Octagenária portadora da mutação do fator V de Leiden submetida à oclusão de apêndice atrial esquerdo: relato de caso / Octagenarian woman with factor V Leiden mutation undergoing left atrial appendage occlusion: case report

INTRODUÇÃO A mutação do fator V de Leiden é uma condição genética que acomete um ponto único no sítio de inativação do fator V impedindo a ligação com a proteína C ativada, resultando em um estado pró-trombótico. A fibrilação atrial (FA) é a arritmia mais comum do mundo com predomínio na população idosa, e está relacionada com elevado risco de eventos tromboembólicos. A oclusão do apêndice atrial esquerdo (OAA) é um procedimento minimamente invasivo, visando a tromboprofilaxia em pacientes com FA e contraindicação de anticoagulação oral (ACO). DESCRIÇÃO DO CASO Paciente M.S.F.R.S., octogenária com fragilidade severa, dependente para atividades básicas e instrumentais da vida diária, portadora da mutação heterozigótica do fator V de Leiden, dislipidêmica, ex-tagabista, obesidade sarcopênica e apresenta FA permanente em uso inicial de varfarina. Antecedentes de trombose venosa profunda em membro inferior direito, comunicação interatrial corrigida por atriosseptoplastia, quatro eventos prévios de acidente vascular encefálico (AVE) com sequela motora à direita, e osteoporose associado a múltiplas fraturas de vértebras com correção cirúrgica. Além disso, apresentava má adesão ao uso de varfarina com acompanhamento irregular do controle de INR, associado com episódios de sangramentos gastrointestinais. Por isso, optou-se pela realização da oclusão do apêndice atrial esquerdo para prevenção secundária de eventos tromboembólicos. A paciente fez uso de ácido acetilsalicílico (AAS) 100mg e clopidogrel 75mg durante 6 meses pós-procedimento, seguido da suspensão dessas medicações e introdução da rivaroxabana 15mg, devido ao risco elevado de eventos tromboembólicos propiciados pela trombofilia. Atualmente em uso de metoprolol 200mg/dia; digoxina 0,125mg/dia; omeprazol 20mg/dia; clonazepam 2mg/dia e rivaroxabana 15mg/dia. CONCLUSÃO Segundo ensaios clínicos randomizados, a OAA não mostrou-se inferior ao uso de ACO quanto a ocorrência de AVE e embolismo sistêmico, como também demonstrou superioridade quanto a menores taxas de mortalidade cardiovascular. O estudo PROTECT-AF recomenda o uso de ACO associado ao AAS por 45 dias, seguido da dupla antiagregação plaquetária durante 6 meses e após isso, uso indeterminado de AAS isolado. Porém a anticoagulação ideal pós-intervenção permanece um desafio. O futuro da OAA está relacionado com a experiência do operador, evolução da tecnologia dos dispositivos, consenso da terapia antitrombótica e manejo das principais complicações.

As trombofilias na perda gestacional de repetição: uma revisão de prevalência e condutas / Thrombophilias in recurrent pregnancy loss: a review of prevalence and conduct

Objetivo: Discutir o papel das trombofilias na perda gestacional de repetição, com foco em prevalência/associação dessas patologias com perdas de repetição e seu tratamento, por meio de resultados de ensaios clínicos, revisões sistemáticas e metanálises. Métodos: Trata-se de uma revisão não sistemática de artigos publi- cados nas bases eletrônicas PubMed, Cochrane e SciELO nos últimos cinco anos, utilizando os seguintes descritores: "recurrent pregnancy loss", "recurrent abortion", "habitual abortion", "thrombophilia", "antiphospholipid syndrome" e "treatment". Resultados: A maioria dos estudos relatou forte associação entre os anticorpos antifosfolípides específicos e a síndrome do anticorpo antifosfolípide com perda gestacional de repetição. Mulheres portadoras da mutação do fator V de Leiden, mutação do gene da protrombina e deficiência de proteína S apresentaram alto risco de perda gestacional de repetição em uma grande revisão sistemática. Estudos recentes demonstraram taxas de prevalência das trombofilias hereditárias e da síndrome do anticorpo antifosfolípide, em mulheres com perda gestacional de repetição, semelhantes às da população em geral. Os estudos atuais endossam o uso da heparina associada à aspirina em mulheres com síndrome do anticorpo antifosfolípide, com aumento da taxa de nascidos vivos, mas sem diferença em re- lação às complicações obstétricas. Conclusão: Apesar de novos estudos demons- trarem que a prevalência das trombofilias hereditárias e adquiridas em mulheres com perda gestacional de repetição é semelhante à da população em geral, reco- menda-se a pesquisa rotineira de síndrome do anticorpo antifosfolípide nessas pacientes. O uso de aspirina em baixas doses associada à heparina é a intervenção farmacológica de primeira linha para a prevenção de perda gestacional de repeti- ção em pacientes com síndrome do anticorpo antifosfolípide.

