - Saskia Middeldorp
- Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
| | | | - Anne-Marie Prabulos
- Department of Obstetrics and Gynecology, University of Connecticut School of Medicine, Farmington, CT
| | - Per Olav Vandvik
- Medical Department, Innlandet Hospital Trust and Norwegian Knowledge Centre for the Health Services, Gjøvik, Norway
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19
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Palareti G. Recurrent venous thromboembolism: what is the risk and how to prevent it. SCIENTIFICA 2012; 2012:391734. [PMID: 24278687 PMCID: PMC3820456 DOI: 10.6064/2012/391734] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2012] [Accepted: 09/10/2012] [Indexed: 05/07/2023]
Abstract
Venous thromboembolism (VTE) that includes deep vein thrombosis and/or pulmonary embolism is a frequent, severe, and potentially lethal disease. After a first episode, VTE has a strong tendency to recur. While VTE is an acute disease, it may have variable outcomes in early and late phases after initial presentation. Furthermore, the incidence of late, clinically important consequences (postthrombotic syndrome and/or chronic thromboembolic pulmonary hypertension) increases in case of recurrent events. The aims of the present review are (i) to analyze the incidence and risk factors for recurrence of VTE (either those related to the type of first thrombotic event or to the patients), the risks associated with occurrence of recurrent events, and the problems linked to the diagnosis, not always easy, of recurrent events; (ii) to discuss whether or not it is possible to predict the individual risk of recurrence after a first event, by stratifying patients at high or low risk of recurrence, and how this can influence their treatment; (iii) to comment what the current guidelines and guidance suggest/recommend about anticoagulant treatment after a first VTE event and, finally, to propose practical indications on how to manage individual patients affected by VTE.
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Affiliation(s)
- Gualtiero Palareti
- Department of Angiology and Blood Coagulation, Via Albertoni 15, 40138 Bologna (BO), Italy
- *Gualtiero Palareti:
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20
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Sakr M, Barakat E, Abdelhakam S, Dabbous H, Yousuf S, Shaker M, Eldorry A. Epidemiological aspects of Budd-Chiari in Egyptian patients: A single-center study. World J Gastroenterol 2011; 17:4704-10. [PMID: 22180713 PMCID: PMC3233677 DOI: 10.3748/wjg.v17.i42.4704] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2011] [Revised: 07/28/2011] [Accepted: 08/04/2011] [Indexed: 02/06/2023] Open
Abstract
AIM: To describe the socio-demographic features, etiology, and risk factors for Budd-Chiari syndrome (BCS) in Egyptian patients.
METHODS: Ninety-four Egyptian patients with confirmed primary Budd-Chiari syndrome were presented to the Budd-Chiari Study Group (BCSG) and admitted to the Tropical Medicine Department of Ain Shams University Hospital (Cairo, Egypt). Complete clinical evaluation and laboratory investigations, including a thrombophilia workup and full radiological assessment, were performed to determine underlying disease etiologies.
RESULTS: BCS was chronic in 79.8% of patients, acute or subacute in 19.1%, and fulminant in 1.1%. Factor V Leiden mutation (FVLM) was the most common etiological cause of disease (53.1%), followed by mutation of the gene encoding methylene tetrahydrofolate reductase (MTHFR) (51.6%). Current or recent hormonal treatment was documented in 15.5% of females, and BCS associated with pregnancy was present in 17.2% of females. Etiology could not be determined in 8.5% of patients. Males had significantly higher rates of MTHFR gene mutation and Behçet’s disease, and females had significantly higher rates of secondary antiphospholipid antibody syndrome. A highly significant positive relationship was evident between the presence of Behçet’s disease and inferior vena caval occlusion, either alone or combined with occlusion of the hepatic veins (P < 0.0001).
CONCLUSION: FVLM is the most common disease etiology and MTHFR the second most common in Egyptian BCS patients. BCS etiology tends to vary with geographic region.
