RESUMO
OBJECTIVES: The naming convention in coagulation may cause confusion in electronic ordering systems, leading to inappropriate test orders. We implemented test utilization efforts and studied utilization before and after interventions for two specialty coagulation assays. METHODS: Two interventions were implemented: test names were changed from factor assay to activity, and residents reviewed all factor V and X requests. A retrospective review of factor V and X activity orders was performed for the period 1 year before and after interventions. RESULTS: After interventions, factor V and X activity orders decreased by approximately 40%. Resulted tests decreased by 53.8% and 47.8%, corresponding to reductions of $2,493.05 and $1,867.80 per year in laboratory charges for factor V and factor X activity, respectively. Abnormal factor V activity results increased from 45% to 59%. Factor V activity orders from outpatient clinics decreased by 21.6%. CONCLUSIONS: Simple interventions can reduce inappropriate specialty coagulation test orders and unnecessary costs.
Assuntos
Testes de Coagulação Sanguínea/estatística & dados numéricos , Técnicas de Laboratório Clínico/estatística & dados numéricos , Fator V/análise , Fator X/análise , Testes de Coagulação Sanguínea/economia , Técnicas de Laboratório Clínico/economia , Fator V/genética , Inibidores do Fator Xa/sangue , Humanos , Mutação , Estudos Retrospectivos , Procedimentos DesnecessáriosRESUMO
OBJECTIVES: To analyze the economic impact of testing for activated protein C resistance (APC-R) due to factor V Leiden (FVL) mutation with APC-R with reflexive FVL genotyping (algorithmic approach) or genotyping alone. METHODS: OptumLabs Data Warehouse (OLDW) data were used to assess testing approaches. Insurance claims for APC-R and FVL in 2013 were compared with the Mayo Clinic database. Centers for Medicare & Medicaid Services diagnostic fee schedules were used to assign costs. RESULTS: Of 19.3 million OLDW-covered individuals, 74,242 (0.385%) received 75,608 tests: APC-R, 2,265 (2.9%); FVL genotyping, 70,619 (90.1%); and both APC-R and FVL, 2,724 (7.0%). In total, 1,317 tests were performed at Mayo Clinic: APC-R with reflex FVL (1,256; 95.4%) and FVL alone (61; 4.6%). Costs per evaluated individual and per total population (person/year) in OLDW and algorithmic approach were $83.77 vs $36.38 and $0.32 vs $0.14, respectively. CONCLUSIONS: The cost-optimized algorithmic approach reduces health care costs.
Assuntos
Resistência à Proteína C Ativada/diagnóstico , Fator V/genética , Trombofilia/diagnóstico , Resistência à Proteína C Ativada/genética , Algoritmos , Testes de Coagulação Sanguínea/economia , Redução de Custos , Feminino , Genótipo , Humanos , Mutação , Trombofilia/genéticaRESUMO
OBJECTIVE: To identify coagulation risk factors in patients with calciphylaxis and the relationship between anticoagulation use and overall survival. PATIENTS AND METHODS: Study subjects were 101 patients with calciphylaxis seen at Mayo Clinic from 1999 to September 2014. Data including thrombophilia profiles were extracted from the medical records of each patient. Survival status was determined using patient registration data and the Social Security Death Index. Survival was estimated using the Kaplan-Meier method, and associations were evaluated using Cox proportional hazards models. RESULTS: Sixty-four of the 101 patients underwent thrombophilia testing. Of these, a complete test panel was performed in 55 and a partial panel in 9. Severe thrombophilias observed in 60% (33 of 55) of the patients included antiphospholipid antibody syndrome protein C, protein S, or antithrombin deficiencies or combined thrombophilias. Of the 55 patients, severe thrombophilia (85%, 23 of 27) was noted in patients who were not on warfarin at the time of testing (27). Nonsevere thrombophilias included heterozygous factor V Leiden (n=2) and plasminogen deficiency (n=1). For the comparison of survival, patients were divided into 3 treatment categories: Warfarin (n=63), other anticoagulants (n=20), and no anticoagulants (n=18). There was no statistically significant survival difference between treatment groups. CONCLUSION: Laboratory testing reveals a strikingly high prevalence of severe thrombophilias in patients with calciphylaxis, underscoring the importance of congenital and acquired thrombotic propensity potentially contributing to the pathogenesis of this disease. These findings may have therapeutic implications; however, to date, survival differences did not vary by therapeutic choice.