Objective: To discuss the role of thrombophilias in recurrent pregnancy loss, focu- sing on the prevalence/association of these pathologies with recurrent abortion and treatment, through results of clinical trials, systematic reviews and meta-analyses. Methods: This is a non-systematic review of articles published in electronic databa- ses PubMed, Cochrane, SciELO in the last five years, using the following descriptors: "recurrent pregnancy loss", "recurrent abortion", "habitual abortion", "thrombophilia", "antiphospholipid syndrome", and "treatment". Results: Most studies have reported a strong association between specific antiphospholipid antibodies and antiphospho- lipid antibody syndrome with recurrent pregnancy loss. Women carrying the factor V Leiden mutation, prothrombin gene mutation, and protein S deficiency were shown to be at high risk of recurrent pregnancy loss in a large systematic review. Recent studies have shown prevalence rates of hereditary thrombophilias and antiphospholipid antibody syndrome, in women with re- current pregnancy loss, similar to those of the general po- pulation. Current studies endorse the use of heparin plus aspirin in women with antiphospholipid antibody syndrome, with an increase in live birth rate, but with no difference in obstetric complications. Conclusion: Although new studies demonstrate that the prevalence of hereditary and acquired thrombophilias in women with recurrent pregnancy loss is si- milar to that of the general population, routine investigation of antiphospholipid antibody syndrome in these patients is recommended. The use of low-dose aspirin plus heparin is the first-line pharmacological intervention for the prevention of recurrent pregnancy loss in patients with antiphospholipid antibody syndrome.

Full-scale network analysis reveals properties of the FV protein structure organization.

Blood coagulation is a vital process for humans and other species. Following an injury to a blood vessel, a cascade of molecular signals is transmitted, inhibiting and activating more than a dozen coagulation factors and resulting in the formation of a fibrin clot that ceases the bleeding. In this process, the Coagulation factor V (FV) is a master regulator, coordinating critical steps of this process. Mutations to this factor result in spontaneous bleeding episodes and prolonged hemorrhage after trauma or surgery. Although the role of FV is well characterized, it is unclear how single-point mutations affect its structure. In this study, to understand the effect of mutations, we created a detailed network map of this protein, where each node is a residue, and two residues are connected if they are in close proximity in the three-dimensional structure. Overall, we analyzed 63 point-mutations from patients and identified common patterns underlying FV deficient phenotypes. We used structural and evolutionary patterns as input to machine learning algorithms to anticipate the effects of mutations and anticipated FV-deficiency with fair accuracy. Together, our results demonstrate how clinical features, genetic data and in silico analysis are converging to enhance treatment and diagnosis of coagulation disorders.

Prevalence of thrombophilia-associated genetic risk factors in blood donors of a regional hospital in southern Brazil