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21
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Safavi-Abbasi S, Di Rocco F, Nakaji P, Feigl GC, Gharabaghi A, Samii M, Valavanis A, Samii A. Thrombophilia Due to Factor V and Factor II Mutations and Formation of a Dural Arteriovenous Fistula: Case Report and Review of a Rare Entity. Skull Base 2011; 18:135-43. [PMID: 18769649 DOI: 10.1055/s-2007-1003926] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Genetic mutations underlying thrombophilia are often recognized in patients with thromboembolic episodes. However, the clinical and therapeutic implications of such findings often remain unclear. We report the first case of a dural arteriovenous fistula (DAVF) in a patient with a combined factor II and factor V Leiden mutation. A 40-year-old man presented with a large left temporal and intraventricular hemorrhage. An initial angiogram showed thrombosis of the left sigmoid sinus but no evidence of a vascular malformation. One year after the hemorrhage, an angiographic study showed the appearance of a right DAVF. During the follow-up period, the patient was found to harbor heterozygosity for a mutation of factor V and a mutation of factor II. Recognition of the patient's thrombophilia led to prolonged oral anticoagulation therapy to reduce the risk of a recurrent thrombotic episode. Despite the increased risk of bleeding, the therapy was considered justified. DAVFs may occur after sinus thrombosis in patients with combined factor II and factor V mutations. This observation indicates the association of multiple hematological disorders with DAVFs in individual patients. Moreover, it raises the clinical conundrum of how to manage patients with thrombophilia, intracranial hemorrhage, and DAVFs.
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Affiliation(s)
- Sam Safavi-Abbasi
- Department of Neurosurgery and Neuroradiology, International Neuroscience Institute, Hannover, Germany
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22
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Christiansen SC, Lijfering WM, Helmerhorst FM, Rosendaal FR, Cannegieter SC. Sex difference in risk of recurrent venous thrombosis and the risk profile for a second event. J Thromb Haemost 2010; 8:2159-68. [PMID: 20738758 DOI: 10.1111/j.1538-7836.2010.03994.x] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
UNLABELLED BACKGROUND The risk of recurrent venous thrombosis is higher in men than in women, and this is so far unexplained. We set out to determine the influence of age, time between first and second event, type of first event, oral contraception, pregnancy and surgery. METHODS We performed a prospective follow-up study of 474 patients with a first objective diagnosis of deep vein thrombosis, aged 18-70 years (Leiden Thrombophilia Study cohort). RESULTS During 3477 person-years of follow-up, 90 recurrences occurred. The overall incidence rates of recurrence (IRs) were 40.9 per 1000 person-years in men and 15.8 per 1000 person-years in women. Men with an unprovoked first event had the highest risk of recurrence, with almost one-third experiencing a second unprovoked event within 8 years (IR 41.2 per 1000 person-years). This risk was three-fold lower in women [IR 14.2 per 1000 person-years; hazard ratio 2.8 (95% confidence interval 1.4-5.7)]. Age at diagnosis had little effect on recurrence rate, and nor had time elapsed since the first event. In women, almost half of the recurrences were provoked and were mainly related to oral contraceptive use or pregnancy. CONCLUSIONS The higher recurrence rate in men than in women is not the result of differences in the environmental or transient risk factors that we studied. The risk profile for a second thrombotic event is clearly different from that of a first.
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Affiliation(s)
- S C Christiansen
- Department of Clinical Epidemiology, Leiden University Medical Centre, the Netherlands
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23
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Palamari B, Breen JF, Wysokinski WE. Lipoma causing upper extremity deep vein thrombosis: a case report. J Thromb Thrombolysis 2009; 30:109-11. [PMID: 19728038 DOI: 10.1007/s11239-009-0395-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2009] [Accepted: 08/18/2009] [Indexed: 11/27/2022]
Abstract
We report a case of lipoma in the right infraclavicular and axillary area compressing subclavian vein there by presenting with upper extremity deep venous thrombosis (UEDVT) and persistent symptoms of venous congestion. Patient was also found to be a heterozygous carrier of prothrombin 20210 gene mutation. Surgical excision of lipomatous tissue performed after 6 months of anticoagulation resulted in a complete resolution of symptoms.
