Paternal thrombophilia and recurrent implantation failure: an exploratory case-control study.

OBJECTIVE: Many pieces of literature have reported that inherited and acquired thrombophilia might be a risk factor for recurrent implantation failure (RIF), however, most studies have only focused on RIF patients and not their male partners. We studied the possible association of paternal thrombophilia with RIF risk. METHODS: Forty-two male partners aged 20-45 suffered from RIF compared with 42 males from couples with at least one successful pregnancy. All participants were investigated for thrombophilia markers. RESULTS: The prevalence of coagulation Factor V activity was significantly higher in the case group (42.9%) than in the control group (16.7%) (p=0.008) (OR=3.75; 95% CI, 1.38, 10.12). The prevalence of protein C and protein S deficiencies in RIF patients were 4.8% and 2.4%, respectively, and 0% in the controls. The prevalence of antithrombin III (ATIII) deficiency was significantly higher in the case group (19%) than in the control group (2.4%) (p=0.01). None of MTHFR C677T and MTHFR A1298C were statistically significant between the two groups. Combined thrombophilia was 45.2% in the men of the RIF group when compared with the control, 14.2% (p=0.001) (OR = 4.95; 95% CI, 1.75-13.86). CONCLUSIONS: Paternal thrombophilia may be related to recurrent implantation failure, so evaluation of this factor in RIF patients could be used to identify relevant risk groups and may help in the proper management of these cases to enhance the chance of implantation.

The addition of Tirofiban infusión to heparin for intraoperative heparin resistance associated with Marfan Syndrome / Adición de una infusión de Tirofiban a heparina en caso de resistencia intraoperatoria a la heparina asociada al Síndrome de Marfan

Abstract Marfan syndrome classically presents with aortic root aneurysms. Aortic ectasia causes diverse blood flow alterations, influencing the behavior of coagulation factors and platelet activity. Heparin resistance has also been reported associated with Marfan Syndrome in a small number of patients, probably due to antithrombin III (ATIII) deficiency or various mutations. The ascending aorta and the aortic valve are replaced with prosthetic material during Bentall- de Bonno procedures. Resistance to anticoagulation during extracorporeal circulation, represents a significant challenge for both anesthesiologists and the surgical team. Resistance to heparin was observed in a patient with Marfan syndrome undergoing a Bentall procedure. ATIII concentrate was not available, and Activated Coagulation Time did not increase despite high doses of heparin. An alternate anticoagulation approach was used successfully.

Resumen El síndrome de Marfan clásicamente se presenta con aneurismas de la raíz de la aorta. La ectasia aórtica produce alteraciones en el flujo sanguíneo que influyen sobre el comportamiento de los factores de la coagulación y la actividad de las plaquetas. También se ha reportado resistencia a la heparina asociada al Síndrome de Marfan en un menor número de pacientes, probablemente debido a deficiencia de antitrombina III (ATIII) o a diversas mutaciones. La aorta ascendente y la válvula aórtica se reemplazan con material prostético en los procedimientos Bentall- de Bonno. La resistencia a la anticoagulación durante circulación extracorpórea significa un enorme desafío tanto para los anestesiólogos, como para el equipo quirúrgico. Se observó resistencia a la heparina en un paciente con Síndrome de Marfan sometido a un procedimiento de Bentall. No había disponibilidad de concentrado ATIII y no aumentó el Tiempo de Coagulación Activada a pesar de las elevadas dosis de heparina. Se utilizó exitosamente un abordaje alterno de anticoagulación.

Púrpura fulminans relacionada con deficiencia de antitrombina III en paciente agudo críticamente enfermo con aislamiento de Enterococcus faecalis / Purpura fulminans related with antithrombin III deficiency in critical ill patient with Enterococcus faecalis isolation / Purpura fulminans relacionada à deficiência de antitrombina III em paciente em estado crítico com isolamento de Enterococcus faecalis

Resumen: La coexistencia entre el fracaso fibrinolítico y la presencia de infección es más frecuente de lo que parece; desafortunadamente muchas veces pasa por alto y es concebido como algo incidental, generando consigo catástrofes vasculares y serias disfunciones endoteliales. Presentamos el caso de un adulto joven quien debuta con choque obstructivo de acuerdo con la cardioscopia invasiva y a la información gasométrica requiere terapias tempranas dirigidas por objetivos en el contexto de sepsis severa con aislamientos de Enterococcus faecalis y púrpura fulminans postinfecciosa aguda en el escenario clínico de deficiencia de antitrombina III. De acuerdo con el perfil hemodinámico referido y manifestaciones eléctricas presentadas se documentaron marcadores de actividad fibrinolítica, por lo cual fue llevado a perfusión pulmonar documentándose enfermedad pulmonar tromboembólica. Evoluciona favorablemente y es trasladado a piso para continuar atención médica en salud por los servicios de neumología y hematología.

