Pre-eclampsia y Trombofilia hereditaria / Pre-eclampsia and hereditary thrombophilia / Pré-eclâmpsia e trombofilia hereditária

Resumen: Los trastornos hipertensivos del embarazo constituyen una de las principales causas de mortalidad materna y perinatal en todo el mundo. Se ha estimado que la pre-eclampsia complica del 2 al 8% de los embarazos a nivel mundial. Se han asociado múltiples factores de riesgo: antecedentes de pre-eclampsia, hipertensión arterial crónica, diabetes pre-gestacional, gestación múltiple, enfermedad renal crónica y algunas enfermedades autoinmunes (como el síndrome antifosfolípidico y el lupus eritematoso sistémico). Se realiza una revisión sobre las medidas generales de prevención de la pre-eclampsia.

Abstract: Hypertensive disorders of pregnancy are one of the leading causes of maternal and perinatal mortality worldwide. Pre-eclampsia has been estimated to complicate 2-8% of pregnancies worldwide. Multiple risk factors have been associated: history of pre-eclampsia, chronic arterial hypertension, pre-gestational diabetes, multiple gestation, chronic kidney disease, and some autoimmune diseases (such as antiphospholipid syndrome and systemic lupus erythematosus). A review is carried out on the general measures of prevention of pre-eclampsia.

Resumo: Os distúrbios hipertensivos da gravidez são uma das principais causas de mortalidade materna e perinatal em todo o mundo. Estima-se que a pré-eclâmpsia complique de 2 a 8% das gestações em todo o mundo. Múltiplos fatores de risco têm sido associados: história de pré-eclâmpsia, hipertensão arterial crônica, diabetes pré-gestacional, gestação múltipla, doença renal crônica e algumas doenças autoimunes (como síndrome antifosfolípide e lúpus eritematoso sistêmico). É realizada uma revisão das medidas gerais de prevenção da pré-eclâmpsia.

Abruptio placentae y trombofilia hereditaria / Abruptio placentae and hereditary thrombophilia / Abruptio placentae e trombofilia hereditária

Resumen: El abruptio placentae o desprendimiento prematuro de placenta normoinserta se define como el desprendimiento parcial o completo de la placenta normalmente implantada que ocurre antes del parto en embarazos mayores a 20 semanas. Entidad de elevada morbimortalidad (75%). La pato-fisiología es multifactorial, disminución de la invasión trofoblástica de las arterias espirales, disfunción endotelial y activación anormal de la coagulación a nivel de la interface materno-fetal. Es controversial si la trombofilia hereditaria contribuye a este proceso y de ser así como lo haría. Se realiza una revisión del tema con recomendaciones de estudio y tratamiento en pacientes que tienen esta patología.

Abstract: Abruptio placentae or premature detachment of the normoinserted placenta is defined as partial or complete detachment of the normally implanted placenta that occurs before delivery in pregnancies greater than 20 weeks. Entity with high morbidity and mortality (75%). The pathophysiology is multifactorial, decreased trophoblastic invasion of the spiral arteries, endothelial dysfunction and abnormal activation of coagulation at the level of the maternal-fetal interface. It is controversial whether and if hereditary thrombophilia contributes to this process. A review of the subject is carried out with study and treatment recommendations in patients who have this pathology.

Resumo: O descolamento da placenta ou descolamento prematuro da placenta normoinserida é definido como o descolamento parcial ou completo da placenta normalmente implantada que ocorre antes do parto em gestações com mais de 20 semanas. Entidade com alta morbimortalidade (75%). A fisiopatologia é multifatorial, diminuição da invasão trofoblástica das artérias espirais, disfunção endotelial e ativação anormal da coagulação ao nível da interface materno-fetal. É controverso se e se a trombofilia hereditária contribui para esse processo. É feita uma revisão do assunto com recomendações de estudo e tratamento em pacientes portadores dessa patologia.

Secondary Thromboprophylaxis in Hereditary Thrombophilia

Aims: The aim of this study is to show how the coagulation laboratory and clinical findings worked together in the management of a patient with hereditary thrombophilia and pulmonary embolism (PE) in terms of diagnosis, the choice of anticoagulation treatment and the duration of secondary thromboprophylaxis. Study Design: A case report with the presentation of clinical and laboratory findings, treatment and long-term follow up of the patient. Place and Duration of Study: Institute of Transfusion Medicine and University Clinics of Cardiology, St Cyril and Methodius University, Skopje, Macedonia in the period from February 2015 and December 2017. Case Presentation: Computer tomography confirmed the diagnosis of PE in a 32-year-old man who was admitted to the cardiology emergency department with D-dimer level of 5980 ng/mL after an episode of syncope. After the initial anticoagulation with unfractionated heparin 30.000i.e./24 h, enoxaparin 80 mg/12 h and acenocoumarol were introduced. The therapeutic INR rang could not be achieved so the acenocoumarol was switched to rivaroxaban 2x15 mg/day. One year later the anticoagulation with rivaroxaban 20 mg/day was discontinued. Thrombophilia testing included: prothrombin (PTB), Factor V Leiden and methylene tetrahydrofolate reductase (MTHFR) C677T gene mutation, as well as antiphospholipid antibodies, antithrombin, protein C and S. Results: The patient was homozygous for the PTB. His parents were heterozygous for the same mutation; his mother also being heterozygous for MTHFR C677T. His brother was compound heterozygote for PTB and MTHFR C677T and his sister was heterozygous for the PTB. Coagulation status monitoring showed hypercoagulability (APTT was 24-26 seconds) and increment of D-dimer (2100-2400 ng/ml) when rivaroxaban was discontinued and normal APTT (28-38 seconds) and D-dimer (< 500 ng/mL) when it was reintroduced. Conclusion: According to the laboratory findings and also having in mind that this was a second episode of a thrombotic event, we decided for an extended secondary thromboprophylaxis. Although it sometimes implies that it will be continued life-long we consider worthwhile to apply the patient-oriented approach to the decision when and whether to terminate anticoagulation.