Assuntos
Calciofilaxia/complicações , Trombofilia/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/complicações , Calciofilaxia/mortalidade , Fator V/genética , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Plasminogênio/deficiência , Varfarina/uso terapêuticoRESUMO
BACKGROUND: Genetics plays an important role in venous thromboembolism (VTE). Factor V Leiden (FVL or rs6025) and prothrombin gene G20210A (PT or rs1799963) are the genetic variants currently tested for VTE risk assessment. We hypothesized that primary VTE risk assessment can be improved by using genetic risk scores with more genetic markers than just FVL-rs6025 and prothrombin gene PT-rs1799963. To this end, we have designed a new genetic risk score called Thrombo inCode (TiC). METHODS AND RESULTS: TiC was evaluated in terms of discrimination (Δ of the area under the receiver operating characteristic curve) and reclassification (integrated discrimination improvement and net reclassification improvement). This evaluation was performed using 2 age- and sex-matched case-control populations: SANTPAU (248 cases, 249 controls) and the Marseille Thrombosis Association study (MARTHA; 477 cases, 477 controls). TiC was compared with other literature-based genetic risk scores. TiC including F5 rs6025/rs118203906/rs118203905, F2 rs1799963, F12 rs1801020, F13 rs5985, SERPINC1 rs121909548, and SERPINA10 rs2232698 plus the A1 blood group (rs8176719, rs7853989, rs8176743, rs8176750) improved the area under the curve compared with a model based only on F5-rs6025 and F2-rs1799963 in SANTPAU (0.677 versus 0.575, P<0.001) and MARTHA (0.605 versus 0.576, P=0.008). TiC showed good integrated discrimination improvement of 5.49 (P<0.001) for SANTPAU and 0.96 (P=0.045) for MARTHA. Among the genetic risk scores evaluated, the proportion of VTE risk variance explained by TiC was the highest. CONCLUSIONS: We conclude that TiC greatly improves prediction of VTE risk compared with other genetic risk scores. TiC should improve prevention, diagnosis, and treatment of VTE.
Assuntos
Fator V/genética , Predisposição Genética para Doença/epidemiologia , Variação Genética , Protrombina/genética , Medição de Risco/métodos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/genética , Adulto , Estudos de Casos e Controles , Feminino , Testes Genéticos , Genótipo , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Mutação , Razão de Chances , Valor Preditivo dos Testes , Análise de Regressão , Espanha/epidemiologia , Tromboembolia Venosa/diagnósticoRESUMO
The authors suggest that functional testing for activated protein C resistance is cheaper and more clinically relevant than genetic testing to detect a factor V Leiden mutation in identifying persons who are at risk for thromboembolism.
Assuntos
Resistência à Proteína C Ativada/diagnóstico , Fator V/genética , Resistência à Proteína C Ativada/genética , Feminino , Genótipo , Humanos , Tempo de Tromboplastina Parcial/economia , Fenótipo , Mutação Puntual , Reação em Cadeia da Polimerase/economiaRESUMO
AIMS: To evaluate the impact of a clinical decision-making tool, designed to educate physicians regarding heritable thrombophilia (HT) testing, on the volume of testing in hospitalised patients in the tertiary care setting. METHODS: We performed a retrospective cohort study over a 6-year period (2007-2012) at a single tertiary care centre intervention site and two regional control sites. In January 2010, the intervention site instituted a policy change whereby physicians ordering HT testing on inpatients needed to complete a pre-preprinted order (PPO) form that outlined the limitations of HT testing in the hospitalised setting. Failure to complete the PPO within 24 h resulted in test cancellation. Our main outcome measure was the volume of HT testing performed at the three study sites. RESULTS: Introduction of the PPO resulted in a 79.4% (95% CI 71.2% to 87.6%) reduction in factor V Leiden (FVL) testing at the intervention site. This decrease was significantly greater compared with those in the two control teaching hospitals over the same time periods (33.7% and 43.6%; both p<0.001). Reductions in FVL testing postintervention were observed among all ordering specialists. Similar postintervention reductions in testing volumes were observed for antithrombin (57.4%), protein C (61.9%) and protein S (62.2%) activity assays. CONCLUSIONS: In a large tertiary care hospital, the introduction of a clinical decision-making tool significantly reduced HT testing in inpatients across clinical specialties. The impact on patient outcome should be assessed in further studies.
