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.

Consensus on the investigation of thrombophilia in women and clinical management / Consenso sobre a investigação de trombofilia em mulheres e manejo clínico

ABSTRACT Objective To standardize the investigation and clinical management of women with laboratory and/or clinical abnormalities suggestive of thrombophilia, in order to optimize antithrombotic approach and indication of laboratory tests. Methodology A discussion was carried out among 107 physicians (gynecologists/obstetricians, hematologists and vascular surgeons) present at a forum held at the Hospital Israelita Albert Einstein, in São Paulo (SP), Brazil. As a minimum criterion, 80% agreement was established in the voting to each recommendation of conduct in the final document. The cases in which there was agreement below 80% were discussed again, reaching a consensual agreement of conduct for the document writing. Conclusion The standardization of an institutional consensus of suggestions of clinical approach contributes to a better management of the group to be evaluated and minimizes risks of intercurrent events. This was the first national consensus on the investigation of thrombophilia in women.

RESUMO Objetivo Padronizar a investigação e o manejo clínico de mulheres com anormalidades clínicas e exames laboratoriais sugestivos de trombofilia, para melhorar a abordagem antitrombótica e otimizar a indicação de exames laboratoriais. Metodologia Foi conduzida discussão incluindo 107 médicos (ginecologistas/obstetras, hematologistas e cirurgiões vasculares) participantes de um fórum realizado no Hospital Israelita Albert Einstein, em São Paulo (SP). Como critério mínimo, estabeleceu-se concordância de 80% em votação para cada recomendação de conduta registrada em documento como diretrizes finais. Os casos em que a concordância esteve abaixo de 80% foram rediscutidos, para definir consenso na conduta. Conclusão A padronização e o estabelecimento de consenso institucional, com sugestões para abordagem clínica, contribui para melhorar o manejo do grupo a ser avaliado e minimizar os riscos de intercorrências. Este foi o primeiro consenso nacional sobre investigação de trombofilia em mulheres.

Síndrome de las plaquetas pegajosas como marcador importante de trombosis en los pacientes con trombofilia / The sticky platelet syndrome. Important markers of thrombosis in patient with thrombophilia

Introducción: el síndrome de las plaquetas pegajosas (SPP), es una entidad que provoca trastornos en la agregación de las plaquetas caracterizados por incremento anormal (hiperagregabilidad plaquetaria) y tendencia a la ocurrencia de trombosis, enfermedad que provoca morbilidad y mortalidad. Objetivo: caracterizar el comportamiento del síndrome de las plaquetas pegajosas como un marcador de trombogénesis en los pacientes con trombofilia y determinar la relación de este síndrome con la aparición y recurrencia de la enfermedad trombótica, asociado o no a otros marcadores de trombosis. Métodos: la muestra quedó constituida por 63 pacientes atendidos en la Consulta de Trombofilia del Hospital Hermanos Ameijeiras y 66 sujetos de ambos sexos y edades inferiores a 45 años, supuestamente sanos, del banco de sangre del hospital, en el período comprendido entre febrero de 2013 y abril de 2014. Como parte del perfil trombofílico, se estudiaron las pruebas de hiperagregación plaquetaria por método de transmisión de luz, la antitrombina, las proteínas C y S y el anticoagulante lúpico, mediante estudios cromogénicos y coagulométricos. Las alteraciones genéticas: factor V Leiden y factor II G20210 A (PG20210A) se evaluaron mediante la reacción en cadena de la polimerasa. Resultados: existen diferencias significativas entre uno y otro sexo a favor del masculino para la aparición de la trombosis (X²= 0,512 para p= 0,004). Predominó el color de piel blanco en el desarrollo de la enfermedad trombótica, hubo mayor número de pacientes con marcadores trombogénicos y combinaciones entre ellos para esta etnia (X²= 92,5 para p= 0,000). El marcador genético prevalente en pacientes con trombosis fue factor V Leiden. Al relacionar los diferentes marcadores trombogénicos en pacientes con trombosis y en sujetos no seleccionados se evidenció que existen diferencias significativas (X²=18,68; p=0,002) entre la presencia de marcadores biológicos y la aparición de la enfermedad trombótica. El SPP tipo I fue el más frecuente en este estudio, seguido del tipo III y el tipo II (OR= 10,5; 7,1 y 2.5). Conclusiones: existen diferencias significativas entre la presencia de marcadores biológicos y la aparición de la enfermedad trombótica. El SPP tipo I fue el más frecuente en este estudio(AU)

