Isquemia intestinal, una manifestación inusual de la embolia paradójica. Un reporte de caso / Intestinal ischaemia as a rare manifestation of a paradoxical embolism. A case report

Introducción. La embolia paradójica es un evento trombótico originado en la circulación venosa, que se manifiesta como embolismo arterial por medio de un defecto anatómico a nivel cardíaco o pulmonar. Se asocia principalmente a eventos cerebrovasculares, aunque se han encontrado casos de infarto agudo de miocardio, infarto renal y otros eventos isquémicos. Caso clínico. Paciente de 47 años, quien consultó por cuadro de dolor abdominal, que requirió manejo quirúrgico de urgencia, donde identificaron isquemia intestinal importante. Los estudios adicionales hallaron déficit de proteína S y persistencia de foramen oval permeable. Resultados. La presencia de trombosis arterial se conoce como trombosis de sitios inusuales y requiere de estudios para descartar trombofilias asociadas u otros estados protrombóticos. El déficit de proteína S es una trombofilia infrecuente, la cual se asocia en la vida adulta a eventos trombóticos de origen venoso. En presencia de defectos anatómicos, como un foramen oval permeable, puede progresar a embolia arterial, configurando un cuadro de embolismo paradójico. La estratificación de estos pacientes requiere imágenes que demuestran el defecto mencionado, así como el posible origen de los émbolos. El manejo se basa en anticoagulación plena, manejo de soporte, resolver las manifestaciones trombóticas existentes y un cierre temprano del defecto anatómico. Conclusiones. El embolismo paradójico debe sospecharse en caso de trombosis de sitios inusuales. Requiere de un estudio exhaustivo con imágenes y su manejo debe basarse en anticoagulación y cierre del defecto.

Introduction. Paradoxical embolism is a thrombotic event originating in the venous circulation, which manifests as arterial embolism through an anatomical cardiac or pulmonary defect. It is mainly associated with stroke, also presenting as acute myocardial infarction, renal infarction, and other ischemic events. Clinical case. A 47-year-old patient was admitted due to abdominal pain, which required emergency surgical management, finding significant intestinal ischemia. Additional studies found protein S deficiency and evidence of a patent foramen ovale. Discussion. Arterial thrombosis is known as unusual thrombosis; this situation requires to rule out associated thrombophilia or other prothrombotic diseases. Protein S deficiency is a rare thrombophilia, which in adults causes venous thrombosis. In the presence of anatomical defects, such as a patent foramen ovale, it can progress to arterial embolism, presenting a picture of paradoxical embolism. The study work of these patients requires imaging that demonstrates the aforementioned defect, as well as the possible origin of the emboli. Management is based on full anticoagulation, treatment of existing thrombotic manifestations, and management of the anatomical defect. Conclusions. Paradoxical embolism should be suspected in case of unusual thrombosis. It requires exhaustive studies based on imaging, and management should consist of anticoagulation and closure of the defect.

Screening for the etiology of non-cirrhotic splanchnic vein thrombosis should be taken seriously in clinical practice / 临床肝胆病杂志

Non-cirrhotic splanchnic vein thrombosis （NC-SVT） mainly includes portal vein thrombosis， superior mesenteric vein thrombosis， splenic vein thrombosis， and hepatic vein thrombosis （Budd-Chiari syndrome）， and its prevalence rate is increasing with the increase in the incidence rates of related underlying diseases. Due to the harm of NC-SVT， there have been significant improvements in the awareness and ability for diagnosis among clinicians. However， anticoagulation and intervention therapies for thrombosis are often taken seriously in treatment， while the screening for risk factors or underlying diseases leading to SVT is ignored， which may affect the treatment outcome of thrombus in some patients and delay the diagnosis and treatment of the underlying disease. This article mainly introduces the acquired， hereditary， systemic， and local underlying diseases associated with the development of NC-SVT.

Predictive value of uterine artery blood flow parameters of Doppler ultrasound combined with coagulation related indicators on the pregnancy outcome of recurrent abortion caused by thrombophilia / 中国医学装备