Abstract: Coexistence between fibrinolytic failure and the presence of infection is more common than it seems; unfortunately it often is not recognized and is conceived as incidental; leading to vascular catastrophes and serious endothelial dysfunctions. We present the case of a young adult who debuts with purpura fulminans related to Enterococcus faecalis isolation in the clinical setting of antithrombin III deficiency and thromboembolic pulmonary disease. According to the hemodynamic profile referred and electrical manifestations presented, markers of fibrinolytic activity were documented, for which it was taken to pulmonary perfusion documenting thromboembolic lung disease. He evolves favorably and is transferred to continue medical health care by the services of pulmonology and hematology.

Resumo: A coexistência entre falência fibrinolítica e presença de infecção é mais frequente do que parece; Infelizmente, muitas vezes é negligenciado e concebido como algo incidental, gerando catástrofes vasculares e graves disfunções endoteliais. Apresentamos o caso de um adulto jovem que apresenta choque obstrutivo de acordo com cardioscopia invasiva e informações gasométricas, requer terapias precoces direcionadas por objetivos no contexto de sepse grave com isolamento de Enterococcus fecalis e púrpura fulminante pós-infecciosa aguda no cenário clínico de deficiência de antitrombina III. De acordo com o perfil hemodinâmico referido e manifestações elétricas apresentadas, foram documentados marcadores de atividade fibrinolítica, para o qual foi encaminhado para perfusão pulmonar, documentando doença pulmonar tromboembólica. O paciente progride favoravelmente e é transferido para o leito para continuar o atendimento médico nos serviços de pneumologia e hematologia.

Manejo obstétrico de la deficiencia hereditaria de antitrombina durante el embarazo y puerperio. Dos casos clínicos / Obstetric management of hereditary antithrombin deficiency in pregnancy and postpartum. Two case studies

La deficiencia de antitrombina III hereditaria es una rara enfermedad que afecta al 0.02-0.2 por cento de la población. Puede presentar mayor frecuencia de complicaciones y resultados adversos tanto en la madre como en el feto. Se presenta el manejo obstétrico de dos gestaciones consecutivas en una mujer con deficiencia de antitrombina III. Descripción: en ambos embarazos la madre realiza profilaxis de la enfermedad tromboembólica con heparina de bajo peso molecular para evitar la aparición de esta patología tanto en el embarazo como en el puerperio y mejorar el flujo útero-placen-tario. Con respecto a las complicaciones obstétricas, sólo existe un enlentecimiento del crecimiento fetal que obliga a un control obstétrico estricto. En ambas gestaciones los estudios eco-Doppler están dentro de la normalidad lo que permite una conducta expectante, consiguiendo llegar a término. Discusión: la profilaxis con heparina de bajo peso molecular en las gestantes con esta trombofilia y las intervenciones preventivas de factores de riesgo de enfermedad tromboembólica, junto con un control obstétrico adecuado, ha conseguido evitar la apari-ción de complicaciones derivadas de esta patología en el embarazo y en el puerperio. Por otra parte, el control del crecimiento fetal y el estudio Eco-Doppler han permitido asegurar el bienestar fetal no adelan-tando el parto, consiguiendo partos a término...

Hereditary antithrombin III deficiency is a rare disease that affects 0.02-0.2 percent of the population. It may be associated with a higher rate of complications and adverse outcomes in both mother and fetus. The present study describes the management of a woman with antithrombin III deficiency and two consecutive pregnancies. Description: in both pregnancies, the woman under went prophylaxis with low molecular weigh heparin, to prevent thromboembolic disease and improve the utero-placental flow during pregnancy and the postpartum period. The only obstetric compli-cation was fetal growth retardation requiring strict obstetric control. In these two cases the eco-Doppler studies offeto-placentalflow were normal, leading to the expectation of managing a term birth. Discussion: low molecular weigh heparin prophylaxis in pregnant women with thrombophilia and preventive interventions for risk factors for throm-boembolic disease, together with appropriate obstetric care managed to avoid the emergence of complications of this disease in pregnancy and puer-perium. Fetal growth control and a Doppler study also help to ensure the well-being of the fetus and avoid a preterm birth...