Introduction: the sticky platelet syndrome is an entity that causes dysfunctions in the aggregation of the platelets characterized by their abnormal increase (platelet hiperaggregability) and tendency to the thrombosis occurrence, illness that causes morbidity and mortality. Objective: to characterize the behaviour of the sticky platelet syndrome as a thrombus-genesis marker in the patients with thrombophilia and to determine the relationship of this syndrome with this illness appearance and recurrence associated or not to other thrombosis markers. Methods: the sample consisted of 63 patients treated in the thrombophilia service at Hermanos Ameijeiras Hospital and 66 subjects of both genders, younger than 45 years age, supposedly healthy, from the hospital blood bank of from February 2013 to April 2014. As part of thrombophilic profile, the hyper-aggregation platelet tests were studied by light transmission method, antithrombin, protein C and S, and the lupus anticoagulant, using chromogenic and coagulometric studies. Genetic alterations: factor V Leiden and factor II G20210A A (PG20210A) were assessed by polymerase chain reaction. Results: there are significant differences between the genders in favour of men for the occurrence of thrombosis (X²= 0.512 p = 0.004). White skin colour predominated to develop thrombotic disease, there were more patients with thrombogenic markers and combinations between them to this ethnic group (X²= 92.5; p = 0.000). The prevalent genetic marker in patients with factor V Leiden was thrombosis. Significant differences (X²= 18.68; p= 0.002) are showed between the presence of biomarkers and development of thrombotic disease when linking the different thrombogenic markers in patients with thrombosis and in unselected subjects. SPP type I was the most frequent in this study, followed by type III and type II. (OR= 10.5, 7.1 and 2.5). Conclusions: there are significant differences between the presence of biomarkers and development of thrombotic disease. The sticky platelet syndrome type I was the most frequent in this study(AU)

Hereditary Thrombophilia in Korean Patients with Idiopathic Pulmonary Embolism

PURPOSE: Hereditary thrombophilia (HT) is a major risk factor for idiopathic pulmonary embolism (iPE) and shows different prevalence among ethnic groups. The prevalence and clinical characteristics of HT in Korean patients with iPE were investigated. MATERIALS AND METHODS: Patients with PE on computed tomography (CT) scan were recruited, and those with malignancy were excluded. Patients were divided into iPE and provoked PE (pPE) groups. The presence of HT in the iPE group was assessed by DNA sequencing of the corresponding gene in patients who had low levels of natural anticoagulants. The clinical characteristics of iPE with HT (iPE/HT+) were compared with those of iPE without HT (iPE/HT-) and pPE. RESULTS: Out of 161 patients, 84 patients had iPE and 77 patients had pPE. Among 54 patients in the iPE group whose coagulation profiles were tested, 28 patients were diagnosed with HT (51.9%; 28/54). Compared with the iPE/HT- and pPE groups, the iPE/HT+ group showed the highest proportion of male patients (71.4%; p<0.001); the youngest mean age (44+/-14 years; p<0.001); and the highest frequencies for history of venous thromboembolism (64.3%; p<0.001), concurrent deep vein thrombosis (75.0%; p=0.021), and adverse clinical outcomes (42.9%, p<0.001). Protein C deficiency was the most common HT. On molecular genetic tests, causative mutation was identified in 13 patients. CONCLUSION: In this study of Korean patients, about half of the patients with iPE had HT. Patients with iPE and HT were mostly young males with deep venous thrombosis (DVT), previous venous thromboembolism (VTE), and frequent adverse clinical outcomes. Therefore, Korean patients with iPE should be tested for HT.