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Affiliation(s)
- Balavani Palamari
- Division of Cardiovascular Medicine, Mayo Clinic and Foundation for Education and Research, Rochester, MN 55905, USA
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24
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White RH, Gosselin RC. Testing for Thrombophilia: Pitfalls, Limitations, and Marginal Impact on Treatment Duration Recommendations. ACTA ACUST UNITED AC 2009; 76:303-13. [DOI: 10.1002/msj.20111] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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25
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Deep Venous Thrombosis Caused by Inferior Vena Cava Atresia and Hereditary Thrombophilia. Am J Med Sci 2009; 337:67-70. [DOI: 10.1097/maj.0b013e31816a8d0d] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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26
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Sándor T. Travel thrombosis: Pathomechanisms and clinical aspects. PATHOPHYSIOLOGY 2008; 15:243-52. [DOI: 10.1016/j.pathophys.2008.10.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2008] [Accepted: 10/04/2008] [Indexed: 11/28/2022] Open
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27
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Scifres CM, Macones GA. The utility of thrombophilia testing in pregnant women with thrombosis: fact or fiction? Am J Obstet Gynecol 2008; 199:344.e1-7. [PMID: 18572147 DOI: 10.1016/j.ajog.2008.04.051] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2007] [Revised: 02/16/2008] [Accepted: 04/30/2008] [Indexed: 10/21/2022]
Abstract
Women who either present with an episode of acute venous thrombosis in pregnancy or who have a history of venous thrombosis who present for prenatal care often undergo testing for inherited thrombophilia. The rationale for screening may include questions about whether screening for inherited thrombophilias can help to alter anticoagulation plans in a pregnancy complicated by venous thrombosis, whether patients with a history of venous thrombosis who present for care in a subsequent pregnancy require anticoagulation and at what intensity, whether knowledge of thrombophilia changes the duration and intensity of anticoagulation outside pregnancy, and whether screening of family members is warranted. Data regarding these issues are reviewed, controversies surrounding thrombophilia testing in this setting are discussed, and clinical recommendations are made.
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28
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Carson MP, Ehrenthal D. Medical issues from preconception through delivery: a roadmap for the internist. Med Clin North Am 2008; 92:1193-225, xi. [PMID: 18721658 DOI: 10.1016/j.mcna.2008.04.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The age of the pregnant population and the number of pregnant women with medical issues are increasing. It is widely recognized that internists have the unique opportunity to identify potential pregnancy issues and address them before a problem arises. Therefore, it's important that we become aware of how to approach these issues. In addition to addressing medical issues in a currently pregnant woman, doctors also have the opportunity to identify issues that occurred during a prior pregnancy, such as gestational diabetes, preeclampsia, or pregnancy loss, and to decrease the risk of complications in future pregnancies. The goal of this article is to provide a roadmap to practicing internists so they will incorporate pregnancy planning into their everyday care plans. The approach is similar to that used when performing a preoperative risk assessment: We want to optimize our patients medically for pregnancy.
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Affiliation(s)
- Michael P Carson
- Jersey Shore University Medical Center, 1945 Route 33, Neptune, NJ 07753, USA.
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29
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Acute venous disease: Venous thrombosis and venous trauma. J Vasc Surg 2007; 46 Suppl S:25S-53S. [DOI: 10.1016/j.jvs.2007.08.037] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2006] [Revised: 08/15/2007] [Accepted: 08/19/2007] [Indexed: 10/22/2022]
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30
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Patiar S, Kirwan CC, McDowell G, Bundred NJ, McCollum CN, Byrne GJ. Prevention of venous thromboembolism in surgical patients with breast cancer. Br J Surg 2007; 94:412-20. [PMID: 17380560 DOI: 10.1002/bjs.5782] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Abstract
Background
No randomized trial has yet studied venous thromboembolism (VTE) prophylaxis in patients undergoing surgery for breast cancer.
Methods
Relevant articles were identified using Medline searches. Secondary articles were identified from the reference lists of key papers.
Results and conclusion
The absence of randomized trials comparing different methods of VTE prophylaxis with controls makes an evidence-based consensus among breast cancer surgeons difficult. Intermittent pneumatic compression (IPC) and graduated compression (GC) are effective in reducing VTE without the haemorrhagic complications associated with heparin; their effects are additive. The authors suggest the following strategy. All patients undergoing surgery for breast cancer should receive both IPC and GC, with heparin reserved for those at very high risk. A controlled trial should randomize women to receive heparin or not, and all women should have both IPC and GC. The primary endpoints should be the development of VTE and/or haemorrhagic complications.