ABSTRACT Introduction: Thromboembolic events occur due to an imbalance in the hemostasis and some factors associated with this condition can be inherited. In order to evaluate the frequency of genotypes considered to be common hereditary risk factors for thrombophilia associated with venous thrombosis (g.1691G>A and g.20210G>A) and hyperhomocysteinemia (g.677C>T and g.1298A>C), samples from voluntary healthy blood donors at the Hospital de Clínicas de Porto Alegre were tested. Methods: We examined 325 blood samples from blood donors collected from October 2017 to July 2018. Blood was collected on filter paper and the DNA was extracted for single nucleotide polymorphisms (SNPs) analysis using the qualitative real time polymerase chain reaction. Results: The calculated frequencies of each genetic variant in heterozygosity were 4% for the FV gene (g.1691G> A), 4% for the F2 gene (g.20210G> A) and 42% and 39% for methylenetetrahydrofolate reductase (MTHFR), g.677C>T and g.1298A>C, respectively. Only the genetic variants of MTHFR were found in homozygosity, with frequencies of 14% and 6% (g.677C>T and g.1298A>C), respectively. Discussion: Altogether, these results describe the frequencies of genetic variants associated with venous thrombosis and hyperhomocysteinemia in the analyzed group and are important to enhance our current knowledge about the genetic profiles of Brazilian blood donors.

High risk of venous thromboembolism after orthopedic surgery in patients with thrombophilia.

OBJECTIVE: This study aimed at evaluating the effect of thrombophilia on the risk of venous thromboembolism (VTE) in patients undergoing any type of orthopedic surgery. BACKGROUND: Patients undergoing orthopedic surgery are at high risk for VTE. Although patients with thrombophilia have an increased risk of VTE, it is currently unclear whether there is a synergetic effect in patients with thrombophilia who undergo orthopedic surgery. METHODS: Data from a large population-based case-control study (the Multiple Environmental and Genetic Assessment [MEGA] of risk factors for venous thrombosis study) were used. Odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for age, sex, and body mass index (BMI) (ORadj) were calculated for patients undergoing any orthopedic intervention. RESULTS: Of 4721 cases and 5638 controls, 263 cases and 94 controls underwent orthopedic surgery. Patients who had any orthopedic intervention in the year before the index date were at higher risk of VTE (ORadj 3.7; 95% CI, 2.9-4.8) than those who did not undergo any orthopedic surgery. There was an additionally increased risk in patients with factor V Leiden (OR 17.5, 95% CI, 4.1-73.6), non-O blood group (OR 11.2; 95% CI, 3.4-34.0), or elevated plasma levels of factor VIII (OR 18.6; 95% CI, 7.4-46.9) all relative to patients without these defects, not undergoing orthopedic surgery. CONCLUSIONS: Patients with factor V Leiden, high levels of factor VIII, or blood group non-O were found to have a high risk of VTE after orthopedic surgery. Identification of these patients may enable individualized thromboprophylactic treatment to efficiently reduce VTE risk.

Prevalence of Factor V Leiden in a healthy population in Santa Catarina, Southern Brazil.

Thrombophilic disorders are found in 50% of patients with venous thromboembolism, and factor V Leiden (FVL) is the most common genetic risk factor for the development of these conditions. FVL prevalence varies according to population group. In Europe, many countries have a high prevalence of the mutation, including Portugal, Germany, and Italy. Santa Catarina State, southern Brazil, was colonized by different European nations; most inhabitants are descendants of Portuguese, Italian, and German immigrants. There are, however, no data on the prevalence of FVL in the state. This study aimed to determine FVL prevalence in a healthy population in Santa Catarina and assess whether there is an association between the mutation and demographic characteristics, thereby contributing to the understanding of the heterogeneity of prevalence of this important VTE risk factor and racial or geographical differences in the incidence of thrombotic diseases. Analysis of the FVL mutation was performed on 400 blood donors using the PCR technique followed by enzymatic digestion. The findings show that 2.5% of the participants were heterozygous for FVL, and none were homozygous. No association was found between the presence of FVL in heterozygosis and individual characteristics. In conclusion, this study found a prevalence of FVL in heterozygosis of 2.5% among healthy individuals in Santa Catarina, Brazil. Further studies are needed to assess the prevalence of FVL in other regions of the country, determine the distribution of the mutation among population groups, and evaluate how these factors affect the incidence of thrombotic diseases.

Leptospira interrogans Bat proteins impair host hemostasis by fibrinogen cleavage and platelet aggregation inhibition.