Importancia del estudio con D-Dímeros en el control biológico del embarazo en pacientes con trombofilia / Importance of D Dimer testing in the biologic control of pregnancy in patients with thrombophilia

Los D-Dímeros por la técnica de ELISA aumentan progresivamente en eltranscurso del embarazo normal y en las pacientes con trombofilia. Son útilescomo control biológico en estas pacientes para detección precoz de complicacionesy poder ajustar dosis del tratamiento con heparina de bajo pesomolecular. El objetivo del trabajo es determinar si los D-Dímeros por otrastécnicas (D-Dímeros: BCS [Enol]) y D-Dímeros: STA Compact (Roche) sonde utilidad en la embarazada con trombofilia o con sospecha de ella. Resultados:de las 226 pacientes analizadas, 93 no presentaron complicacionesy, si bien existe un aumento leve de los valores de la mediana de D-Dímerohacia el final del embarazo, el aumento no alcanza los niveles esperados. Enlas 133 pacientes que presentaron complicaciones no se demostró aumentodestacable de D-Dímero vinculable a la presencia de ninguna de las complicaciones.Conclusión: no se demostró, con las técnicas utilizadas BCS (Enol)y STA Compact (Roche), la variación esperada del D-Dímero en los distintostrimestres del embarazo, ni con la presencia complicaciones, en pacientescon trombofilia, a diferencia de lo publicado sobre D-Dímero con la técnicade ELISA.

Prevalence of common thrombophilia markers and risk factors in Indian patients with primary venous thrombosis / Prevalência de marcadores comuns de trombofilia e fatores de risco em pacientes indianos com trombose venosa primária

CONTEXT AND OBJECTIVE: Venous thrombosis occurs as a result of interaction of genetic and acquired factors including activated protein C resistance (APC-R), fibrinogen levels, antithrombin, protein C, protein S, lupus anticoagulants and anticardiolipin antibodies. This study was aimed at determining the prevalence of these common thrombophilia markers in Asian Indians with primary venous thrombosis. DESIGN AND SETTING: This was a cross-sectional study carried out in Mumbai. METHODS: Samples from 78 patients with a confirmed diagnosis of venous thrombosis and 50 controls were tested. Semi-quantitative estimation (functional assays) of protein C, protein S and antithrombin was performed. Quantitative estimation of fibrinogen was done using the Clauss method. Lupus anticoagulants were screened using lupus-sensitive activated partial thromboplastin time and β2-glycoprotein-I dependent anticardiolipin antibodies were estimated by ELISA. APC-R was measured using a clotting-based method with factor V deficient plasma and Crotalus viridis venom. Statistical analysis was performed using Epi-info (version 6). RESULTS: The popliteal vein was the most commonly involved site. Forty-four samples (56 percent) gave abnormal results. The commonest were elevated fibrinogen and APC-R (17.9 percent each), followed by low protein S (16.6 percent). CONCLUSIONS: This study confirms the literature findings that fibrinogen level estimation and screening for APC-R are important for the work-up on venous thrombosis patients since these, singly or in combination, may lead to a primary thrombotic episode. The frequency of the other thrombophilia markers was higher among the patients than among the controls, but without statistically significant difference.

CONTEXTO E OBJETIVO: A trombose venosa ocorre como resultado da interação de fatores genéticos e adquiridos, incluindo resistência à proteína C ativada (APC-R), os níveis de fibrinogênio, antitrombina, proteína C, proteína S, anticoagulante lúpico e anticorpos anticardiolipina. Este estudo teve como objetivo verificar a prevalência de fatores trombofílicos frequentes em indianos com trombose venosa primária. TIPO DE ESTUDO E LOCAL: Estudo transversal analítico realizado em Mumbai. MÉTODOS: Foram testadas amostras de 78 pacientes com diagnóstico confirmado de trombose venosa e 50 controles. Foi realizada a dosagem sérica semiquantitativa (funcional) de proteína C, proteína S e antitrombina e a dosagem quantitativa de fibrinogênio (método de Clauss). Anticoagulantes lúpicos foram identificados por meio do tempo de tromboplastina parcial ativada sensível ao lúpus, e anticorpos anticardiolipina dependentes de β2-glycoproteína-I por ELISA. APC-R foi medida por método baseado em coagulação com plasma deficiente em fator V e veneno de Crotalus viridis. A análise estatística utilizou Epi-info (versão 6). RESULTADOS: A veia poplítea foi o local mais frequentemente afetado; 44 amostras (56 por cento) tiveram resultados anormais. Os achados mais frequentes foram elevação do fibrinogênio e APC-R (17,9 por cento cada), e baixa proteína S (16,6 por cento). CONCLUSÕES: Corroborando com a literatura, este estudo mostrou que a elevação do nível de fibrinogênio e a triagem para APC-R são importantes na avaliação de pacientes com trombose venosa, pois, individualmente ou em combinação, podem ter levado ao episódio trombótico primário. A frequência dos outros marcadores de trombofilia foi mais alta entre os doentes quando comparados aos controles, porém sem diferença estatisticamente significante.