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Affiliation(s)
- S Patiar
- Department of Surgery, South Manchester University Hospitals NHS Trust, Wythenshawe Hospital, Southmoor Road, Manchester M23 9LT, UK
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31
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Jukic I, Titlic M, Tonkic A, Rosenzweig D. Cerebral venous sinus thrombosis as a recurrent thrombotic event in a patient with heterozygous prothrombin G20210A genotype after discontinuation of oral anticoagulation therapy: How long should we treat these patients with warfarin? J Thromb Thrombolysis 2007; 24:77-80. [PMID: 17245631 DOI: 10.1007/s11239-006-0005-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2006] [Accepted: 12/21/2006] [Indexed: 11/30/2022]
Abstract
BACKGROUND Cerebral venous sinus thrombosis is an uncommon condition with many clinical manifestations, and hereditary prothrombotic conditions such as factor Leiden V, deficiency of protein S, protein C and antithrombin III, as well as prothrombin gene mutation, may account for 10-15% of cases. To date, conflicting results have been reported for recurrent venous thrombosis in the patients with factor V Leiden and prothrombin G20210A mutation, since some studies have shown a higher risk for recurrent venous thrombosis in carriers of these two mutations than in non-carriers, and the last study showed higher risk only for carriers of double defect (homozygous or double heterozygous for this mutations). METHODS Case report is presented. RESULTS We report a case of cerebral sinus thrombosis as a recurrent thrombotic event in a patient with heterozygous prothrombin G20210A genotype after discontinuation of oral anticoagulation therapy. CONCLUSION Since many facts are controversial, the use of secondary prophylaxis for thrombosis in these patients is still a matter of debate without clear consensus recommendation. Data on the risk of recurrent thrombotic events in thrombophilic patient is insufficient. The main unclear question concerning these patients is: how long and whom should we treat with long-term anticoagulant therapy as secondary prophylaxis of DVT? The problem for practitioner is that we do not have guidelines and precise recommendations for secondary thromboprophylaxis in this or similar cases. This case is remarkable for its favorable and quick outcome and its rarity, because CSVT is an uncommon condition and heterozygous prothrombin G20210A genotype was only found predisposing factor for CSVT. Further studies of risk of recurrent venous thrombosis in patients with heterozygous prothrombin G20210A genotype with the larger sample size are required.
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Affiliation(s)
- Ivana Jukic
- Department of Internal medicine, University Hospital Split, Spinciceva 1, 21 000, Split, Croatia.
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Abstract
Thrombophilia is a disorder of haemostasis in which there is a tendency for the occurrence of thrombosis. This tendency can be inherited or acquired. This review outlines common acquired and inherited thrombophilic conditions and discusses indications for testing. It is concluded that testing for acquired thrombophilic conditions should be considered in all cases of venous thrombosis, whereas testing for inherited thrombophilic conditions is unlikely to be helpful. If testing for inherited thrombophilia is to be carried out, the benefits, pitfalls and unwanted consequences of such testing should be taken into account.
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Affiliation(s)
- L Merriman
- Department of Haematology, Aberdeen Royal Infirmary, Aberdeen, UK.