Objective:To explore the predictive value of uterine artery blood flow parameters of Doppler ultrasound combined with coagulation related indicators on the pregnancy outcome of recurrent abortion caused by thrombophilia.Methods:A total of 82 patients with recurrent abortion who admitted to the department of gynecology outpatient of Beijing Haidian Hospital from January 2020 to January 2023 were selected.All patients received relevant treatment,and the follow-up results were calculated as statistic method.Before treatment on the day after admission,uterine artery pulse index(PI),resistance index(RI),the ratio of the maximum blood flow velocity of systolic pressure(S)to the maximum blood flow velocity of end-diastolic(D)(S/D),and activated partial thromboplastin time(APTT),prothrombin time(PT),fibrinogen(FIB),thrombin time(TT)and D-dimer(D-D)of all patients were detected.Pearson correlation analysis was adopted to analyze the correlations between PI,RI,S/D and each of APTT,PT,FIB,TT and D-D.Receiver operating characteristic(ROC)curve was used to analyze the values of single PI,RI,S/D,APTT,PT,FIB,TT and D-D,and the value of the combined detection of them in predicting the pregnancy outcome of recurrent abortion caused by thrombophilia.Results:Follow up results showed that 49 cases of 82 patients with recurrent abortion were successful pregnancy and 33 cases of them occurred pregnancy loss,and the PI,RI and S/D of pregnant women with successful pregnancy were significantly lower than those of pregnant women who occurred pregnancy loss,with statistical significance(t=10.598,6.693,3.059,P<0.05).The levels of APTT,PT,FIB,TT and D-D of pregnant women with successful pregnancy were significantly lower than those of pregnant women who occurred pregnancy loss,and the differences were statistically significant(t=9.552,96.462,22.767,5.100,95.805,P<0.05),respectively.PI appeared respectively positive correlation with APTT,PT,FIB,TT and D-D(r=3.178,P<0.05),and RI appeared respectively positive correlation with APTT,PT,FIB and D-D(r=3.246,P<0.05),and S/D also appeared respectively positive correlation with PT,FIB,TT and D-D(r=3.246,P<0.05).The sensitivities of single PI,RI,S/D,APTT,PT,FIB,TT and D-D detection,and the combined detection of them were respectively 42.40%,48.50%,39.40%,48.50%,63.60%,72.70%,42.40%,39.40%and 84.80%in predicting the pregnancy outcome of recurrent abortion caused by thrombophilia.The specificities of them were respectively 98.00%,71.40%,55.10%,75.50%,59.20%,71.40%,77.60%,85.70%and 98.80%,and the AUC values of them were respectively 0.674,0.685,0.409,0.646,0.784,0.788,0.566,0.563 and 0.941.Conclusion:Both single and combination of PI,RI and S/D of uterine artery blood flow parameters,as well as APTT,PT,FIB,TT and D-D of coagulation related indicators,have a certain value in predicting pregnancy outcome of recurrent abortion caused by thrombophilia,and the combined detection has higher predictive value.

Estudio de las trombofilias por el laboratorio clínico

La trombofilia se define como una predisposición individual a padecer episodios tromboembólicos. Debido a la elevada y creciente incidencia tanto mundial como en Cuba de eventos cardiovasculares, cerebrovasculares y vasculares periféricos, cuya patogenia involucra la trombofilia, se hace necesaria una actualización de la utilidad de las pruebas de laboratorio clínico para su estudio. Esta revisión tiene como objetivo actualizar la información sobre la indicación e interpretación de los exámenes de laboratorio clínico útiles en el estudio de las trombofilias. Se realizaron búsquedas en las bases de datos PubMed, SciELO, LILACS y ClinicalKey, con las palabras clave "trombofilia" y "laboratorio clínico", en inglés y español. La búsqueda reveló 120 artículos, de los cuales 27 fueron novedosos y relevantes para el tema. Se debe investigar el estado trombofílico en cualquier paciente que presente trombosis venosa antes de los 45 años -recurrente o en sitios inusuales-, trombosis neonatal inexplicable, necrosis cutánea por cumarínicos, resistencia a anticoagulantes, trombosis arterial antes de los 30 años, historia familiar trombofílica, pérdida recurrente de embarazos, púrpura trombocitopénica trombótica o lupus eritematoso sistémico. Las investigaciones iniciales serán: hemograma completo, observación de extensión coloreada de sangre periférica y tiempo parcial de tromboplastina activada. Los exámenes más específicos incluirán el estudio genético del factor V Leiden, ensayos para detectar déficits de antitrombina, proteína C o proteína S; análisis del ADN para el alelo G20210A de la protrombina, determinación del factor VIII y de homocisteína, y detección de anticoagulante lúpico, anticuerpos anti-β2-glicoproteína I y anticardiolipina.

Thrombophilia is defined as an individual predisposition to suffer thromboembolic episodes. Due to high and growing incidence both worldwide and in Cuba of cardiovascular, cerebrovascular and peripheral vascular events whose pathogenesis involves thrombophilia, it becomes necessary an update of the usefulness of clinical laboratory tests used for their study. The review aims to update information on indication and interpretation of clinical laboratory tests useful in the study of thrombophilia. Searches were carried out in the databases PubMed, SciELO, LILACS and ClinicalKey with key words thrombophilia and clinical laboratory, in English and Spanish, the search reveled 120 articles, of which 27 were novel and relevant to the topic. Thrombophilic status should be investigated in any patient who presents venous thrombosis before the age of 45-recurrent or in unusual sites-unexplained neonatal thrombosis, coumarin skin necrosis, resistance to anticoagulant, arterial thrombosis before the age of 30, thrombophilic familiar history, recurrent pregnancy loss, thrombotic thrombocytopenic purpura or systemic lupus erythematosus. Initial tests should be: complete blood count, observation of colored smear of peripheral blood, and activated partial of thromboplastin time. More specific tests will include the genetic study of factor V Leiden, tests to detect antithrombin, protein C or protein S deficiencies; DNA analysis for the G20210A allele of prothrombin, factor VIII and homocysteine measurement, and detection of lupus anticoagulant, anti-β2-glycoprotein I and anticardiolipin antibodies.