Mutação G20210A no gene da protrombina, fator V de Leiden e anticorpos anticardiolipina não influenciam a sobrevida do enxerto renal após o transplante / Prothrombin G20210A gene mutation, factor V Leiden and anticardiolipin antibodies do not influence renal graft survival after transplantation

Introdução: Complicações tromboembólicas são importantes fatores de risco para perda do enxerto e pior evolução após o transplante renal. pacientes com defeito trombofílico apresentam maior risco de complicações tromboembólicas. Foram analisados, entre receptores de transplante renal, a prevalência de defeito trombofílico e o risco atribuído a esta condição para a perda do enxerto e para o desenvolvimento de tromboses intravasculares. Métodos: estudo do tipo coorte incluindo 388 receptores adultos analisados quanto à presença de trombofilia de acordo com a pesquisa de anticorpos anticardiolipidina (aCL) por ELISA e das mutações G1691A no gene do fator V (FV) e G20210A no gene da protrombina (PT) por PCR multiplex. Resultados: Defeito trombofílico foi identificado em 25,8% dos pacientes. As taxas de sobrevida de 2 anos do enxerto foram semelhantes entre os pacientes com e sem defeito trombofílico (94%, p=0,53), bem como a sobrevida dos enxertos livres de tromboses intravasculares (97% versus 97%, p=0,83). pacientes com defeito trombofílico apresentaram prevalência de tromboses intravasculares semelhante à do grupo-controle (3% versus 3,5%, p=0,82). O transplante renal anterior foi associado a maior risco de perda de enxerto (OR 20,8, p<0,001) e de ocorrência de trombose intravasculares (OR 6,8, p=0,008). Conclusões: As prevalências das mutações FVG1691A e PTG20210A na população estudada foram semelhantes às da população geral não transplantada, e a prevalência de anticorpos aCL superou a observada entre os indivíduos sadios. Não houve associação entre os marcadores de trombofilia estudados e a sobrevida em médio prazo do transplante renal.

Introduction: Thromboembolic complications are important risk factors for graft loss and poor outcome after renal transplantation. patients with thrombophilic defects are at increased risk of thromboembolic complications. Were analyzed, among kidney transplant recipients, the prevalence of thrombophilic defects and the risk attributed to this condition for graft loss and the development of intravascular thrombosis. Methods: A cohort study including 388 adult recipients analyzed for the presence of thrombophilia according to anticardiolipidina antibodies (aCL) by ELISA and gene mutations G1691A in factor V (FV) and prothrombin gene G20210A (PT) by multiplex PCR. Results: thrombophilic defect was identified in 25.8% of patients. The survival rates of two years of the graft were similar between patients with and without thrombophilic defect (94%, p = 0.53), and the survival of free grafts of intravascular thrombosis (97% versus 97%, p = 0 , 83). patients with an increased prevalence of thrombophilic defect intravascular thrombosis similar to the control group (3% versus 3.5%, p = 0.82). Previous renal transplantation was associated with increased risk of graft loss (OR 20.8, p <0.001) and intravascular thrombosis (OR 6.8, p = 0.008). Conclusions: The prevalence of mutations and FVG1691A PTG20210A in this study were similar to those of the general population not transplanted, and the prevalence of aCL antibodies exceeded that observed among healthy individuals. There was no association between markers of thrombophilia studied and medium-term survival in renal transplantation.