Assuntos
Testes Genéticos/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Trombofilia/diagnóstico , Colúmbia Britânica , Estudos de Coortes , Tomada de Decisões , Prática Clínica Baseada em Evidências , Fator V/genética , Testes Genéticos/economia , Hospitais de Ensino , Humanos , Pacientes Internados , Médicos , Estudos Retrospectivos , Centros de Atenção Terciária , Trombofilia/economia , Trombofilia/genéticaRESUMO
BACKGROUND: Current anticoagulation guidelines suggest that optimal anticoagulation duration for unprovoked venous thromboembolism is determined by an individual risk assessment, balancing risks of anticoagulation bleeding with venous thromboembolism recurrence. Among individuals heterozygous for the factor V Leiden mutation, while venous thromboembolism recurrence risk is greater, the risk for bleeding is recognized to be lower, suggesting longer duration anticoagulation could be considered. OBJECTIVE: The objective of this study was to compare standard vs. lifelong anticoagulation in 20-year-old factor V Leiden heterozygotes with unprovoked venous thromboembolism. METHODS: A Markov state-transition model was used, incorporating risks of major, minor, and fatal anticoagulation bleeding, bleeding and thromboembolism morbidity and mortality, and quality of life utilities. Model parameter values favoring lifelong anticoagulation in factor V Leiden heterozygotes were determined in sensitivity analyses. Outcomes were in quality-adjusted life years, discounted at 3% per year. RESULTS: In general population groups with odds ratios for venous thromboembolism recurrence and anticoagulation bleeding of 1.0, a short-term anticoagulation strategy gained 0.09 quality-adjusted life years more than a lifelong anticoagulation strategy. By contrast, in factor V Leiden heterozygotes, lifetime anticoagulation was favored if their relative risk of venous thromboembolism was greater than 1.07 or their relative risk for bleeding was less than 0.91. Results were relatively insensitive to individual variation in other parameter values. CONCLUSION: Lifelong anticoagulation may benefit individuals heterozygous for factor V Leiden and previous idiopathic venous thromboembolism. Studies assessing bleeding risk with anticoagulation in factor V Leiden heterozygotes and the costs of indefinite anticoagulation are needed to determine if lifelong anticoagulation is the optimal strategy.
Assuntos
Anticoagulantes/administração & dosagem , Técnicas de Apoio para a Decisão , Fator V/metabolismo , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/metabolismo , Esquema de Medicação , Fator V/genética , Predisposição Genética para Doença , Heterozigoto , Humanos , Cadeias de Markov , Qualidade de Vida , Medição de Risco , Tromboembolia Venosa/genéticaRESUMO
OBJECTIVES: In the Italian health care system, genetic tests for factor V Leiden and factor II are routinely prescribed to assess the predisposition to venous thromboembolism (VTE) of women who request oral contraception. With specific reference to two subpopulations of women already at risk (i.e., familial history or previous event of VTE), the study aimed to assess whether current screening practices in Italy are cost-effective. METHODS: Two decisional models accrued costs and quality-adjusted life-years (QALY) annually from the perspective of the National Health Service. The two models were derived from a decision analysis exercise concerning testing practices and consequent prescribing behavior for oral contraception conducted with 250 Italian gynecologists. Health care costs were compiled on the basis of 10-year hospital discharge records and the activities of a thrombosis center. Whenever possible, input data were based on the Italian context; otherwise, the data were taken from the international literature. RESULTS: Current testing practices on women with a familial history of VTE generate an incremental cost-effectiveness ratio of 72,412/QALY, which is well above the acceptable threshold of cost-effectiveness of 40,000 to 50,000/QALY. In the case of women with a previous event of VTE, the most frequently used testing strategy is cost-ineffective and leads to an overall loss of QALY. CONCLUSIONS: This study represents the first attempt to conduct a cost-utility analysis of genetic screening practices for the predisposition to VTE in the Italian setting. The results indicate that there is an urgent need to better monitor the indications for which tests for factor V Leiden and factor II are prescribed.
