Estudio unicéntrico del tratamiento con trombolíticos dirigidos por catéter en el tromboembolismo pulmonar agudo / Single center retrospective study of catheter directed thrombolysis in patients with acute pulmonary embolism

Resumen Se realizó un estudio unicéntrico retrospectivo para evaluar la eficacia y seguridad de trombolisis dirigida por catéter (TDC) en pacientes con tromboembolismo pulmonar agudo (TEP) de 2014 a 2020. Se analizó la efectividad (mejoría de presión pulmonar), y seguridad (sangrado intracraneal y grave definido por compromiso hemodinámico). Se incluyeron 43 pacientes, de 67(56-79) años, 5 (12%) con shock, 41 (95%) con dilatación del ventrículo derecho y TEP bilateral. La decis ión de TDC fue: tratamiento inicial (53%), escalada de anticoagulación (42%) y rescate de trombolisis sistémica (5%). Se utilizó TDC facilitada por ultrasonido en 40 casos (93%), utilizándose 30 (25-35) mg de activador tisular del plasminógeno recombinante (rtPA) durante 20 h. Se administró un bolo de rtPA en 38 (89%) casos, que fue 5 mg (95%) o 1 mg (5%). Se utilizó un solo catéter por paciente. En 4 (9%) se decidió recolocación (mismo pulmón) para continuar infusión en otro sector. Se observó una disminución significativa de la presión media pulmonar (pre 35 [29-41] mmHg vs. post 24 [20-34] mmHg, p<0.001). No se observó ningún caso de hemorragia intracraneal, y un caso (2%) de sangrado grave. Se observó hematoma del sitio de punción en 5 (12%) (incluyendo el sangrado grave), y requirió transfusiones en 3 (7%). La mortalidad intrahospitalaria fue 12%, siendo un solo c aso (2%) atribuido al TEP. El tratamiento con TDC fue efectivo asociándose a una reducción significativa de la presión pulmonar, sin observarse ningún sangrado intracraneal y con un sangrado grave. Nuestros resultados se asemejan a lo publicado en otros estudios.

Abstract We performed a single center retrospective study in patients with pulmonary embolism (PE) undergoing catheter directed thrombolysis (CDT) from 2014 to 2020. Efficacy was defined by mean pulmonary pressure drop, and safety was assessed by intracranial and severe bleeding (defined by GUSTO). Forty-three patients were included, aged 64 (56-79) years old, 5 (12%) with shock, most with right ventricle dilation (95%) and bilateral PE (95%) or unilateral (5%) in patients with only one functional lung. CDT was used as first treatment (53%), upscale after anticoagulation alone (42%), or after failed systemic thrombolytics (5%). Median recombinant tissue plasminogen activator (rtPA) dose was 30 (25-35) mg over 20 (20-20) hours, and rtPA bolus was used after catheter placement in 38 cases (89%), consisting of 5 mg (95%) or 1 mg (5%). Only one lung was treated for technical reasons, and 4 (9%) were repositioned in the same lung for continuation of infusion. A significant reduction in mean pulmonary pressure was observed (pre 35 [29-41] mmHg vs. post 24 [20-34] mmHg, p<0.001) with no intracranial bleeding. One patient (2%) experienced severe bleeding, while 5 (12%) presented access site bleeding, and 3 (7%) required blood transfusions. In-hospital mortality was 12% but only one case (2%) due to PE. Our results are similar to previously reported studies.

Trombolisis intravenosa en accidente cerebro vascular isquémico agudo en un hospital público de Chile: análisis prospectivo de 54 casos / Intravenous thrombolysis for ischemic stroke: experience in 54 patients

Background: Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) reduces disability in patients with ischemic stroke. However, its implementation in Chilean public general hospitals has been slow and faces some difficulties. Aim: To analyze the results of an intravenous thrombolysis protocol implementation in a public general hospital. Material and Methods: During a lapse of 28 months a standardized protocol for intravenous thrombolysis implemented in the emergency room of a public hospital, was prospectively evaluated. Fifty four patients with ischemic stroke were treated and assessed three months later as outpatients. Results: At three months of follow-up, 66.4% of patients subjected to thrombolysis had a favorable evolution, defined as having 0 to 1 points in the modified Rankin scale. Intracerebral hemorrhage rate was 11.1%, including 5.5% of symptomatic intracerebral hemorrhage. Four percent of patients had systemic bleeding complications after thrombolysis. The mortality rate was 14.8%. Conclusions: The success rates, mortality, and complications rate were comparable to the results obtained in international studies, despite of the absence of a stroke unit to manage stroke and its complications.