Accidente vascular encefálico en recién nacidos de término y pretérmino tardíos / Brain strokes in late preterm and term newborns

Background: Brain strokes are uncommon in term and late preterm newborns. Nevertheless, they can appear and may be diagnosed when suspected. Appropriate diagnostic techniques, available nowadays, allow a better etiologic and therapeutic approach. Objective: To report late preterm and term newborns who presented an hemorrhagic or ischemic brain stroke. Methods: Retrospective analysis of clinical charts at the Neonatology Service of Clínica Las Condes, Santiago-Chile, between January 2001 and March 2008. Results: 0.07 percent (8/10639) of these newborns presented brain stroke; 6 hemorrhagic and 2 ischemic strokes. 2 cases were diagnosed as congenital thrombophylia. No deaths were found in this survey. Conclusions: No differences in frequency were found in relation to data reported. Seizures can be the first clinical manifestation; however, subtle forms must lead to diagnostic suspicion. Appropriate diagnostic techniques may allow an accurate diagnosis and integral therapeutic approach of these patients.

Introducción: Los Accidentes Vasculares Encefálicos (AVE) no constituyen un diagnóstico frecuente en el grupo de Recién Nacidos de término (RNT) y pretérmino tardíos (PTT). A pesar de esto, tampoco es una situación inusual y su diagnóstico dependerá en forma importante del grado de sospecha. El uso de las apropiadas técnicas diagnósticas ha permitido una mejor caracterización de estos eventos, lo que permite en ocasiones llegar a un diagnóstico etiológico con la consiguiente optimización en el manejo. Objetivo: Caracterizar el AVE en recién nacidos de término y pretérmino tardíos. Método: Análisis retrospectivo de la ficha clínica de los pacientes RNT y RNPTT con diagnóstico de AVE nacidos entre Enero del año 2001 a Marzo del año 2008 en el Servicio de Neonatología de la Clínica Las Condes, Santiago. Resultados: Se incluyeron 8 casos, lo que corresponde al 0,07 por ciento de la muestra estudiada (n= 10 639), 6 de ellos presentaron AVE hemorrágico y los 2 restantes se trataron de AVE isquémicos. En 2 casos de la serie se pesquisó trombofilia congénita. No hubo mortalidad asociada en los casos analizados. Conclusiones: La frecuencia fue similar a la de diferentes series anteriormente publicadas. La crisis convulsiva puede ser la primera manifestación clínica, pero hay otras manifestaciones clínicas más sutiles que pueden hacer sospechar el diagnóstico. El uso apropiado de las actuales técnicas diagnósticas puede llevar a un diagnóstico de certeza facilitando el manejo integral del paciente.

Trombofilias congénitas impacto reproductivo y perspectivas de tratamiento / Congenital thrombophilias reproductive impact and treatment

La intención de esta publicación ha sido revisar la relación existente entre las condiciones pro-trombóticas hereditarias conocidas como trombofilias congénitas y algunas de las patologías más severas que pueden ocurrir durante la gestación. Las trombofilias pueden afectar desde la implantación, formación y funcionamiento de la placenta, manifestándose como abortos a repetición, cuadros hipertensivos severos, restricción de crecimiento y hasta la muerte fetal. Estas enfermedades, al estar relacionadas a trombofilias, abren una ventana a la posibilidad de establecer nuevas estrategias de prevención, diagnóstico y tratamiento.

Accidente cerebrovascular recurrente y adenocarcinoma mucinoso de páncreas / Mucin-secretine adenocarcinomas of pancreatobiliary origin, hypercoagulable states and stroke

El adenocarcinoma mucinoso de páncreas se caraacteriza por su rápido crecimiento, su alta mortalidad y su frecuente asociación a los síndromes de hipercoagulabilidad. Sin embargo, el accidente cerebrovascular recurrente (ACV) como manifestación inicial, es excepcional. Se prestenta un paciente masculino de 57 años con diagnóstico de adenocarcinoma mucinoso de probable origen pancreático con diseminación hepática, que presentó ACV múltiples. En la resonancia magnética nuclear (RMN) de encéfalo inicial se constató una lesión isquémica aguda temporoparietal izquierda, y desarrolló lesiones isquémicas agudas en diversos territorios vasculares. Ante la sospecha de síndrome de Trousseau, un síndrome paraneoplásico de hipercoagulabilidad y fenómenos trombóticos, se solicitó un ecocardiograma transesofágico que descartó focos embolígenos cardíacos (endocarditis trombótica no bacteriana o ETNB) pero visualizó pequeñas placas fibrocálcicas en el cayado aórtico. Este caso ilustra la asociación sinérgica de síndrome de Trousseau y embolias del cayado aórtico en un paciente con ACV recurrente multifocal y adenocarcinoma mucinoso.