Evaluación de parámetros inflamatorios, trombóticos y variantes genéticas en pacientes con ataque cerebrovascular isquémico que se asisten en un hospital de Uruguay

Introducción: El ataque cerebrovascular es la segunda causa de muerte en adultos en el mundo occidental y una de las principales causas de discapacidad permanente, aumentando su frecuencia con la edad, el 85 % es de tipo isquémico. Objetivos: Analizar parámetros trombofílicos, hipofibrinolíticos y genéticos en pacientes con ataque cerebrovascular isquémico y evaluar la posible asociación de estos con factores de riesgo cardiovascular. Metodología: Se utilizó un cuestionario para evaluar la presencia de factores de riesgo cardiovascular en 114 pacientes incluidos en el estudio con diagnóstico de ataque cerebrovascular isquémico. Proteína C y antitrombina fueron determinados mediante métodos cromogénicos, resistencia a la proteína C activada e inhibidor lúpico mediante métodos coagulométricos y proteína S libre, inhibidor del activador del plasminógeno-1, homocisteína y lipoproteína (a) por métodos inmunoquímicos. Fibrinógeno fue determinado por coagulometría y proteína C reactiva por inmunoturbidimetría, ambos contra un grupo control. Las variantes genéticas factor V Leiden, protrombina G20210A, rs1205 (gen PCR), rs1800779 (gen NOS3) y rs2257073 (gen ASB10) fueron analizadas mediante real-time PCR, comparando los últimos tres con una población de referencia. La alteración de las frecuencias de las variables fue determinada por análisis estadístico chi-cuadrado. Resultados: Tres de los cuatro pacientes jóvenes estudiados presentaron indicadores de trombofilia. El resto de los parámetros alterados fueron homocisteína 30.1% (22.4-39.1), lipoproteína (a) 32.1% (24.1-41.4), inhibidor del activador del plasminógeno-1 36.0% (27.8-45.1), fibrinógeno 12.3% (7.5-19.6) y proteína C reactiva 78.1% (69.6-84.7). Se encontró asociación (p < 0.05) entre ciertos factores de riesgo cardiovascular y los parámetros evaluados como hipertensión/proteína C reactiva, dislipemia/lipoproteína (a), arritmia/lipoproteína (a) y arritmia/fibrinógeno. Para pacientes con ataque cerebrovascular isquémico solo la variante rs1205 mostró una frecuencia más alta del alelo T. Conclusiones: Este estudio revela la importancia de analizar la trombofilia en pacientes jóvenes, especialmente en aquellos sin factores de riesgo cardiovascular, así como el rol de la hipofibrinolisis, inflamación y algunas variantes genéticas en el desarrollo de ataque cerebro vascular isquémico.

Introduction: Stroke is the second cause of death in adults in the Western world and one of the main causes of permanent disability, increasing in frequency with age; 85% are ischemic. Objectives: To analyze thrombophilic, hypofibrinolytic, inflammatory, and genetic parameters in patients with ischemic stroke and evaluate possible associations with vascular risk factors. Methodology: Questionnaires were used to evaluate vascular risk factors in 114 patients included in the study with ischemic stroke diagnosis. Protein C and Antithrombin were determined by chromogenic assays, Activated Protein C Resistance and Lupus Anticoagulant were determined with by coagulometry and Free Protein S, Plasminogen activator inhibitor-1, Homocysteine and Lipoprotein (a) by immunochemistry. Fibrinogen was assayed by coagulometry and C-reactive protein by immunoturbidimetry, both against a control group. Factor V Leiden, Prothrombin G20210A, rs1205 (CRP gene), rs1800779 (NOS3 gene) and rs2257073 (ASB10 gene) genetic variants were analyzed by Real-Time PCR, comparing the last three with a reference population. Alteration frequencies of the variables were determined by chi-square statistical analysis. Results: Three out of four of the young patients studied presented indicators of thrombophilia. The rest of the altered parameters were Homocysteine 30.1% (22.4-39.1), Lipoprotein (a) 32.1% (24.1-41.4), Plasminogen activator inhibitor-1 36.0% (27.8-45.1), Fibrinogen 12.3% (7.5-19.6) and C-reactive protein 78.1% (69.6-84.7). Associations were found (p<0.05) between certain vascular risk factors and parameters evaluated, namely hypertension/C-reactive protein, dyslipidemia/lipoprotein (a), arrhythmia/lipoprotein (a) and arrhythmia/fibrinogen. For ischemic stroke patients only the genetic variant rs1205 showed higher frequency of the T allele. Conclusions: This study reveals the importance of analyzing thrombophilia in young patients, especially those without vascular risk factors, as well as the role of hypofibrinolysis, inflammation and some genetic variants in the development of ischemic stroke.

