Activador del plasminógeno tisular recombinante en el manejo de trombos cardiacos en recién nacidos / Recombinant tissue plasminogen activator for the management of intracardiac thrombi in newborns

Introducción: La incidencia de trombos cardíacos en recién nacidos (RN) ha aumentado con el uso de catéteres venosos centrales. La trombólisis con activador del plasminógeno tisular recombinante (rTPA) se ha utilizado como alternativa a la heparina en trombos gigantes con riesgo vital y de embolización. Nuestro objetivo fue describir la respuesta y las complicaciones relacionadas con el uso del rTPA en el manejo de trombos cardíacos con riesgo vital en RN. Pacientes y método: Estudio retrospectivo de 8 RN, 7 prematuros, con trombos cardíacos en los cuales se utilizó rTPA. Se analizó la edad gestacional y al diagnóstico, peso, sexo, enfermedades asociadas, hemograma, niveles de fibrinógeno, dímero D, tiempo parcial de tromboplastina activada y de protrombina, antes y al término de la infusión de rTPA. El diagnóstico del trombo se realizó por ecocardiografía doppler. La indicación de rTPA fue trombo mayor de 10 mm o que ocupara más del 50% de la cavidad donde se localizaba; aumento del tamaño a pesar del tratamiento con heparina, aspecto fragmentado y lobulado con riesgo embólico pulmonar o sistémico o que comprometiera la función valvular o cardíaca. Resultados: Cuatro hombres; peso promedio de 1.580 g. La principal enfermedad fue la sepsis (7/8), se usó catéter venoso central en todos, la vena cava superior fue la localización más frecuente, con tiempo promedio de instalación previo al diagnóstico de 12 días. En 7/8 RN los trombos se ubicaron en la aurícula derecha, con un tamaño entre 7 a 20 mm. Tres pacientes recibieron heparina de bajo peso molecular previo al uso de rTPA, se realizaron entre uno a 5 ciclos con rTPA. En 4 pacientes se logró resolución completa del trombo a los 3,5 días en promedio. No hubo embolia ni fallecidos. Cuatro pacientes presentaron hemorragia intracraneana grado I, sin secuelas en el seguimiento. Conclusión: Este estudio constituye la primera serie de neonatos tratados con rTPA en Chile, lográndose la resolución completa del trombo en un 50% de los RN y parcial en el resto, permitiendo con ello disminuir el riesgo vital secundario a este proceso patológico.

Introduction: The incidence of cardiac thrombi in newborns has increased with the use of central venous catheters. Thrombolysis with recombinant tissue plasminogen activator (rTPA) has been used as an alternative to heparin in life threatening giant thrombus and embolization. The aim of this study is to describe the response and complications related to the use of rTPA in the management of life- threatening cardiac thrombi in newborns. Patients and method: The medical records of 8 newborn were reviewed in a retrospective study, of whom 7 were preterm with cardiac thrombi, and rTPA was used in all of them. Results: The patients included 4 males with a mean weight of 1580 gr. The principal pathology was sepsis (7/8), all of them used venous central catheter. The superior vena cava was the most frequent location, with a mean time of installation before the diagnosis of 12 days. RN 7/8 thrombi were located in the right atrium with a size between 7 to 20 mm. Three patients received low molecular weight heparin prior to using rTPA. They received between 1 to 5 cycles with rTPA. In 4 patients complete resolution of the thrombus was achieved in a mean of 3.5 days. Four patients had intracranial haemorrhage grade I, without sequelae at follow-up. There were no deaths or embolism. Conclusion: This study is the first series of infants treated with rTPA in Chile, and where its use has quickly achieved complete resolution of the thrombus in 50% of cases, and partially in the others, thus reducing the secondary life-threatening risk of this disease.

Frequency and predictors of symptomatic intracranial hemorrhage after intravenous thrombolysis for acute ischemic stroke in a Brazilian public hospital

OBJECTIVE: Scarce data are available on the occurrence of symptomatic intracranial hemorrhage related to intravenous thrombolysis for acute stroke in South America. We aimed to address the frequency and clinical predictors of symptomatic intracranial hemorrhage after stroke thrombolysis at our tertiary emergency unit in Brazil. METHOD: We reviewed the clinical and radiological data of 117 consecutive acute ischemic stroke patients treated with intravenous thrombolysis in our hospital between May 2001 and April 2010. We compared our results with those of the Safe Implementation of Thrombolysis in Stroke registry. Univariate and multiple regression analyses were performed to identify factors associated with symptomatic intracranial transformation. RESULTS: In total, 113 cases from the initial sample were analyzed. The median National Institutes of Health Stroke Scale score was 16 (interquartile range: 10-20). The median onset-to-treatment time was 188 minutes (interquartile range: 155-227). There were seven symptomatic intracranial hemorrhages (6.2%; Safe Implementation of Thrombolysis in Stroke registry: 4.9%; p = 0.505). In the univariate analysis, current statin treatment and elevated National Institute of Health Stroke Scale scores were related to symptomatic intracranial hemorrhage. After the multivariate analysis, current statin treatment was the only factor independently associated with symptomatic intracranial hemorrhage. CONCLUSIONS: In this series of Brazilian patients with severe strokes treated with intravenous thrombolysis in a public university hospital at a late treatment window, we found no increase in the rate of symptomatic intracranial hemorrhage. Additional studies are necessary to clarify the possible association between statins and the risk of symptomatic intracranial hemorrhage after stroke thrombolysis.