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González-Porras JR, García-Sanz R, Alberca I, López ML, Balanzategui A, Gutierrez O, Lozano F, San Miguel J. Risk of recurrent venous thrombosis in patients with G20210A mutation in the prothrombin gene or factor V Leiden mutation. Blood Coagul Fibrinolysis 2006; 17:23-8. [PMID: 16607075 DOI: 10.1097/01.mbc.0000201488.33143.09] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
The impact of the G20210A prothrombin mutation, factor V Leiden and 677T mutation of methylene tetrahydrofalate reductase (MTHFR) in recurrent deep venous thrombosis (DVT) is not so clear. We have prospectively monitored 259 patients following a first episode of DVT in order to determine which factors influence the development of a recurrent event. Several clinical and biological factors together with the genetic polymorphisms of factor V Leiden, G20210A prothrombin and 677T MTHFR were assessed. During a median follow-up of 786 patient-years, 27 patients (14%) developed one objective episode of recurrent venous thrombosis. The carriers of a double defect, homozygous or double heterozygous for factor V Leiden and G20210A, had an increased risk after a first episode of DVT, while patients who were isolated heterozygous for factor V Leiden or G20210 had a risk of recurrent DVT similar to patients who had neither mutation (annual incidence of 12.1, 3.1, 2.9 and 2.8%). The 677T MTHFR mutation alone or combined with hyperhomocysteinemia was not associated with an increased risk of recurrent events. The development of proximal DVT (P=0.01) and the presence of a double defect (P=0.01) were the only two risk factors independently associated with a high recurrence ratio in the multivariate analysis. Thus, the annual incidence of DVT recurrence in patients without any of these two risk factors was only 0.6% (95% confidence interval, 0.2-0.9). We have identified a group of patients with DVT but at very low risk of re-thrombosis in whom an extended secondary thromboprophylaxis should be carefully considered.
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Rondina MT, Pendleton RC, Wheeler M, Rodgers GM. The treatment of venous thromboembolism in special populations. Thromb Res 2006; 119:391-402. [PMID: 16879860 DOI: 10.1016/j.thromres.2006.05.015] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2006] [Revised: 04/14/2006] [Accepted: 05/30/2006] [Indexed: 10/24/2022]
Abstract
Anticoagulant therapy for the typical venous thromboembolism patient is straightforward with predictably favorable outcomes. However, for certain patients with venous thromboembolism, there remains uncertainty and controversy about optimal treatment. These controversial areas include venous thromboembolism patients with: heparin resistance, renal insufficiency, morbid obesity, cancer, antiphospholipid antibody syndrome, recurrent thrombosis despite appropriate anticoagulation, and patients with unprovoked VTE who may or may not benefit from thrombophilia testing. This review summarizes the current data for these special patient populations with venous thromboembolism and provides our recommendations for management.
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Affiliation(s)
- Matthew T Rondina
- The University of Utah Health Sciences Center, Department of Internal Medicine, Salt Lake City, UT 84132, USA.
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Abstract
PURPOSE OF REVIEW Although several clinical studies have investigated the effects of different treatment periods in subjects after a VTE event, the optimal duration of oral anticoagulation is still uncertain. Our review focused on studies that evaluated different risk factors that might be useful to stratify patients into categories at different risk for recurrence. RECENT FINDINGS The presence of irreversible, persistent, or transient risk factors affects the risk of recurrence. The inherited and acquired thrombophilic conditions that are associated with an increased risk of VTE may also be responsible for an increased risk of recurrence. Although this is still a matter of debate for the more common alterations, it is accepted for antithrombin, protein C, protein S deficiency, homozygous factor V Leiden, double heterozygosity, and antiphospholipid syndrome. It has been shown that high factor VIII levels are associated to increased risk of VTE recurrence. The presence of cancer is one of the most important persistent factors associated with VTE. Several studies have recently shown that D-dimer levels measured during and especially after oral anticoagulation interruption in subjects with a previous VTE, carriers or not of congenital thrombophilia have a high NPV for recurrence. The relation between the persistence of residual venous thrombosis and the risk of VTE recurrence has been investigated in two recent studies and both concluded that the persistence of a residual venous thrombosis is an important risk factor for recurrent thromboembolism and that its assessment may help clinicians modify the duration of anticoagulation in patients with DVT. SUMMARY Both the clinical aspects of the first VTE event and individual characteristics (such as associated diseases, inherited or acquired thrombophilic conditions, altered D-dimer results, or the presence of residual venous thrombosis) concur in determining the recurrence risk of each patient. Whether the evaluation of these risk factors may help to tailor the secondary prevention treatment in each patient should be assessed by specifically designed intervention studies.
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Affiliation(s)
- Gualtiero Palareti
- Department of Angiology and Blood Coagulation, University Hospital, S. Orsola-Malpighi, Via Albertoni 15, 40138 Bologna, Italy.