Introdução: O AVC é a segunda causa de morte em adultos no mundo ocidental e uma das principais causas de incapacidade permanente, aumentando de frequência com a idade; 85% são isquémicos. Metas: Analisar os parâmetros trombofílicos, hipofibrinolíticos e genéticos em pacientes com acidente vascular cerebral isquêmico e avaliar a possível associação com fatores de risco cardiovascular. Metodologia: Um questionário foi utilizado para avaliar a presença de fatores de risco cardiovascular em 114 pacientes incluídos no estudo com diagnóstico de acidente vascular cerebral isquêmico. Proteína C e antitrombina foram determinadas por métodos cromogênicos, resistência à proteína C ativada e inibidor de lúpus por métodos coagulométricos e proteína S livre, inibidor do ativador do plasminogênio-1, homocisteína e lipoproteína (a) por métodos imunoquímicos. O fibrinogênio foi determinado por coagulometria e a proteína C-reativa por imunoturbidimetria, ambos contra um grupo controle. As variantes genéticas fator V Leiden, protrombina G20210A, rs1205 (gene PCR), rs1800779 (gene NOS3) e rs2257073 (gene ASB10) foram analisadas por PCR em tempo real, comparando as três últimas com uma população de referência. As frequências de alteração das variáveis ​​foram determinadas pela análise estatística qui-quadrado. Resultados: Três dos quatro pacientes jovens estudados apresentaram indicadores de trombofilia. O resto dos parâmetros alterados foram homocisteína 30,1% (22,4-39,1), lipoproteína (a) 32,1% (24,1-41,4), inibidor do ativador de plasminogênio-1 36,0% (27,8-45,1), fibrinogênio 12,3% (7,5-19,6) e proteína C reativa 78,1% (69,6-84,7). Foi encontrada associação (p<0,05) entre alguns fatores de risco cardiovascular e os parâmetros avaliados como hipertensão/proteína C reativa, dislipidemia/lipoproteína (a), arritmia/lipoproteína (a) e arritmia/fibrinogênio. Para pacientes com acidente vascular cerebral isquêmico apenas a variante rs1205 apresentou maior frequência do alelo T. Conclusões: Este estudo revela a importância de analisar a trombofilia em pacientes jovens, especialmente aqueles sem fatores de risco cardiovascular, bem como o papel da hipofibrinólise, inflamação e algumas variantes genéticas no desenvolvimento do acidente vascular cerebral isquêmico.

ACV isquémico en población joven: ¿existe un enfoque diferencial del riesgo? / Ischemic stroke in a young population: is there a differential approach to risk factors?

Introducción: El ataque cerebrovascular isquémico en el adulto joven se define como aquel que ocurre en la población entre los 18 y los 55 años, y representa el 15-18 % de todos los ACV isquémicos. Los factores de riesgo en jóvenes son comunes a los encontrados en adultos mayores. El objetivo de este trabajo es describir las características clínicas y los factores de riesgo de una población menor de 55 años con ACV isquémico atendida en un centro de referencia hospitalario en Colombia. Materiales y métodos: Estudio descriptivo, retrospectivo de corte transversal en pacientes entre los 18 y los 55 años; se incluyeron 100 pacientes sobrevivientes a un primer ACV isquémico agudo confirmado por neuroimagen, atendidos entre enero de del 2019 y noviembre del 2021. Resultados: De 1023 pacientes con diagnóstico de ACV isquémico agudo, el 9,8 % fueron adultos jóvenes. La media de edad fue de 45 ± 8,7 años, y el 59 % de estos pacientes fueron hombres. Discusión: Los factores de riesgo "tradicionales" se presentan en la mayoría de los jóvenes con ACV isquémico. La hipertensión arterial se mantiene como el antecedente más frecuente. Las mujeres presentan eventos de mayor severidad y peor desenlace funcional. Conclusión: Los pacientes mayores de 45 años tienen un perfil de factores de riesgo similar a lo observado en adultos mayores con ACV, mientras que en los menores de 45 años se encuentra un perfil de factores de riesgo diferente que plantea un diagnóstico etiológico particular de esta población.

Introduction: Ischemic stroke in young adults is defined as occurring in individuals between the ages of 18 and 55, representing 15-18 % of all ischemic strokes. Risk factors in young adults are similar to those found in older adults. The objective of this study is to describe the clinical characteristics and risk factors of a population under 55 years of age with ischemic stroke treated at a hospital reference center in Colombia. Materials and methods: Descriptive, retrospective cross-sectional study in patients between 18 and 55 years old. A total of 100 patients between 18 and 55 years old who survived a first confirmed acute ischemic stroke, as confirmed by neuroimaging, were included. The study period was from January 2019 to November 2021. Results: Out of 1023 patients diagnosed with acute ischemic stroke, 9.8 % occurred in young adults. The mean age was 45 ± 8.7 years, of which 59 % were male. Discussion: "Traditional" risk factors are present in the majority of young adults with ischemic stroke. Hypertension remains the most common antecedent. Women experience more severe events and worse functional outcomes. Conclusion: Patients over 45 years old have a risk factor profile similar to what is observed in older adults with stroke, while in those under 45, a different risk factor profile is found, which poses a particular etio-logical diagnosis for this population.

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.

Complicaciones hemorrágicas y trombóticas del embarazo: diagnóstico, prevención y tratamiento

Las hemorragias y la enfermedad tromboembólica venosa (ETEV) figuran entre las cinco causas más frecuentes de morbilidad y mortalidad materna en el mundo. Revisamos la evaluación y el manejo actualizado de las causas obstétricas de la hemorragia posparto (HPP), así como el diagnóstico y manejo de condiciones hematológicas que pueden causar o agravar la HPP, por ejemplo: coagulación intravascular diseminada, enfermedad de von Willebrand, trombocitopenia autoinmune y las microangiopatías trombóticas. Revisamos el rol del síndrome antifosfolípido y las trombofilias hereditarias como factores predisponentes a pérdidas fetales recurrentes y la ETEV en el embarazo y las recomendaciones actuales para la prevención de ambas complicaciones. Asimismo, repasamos el abordaje diagnóstico y líneas de manejo de la ETEV. Un objetivo adicional fue enfatizar la importancia del trabajo colaborativo multidisciplinario para lograr el manejo exitoso de las gestantes con las complicaciones obstétricas y hematológicas descritas.