Assuntos
Predisposição Genética para Doença , Testes Genéticos/economia , Padrões de Prática Médica/economia , Tromboembolia Venosa/genética , Adolescente , Adulto , Custos e Análise de Custo/métodos , Sistemas de Apoio a Decisões Clínicas , Fator V/genética , Feminino , Humanos , Itália/epidemiologia , Pessoa de Meia-Idade , Modelos Teóricos , Razão de Chances , Protrombina/genética , Anos de Vida Ajustados por Qualidade de Vida , Inquéritos e Questionários , Tromboembolia Venosa/epidemiologia , Adulto JovemRESUMO
AIMS: Nephrotic syndrome (NS) may occur with acquired hypercoagulability, however, the fact that it is accompanied by an underlying hereditary thrombophilia, especially combined hereditary thrombophilia would lead to thrombotic events. In this study, we aimed to evaluate the contribution of genetic thrombophilia to development of thrombotic events in adult patients with NS. MATERIAL AND METHODS: Factor V Leiden (FVL), prothrombin, and methylenetetrahydrofolate reductase (MTHFR) gene mutation were studied in 51 newly diagnosed idiopathic NS patients and age- and gender-matched 20 healthy control subjects included in the study. Renal vein Doppler ultrasound was conducted in order to investigate the prevalence of subclinical renal vein thrombosis. RESULTS: Of 51 patients, 6 (11.8%) were established to have thromboembolic (TE) complications at the time of diagnosis (4 symptomatic, 2 subclinical), and no recurring thrombotic episode was observed. Genetic mutation was established in all patients that were found to have TE complications. Acquired hypercoagulability factors were similar in patients without and with TE complication. CONCLUSIONS: The coexistence of inherited thrombophilia in NS may facilitate thromboembolic complications. If the cause of thrombosis cannot be explained by the usual factors attributed to the occurrence of thrombosis in NS, screening for the other factors, such as FVL, MTHFR, and prothrombin gene mutation, may be beneficial.
Assuntos
Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Síndrome Nefrótica/genética , Veias Renais , Trombofilia/genética , Tromboembolia Venosa/genética , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Fator V/genética , Feminino , Seguimentos , Predisposição Genética para Doença , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mutação , Síndrome Nefrótica/complicações , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Prognóstico , Estudos Prospectivos , Protrombina/genética , Veias Renais/diagnóstico por imagem , Medição de Risco , Fatores de Risco , Trombofilia/complicações , Trombofilia/diagnóstico , Trombofilia/tratamento farmacológico , Resultado do Tratamento , Ultrassonografia , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologiaRESUMO
PURPOSE: We sought to assess the benefits, risks, and personal utility of factor V Leiden mutation testing to improve pregnancy outcomes and to assess the utility of decision-analytic modeling for complex outcomes in genomics. METHODS: We developed a model to evaluate factor V Leiden testing among women with a history of recurrent pregnancy loss, including heparin therapy during pregnancy in mutation-positive women. Outcomes included venous thromboembolism, major bleeds, pregnancy loss, maternal mortality, and quality-adjusted life-years. RESULTS: Factor V Leiden testing in a hypothetical cohort of 10,000 women led to 7 fewer venous thromboembolic events, 90 fewer pregnancy losses, and an increase of 17 major bleeding events. Small improvements in quality-adjusted life-years were largely attributable to reduced mortality but also to improvements in health-related quality of life. However, sensitivity analyses indicate large variance in results due to data uncertainty. Furthermore, the complexity of outcomes limited our ability to fully capture the repercussions of testing in the quality-adjusted life-year measure. CONCLUSION: Factor V Leiden testing involves tradeoffs between clinical and personal utility, and additional effectiveness data are needed for heparin use to prevent pregnancy loss. Decision-analytic methods offer somewhat limited value in assessing these tradeoffs, suggesting that evaluation of complex outcomes will require novel approaches to appropriately capture patient-centered outcomes.Genet Med 2013:15(5):374-381.
Assuntos
Fator V/genética , Testes Genéticos , Resultado da Gravidez , Adulto , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Árvores de Decisões , Feminino , Testes Genéticos/economia , Genômica/economia , Genômica/métodos , Humanos , Mutação , Gravidez , Resultado da Gravidez/economia , Anos de Vida Ajustados por Qualidade de Vida , Estados UnidosRESUMO
PURPOSE: Role of thrombophilic factor (FV) in the etiology of recurrent miscarriages is not confirmed till date. It has been hypothesized that thrombophilic G1691A factor V Leiden (FVL), if detected well ahead in time among recurrent miscarriages may be a treatable. The role of FVL mutation in the pathogenesis of sporadic and recurrent miscarriages among North Indian women was studied to construct the frequency data in this part of the country. Further, we have evaluated the cost-benefit factor. METHODS: This is a case-control study, women with recurrent miscarriages (n = 1,000) as cases and healthy parous women (n = 500) as controls were enrolled in the study between January 2003 and January 2012. DNA was extracted from peripheral blood and analyzed for the presence of FVL mutation and prothrombin gene polymorphism (G20210A). We have carried out the meta-analysis taking into consideration 20 other world populations. RESULTS: In total, 50 (5.0 %) cases and 12 (2.4 %) controls were heterozygous for the FVL mutation. The incidence of FVL was higher in recurrent miscarriage cases as compared to the control group (OR 2.14; 95 % CI 1.12-4.05). CONCLUSION: Our results revealed the absence of FVL mutation in a homozygous state among patients and controls. Although the heterozygous mutation is almost double in cases as compared to controls, we still suggest that looking at the cost-benefit analysis this test may not be included in the battery of tests performed on recurrent miscarriages among North Indians from this part of the country.