Alterações hemodinâmicas e intracranianas em cães com hemorragia aguda, anestesiados com isofluorano / Hemodynamic and intracranial alterations in dogs with acute hemorrhage anesthetized with isoflurane

Estudaram-se possíveis alterações hemodinâmicas e intracranianas em cães submetidos à hemorragia aguda e anestesiados pelo isofluorano. Verificou-se também a influência do anestésico no mecanismo de auto-regulação cerebral. Utilizaram-se 20 cães adultos que foram induzidos à anestesia geral com isofluorano por máscara naso-oral a 3,5V por cento (volume por cento). Após a intubação orotraqueal, reajustou-se o vaporizador para 2,1V por cento. Induziu-se a hipovolemia retirando-se volume total de 35ml/kg de sangue. Avaliaram-se pressão intracraniana (PIC), temperaturas intracraniana (TIC) e corpórea (T), pressão de perfusão cerebral (PPC), pressões arteriais sistólica (PAS), diastólica (PAD) e média (PAM), freqüências cardíaca (FC) e respiratória (FR), índices cardíaco (IC) e sistólico (IS), pressão venosa central (PVC), pressão da artéria pulmonar (PAP), concentração de dióxido de carbono ao final da expiração (ETCO2) e saturação de oxihemoglobina (SpO2). Imediatamente após a hipovolemia, houve redução significativa da PIC, PPC, PAS, PAD, PAM, IC, IS e PAP. Após 10 minutos, houve aumento gradativo das médias, permanecendo neste patamar até o final do período experimental. Concluiu-se que a hemorragia aguda promoveu redução das variáveis hemodinâmicas, sendo possível verificar a ativação de mecanismos compensatórios. Além disso, houve redução da perfusão sangüínea e ativação do mecanismo de auto-regulação cerebral, conseqüentes à hipovolemia associada à anestesia com isofluorano.

Intracranial and hemodynamic alterations in 20 adult dogs anesthetized with isoflurane and submitted to acute hemorrhage were studied. Anesthetic influence on cerebral auto-regulation mechanism was also observed. General anesthesia was induced with at 3.5V percent (volume percent) isoflurane. Thereafter, orotracheal intubation was performed and vaporizer was calibrated to 2.1V percent. To induce hypovolemia, a total amount of 35 ml/kg-1 of blood was taken from each dog. Intracranial pressure (ICP); intracranial (ICT) and body temperatures (BT); cerebral perfusion pressure (CPP); systolic (SAP), diastolic (DAP) and mean arterial pressures (MAP); heart (HR) and respiratory rates (RR); cardiac (CI) and stroke indexes (SI); central venous pressure (CVP); pulmonary arterial pressure (PAP); end tidal dioxide carbon (ETCO2); and oxyhemoglobin saturation (SpO2) were evaluated. Immediately after hypovolemia, there was significative reduction of ICP, CPP, SAP, DAP, MAP, CI, SI, and PAP. Ten minutes after, the values increased gradually until the end of the experimental period. Indeed, acute hemorrhage caused reduction of hemodynamic variables and activation of the compensatory mechanisms. Cerebral blood perfusion was reduced and cerebral auto-regulation mechanism was activated due to hypovolemia associated to isoflurane anesthesia.

Warfarin-associated Fetal Intracranial Hemorrhage: A Case Report

A 27-yr-old woman who had been taking warfarin for 10 yr after mitral valve replacement became pregnant. After knowing her pregnancy, she received heparinization for nine weeks instead of warfarin, and took oral anticoagulant again. At 24 weeks of gestation, fetal ultrasound and MRI showed a left subdural hematoma, and the pregnancy was terminated. Subdural hematoma was demonstrated on autopsy. Fatal bleeding of the fetus is a rare complication of maternal warfarin medication, occurring mostly in the second or third trimester. There is no alternative regimen available, so that regular monitoring by fetal ultrasound and strict control of warfarin dose with regular measurement of prothrombin time are the best way to prevent intrauterine fetal death due to bleeding.

Fetal intracranial hemorrhage due to antenatal low dose aspirin intake.

Antenatal intake of low dose aspirin is advised for prevention of pregnancy induced hypertension, intrauterine growth retardation and pre-term labour. Aspirin has an anticoagulant effect due to its action on Cyclo-oxygenase and vitamin K dependent coagulation factors. It can readily cross the placental barrier and be a potential cause for bleeding tendency in the fetus. Fetal intracranial hemorrhage, following low dose aspirin administration in a mother and subsequent effect after delivery is being reported.