Bleeding and venous thromboembolism (VTE) are among the five most common causes of morbidity and mortality in pregnant women worldwide. This review describes the current evaluation and management of the obstetric causes of postpartum hemorrhage (PPH), as well as the diagnosis and management of hematologic conditions which can cause or worsen PPH, such as disseminated intravascular coagulation, von Willebrand disease, autoimmune thrombocytopenia and the thrombotic microangiopathies. It also describes the role of the antiphospholipid syndrome and inherited thrombophilia as predisposing factors for recurrent pregnancy loses and VTE, and the current recommendations for the prevention of both complications. As well, the current diagnostic approach and management of ETEV are described. An additional objective of this Review is to emphasize the importance of a collaborative multidisciplinary approach for the successful management of the obstetric and hematologic complications herein described.

Hereditary thrombophilia and low -molecular -weight heparin in women: useful determinants, including thyroid dysfunction, incorporating the management of treatment and outcomes of the entity

SUMMARY OBJECTIVE: Our study purposed to examine the complex relationship between low-molecular-weight heparin therapy, multiple pregnancy determinants, and adverse pregnancy outcomes during the third trimester in women with inherited thrombophilia. METHODS: Patients were selected from a prospective cohort of 358 pregnant patients recruited between 2016 and 2018 at the Clinic for Obstetrics and Gynecology, University Clinical Centre of Serbia, Belgrade. RESULTS: Gestational age at delivery (β=-0.081, p=0.014), resistance index of the umbilical artery (β=0.601, p=0.039), and D-dimer (β=0.245, p<0.001) between 36th and 38th weeks of gestation presented the direct predictors for adverse pregnancy outcomes. The model fit was examined using the root mean square error of approximation 0.00 (95%CI 0.00-0.18), the goodness-of-fit index was 0.998, and the adjusted goodness-of-fit index was 0.966. CONCLUSION: There is a need for the introduction of more precise protocols for the assessment of hereditary thrombophilias and the need for the introduction of low-molecular-weight heparin.

Diagnostic thought of pediatric thrombophilia / 中国小儿急救医学

Thrombophilia is not a specific disease, but a disease state that is prone to thromboembolism due to hereditary or acquired factors.The incidence and mortality of venous thromboembolism in children caused by thrombophilia are increasing year by year.Timely identification of the symptoms and signs of thromboembolic diseases, familiarity with and mastering the etiology, diagnosis and screening indications of thrombophilia are of great significance for timely diagnosis, treatment, prevention and improvement of prognosis of thromboembolic diseases in children.

Inherited protein C deficiency in pregnancy: a case report / 中华围产医学杂志

This paper reported the management of a pregnant women with inherited protein C deficiency. The patient had a history of recurrent deep vein thrombosis before pregnancy and was diagnosed with inherited protein C deficiency by a pedigree-based whole exome sequencing, which revealed PROC gene mutations. She received anticoagulation treatment and was managed by a multidisciplinary team during pregnancy. No significant abnormalities were found during routine prenatal examination and a male infant was delivered vaginally at 38 +2 gestational weeks. No postpartum hemorrhage was reported and the maternal and infant outcomes were good. The management of such patients during pregnancy mainly relied on anticoagulation therapy to avoid serious thrombotic events and ensure the safety of the mothers and fetuses.

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.

Paciente joven con accidente cerebrovascular isquémico: ¿Se debe buscar una trombofilia? / Ischemic stroke in a young patient, is it needed to look for a thrombophilia?

Resumen El accidente cerebrovascular isquémico es un evento de gran importancia debido a las implicaciones y el impacto en la calidad de vida de la población afectada. Su incidencia es más alta en adultos mayores y en personas con factores de riesgo cardiovascular. Existe un grupo de pacientes jóvenes (18-44 años) sin factores de riesgo que presentan dicho evento, por lo que, en la práctica clínica, se tiende a evaluar rutinariamente las trombofilias hereditarias y adquiridas como factor etiológico principal para los eventos isquémicos en este grupo etario. No obstante, son pocos los casos donde se documenta algún trastorno de este tipo, ya que es más frecuente la presencia de otras etiologías como el cardioembolismo y trastornos vasculares. La evaluación de las trombofilias es compleja, dado el alto costo, las limitaciones técnicas para hacerlo y el impacto clínico y terapéutico incierto al documentarse estos estados. Se realiza esta revisión de tema con el fin de orientar al clínico acerca de la pertinencia de objetivar estas condiciones en el paciente joven con accidente cerebrovascular isquémico.