Leptospirosis is a worldwide spread zoonosis, caused by pathogenic Leptospira. Evidences suggest that compromised hemostasis might be involved in the leptospirosis pathophysiology. In the genome of L. interrogans serovar Copenhageni, we found two genes coding for proteins which comprise von Willebrand factor (VWF) A domains (BatA and BatB). As VWF A domains exhibit multiple binding sites which contributes to human VWF hemostatic functions, we hypothesized that the L. interrogans BatA and BatB proteins could be involved in the hemostatic impairment during leptospirosis. We have cloned, expressed in Escherichia coli, and purified recombinant BatA and BatB. The influence of recombinant BatA and BatB on different in vitro hemostatic assays evaluating the enzymatic activity, platelet aggregation and fibrinogen integrity was investigated. We describe BatB as a new serine protease which is able to cleave thrombin chromogenic substrate, fibrin, fibrinogen, gelatin and casein; while BatA is active only towards fibrinogen. BatA and BatB interfere with the platelet aggregation induced by VWF/ristocetin and thrombin. Our results suggest an important role of the L. interrogans serovar Copenhageni Bat proteins in the hemostasis dysfunction observed during leptospirosis and contribute to the understanding of the leptospirosis pathophysiological mechanisms.

Lipase and factor V (but not viral load) are prognostic factors for the evolution of severe yellow fever cases.

BACKGROUND: Despite a highly efficacious vaccine, yellow fever (YF) is still a major threat in developing countries and a cause of outbreaks. In 2018, the Brazilian state of São Paulo witnessed a new YF outbreak in areas where the virus has not been detected before. OBJECTIVE: The aim is to describe the clinical and laboratorial characteristics of severe cases of YF, evaluate viral to determine markers associated with fatal outcome. METHODS: Acute severe YF cases (n = 62) were admitted to the Intensive Care Unit of a reference hospital and submitted to routine laboratorial evaluation on admission. YFV-RNA was detected in serum and urine by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and then sequenced. Patients were classified in two groups: survival or death. FINDINGS: In the univariate analysis the following variables were associated with outcome: alanin aminotransferase (ALT), aspartat aminotransferase (AST), AST/ALT ratio, total bilirubin (TB), chronic kidney disease epidemiology collaboration (CKD-EPI), ammonia, lipase, factor V, international normalised ratio (INR), lactate and bicarbonate. Logistic regression model showed two independent variables associated with death: lipase [odds ratio (OR) 1.018, 95% confidence interval (CI) 1.007 to 1.030, p = 0.002], and factor V (OR -0.955, 95% CI 0.929 to 0.982, p = 0.001). The estimated lipase and factor V cut-off values that maximised sensitivity and specificity for death prediction were 147.5 U/L [area under the curve (AUC) = 0.879], and 56.5% (AUC = 0.913). MAIN CONCLUSIONS: YF acute severe cases show a generalised involvement of different organs (liver, spleen, heart, kidneys, intestines and pancreas), and different parameters were related to outcome. Factor V and lipase are independent variables associated with death, reinforcing the importance of hemorrhagic events due to fulminant liver failure and pointing to pancreatitis as a relevant event in the outcome of the disease.

Coronary artery disease associated with factor V Leiden mutation: a case report.

The prevalence of coronary artery disease in young adults (<45 years of age) has been increasing steadily in recent decades. Although traditional cardiovascular risk factors can be identified in most cases, newly recognized associations are becoming progressively more relevant. The relationship between the factor V Leiden mutation and atherosclerosis has been a matter of debate due to conflicting data presented in previous studies. Presently described is the case of a previously asymptomatic 37-year-old woman with a significant family history of coronary artery disease who developed rapidly progressive angina within 1 month. After a positive non-invasive evaluation, coronary angiography demonstrated a significant obstruction in the proximal left anterior descending artery. Optical coherence tomography revealed a highly vulnerable lipid-rich atherosclerotic plaque. Coronary angioplasty followed by the implantation of 1 drug-eluting stent was successfully performed. A subsequent thrombophilia screening identified a heterozygous factor V R506Q mutation (factor V Leiden). Since there was no history of thromboembolic events, the patient was discharged using only aspirin, clopidogrel, atorvastatin, and atenolol. Further studies are needed to define the most appropriate management of young patients who manifest clinically significant atherosclerotic disease in association with hereditary thrombophilia.