A Case of Pediatric Unprovoked Deep Vein Thrombosis due to Combined Hereditary Thrombophilia of Antithrombin III and Protein S Deficiency / 임상소아혈액종양

Unprovoked deep vein thrombosis (DVT) is uncommon in pediatric patients and, among those, combined hereditary thrombophilia is particularly rare. We present a 9-year-old Korean boy who developed lower extremity pain with swelling, and was diagnosed with unprovoked DVT due to hereditary (combined hereditary thrombophilia). Coagulation test revealed antithrombin III and protein S deficiency. The genetic work up confirmed the first case of combined antithrombin III deficiency and protein S deficiency by SERPINC1 heterozygous termination mutation [c.685C>T (p.Arg229*)] and PROS1 heterozygous missense mutation [c.1597G>A (p.Val533Met)]. He was treated with continuous heparin and catheter intervention but those were ineffective or transiently effective. His DVT gradually improved only after prolonged anticoagulation.

The clinical value of the detection of obstetrical thrombophilia in the diagnosis of recurrent spontaneous abortion / 中华检验医学杂志

The obstetrical thrombophilia will lead to the dysfunction of coagulation and fibrinolysis system, which increases the risk of thrombosis in parturient women.It can even cause pregnancy complications, such as abortion, premature birth, placental abruption.The relationship between thrombophilia and recurrent spontaneous abortion, and the significance of some relevant detection of obstetrical thrombophilia in the diagnosis of recurrent spontaneous abortion(RSA)are reviewed in the study.

Systematic review: hereditary thrombophilia associated to pediatric strokes and cerebral palsy / Revisão sistemática: trombofilias hereditárias associadas aos acidentes vasculares cerebrais pediátricos e a paralisia cerebral

OBJECTIVES: This review aimed to organize and consolidate the latest knowledge about mutations and genetic polymorphisms related to hereditary thrombophilia and their potential association with pediatric stroke and cerebral palsy (CP). SOURCES: Scientific articles published from 1993 to 2013, written in Portuguese, English, French, and Spanish, were selected and reviewed. The publications were searched in electronic databases, and also in the collections of local libraries. The terms "hereditary thrombophilia", "polymorphisms", "mutation", "pediatric strokes", and "cerebral palsy" were used for the research. SUMMARY OF THE FINDINGS: The search in databases and in the bibliographic references retrieved 75 articles for inclusion in this review. Studies that investigated hereditary thrombophilias and their associations to CP and arterial and venous pediatric stroke presented contradictory results. The meta-analysis and case-control studies that showed positive results for this association described only slightly increased relative risks and sometimes had questionable conclusions. The association of two or more hereditary thrombophilias, or the association between thrombophilia and other specific clinical risk factors, suggest a higher risk of CP and pediatric stroke than isolated hereditary thrombophilia. CONCLUSIONS: Larger, multicenter studies should be developed in order to elucidate the role of mutations leading to hereditary thrombophilia and the development of CP and pediatric stroke. The complex and multifactorial etiology of CP and stroke makes this an arduous and difficult task; however, the benefits generated by these studies are immeasurable. .

OBJETIVO: Sistematizar e integrar os últimos conhecimentos sobre mutações e polimorfismos genéticos relacionados às trombofilias hereditárias e suas potenciais associações com acidentes vasculares cerebrais pediátricos (AVC) e paralisia cerebral (PC). MATERIAL: Artigos científicos publicados de 1993 a 2013, escritos em português, inglês, francês e espanhol foram selecionados e revisados. As publicações foram pesquisadas nas bases de dados eletrônicas, como também nos acervos das bibliotecas locais. Os termos mutação, polimorfismos, trombofilias hereditárias, acidentes vasculares cerebrais pediátricos e paralisia cerebral foram usados para a pesquisa. RESULTADOS: A pesquisa nas bases de dados e nas referências bibliográficas identificou 75 artigos para inclusão nesta revisão. Os estudos que investigaram as trombofilias hereditárias e suas associações à PC e aos AVC pediátricos arteriais e venosos apresentaram resultados contraditórios. As metanálises e os estudos caso-controle que demonstraram resultados positivos para essa associação descreveram riscos relativos discretamente aumentados e, algumas vezes, questionáveis. A associação de duas ou mais trombofilias hereditárias, ou a junção de trombofilias específicas com demais fatores de riscos clínicos, sugerem maior risco no aparecimento da PC e do AVC pediátrico do que as trombofilias hereditárias isoladas. CONCLUSÃO: Estudos multicêntricos de grande porte devem ser conduzidos para elucidar o papel real das mutações que levam às trombofilias hereditárias e ao aparecimento da PC e AVC pediátricos. A etiologia multifatorial e complexa da PC e dos AVC torna essa tarefa árdua e difícil, porém, os benefícios gerados por esses estudos são incalculáveis. .

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.