Abstract Acute ischemic stroke is a pathology of great complexity due to the implications and impact on the quality of life of the affected population. The incidence of this pathology is higher in older adults and in people with cardiovascular risk factors. There is a group of young patients with no risk factors who present these events. Therefore, in clinical practice, hereditary thrombophilias tend to be frequently evaluated as the main etiological factor for this age group. However, there are few cases where a disorder of this type is documented and the presence of other etiologies such as cardioembolism and vascular disorders are more frequent. Thus, the evaluation of thrombophilia is complex due to its high cost, technical limitations when evaluating, and its uncertain clinical and therapeutic impact when documented. For this reason, this review is carried out in order to guide the clinician about the relevance of objectifying these conditions in young patient with acute ischemic stroke

Splanchnic vein thrombosis as a manifestation of latent myeloproliferative neoplasm associated with sticky platelet syndrome / Trombosis esplácnica como presentación de neoplasia mieloproliferativa latente asociada con síndrome de plaqueta pegajosa

Abstract Vein thrombosis of unusual sites such as the splanchnic region continues to be not only a diagnostic but also a therapeutic challenge for the clinician due to its manifestation and associated pathologies. Latent JAK2 (Janus kinase 2) positive myeloproliferative neoplasm associated with sticky platelet syndrome is unusual. We present a clinical case of a 38-year-old female patient who presented with sudden onset abdominal pain of a possible vascular origin. Splanchnic thrombosis was diagnosed in latent myeloproliferative neoplasm by identifying the JAK2V617F mutation and sticky platelet syndrome via platelet aggregometry. Off-label anticoagulation with rivaroxaban 20 mg/day was administered. During her outpatient follow-up, she did not suffer any new thrombotic episodes.

Resumen La trombosis venosa de sitios inusuales como la esplácnica continúa siendo un reto no solo diagnóstico sino también terapéutico para el clínico debido a su forma de presentación y las patologías asociadas. La neoplasia mieloproliferativa latente JAK2 (cinasa de Janus 2) positiva asociada con síndrome de plaqueta pegajosa es inusual. Se presenta un caso clínico de una paciente de 38 años de edad que debutó con dolor abdominal de inicio súbito que sugirió un posible origen vascular. Se diagnosticó trombosis esplácnica en relación con neoplasia mieloproliferativa latente por la identificación de la mutación de la JAK2V617F y síndrome de plaqueta pegajosa mediante agregometría plaquetaria. Se administró de manera off-label anticoagulación con rivaroxabán 20 mg/día. Durante su seguimiento ambulatorio no ha presentado nuevos episodios trombóticos.

Detection of paroxysmal nocturnal haemoglobinuria clones in cases of deep vein thrombosis in a tertiary care centre, western Rajasthan

Background & objectives: Paroxysmal nocturnal haemoglobinuria is a rare acquired disease characterized by bone marrow failure, intravascular haemolysis and thrombophilia. Thrombosis is the deadliest complication of paroxysmal nocturnal haemoglobinuria (PNH). The present study was conducted to study the prevalence of PNH in cases of deep vein thrombosis (DVT) which was previously undocumented from western Rajasthan. Methods: In the present cross-sectional study, 61 adult patients with DVT were tested using flow cytometry to detect PNH clones. Blood samples were processed using fluorescein-labelled proaerolysin, CD14, CD24, CD33 and CD45 panels for granulocytes and monocytes and CD59 and CD235a panel for red blood cells. Results: Three cases (4.92%) having large clones on monocytes as well as granulocytes, which fulfilled the diagnostic criteria of PNH were detected. Further, three cases (4.92%) showed small clones on both granulocytes and monocytes. Nine (15%) cases showed small clones only on granulocytes, and 11 (18%) cases showed small clones only on monocytes. Interpretation & conclusions: The results of the present study suggest that a higher proportion of patients had PNH in western Rajasthan compared to previously reported studies from elsewhere. It is suggested that PNH testing should be added to the procoagulant work-up panel in institutions of this region where it is not routinely done. This provides an otherwise missed opportunity to diagnose this disorder. Eculizumab may be employed, which is effective in reducing thrombophilic events in cases of PNH

Clinical manifestations and genetic analysis of 5 cases with inherited thrombophilia / 中华实用儿科临床杂志

Objective:To analyze the clinical manifestations, genetic variations, diagnosis and treatment of children with inherited thrombophilia(IT).Methods:Retrospective study.Children with IT treated in Department of Respiratory Diseases 1 of Beijing Children′s Hospital, Capital Medical University from October 2016 to August 2021 were included in the study and followed up.Results:A total of 5 children met the inclusion criteria, with 3 boys and 2 girls; the age of diagnosis ranged from 7 years to 13 years and 6 months.There were 2 cases of protein C deficiency, 1 case of congenital protein S deficiency, 1 case of activated protein C resistance and 1 case of congenital afibrinogenemia.All 5 cases had pulmonary embolism, 2 cases had deep venous thrombosis of lower limbs, and 1 case had cardiac thrombosis and arterial embolism.The level of protein C was significantly decreased in 1 case, and the level of protein S in 1 case was significantly decreased in the laboratory test of thrombophilia; 2 cases were positive for antiphospholipid antibodies in the acute phase, but negative after 3-6 months of re-examination.Genetic analysis showed 2 cases of PROC gene mutation, 1 case of PROSI gene mutation, 1 case of F5 gene mutation, and 1 case of FGA gene mutation.All children were treated with anticoagulation drugs for long-term, including 4 patients with Warfarin and 1 patient with Rivaroxaban.The follow-up time ranged from 3 months to 5 years.During the follow-up, 1 patient experienced thrombosis recurrence due to infection incentives 1 month after discontinuing anticoagulant drugs on his own. Conclusions:The clinical manifestations of children with IT are the same as those of adults, mainly including venous thromboembolism(VTE); there are limitations in laboratory detection of thrombophilia, and gene analysis is of great significance.Children diagnosed with IT need long-term anticoagulant therapy to reduce the recurrence of VTE.