Assuntos
Aborto Habitual/genética , Fator V/genética , Testes Genéticos , Mutação Puntual , Polimorfismo de Nucleotídeo Único , Protrombina/genética , Aborto Habitual/economia , Adulto , Estudos de Casos e Controles , Análise Custo-Benefício , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Marcadores Genéticos , Testes Genéticos/economia , Técnicas de Genotipagem , Heterozigoto , Humanos , Índia , Gravidez , Estudos RetrospectivosAssuntos
Fator V/genética , Reação em Cadeia da Polimerase/métodos , Protrombina/genética , Trombofilia/genética , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação Puntual , Reação em Cadeia da Polimerase/economia , Fatores de Risco , Trombofilia/diagnóstico , Adulto JovemRESUMO
Inherited thrombophilia is defined as a genetically determined tendency to develop venous thromboembolism. In children, inherited thrombophilia contributes to the development of pediatric thromboembolic disease. As a consequence, pediatric hematologists are increasingly requested to test thrombophilia in pediatric patients with thrombosis or asymptomatic children from thrombophilic families. This article reviews the benefits and limitations of testing for thrombophilic disorders, for example, factor V Leiden, prothrombin mutation, and deficiencies of antithrombin, protein C, or protein S in childhood.
Assuntos
Trombofilia/genética , Adolescente , Adulto , Anticoagulantes/economia , Antitrombina III/genética , Deficiência de Antitrombina III/diagnóstico , Deficiência de Antitrombina III/epidemiologia , Criança , Testes Diagnósticos de Rotina/economia , Fator V/genética , Reações Falso-Positivas , Feminino , Humanos , Mutação , Gravidez , Prevalência , Proteína C/genética , Deficiência de Proteína C/diagnóstico , Deficiência de Proteína C/epidemiologia , Proteína S/genética , Deficiência de Proteína S/diagnóstico , Deficiência de Proteína S/epidemiologia , Protrombina/genética , Recidiva , Trombofilia/diagnósticoRESUMO
Increased risk of vascular diseases in hypercoagulable states is assumed to be the major cause for prevalence of vascular problems in type 2 diabetes mellitus patient. The present study was undertaken to explore the basis underlying the correlation between the aforesaid three coagulation factors with reference to the relevant mechanistic findings using statistical calculation. Our findings showed that the correlation between each pairs of coagulation factors, FV, FVIII and vWF could be easily interpreted using previously characterized interactions between these factors. Also, given the sequence similarities between FV and FVIII as well as the results of this study, it was indicated, for the first time, that FV may bind to vWF in the same way as FVIII binds. This finding seems to be of great importance to be evaluated through experimental techniques.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Fator VIII/metabolismo , Fator V/metabolismo , Fator de von Willebrand/metabolismo , Estudos de Casos e Controles , Proposta de Concorrência , Interpretação Estatística de Dados , Diabetes Mellitus Tipo 2/genética , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/genética , Fator V/biossíntese , Fator V/genética , Fator VIII/biossíntese , Fator VIII/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fator de von Willebrand/biossíntese , Fator de von Willebrand/genéticaRESUMO
The Factor V Leiden mutation (FVL; c.1601G>A, p.Arg534Gln), the most common aberration underlying activated Protein C resistance, results in disruption of a major anticoagulation pathway and is a leading cause of inherited thrombophilia. A high-throughput assay for FVL mutation detection was developed using a single unlabeled probe on a high-resolution platform, the 96-well Roche 480 LightCycler (LC480) instrument. This method replaced the U.S. Food and Drug Administration-approved Roche Factor V Leiden kit assay on the LightCycler PCR instrument, decreasing total cost by 48%. The analytical sensitivity and specificity of the LC480 high-resolution assay approached 100% for the FVL mutation. Factor V mutations in proximity to the FVL locus may influence probe binding efficiency and melt characteristics. One out of three very rare variants tested in a separate study, 1600delC, was not distinguishable from FVL using the described high-resolution assay. However, a c.1598G>A variant, which changes the amino acid sequence from arginine to lysine at position 533, was detected by this high-resolution assay and confirmed by bidirectional sequencing. In the labeled probe LightCycler assay, the c.1598G>A variant was indistinguishable from the heterozygous FVL control. The c.1598G>A variant has not been described previously and its clinical significance is uncertain. In conclusion, the LC480 FVL assay is cost effective in a high-throughput setting, with capability to detect both previously described and novel FV variants.