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Abstract
The genetic thrombophilias are an important cause of venous thrombotic events. Much has been learned about the natural history of these disorders, their genetics, and, to a lesser degree, their treatment. This article provides an overview of the genetics of thrombophilia. Specific information on the factor V Leiden mutation;the prothrombin G20210A mutation; and protein C, proteinS, and antithrombin deficiency is reviewed. Current testing and treatment options for the genetic thrombophilias also are discussed.
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Affiliation(s)
- W Gregory Feero
- Department of Community and Family Medicine, Dartmouth Medical School, Hanover, NH, 03755, USA.
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Abstract
Rapid advances in genetic research are leading to an expanding array of genetic tests. Primary care providers will increasingly be challenged to identify patients whose symptoms, physical findings, or family history indicate the need for genetic testing, and to determine how to use genetic information most effectively to improve disease prevention. In addressing these challenges, practitioners will need to consider the range of different uses of genetic testing, including diagnosis in symptomatic and asymptomatic people, risk assessment, reproductive decision-making, and population screening. They will need a set of core skills and knowledge to evaluate family history and to recognize clinical findings that indicate genetic risk. At the same time, the primary care perspective will contribute to the evaluation of appropriate uses of genetic testing. A partnership between medical genetics and primary care will help to ensure the development of effective policies, educational tools, and practice guidelines for the coming era of genomic health care.
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Affiliation(s)
- Wylie Burke
- Department of Medical History and Ethics, University of Washington , Seattle, Washington 98195-7120, USA.
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Affiliation(s)
- Elizabeth A Varga
- Division of Maternal-Fetal Medicine, University of Kansas Medical Center, Kansas, USA
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Deitcher SR, Gomes MPV. Hypercoagulable state testing and malignancy screening following venous thromboembolic events. Vasc Med 2003; 8:33-46. [PMID: 12866610 DOI: 10.1191/1358863x03vm461ra] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Mounting interest in hypercoagulability, increased availability of hypercoagulable state test 'panels' and enhanced ability to identify abnormalities in tested patients have prompted widespread testing. Testing for acquired and inherited hypercoagulable states uncovers an abnormality in over 50% of patients presenting with an initial venous thromboembolic event (VTE) but may have minimal actual impact on management in most of these patients. Such laboratory screening should be reserved for patients in whom the results of individual tests will significantly impact the choice of anticoagulant agent, intensity of anticoagulant therapy, therapeutic monitoring, family screening, family planning, prognosis determination, and most of all duration of therapy. Testing 'just to know' is neither cost-effective nor clinically appropriate. The most important testing in patients following acute VTE may be age- and gender-specific cancer screening. Cancer screening following VTE seems most prudent in older individuals and in those with idiopathic VTE and no laboratory evidence for an inherited hypercoagulable state. Cancer screening should focus on identification of treatable cancers and those where diagnosis in an early stage favorably impacts patient survival. Extensive searches for occult malignancy employing whole-body computed tomography and serum tumor markers may identify more cancers but without affecting patient outcome. We advocate that physicians should focus their attention more on VTE prophylaxis and proper treatment and less on costly and, at times, invasive testing of questionable value.
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Affiliation(s)
- Steven R Deitcher
- Department of Hematology and Medical Oncology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
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Vink R, Kraaijenhagen RA, Levi M, Büller HR. Individualized duration of oral anticoagulant therapy for deep vein thrombosis based on a decision model. J Thromb Haemost 2003; 1:2523-30. [PMID: 14675087 DOI: 10.1046/j.1538-7836.2003.00466.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND The optimal duration of oral anticoagulant therapy for patients with a first episode of deep vein thrombosis (DVT) is still a matter of debate. However, according to the ACCP consensus strategy a limited stratification in treatment duration is advocated, i.e. 3 months for patients with a transient risk factor and 1 year or longer for patients with recurrent disease or a consistent risk factor such as thrombophilia or cancer. This consensus strategy is founded on the mean optimal duration of therapy obtained in large cohorts of patients and is mainly based on the risk of recurrent venous thromboembolism (VTE), with only minimal consideration for the patient's bleeding risk. OBJECTIVE The aim of this study is to optimize the anticoagulant treatment strategy with vitamin K antagonists for the individual patient with DVT. METHODS Based on an extensive literature study, a mathematical model was constructed to balance the risk of recurrent VTE against the risk of major hemorrhagic complications. The following parameters are incorporated in the model: baseline estimates and risk factors for recurrent VTE and bleeding, clinical course of DVT, and efficacy of treatment with vitamin K antagonists. With the use of these parameters, the risk for a recurrent VTE and a bleeding episode can be calculated for the individual patient. The optimal duration of anticoagulant therapy can be defined as the timepoint at which the benefit of treatment (prevention of VTE) is counterbalanced by its risk (bleeding). RESULTS/CONCLUSIONS How long a patient should receive anticoagulant treatment is a matter of balancing the benefits and risks of treatment. The model shows that the optimal treatment duration varies greatly from patient to patient according to the patient's unique bleeding and recurrence risk.