Analysis of current status of antithrombotic therapy in 136 patients with nonvalvular atrial fibrillation / 中国基层医药

Objective:To analyze the current status and effectiveness of different antithrombotic regimens in patients with non-valvular atrial fibrillation.Methods:The clinical data of 136 patients with non-valvular atrial fibrillation who received treatment in The Second People's Hospital of Yongkang from May 2018 to May 2019 were retrospectively analyzed. According to the treatment plan, they were divided into no antithrombosis group ( n = 32), rivaroxaban group ( n = 41), warfarin group ( n = 42), and aspirin group ( n = 21). Based on treatment of primary disease and complications, patients in the no antithrombosis group were not given anticoagulation or antiplatelet therapy, those in the rivarxaban group were given rivarxaban (10 mg/d), those in the warfarin group were given warfarin (2.5 mg/d), and those in the aspirin group were given aspirin (0.1 g/d). The incidence of thromboembolism and bleeding, all-cause mortality and readmission rate within 1 year were compared among groups. Results:There were significant differences in age, type of atrial fibrillation, coronary heart disease, heart failure, and hypertension among groups (all P < 0.05). There were no significant differences in sex, history of stroke/transient ischemic attack, and the percentage of patients developing diabetes mellitus and hyperlipidemia among groups (all P > 0.05). The incidence of thromboembolic events within 1 year in the no antithrombosis, rivaroxaban, warfarin, and aspirin groups were 21.87% (7/32), 7.32% (3/41), 2.38% (1/42), and 19.05% (4/21), respectively, and there were significant differences among groups ( χ2 = 8.98, P < 0.05). The 1-year incidence of bleeding events in the no antithrombosis, rivaroxaban, warfarin, and aspirin groups were 18.75% (6/32), 29.27% (12/41), 4.76% (2/42), 4.76% (61/21), respectively, and there were significant differences among groups ( χ2 =11.77, P < 0.05). There were no significant differences in the 1-year incidence of thromboembolism events and bleeding events among patients aged < 65 years, 65-75 years, and > 75 years (all P > 0.05), but there were significant difference in all-cause mortality and readmission rate ( χ2 = 6.76, 7.56, both P < 0.05). Conclusion:Early antithrombotic therapy is very important for patients with non valvular atrial fibrillation. The treatment regimens should be individualized, and the risk of death increases with age.

The 492nd case: recurrent thrombosis, thrombocytopenia / 中华内科杂志

A 43-year-old female patient was admitted with recurrent thrombosis for more than 2 years and thrombocytopenia for more than 1 year. Both arterial and venous thromboses developed especially at rare sites even during anticoagulation therapy such as cerebral venous sinus thrombosis. Antinuclear antibody, anti-ENA antibody and antiphospholipid antibody were all negative. Platelet count elevated to normal after high dose glucocorticoid and intravenous immunoglobulin (IVIG). Immune thrombocytopenia was suspected. When 4 grade thrombocytopenia recurred, intravenous heparin, rituximab 600 mg, IVIG and eltrombopag were administrated. After 3 weeks, thrombocytopenia did not improve, and new thrombosis developed instead. Screening of thrombophilia related genes revealed PROS1 gene heterozygous mutation and MTHFR TT genotype. Low amount of serum IgG κ monoclonal protein was detected. Heparin-induced thrombocytopenia was differentiated and excluded. Finally, serum negative antiphospholipid syndrome was considered the most likely diagnosis. Dexamethasone 20 mg/day × 4 days combined with sirolimus 2 mg/day was prescribed. The patient was discharged with low molecular weight heparin. At one month, her headache was greatly relieved. The platelet count raised to 20-30×10 9/L, and no new thrombosis or bleeding was reported.