Assuntos
Fator V/genética , Testes Genéticos/métodos , Mutação , Reação em Cadeia da Polimerase/economia , Reação em Cadeia da Polimerase/métodos , Análise Custo-Benefício , Sondas de DNA , Genótipo , Ensaios de Triagem em Larga Escala , Humanos , Reação em Cadeia da Polimerase/instrumentação , Trombofilia/genética , Temperatura de TransiçãoRESUMO
Venous thrombosis is a common disease that frequently recurs. Recurrence can be prevented by anticoagulants, albeit at the cost of bleeding. Thus, assessment of the risk of recurrence is important to balance the risks and benefits of anticoagulation treatment. Many clinical and laboratory risk factors for recurrent venous thrombosis have been established. Nevertheless, prediction of recurrence in an individual patient remains a challenge. Detection of some laboratory markers is associated with only a moderate risk of recurrence, and the relevance of others is not known. Many patients have several risk factors and the effect of combined defects is obscure. Routine screening for these laboratory markers should therefore be abandoned. Risk assessment can be improved by measurement of global markers that encompass the effects of clotting and fibrinolytic disorders. Analysis of preliminary data suggests that risk assessment can also be refined through integration of prothrombotic coagulation changes and clinical risk factors.
Assuntos
Trombose Venosa/etiologia , Biomarcadores/sangue , Coagulação Sanguínea , Fator V/genética , Humanos , Incidência , Estimativa de Kaplan-Meier , Mutação , Protrombina/genética , Embolia Pulmonar/etiologia , Embolia Pulmonar/prevenção & controle , Medição de Risco , Fatores de Risco , Prevenção Secundária , Trombose Venosa/complicações , Trombose Venosa/diagnóstico , Trombose Venosa/epidemiologia , Trombose Venosa/prevenção & controleRESUMO
BACKGROUND: The factor V Leiden mutation is a common genetic risk factor for thromboembolism. After liver transplantation, patients may present with an acquired factor V phenotype - genotype discrepancy. CASE REPORT: We present the history of a heterozygous carrier of the factor V Leiden mutation who needed liver transplantation because of coumarin-induced acute liver failure. This led to a phenotype - genotype discrepancy with apparent cure from the factor V Leiden carrier status. CONCLUSIONS: To date the thromboembolic risk assessment regarding the need for postoperative prophylactic anticoagulation in such patients has remained controversial with respect to the intracellular fraction of factor V in platelets. However, recent observations have shown that platelet factor V Leiden is endocytosed by megacaryocytes from plasma. Therefore, former assessments of an ongoing risk for thromboembolic events despite apparent cure of the factor V Leiden carrier status after liver transplantation should be corrected.
Assuntos
Fator V/genética , Transplante de Fígado/efeitos adversos , Tromboembolia/epidemiologia , Alanina Transaminase/sangue , Anticoagulantes/uso terapêutico , Aspartato Aminotransferases/sangue , Portador Sadio , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Femprocumona/uso terapêutico , Complicações Pós-Operatórias/epidemiologiaRESUMO
Factor V leiden (FVL) is an abnormality of factor V (FV), a blood coagulation factor. It is a hereditary blood coagulation disorder with a high frequency (3-7% of general population). The most common type of FVL is caused by a single amino acid mutation and, therefore, its diagnosis is currently done only by DNA analysis, which takes a long time and is expensive. We have developed a rapid, accurate, and cost-effective, sandwich immuno-optical sensing method. To produce monoclonal antibodies against FV or FVL, having minimal cross-reactivity with the other molecule, a 20 amino acid sequence (20-mer) of FV or FVL at around the mutation site was utilized. The antibodies were screened first with the 20-mers and then the ones showing no cross-affinity were reacted with native FV or FVL molecules and they showed some cross-reactivity. Using two antibodies having strongest affinity to either FV or FVL molecule, a FV and a FVL preferred sensors, were produced. After verifying that the levels of the antibody affinity to the two different molecules remained constant with changes in analyte concentration, a two-sensor system is developed to quantify FV and FVL in plasma samples. The system quantified the levels of FV and FVL at the maximum error of 0.5 microg/ml-plasma, in their physiological concentration range of 0-12 microg/ml-plasma. The levels of both molecules may provide us whether the patient has FVL or not but also the seriousness level of the disease (homozygous and different level of heterozygous).