Protein-c deficiency presenting with subacute intestinal obstruction due to mesenteric vein thrombosis.

We describe a patient with protein C deficiency who presented with subacute intestinal obstruction due to ischaemic small bowel stricture. The patient also had left sided ileofemoral thrombosis. Venous thrombosis at unusual sites especially if associated with deep vein thrombosis of lower limb warrants a thorough screen for underlying thrombophilia. This, however, is a rare cause for ischaemic small bowel stricture.

Trombofilia primaria: 41 nuevos casos / Primary thrombophilias: 41 new cases

Se presentan 37 casos de trombosis, en su mayoría jóvenes, con antecedentes trombóticos familiares y con diagnóstico de trombofilia primaria o hereditaria además de cuatro familiares de primer grado de estos pacientes en los cuales se confirmó la portación familiar de trombofilia. La anamnesis reveló que el 82 por ciento presentó la primera trombosis antes de los 45 años; tuvo más de una trombosis en un 59 por ciento y tenía antecedentes familiares en 49 por ciento. Los defectos trombofílicos determinantes encontrados fueron: deficiencia de proteína S (27 por ciento); resistencia a proteína C activada por factor V Leiden (24,3 por ciento); deficiencia proteína C (21,6 por ciento) y antotrombina III (16,2 por ciento); mutación G20210 A del gen protrombina (8,1 por ciento). Entre los defectos adquiridos estudiados simultáneamente, un 27,2 por ciento de los casos presentaron anticoagulante lupico y ninguno hiperhomocisteína. La existencia de mas de un factor de riesgo trombofílico se observó en el 24.3 por ciento de los pacientes. En el estudio de los 4 parientes de primer grado se encontró factor V Leiden en uno; factor V Leiden mas anticoagulante lupico en uno y deficiencia proteína S en dos. El trabajo anterior publicado en 2004 motivó a los pacientes que no se hicieron el estudio a tomar conciencia de su situación y de la necesidad de controlarse, lo que demuestra la importancia de difundir esta patología aún poco conocida.

relationship between pregnancy induced hypertension and congenital thrombophilia

To investigate the relationship between some thrombophilic parameters and pregnancy induced hypertension [PIH]. The study took place at the Department of Obstetrics and Gynecology, Perinatology Unit, Faculty of Medicine, Cukurova University, Turkey, between January 2002 and December 2002. We evaluated 202 patients. Patients were divided into 2 groups: control group comprised 102 normotensive patients >20 weeks of pregnancy without any medical or pregnancy related pathologies and the study group comprised 100 patients over 20 weeks of pregnancy with PIH. These hypertensive patients were divided into 6 sub-groups as follows: eclampsia, severe preeclampsia, preeclampsia, chronic hypertension plus superimposed preeclampsia, eclampsia, and hemolysis elevated liver enzymes and thrombocytopenia [HELLP] syndrome. In all cases, complete blood count, antithrombin III, protein S levels, factor V Leiden mutation, prothrombin 20210 mutation, methylenetetrahydrofolate reductase [MTHFR] 677 mutation and homocysteine levels were studied. Statistical analysis of the data was carried out using SPSS version 11.0 program. In comparing the 2 groups we used Mann-Whitney U tests. In comparing the PIH subgroups we used Kruskal-Wallis tests. The levels of p<0.05 were accepted as statistically significant. Antithrombin III deficiency, protein C deficiency, hyperhomocysteinanemia were found to be associated with PIH groups. But protein S deficiency, and homozygote factor V Leiden mutation, prothrombin 20210, MTHFR 677 mutation were not found to be related with PIH

Pregnancy-associated venous thromboembolism in combined heterozygous factor V Leiden and prothrombin G20210A mutations