Inherited thrombophilia and pregnancy loss. Study of an Argentinian cohort. / Trombofilia hereditaria y pérdidas de embarazo. Estudio de una cohorte de Argentina.

BACKGROUND AND OBJECTIVES: Thrombophilia might increase the risk of suffering from obstetric complications by adversely affecting the normal placental vascular function. Our aim was to study the distributions of five thrombosis-associated genetic variants: factor V Leiden, prothrombin G20210A, -675 4G/5G PAI-1, 10034C/T gamma fibrinogen and 7872C/T factor XI and the frequencies of the deficiencies of protein C, S and antithrombin in Argentinian patients with recurrent pregnancy loss (RPL) and, therefore, to analyse their association with the risk and timing of RPL and the risk of suffering other vascular obstetric pathologies. PATIENTS AND METHODS: We performed a case-control study that included 247 patients with idiopathic RPL (cases), 107 fertile controls and 224 subjects from general population (reference group). Cases were stratified according to the gestational time of the losses (early RPL, n = 89; late losses, n = 158; foetal losses, n = 107) and according to the type of vascular obstetric pathologies. RESULTS: No differences were found in the distribution of the genetic variants among RPL group vs. control/reference group (p >.05). Similarly, no differences were observed in their distributions when analysing RPL patients stratified according to gestational times or vascular obstetric pathologies (p >.05), except for the factor V Leiden carriage in patients with foetal growth retardation vs. controls (11.8%, 4/34 vs. 1.9%, 2/107; p = .04) (OR = 7.11 [1.24-40.93], p = .03). CONCLUSIONS: Factor V Leiden might have a significant impact on certain obstetric pathologies such as foetal growth retardation. The genetic variants, 10034C/T gamma fibrinogen and 7872C/T factor XI, associated with thromboembolic disease, would not have an impact on PRE.

Serum Factor V Is a Continuous Biomarker of Graft Dysfunction and a Predictor of Graft Loss After Liver Transplantation.

BACKGROUND: Factor V has never been compared to a validated early allograft dysfunction (EAD) definition. We aimed to assess factor V as a biomarker of EAD and a predictor of graft loss after liver transplantation (LT). METHODS: We retrospectively assessed the serum factor V levels on postoperative day 1 after LT. Patients were divided according to their factor V levels into the ≤36.1 U/mL and > 36.1 U/mL groups. The primary outcome was graft loss within 1, 3, and 6 months. The secondary outcome was EAD, as defined by Olthoff et al. Predictors of outcomes were identified by multivariable logistic regression. RESULTS: Two hundred twenty-seven patients were included in the study: 74 with factor V of 36.1 U/mL or less and 153 with factor V >36.1 U/mL. EAD was diagnosed in 41 (55.4%) of 74 patients with factor V of 36.1 U/mL or less and in 20/153 (13.1%) patients with factor V >36.1 U/mL (P < 0.001). According to the multivariable regression model, factor V was a continuous marker of EAD (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.94-0.98 per U/mL). Among the study groups, the 1-, 3-, and 6-month graft survival rates were 82%, 74%, and 74%, respectively, for patients with factor V of 36.1 U/mL or less and 98%, 95%, and 95%, respectively, for patients with factor V >36.1 U/mL (P = 0.001). Factor V was a continuous predictor for 3- and 6-month graft losses (OR, 0.96; 95% CI, 0.94-0.99 and OR, 0.97; 95% CI, 0.94-0.99 per U/mL), whereas EAD was not significant when adjusted for factor V. CONCLUSION: Factor V is an early marker for EAD and is a continuous predictor of short-term graft loss after LT.