Síndrome moyamoya en paciente con síndrome de Down y déficit de antitrombina III / Moyamoya disease in a girl with Down syndrome. Report of one case

Moyamoya disease is a unique chronic progressive cerebrovascular disease characterized by bilateral stenosis or occlusion of the arteries around the circle of Willis with prominent arterial collateral circulation. It can be primary or secondary to genetic syndromes such as Down syndrome. We report a seven year-old girl with a Down syndrome that presented with a disturbance of consciousness, seizures and a right hemiparesia at the age of five. Magnetic resonance imaging showed old cortical ischemic lesions in both cerebral hemispheres and a recent infarction in the territory of the ¡eft middle cerebral artery. Brain angiography showed a proximal stenosis of both medial cerebral arteries and a net of collateral vessels, consistent with the diagnosis of moyamoya syndrome. The patient had also an antithrombin III deficiency. Aspirin was indicated and a surgical correction was recommended. However, prior to the procedure, the patient had a new infarction in the territory of the right middle cerebral artery, which caused a severe disability.

Effect of estrogen-progestin hormonal replacement therapy on blood coagulation and fibrinolysis in postmenopausal women

OBJECTIVE: To evaluate antithrombin III (AT), thrombin (Fragment 1+2 [F1+2] and thrombin-antithrombin [TAT]) generation markers, as well as other coagulation parameters, such as prothrombin time, partial activated thromboplastin time, thrombin time, fibrinogen, euglobulin lysis time, and platelet count, in postmenopausal women after hormonal therapy. STUDY DESIGN: Forty-five patients who received either 0.625 mg/day unopposed oral conjugated equine estrogen (CEE), 0.625 mg/day oral CEE plus medroxyprogesterone acetate (MP), or 50 µg/day transdermal 17beta-estradiol plus MP, were included. Tests were performed before (T0) and after 3 (T3), 6 (T6) and 12 (T12) months of treatment. AT was determined by an amidolytic method, whereas F1+2 and TAT complex were measured by ELISA. RESULTS: There was a significant reduction in the AT level of patients who received oral CEE plus MP at T3. There was no AT reduction in patients taking either oral CEE alone or transdermal 17beta-estradiol plus MP. F1+2 increased in all patients, but it reached statistical significance only in patients receiving transdermal 17beta-estradiol MP at T3. CONCLUSIONS: The CEE associated with MP treatment may reduce AT levels, whereas unopposed CEE or transdermal 17beta-estradiol plus MP does not change AT. These changes might not be clinically relevant in the general population; however, hormonal replacement therapy may increase the risk of thrombosis in women with congenital or acquired thrombophilia.

OBJETIVO: Avaliar os marcadores antitrombina III (AT), fragmento 1 + 2 da trombina (F1+2) e complexo trombina-antitrombina (TAT), bem como outros parâmetros da coagulação, como tempo de pró-trombina, tempo parcial de tromboplastina ativado, tempo de trombina, fibrinogênio e tempo de lise da euglobulina em mulheres na pós-menopausa após terapia hormonal. DESENHO DO ESTUDO: Foram incluídas 45 voluntárias que receberam estrogênios conjugados eqüinos (ECE) 0,625 mg/dia, isoladamente ou associado ao acetato de medroxiprogesterona (AMP) ou usaram o 17beta-estradiol (50 µg/dia) transdérmico com AMP. Os exames foram realizados antes do tratamento (T0) e após três (T3), seis (T6) e doze (T12) meses após o início do tratamento. AT foi avaliada pelo método amidolítico, enquanto que o F1+2 e o complexo TAT por ELISA. RESULTADOS: Houve redução significante nos níveis de AT em pacientes que receberam ECE associado ao AMP no T3. Não houve redução na AT em mulheres que usaram ECE isoladamente ou aquelas com 17beta-estradiol transdérmico e AMP. O F1+2 aumentou em todos os grupos, mas apenas o grupo com 17beta-estradiol transdérmico e AMP apresentou diferença significante durante o T3. CONCLUSÕES: A associação de ECE e AMP pode reduzir os níveis de AT, enquanto ECE isoladamente ou 17beta-estradiol transdérmico com AMP não modificam-o acentuadamente. Essas alterações poderiam ser mais relevantes clinicamente na análise populacional. Todavia, a terapia de reposição hormonal aumentaria o risco de trombose em mulheres com trombofilia prévia congênita ou adquirida.