Trombolisis con activador plasmático del plasminógeno, en un modelo de trombosis de vena femoral en conejos / Trombolisis with plasmatic activator of the plasminógeno, in a model of thrombosis of femoral vein in rabbits

Antecedentes: La trombosis venosa profunda (TVP), es una patología altamente prevalente, de difícil diagnóstico y con graves complicaciones. En la actualidad, los objetivos del tratamiento de esta enfermedad se enfocan en conseguir su control y evitar las complicaciones tanto de la patología como de su tratamiento. Objetivo: Analizar los resultados obtenidos con la nueva fracción proteica con actividad fibrinolítica, en un modelo de trombosis de la vena femoral en conejos. Lugar de trabajo: Laboratorio de Cirugía Experimental, Facultad de Medicina, Universidad Católica de Córdoba. Diseño: Registro prospectivo de datos. Población: 15 conejos New Zeland. Material y Métodos: Para la formación del trombo, se aisló la vena femoral y se generó la trombosis colocando sobre la vena un trozo de papel de filtro embebido con cloruro férrico. Se evalúo y registró seriadamente el flujo venoso, tanto en la pretrombosis como a los 10, 20 y 30 minutos, mediante Eco-Doppler. Comprobada la trombosis se inició la trombolisis. Resultados: En el grupo A, luego de la aplicación de APP, el análisis por eco-Doppler determinó la reperfusión en 11/11 animales (100%). En tanto, en el grupo B, que se aplicó placebo, la reperfusión fue negativa (0/4 conejos) (p=0,001). Conclusión: Posterior a la inducción de la trombosis con cloruro férrico en vena femoral, la infusión de APP (lote A) mostró reperfusión en 11/11, mientras que el resultado en la infusión de placebo (lote B) fue 0/4. Registro con Doppler vascular de la trombosis y fibrinolisis resultó ser método sensible y específico.

Role of thrombolytic therapy for stuck prosthetic valves: a serial echocardiographic study.

BACKGROUND: Thrombotic occlusion of a prosthetic valve continues to be an uncommon but serious complication. Intravenous thrombolytic therapy has been proposed as an alternative to surgical treatment, but only in critically ill patients. METHODS AND RESULTS: Forty-one consecutive patients presenting with 48 episodes of prosthetic valve thrombosis (44 mitral and 4 aortic) were treated with thrombolytic therapy under serial echocardiographic guidance. There were 14 male and 27 female patients. The anticoagulation status was inadequate in 89.6% of episodes. Atrial fibrillation was present in 47.9% of episodes. The prostheses involved in these episodes were tilting disc in 45, bileaflet in 2, and ball and cage type in 1. The Sorin prosthetic valve was the most commonly involved. The time interval between valve replacement and thrombosis ranged from 1 month to 108 months (mean 20.4+/-20.6 months). Patients were in New York Heart Association functional class III in 47.9% and in class II in 43.9% of episodes. Thrombolytic agents used were streptokinase and urokinase in 44 and 4 episodes, respectively. The mean duration of thrombolytic therapy was 27.9+/-15.0 hours and the overall success rate was 87.5%. Patients developed peripheral embolism with almost complete recovery in 5 episodes while significant bleeding that required termination of thrombolytic therapy was observed in 2 episodes. Redo valve replacement was done in 3 episodes because these patients did not improve on thrombolytic therapy (all 3 cases were of recurrent prosthetic valve thrombosis and were found to have pannus peroperatively). Three patients died during thrombolytic therapy because of persistent heart failure. Six patients experienced a total of 13 epidoses of recurrent prosthetic valve thrombosis including index episodes (rethrombosis in 5, re-rethrombosis in 1). They were treated with repeated thrombolysis with a success rate of 76.92%. The mean duration of thrombolytic therapy in these episodes was 36.1+/-14.0 hours. CONCLUSIONS: In patients with prosthetic valve thrombosis, intravenous thrombolysis guided by echocardiography is a safe and effective method that may expand the indications for nonsurgical treatment of prosthetic valve thrombosis. By using serial echocardiography, the duration of thrombolytic therapy can be tailored to the patient's requirement for normalization of valve hemodynamics.