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Affiliation(s)
- R Vink
- Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
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Affiliation(s)
- Elizabeth G Nabel
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md 20892, USA.
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Slaybaugh RS, Beasley BD, Massa EG. Deep venous thrombosis risk assessment, incidence, and prophylaxis in foot and ankle surgery. Clin Podiatr Med Surg 2003; 20:269-89. [PMID: 12776981 DOI: 10.1016/s0891-8422(03)00007-7] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
As discussed in this review, DVT and PE are dangerous clinical diagnoses that can occur following foot and ankle surgery. The authors have provided a clinical protocol, a risk assessment tool, and treatment guidelines for this condition that can be applied to the everyday practice of foot and ankle surgeons. Unlike recommendations in previous studies, the authors believe that podiatric and orthopedic surgeons operating on the foot and ankle should evaluate each patient carefully and consider pharmacologic prophylaxis against DVT formation when significant risk factors are present.
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Simioni P. Risk of recurrent venous thromboembolism and thrombophilia: does discrepancy make complexity or vice versa? J Thromb Haemost 2003; 1:16-8. [PMID: 12871534 DOI: 10.1046/j.1538-7836.2003.00094.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Affiliation(s)
- P Simioni
- Department of Medical and Surgical Sciences, University of Padua Medical School, Padua, Italy.
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Affiliation(s)
- J M C Yeung
- Department of Vascular Surgery, Derbyshire Royal Infirmary, Derby.
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McGlennen RC, Key NS. Clinical and laboratory management of the prothrombin G20210A mutation. Arch Pathol Lab Med 2002; 126:1319-25. [PMID: 12421139 DOI: 10.5858/2002-126-1319-calmot] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECTIVE To make recommendations regarding the appropriate evaluation for the prothrombin G20210A mutation, as reflected by published evidence and the consensus opinion of recognized experts in the field. DAT SOURCES: Review of the medical literature, primarily since 1996. DATA EXTRACTION AND SYNTHESIS After an initial assessment of the literature, key points defining the condition, and review of the clinical study design, a draft manuscript was prepared and circulated to every participant in the College of American Pathologists Conference on Diagnostic Issues in Thrombophilia before the meeting. Each of the key points and associated recommendations were then presented for discussion at the conference. Recommendations were accepted if a consensus of 70% of experts attending the conference was reached. The results of the discussion were used to revise the manuscript into its final form. CONCLUSIONS Consensus was reached on several recommendations concerning the criteria for testing for the prothrombin G20210A mutation and for the method of testing. First, a major point of consensus was that the prothrombin G20210A mutation is a significant risk factor for venous thromboembolism (VTE) and that testing should be considered in the initial evaluation of suspected inherited thrombophilia. Second, although several analytic methods are commonly used for genetic testing for the prothrombin mutation, all are generally robust and reliable. The recommendations for testing for the prothrombin mutation parallel those for the factor V Leiden mutation and include patients with a history of recurrent VTE, a first episode of VTE before the age of 50 years, a history of an unprovoked VTE at any age, thromboses in unusual anatomic sites, or an affected first-degree relative with VTE. A history of VTE related to pregnancy or estrogen use and unexplained pregnancy loss during the second or third trimesters were also considered to be indications for testing. Other scenarios remain controversial or not recommended, including general population screening.