CONTEXTO: A gravidez e o puerpério aumentam os risco de eventos tromboembólicos, e estes riscos são maiores em mulheres portadoras de trombofilias. As mutações (FII) G20210A do gene da protrombina e a heterozigose da mutação do fator V de Leiden conferem risco moderado de trombose. A associação desses dois fatores é muito rara e o real risco de trombose é desconhecido. RELATO DE CASO: Descrevemos o caso de uma gestante portadora de ambos os fatores. Cinco anos antes da gestação, apresentou um episódio de trombose venosa associada ao uso de contraceptivos orais, e na sexta semana de gestação apresentou novo episódio. Foi tratada desde então com heparina de baixo peso molecular (nadroparina) até o parto. A gestação evoluiu sem nenhuma morbidade obstétrica significativa, e a paciente deu à luz um recém-nascido no termo, de parto cesariana. No puerpério, foi mantida nadroparina por seis semanas, e não ocorreram complicações. Mulheres portadoras de trombofilias e com antecedente de trombose devem ser mantidas em anticoagulação por toda a gestação e puerpério com heparina não-fracionada ou de baixo peso molecular. Recomenda-se a anticoagulação durante a gravidez pois não se conhece a magnitude real do risco de eventos tromboembólicos potencialmente fatais.

Coagulating like conditions thrombophilia

Fluidity of blood inside the vessels on one hand, and formation of thrombus just at the site of vessel injury on the other hand, is the result of an exact interactive equilibrium of multiple procoagulant and anticoagulant factors, and their activators and inhibitors. Destruction or stimulation of endothelial cells and platelets, and contact of blood and platelets with subendothelial tissues are among the main procoagulant factors. Integrity and function of endothelial cells, washing property of blood stream, fibrinolysis system [plasminogen] and thrombomodulin system, protein C and antithrombin are the most important anticoagulant factors. Dysfunction of procoagulant factors leads to bleeding tendency, whereas dysfunction of anticoagulant factors causes predisposition to the thrombosis [thrombophilia]. Despite recent progresses, we can only diagnose half of hereditary thrombophilias, among these, the factor V Leiden, antithrombin deficiency; protein C deficiency and protein S deficiency are more common. Elevation of plasma factor VIII levels has been considered as a common but weak risk factor for hereditary thrombophilia. Mutation of prothrombin G20210A which leads to elevation of prothrombin levels, has the same importance as the factor VIII elevation. Presence of hereditary thrombophilia in an individual does not inevitably end up in the formation of pathologic thrombosis, for clinical presentation of thromboembolic syndromes, coincidence of one [or more] hereditary thrombophilia along with one [or more] acquired thrombophilia [such as pregnancy, immobility, surgery, OCP use] are usually evident. Individuals with hereditary thrombophilia are more prone to the recurrence of thrombosis than normal individuals, so long term use of anticoagulant drugs in such patients is recommended. Screening for hereditary thrombophilia must be considered when [1] there is not an acceptable acquired risk factor for thrombosis in history and physical examination; [2]venous thrombosis before age 40, [3]recurrent thrombosis, [4]arterial thrombosis before age 30, [5]family history of thrombosis, [6]thrombosis in unusual sites such as mesenteric or cerebral veins

Trombofilia primaria: detección y manifestación clínica en 105 casos / Primary thombophilia: Report of 93 cases and 12 asymptomatic relatives

Background: Thrombophilia is defined as an altered hemostasis that predisposes to thrombosis. It can be primary when there is a family clustering of the disease or secondary, when it is associated to an acquired risk factor. Aim: To report clinical features in a series of patients with primary thrombophilia. Material and methods: Review of clinical records of patients with thrombotic episodes that lead to the suspicios of primary thrombophilia. Analysis of asymptomatic adult close relatives of these patients. Results: We report 93 subjects (56 females, age range 14-77 years) with repeated episodes of thrombosis and a family history of thrombosis and 12 asymptomatic close relatives. Seventy one percent had the first thrombotic episode before the age of 40 years, 62% had more than one thrombotic episode and 37% had a family history of thrombosis. Twenty four percent had protein C deficiency, 24% had antithrombin III deficiency, 18% had resistance to activated C protein by factor V Leiden, 10% had protein S deficiency, and 10% had the G20210 mutation of prothrombin gene. Among acquired defects studied simultaneously, 30% had lupus anticoagulant and 11% had hyperhomocysteinemia. Twenty four percent of cases had more than one thrombophilic risk factor. Among asymptomatic relatives, five had factor V Leiden, four had protein C deficiency and three had the G20210 mutation of prothrombin gene. Conclusions: Thrombophilia must be suspected in young subjects with thrombotic episodes and a family history. The type of coagulation defect will determine prognosis, and the type of treatment.