Lipase and factor V (but not viral load) are prognostic factors for the evolution of severe yellow fever cases

BACKGROUND Despite a highly efficacious vaccine, yellow fever (YF) is still a major threat in developing countries and a cause of outbreaks. In 2018, the Brazilian state of São Paulo witnessed a new YF outbreak in areas where the virus has not been detected before. OBJECTIVE The aim is to describe the clinical and laboratorial characteristics of severe cases of YF, evaluate viral to determine markers associated with fatal outcome. METHODS Acute severe YF cases (n = 62) were admitted to the Intensive Care Unit of a reference hospital and submitted to routine laboratorial evaluation on admission. YFV-RNA was detected in serum and urine by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and then sequenced. Patients were classified in two groups: survival or death. FINDINGS In the univariate analysis the following variables were associated with outcome: alanin aminotransferase (ALT), aspartat aminotransferase (AST), AST/ALT ratio, total bilirubin (TB), chronic kidney disease epidemiology collaboration (CKD-EPI), ammonia, lipase, factor V, international normalised ratio (INR), lactate and bicarbonate. Logistic regression model showed two independent variables associated with death: lipase [odds ratio (OR) 1.018, 95% confidence interval (CI) 1.007 to 1.030, p = 0.002], and factor V (OR -0.955, 95% CI 0.929 to 0.982, p = 0.001). The estimated lipase and factor V cut-off values that maximised sensitivity and specificity for death prediction were 147.5 U/L [area under the curve (AUC) = 0.879], and 56.5% (AUC = 0.913). MAIN CONCLUSIONS YF acute severe cases show a generalised involvement of different organs (liver, spleen, heart, kidneys, intestines and pancreas), and different parameters were related to outcome. Factor V and lipase are independent variables associated with death, reinforcing the importance of hemorrhagic events due to fulminant liver failure and pointing to pancreatitis as a relevant event in the outcome of the disease.

[Polimorfismos asociados a disfunción endotelial y a un estado protrombótico en jóvenes mexicanos con infarto cerebral].

OBJECTIVE: To examine the contribution the polymorphisms G20210A, G1691A and G10976A in the coagulation factors FII, FV, FVII, respectively; Glu298Asp and C677T in eNOS and 5,10 MTHFR in young Mexican population with cerebral infarction (CI). METHODS: 224 patients ≤ 45 years of age with CI and 224 controls matched by age and gender were recruited from 2006 and 2014. The polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We identified a significant difference in the genotype distribution of Glu298Asp (p = 0.001) and C677T (p = 0.01) polymorphisms between CI patients and control groups. The genotype distribution in the FII G20210A, FV G1691A and FVII G10976A polymorphisms were similar. There were independent factors for ischemic stroke: Glu298Asp and C677T polymorphisms, smoking; hypertension, and familial history of thrombotic disease. CONCLUSIONS: The Glu298Asp and C677T, but not FII G20210A, FV G1691A and FVII G10976A polymorphisms were associated with CI. Our results suggest that endothelial dysfunction and the synergist interaction with other factors such as smoking and hypertension contribute to CI in young individuals.

OBJETIVO: Examinar la contribución de los polimorfismos G20210A, G1691A y G10976A en los factores de coagulación FII, FV y FVII respectivamente; Glu298Asp y C677T en la óxido nítrico sintasa endotelial y 5,10 metilentetrahidrofolato reductasa, en población joven mexicana con infarto cerebral (IC). MÉTODO: Se incluyeron 224 pacientes ≤ 45 años de edad con diagnóstico de IC y 224 controles pareados por edad y sexo, de 2006 a 2014. Los polimorfismos fueron determinados por la técnica de reacción en cadena de la polimerasa-polimorfismos de longitud de fragmentos de restricción. RESULTADOS: Identificamos una diferencia significativa en la distribución genotípica de los polimorfismos Glu298Asp (p = 0.001) y C677T (p = 0.01) entre el grupo de pacientes con IC y el control. La distribución genotípica de los polimorfismos FII G20210A, FV G1691A y FVII G10976A fue similar entre ambos grupos. Se identificaron como factores independientes de IC los polimorfismos Glu298Asp y C677T, el tabaquismo, la hipertensión y el antecedente de familiar de enfermedad trombótica. CONCLUSIONES: Los polimorfismos Glu298Asp y C677T, pero no FII G20210A, FV G1691A y FVII G10976A, se asociaron con IC. Nuestros resultados sugieren que la disfunción endotelial en interacción sinérgica con otros factores de riesgo, como tabaquismo e hipertensión, contribuye al IC en individuos jóvenes.

The first reported case of factor V Leiden mutation with agenesis of superior vena cava: A case report.