Changes of coagulation function in patients with adenomyosis / 中华妇产科杂志

Objective:To explore the different coagulation state in patients with adenomyosis and its clinical significance.Methods:Clinical data of the patients admitted to the First Affiliated Hospital of Nanjing Medical University from January 2017 to December 2021 were retrospectively analyzed. (1) Differential coagulation state between 25 healthy women and 25 patients with adenomyosis were compared during menstrual and non-menstrual periods. (2) The coagulation indexes of 145 patients with adenomyosis (observation group 1) and 129 patients with cervical intraepithelial neoplasia grade Ⅲ (control group 1) who underwent hysterectomy in non-menstrual period were compared. (3) The coagulation indexes of 154 patients with adenomyosis (observation group 2) and 147 women without myometrial lesions (control group 2) who underwent endometrial curettage during uterine bleeding period were compared. (4) Correlations of coagulation index with cancer antigen 125 (CA 125), cancer antigen 19-9 (CA 19-9) and uterine volume in patients with adenomyosis were analyzed. Results:(1) The coagulation state of each health women during the menstrual and non-menstrual period showed no significant differences (all P>0.05). For the 25 patients with adenomyosis, fibrinogen [FIB; 2.61 g/L(2.50-3.10 g/L)] and D-dimer [0.60 mg/L (0.40-1.00 mg/L)] in the menstrual period were significantly higher than those in the non-menstrual period [2.25 g/L (1.90-2.70 g/L) and 0.27 mg/L (0.20-0.40 mg/L), respectively; both P<0.01], while thrombin time [TT; 16.70 s (16.10-17.40 s)] in the menstrual period was significantly lower than that in the non-menstrual period [17.95 s (17.20-18.40 s); P<0.01]. (2) In the non-bleeding period, D-dimer [0.26 mg/L (0.20-0.40 mg/L)] and platelet count [257.0×10 9/L (212.0×10 9/L-308.5×10 9/L)] of observation group 1 were significantly higher than those of control group 1 (all P<0.01). Besides, FIB ( r=0.237, P=0.004) and D-dimer ( r=0.373, P<0.001) were positively correlated with CA 125, while prothrombin time (PT; r=-0.208, P=0.012) and internationalized normalized ratio of plasma prothrombin time (PT-INR; r=-0.201, P=0.015) were negatively correlated with CA 19-9. (3) In the bleeding period, PT [10.70 s (10.10-11.20 s)] and PT-INR [0.93 (0.90-1.00)] of observation group 2 were significantly lower than those of control group 2 (all P<0.01), while D-dimer [0.41 mg/L (0.20-0.80 mg/L)] was significantly higher than that in the control group 2 ( P<0.001). Furthermore, FIB ( r=0.252, P=0.038) and D-dimer ( r=0.321, P=0.008) were positively correlated with uterine volume, while activated partial thromboplastin time (APTT; r=-0.190, P=0.018) and TT ( r=-0.304, P=0.012) were negatively correlated with uterine volume. (4) During non-menstrual period and uterine bleeding period, APTT and TT in patients of observation group 1 and 2 combined with anemia were significantly lower than those of non-anemia patients (all P<0.05). Conclusion:Patients with adenomyosis have a tendency to hypercoagulability in both the uterine bleeding and non-bleeding periods, which may be related to enlarged uterine volume, increased serum CA 125 and anemia.

Trombosis venosa profunda y trombofilia congénita / Deep-vein thrombosis and congenital thrombophilia

Introducción: La trombofilia es un desorden de la hemostasia congénito o adquirido que predispone al desarrollo de trombosis. Las trombofilias congénitas más frecuentes son las deficiencias de antitrombina III, proteína C y proteína S, el factor V Leiden, la mutación del gen de la protrombina (G20210A) y las mutaciones de la enzima metilentetrahidrofolato reductasa (MTHFR). Objetivo: Describir el manejo anestésico en un paciente portador de trombofilia congénita. Presentación del caso: Se reporta un paciente de 19 años de edad con antecedentes de historia familiar y personal de trombosis venosa profunda, tratamiento con doble antiagregación plaquetaria y asociación de tres mutaciones para trombofilia congénita, G20210A, A1298C MTHFR y C677T MTHFR que recibe anestesia espinal para una herniorrafia inguinal. Se mantiene tratamiento con aspirina, se suspende clopidogrel 7 días antes de la cirugía y durante ese tiempo se administra fraxiparina 0.6 Uds. subcutánea diarias hasta 12 h antes de la cirugía, se utiliza medias elásticas, deambulación precoz y reinicio de clopidogrel 24 h después de la cirugía, con evolución satisfactoria. Conclusiones: La tromboprofilaxis en pacientes portadores de trombofilia congénita es mandatoria, por eso resulta determinante la utilización de heparina de bajo peso molecular junto al resto de las medidas de prevención de la trombosis venosa profunda(AU)

Introduction: Thrombophilia is a congenital or acquired hemostasis disorder that predisposes to thrombosis development. The commonest congenital thrombophilias are deficiencies of antithrombin III, protein C and protein S, factor V Leiden, prothrombin gene mutation (G20210A), and methylenetetrahydrofolate reductase (MTHFR) mutations. Objective: To describe the anesthetic management in a patient with congenital thrombophilia. Case presentation: The case is reported of a 19-year-old patient with a family and personal history of deep-vein thrombosis, treatment with double antiplatelet therapy and association of three mutations for congenital thrombophilia (G20210A, A1298C MTHFR and C677T MTHFR), who receives spinal anesthesia for an inguinal herniorrhaphy. Aspirin treatment is maintained. Clopidogrel is suspended seven days before surgery. During this time, fraxiparin is administered subcutaneously in 0.6-mL units daily, up to twelve hours before surgery. Elastic stockings are used, early ambulation is allowed, and clopidogrel is restarted 24 hours after surgery, with satisfactory evolution. Conclusions: Thromboprophylaxis in patients with congenital thrombophilia is mandatory, a reason why the use of low-molecular-weight heparin, together with the rest of the prevention measures against deep-vein thrombosis, is decisive(AU)