Assuntos
Técnicas Biossensoriais/métodos , Fator V/análise , Imunoensaio/métodos , Fibras Ópticas , Mutação Puntual , Anticorpos Monoclonais/análise , Anticorpos Monoclonais/imunologia , Técnicas Biossensoriais/economia , Fator V/genética , Fator V/imunologia , Humanos , Imunoensaio/instrumentação , Plasma/química , Sensibilidade e Especificidade , Fatores de TempoRESUMO
BACKGROUND: The factor V Leiden (FVL) genetic test is used by many physicians despite its uncertain clinical utility. METHODS: We investigate whether self-reported motivations and behaviors concerning FVL genetic testing differ between 2 groups of primary care physicians defined by frequency of previous FVL test use. In January 2007, 112 physicians (60 frequent and 52 infrequent FVL test users) at Group Health, a large health care delivery system, were surveyed. Survey content areas included primary reasons and motivating factors for ordering the FVL test, the likelihood of ordering the FVL test for hypothetical patients, potential barriers to genetic testing, and practices and skills regarding FVL test ordering. RESULTS: Responses between groups agreed concerning most clinical- and patient-related factors. Frequent-FVL physicians were more likely than infrequent-FVL physicians to report ordering the FVL test for hypothetical patients with mesenteric venous thrombosis (adjusted odds ratio, 4.57; 95% confidence interval, 1.55-13.53) or venous thrombosis after hospital discharge (adjusted odds ratio, 3.42; 95% confidence interval, 1.30-8.95). Frequent-FVL physicians were also less likely to identify several items on the survey as barriers to genetic testing and were more likely to report high confidence in interpreting and explaining FVL test results. CONCLUSIONS: Generally, both physician groups reported similar motivating factors for ordering FVL tests, and reported behaviors were consistent with existing guidelines. More striking differences were observed for measures such as barriers to and confidence in using genetic tests. Although additional research is necessary to evaluate the impact of these results, they inform several knowledge-to-practice translation issues that are important for the successful integration of genetic testing into primary care.
Assuntos
Fator V/genética , Predisposição Genética para Doença/epidemiologia , Testes Genéticos/estatística & dados numéricos , Atenção Primária à Saúde/normas , Tromboembolia Venosa/genética , Adulto , Atitude do Pessoal de Saúde , Intervalos de Confiança , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Motivação , Análise Multivariada , Razão de Chances , Padrões de Prática Médica , Atenção Primária à Saúde/tendências , Qualidade da Assistência à Saúde , Medição de Risco , Sensibilidade e Especificidade , Inquéritos e Questionários , Tromboembolia Venosa/prevenção & controleRESUMO
BACKGROUND: Recent years have seen increased concern about direct-to-consumer (DTC) genetic testing (i.e., the sale and use of genetic tests without involving a health care provider). Numerous professional organizations have developed policies in this area. However, little systematic evidence exists to inform public policy about these tests. METHODS: We conducted a systematic search to identify genetic tests that are sold DTC without involving a health care provider. We evaluated the practices of companies offering DTC genetic tests for risk of thrombosis using criteria from multiple sources and a minimal set of key practices. RESULTS: We identified 84 instances of currently available health-related DTC genetic tests sold on 27 Web sites; the most common were for pharmacogenomics (12), risk of thrombosis (10), and nutrigenomics (10). For the DTC genetic tests for risk of thrombosis, we found low adherence to recommendations. Online information was frequently incomplete and had low agreement with professional recommendations. CONCLUSION: Our findings document the rapid growth in the availability of health-related DTC genetic tests and highlight the need to improve the delivery of DTC genetic tests. A major implication of this study is the need for the scientific and medical community to develop consistent recommendations to increase their impact.