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Affiliation(s)
- Ronald C McGlennen
- Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, USA.
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Bradbury AW, MacKenzie RK, Burns P, Fegan C. Thrombophilia and chronic venous ulceration. Eur J Vasc Endovasc Surg 2002; 24:97-104. [PMID: 12389230 DOI: 10.1053/ejvs.2002.1683] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
It is known that thrombophilia (TP) is a risk factor for deep venous thrombosis (DVT), and that DVT predisposes to chronic venous ulceration (CVU). However, the relationship between TP and CVU has not been well studied. Review of the literature reveals that the prevalence of TP in CVU patients is high--similar to the prevalence found in patients with a history of DVT. This is despite many patients with CVU having no clear history, or duplex evidence of previous DVT. TP may predispose to CVU by leading to macro- or micro-vascular thrombosis. This association raises several issues regarding the investigation, prevention and management of patients with venous disease.
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Affiliation(s)
- A W Bradbury
- University Department of Vascular Surgery, Lincoln House (Research Institute), Birmingham Heartlands Hospital, Bordesley Green East, Birmingham, B9 5SS, U.K
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Pérez-Ceballos E, Corral J, Alberca I, Vayá A, Llamas P, Montes R, González-Conejero R, Vicente V. Prothrombin A19911G and G20210A polymorphisms' role in thrombosis. Br J Haematol 2002; 118:610-4. [PMID: 12139755 DOI: 10.1046/j.1365-2141.2002.03624.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
The prothrombin G20210A polymorphism, which correlates with the plasmatic prothombin levels, is the second genetic risk factor for deep venous thrombosis (DVT), although its prothrombotic role is mild. Recently, the prothrombin A19911G polymorphism, also associated with slight variations of the prothrombin level, has been suggested to modulate the thrombotic risk of the G20210A polymorphism in a preliminary study including few patients and controls. Our study evaluated the effect of the A19911G polymorphism in the arterial and venous thrombotic risk of the prothrombin 20210G/A genotype, analysing 204 consecutive DVT patients and 204 matched controls. Moreover, we analysed 213 carriers of the 20210G/A genotype (152 with DVT, 26 with arterial thrombosis and 35 healthy subjects) and 10 homozygous 20210 A/A carriers. We developed a simple method to simultaneously determine the genotype of both polymorphisms. In accordance with our case/control study, the A19911G polymorphism did not play a significant role in the development of DVT. Analysis of 120 20210 A alleles demonstrated a complete linkage disequilibrium with the 19911 A allele. These polymorphisms (alone or combined) did not modify the risk of arterial thrombosis. However, the 19911A/G genotype slightly increased the risk of developing DVT in carriers of the 20210G/A genotype (OR 3.34 vs 5.86), supporting that the prothrombin 19911 polymorphism could modulate the risk of the G20210A polymorphism in developing DVT.
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Best IM, Bumpers HL. Venous Claudication in a Child with Thrombophilia. Am Surg 2002. [DOI: 10.1177/000313480206800109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
Abstract
Deep venous thrombosis (DVT) rarely occurs in active children. Its presence usually suggests an inherited or acquired hypercoagulable state. Occasionally mechanical obstruction may be the inciting factor in this process. Initial management usually consists of sequential heparin and warfarin anticoagulation. We present the management of DVT in an adolescent girl with elevated levels of C-reactive protein and lupus anticoagulant. Venous claudication and severe lower-extremity swelling on ambulation complicated her course. After more than 2 weeks of conservative therapy with anticoagulation thrombolytic therapy was instituted. This was terminated early because of mild hematuria. However, follow-up duplex scan at 2 years has shown complete resolution of the iliofemoral thrombosis. Spontaneous DVT in children differ from that in adults in that an underlying etiology can usually be uncovered. These differences are explored.
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Affiliation(s)
- Irwin M. Best
- From the Department of Surgery, Morehouse School of Medicine, Atlanta, Georgia
| | - Harvey L. Bumpers
- From the Department of Surgery, Morehouse School of Medicine, Atlanta, Georgia
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