RATIONALE: Total absence of superior vena cava (ASVC) is a very rare anomaly, and the patient usually suffers from superior vena cava syndrome (SVCS) or conduction disturbances. PATIENT CONCERNS: We report a 36-year-old white male, born and living in Brazil, without comorbidities presented to hematologist thrombotic episodes even under anticoagulant therapy. On his first hematologic appointment, he had no active complaints except by the fullness after meals, and his physical examination presented remarkable collateral circulation in the chest. DIAGNOSES: Congenital ASVC associated with factor V Leiden mutation. OUTCOMES: In his magnetic resonance angiography of the thorax, a great amount of collateral circulation and communication of the azygos and hemiazygos veins with inferior vena cava were evident, as well as the absence of the upper cava vein. Furthermore, heterozygous genetic mutation was found for Leiden factor V. LESSONS: This case gives us the lesson that we need to include ASVC in the differential diagnosis of SVCS. The importance of the V-Leiden factor as a joint risk with this congenital defect for venous thromboembolism episodes was also highlighted.

Anti-phospholipid syndrome in seven leprosy patients with thrombotic events on corticosteroid and/or thalidomide regimen: insights on genetic and laboratory profiles.

INTRODUCTION: Corticosteroids and/or thalidomides have been associated with thromboembolism events (TBE) in multibacillary (MB) leprosy. This report aimed to determine genetic and laboratory profiles associated with leprosy and TBE. METHODS: Antiphospholipid antibodies (aPL), coagulation-related exams, prothrombin and Leiden's factor V mutations, and ß2-glycoprotein-I (ß2GPI) Val247Leu polymorphism were assessed. RESULTS: Six out of seven patients with leprosy were treated with prednisone and/or thalidomide during TBE and presented at least one positive aPL. All patients presented ß2GPI polymorphism, and one showed prothrombin mutation. CONCLUSIONS: Corticosteroid or thalidomide adverse effects and aPL and ß2GPI polymorphisms may cause TBE in patients with MB leprosy.

Anti-phospholipid syndrome in seven leprosy patients with thrombotic events on corticosteroid and/or thalidomide regimen: insights on genetic and laboratory profiles

Abstract INTRODUCTION Corticosteroids and/or thalidomides have been associated with thromboembolism events (TBE) in multibacillary (MB) leprosy. This report aimed to determine genetic and laboratory profiles associated with leprosy and TBE. METHODS Antiphospholipid antibodies (aPL), coagulation-related exams, prothrombin and Leiden's factor V mutations, and ß2-glycoprotein-I (ß2GPI) Val247Leu polymorphism were assessed. RESULTS Six out of seven patients with leprosy were treated with prednisone and/or thalidomide during TBE and presented at least one positive aPL. All patients presented ß2GPI polymorphism, and one showed prothrombin mutation. CONCLUSIONS Corticosteroid or thalidomide adverse effects and aPL and ß2GPI polymorphisms may cause TBE in patients with MB leprosy.

Paciente con trombosis venosa profunda recidivante por factor V Leiden y respuesta al tratamiento homeopático / Patient with recurrent deep venous thrombosis by factor V Leiden and response to homeopathic treatment

El tromboembolismo venoso (TEV) es un problema de salud significativo, con morbimortalidad cercana al 30%. El factor V Leiden (FVL) es una forma "mutada" del factor V normal que se inactiva 10 veces más lentamente, produciendo estados de hipercoagulación y trombosis. En este artículo se presenta el caso de una mujer de 23 años de edad en quien, a raíz de un episodio de TVP se diagnosticó su condición de portadora de enfermedad por FVL de carácter homocigota. Transcurridos 8 años del primer episodio y estando aún bajo tratamiento convencional, el alto nivel de dímeroD (DD) señalaba alto riesgo de sufrir nuevos episodios de TVP. En ese momento se inició tratamiento con medicación homeopática unicista constitucional, en baja dinamización y dosis diarias, observándose una rápida caída en las cifras de DD cambiando así el pronóstico de futuras recidivas y llevando a los hematólogos a suspender el tratamiento convencional. No hubo recidivas hasta el presente y el Doppler venoso muestra rehabilitación del lecho venoso. (AU)

Venous thromboembolism (VTE) is a significant health problem with morbidity and mortality around 30%. Factor V Leiden (FVL) is a "mutated" form of the normal factor V which is inactivated 10 times slower causing hypercoagulation states and thrombosis. The present articles describes the case of a 23-year-old women in whom that status of homozygous was diagnosed on the occasion of a VTE episode. High dimer-D (DD) levels 8 years later and still under conventional treatment high pointed to high risk for recurrence of VTE. Homeopathic treatment was started (constitutional unicast) in low potency and daily doses. DD fell rapidly, and thus the prognosis changed, leading hematologists to withdraw conventional treatment. Disease did not relapse to this day and venous Doppler sonography evidenced rehabilitated vein system. (AU)

Paciente con trombosis venosa profunda recidivante por factor V Leiden y respuesta al tratamiento homeopático / Patient with recurrent deep venous thrombosis by factor V Leiden and response to homeopathic treatment

El tromboembolismo venoso (TEV) es un problema de salud significativo, con morbimortalidad cercana al 30%. El factor V Leiden (FVL) es una forma "mutada" del factor V normal que se inactiva 10 veces más lentamente, produciendo estados de hipercoagulación y trombosis. En este artículo se presenta el caso de una mujer de 23 años de edad en quien, a raíz de un episodio de TVP se diagnosticó su condición de portadora de enfermedad por FVL de carácter homocigota. Transcurridos 8 años del primer episodio y estando aún bajo tratamiento convencional, el alto nivel de dímeroD (DD) señalaba alto riesgo de sufrir nuevos episodios de TVP. En ese momento se inició tratamiento con medicación homeopática unicista constitucional, en baja dinamización y dosis diarias, observándose una rápida caída en las cifras de DD cambiando así el pronóstico de futuras recidivas y llevando a los hematólogos a suspender el tratamiento convencional. No hubo recidivas hasta el presente y el Doppler venoso muestra rehabilitación del lecho venoso. (AU)

Venous thromboembolism (VTE) is a significant health problem with morbidity and mortality around 30%. Factor V Leiden (FVL) is a "mutated" form of the normal factor V which is inactivated 10 times slower causing hypercoagulation states and thrombosis. The present articles describes the case of a 23-year-old women in whom that status of homozygous was diagnosed on the occasion of a VTE episode. High dimer-D (DD) levels 8 years later and still under conventional treatment high pointed to high risk for recurrence of VTE. Homeopathic treatment was started (constitutional unicast) in low potency and daily doses. DD fell rapidly, and thus the prognosis changed, leading hematologists to withdraw conventional treatment. Disease did not relapse to this day and venous Doppler sonography evidenced rehabilitated vein system. (AU)

Identifying and enriching platelet-producing human stem cell-derived megakaryocytes using factor V uptake.

Stem cell-derived platelets have the potential to replace donor platelets for transfusion. Defining the platelet-producing megakaryocytes (MKs) within the heterogeneous MK culture may help to optimize the in vitro generation of platelets. Using 2 human stem cell models of megakaryopoiesis, we identified novel MK populations corresponding to distinct maturation stages. An immature, low granular (LG) MK pool (defined by side scatter on flow cytometry) gives rise to a mature high granular (HG) pool, which then becomes damaged by apoptosis and glycoprotein Ib α chain (CD42b) shedding. We define an undamaged HG/CD42b+ MK subpopulation, which endocytoses fluorescently labeled coagulation factor V (FV) from the media into α-granules and releases functional FV+CD42b+ human platelet-like particles in vitro and when infused into immunodeficient mice. Importantly, these FV+ particles have the same size distribution as infused human donor platelets and are preferentially incorporated into clots after laser injury. Using drugs to protect HG MKs from apoptosis and CD42b shedding, we also demonstrate that apoptosis precedes CD42b shedding and that apoptosis inhibition enriches the FV+ HG/CD42b+ MKs, leading to increased platelet yield in vivo, but not in vitro. These studies identify a transition between distinct MK populations in vitro, including one that is primed for platelet release. Technologies to optimize and select these platelet-ready MKs may be important to efficiently generate functional platelets from in vitro-grown MKs.