Fator tecidual ativador de plasmogênio recombinante (rt-PA) intravítreo em obstrução venosa retiniana / Intravitreous tissue plasminogen activator for retinal vein occlusion

Objetivos: Analisar os resultados, anatômicos e funcionais, do tratamento das obstruções venosas retinianas pelo fator tecidual ativador de plasminogênio recombinante (rt-PA) intravítreo. Pacientes e Métodos: Cinco pacientes com obstrução da veia central da retina (OVCR) e um paciente com obstrução venosa hemi-retiniana foram submetidos a uma injeção intravítrea de 75mg de rt-PA e reavaliados através de exame oftalmológico completo, retinografia e retinografia flourescente. Resultados: Observou-se melhora anatômica em dois dos seis pacientes estudados, dentre os quais o paciente que apresentava obstrução venosa hemi-retiniana que evoluiu com rápida e acentuada resolução do quadro obstrutivo. Nenhum dos pacientes apresentou melhora funcional. Um dos pacientes apresentou hemorragia vítrea de pequena magnitude e rápida resolução, um mês após a terapêutica, e outro paciente apresentou hemorragia vítrea quanze meses após, tendo esta ocorrido após cirurgia cardíaca.

Intravitreal tissue plasminogen activator in submacular haemorrhage.

Submacular haemorrhage is a major cause of sudden visual loss in age-related macular degeneration (AMD). If left untreated it often results in permanent central visual loss. We present our experience in the use of intravitreal tissue plasminogen activator (tPA) in a 65-year-old male with submacular haemorrhage.

Newer thrombolytic drugs for acute myocardial infarction.

Arterial thrombosis is the underlying cause of a wide variety of cardiovascular diseases such as myocardial infarction, stroke and pulmonary thromboembolism. All the currently used thrombolytic agents are plasminogen activators, which are very efficient in restoring the blood flow. The fibrinolytic system comprises an inactive proenzyme plasminogen, that is converted by plasminogen activators to the enzyme plasmin, that degrades fibrin. Despite the widespread use of established thrombolytic agents such as streptokinase, tissue-plasminogen activator and urokinase, all these agents suffer from a number of inadequacies including resistance to reperfusion, occurrence of acute coronary reocclusion and bleeding complications. The quest continues for thrombolytic agents with a higher potency, specific thrombolytic activity and fibrin selectivity. Several lines of research towards improvement of thrombolytic agents are being explored including the construction of mutants and variants of plasminogen activators, chimeric plasminogen activators and conjugates of plasminogen activators with monoclonal antibodies. Newer molecules such as pro-urokinase, saruplase, alteplase, K1K2Pu and staphylokinase have shown promise in animal models of arterial and venous thrombosis and also in pilot scale clinical studies in patients with myocardial infarction. However, more clinical trials are needed to determine whether these novel recombinant thrombolytic agents shows improved efficacy and fibrin specificity with minimal bleeding tendencies.

Uso do fator ativador do plasminogênio tecidual no acidente vascular cerebal isquêmico agudo / Tissue Plasminogen Activator for Acute Ischemic Stroke

OBJETIVO: Avaliar se o uso do fator ativador do plasminogênio (rt-PA) nas primeiras 6h do acidente vascular cerebral isquêmico agudo melhora a capacidade funcional. MÉTODOS: Foram estudados 6 pacientes, sendo 4 mulheres, com média de idade 63ñ18 anos, portadores de déficit neurológico há menos de 6h e sem recuperaçäo espontânea, sendo a causa na metade dos casos embólica e nos demais trombótica. Foi realizada tomografia computadorizada do crânio (CT) seguida da angiografia cerebral seletiva (3 casos) ou Doppler transcraniano (3 casos), para demostraçäo da oclusäo arterial e desua recanalizaçäo após o fibrinolítico. A infusäo do rt-PA foi endovenosa periférica em 5 casos, na dose de 0,9/kg, ou intra-arterial em 1 caso, na dose de 0,5 mg/kg, ambas durante 60 min. Após 24h do uso rt-PA foi realizado CT crânio para controle de complicaçäo hemorrágica e novo exame neurológico. RESULTADOS: Todos apresentam oclusäo arterial, sendo o território da artéria cerebral média em 5 caos e da cerebra posterior em um. A recanalizaçäo foi obtida em 4 casos com manutençäo da sua perviabilidade na 24a hora. A recuperaçäo neurológica foi completa em um, parcial em 3 e inalterada em 2, os quais näo obtiveram recanalizaçäo arterial. O controle tomográfico de 24h demostrou transformaçäo hemorrágica em somente um paciente, porém dentro da área isquêmica e sem piora clínica. Näo ocorreram complicaçöes fatais pelo uso do rt-PA e um paciente faleceu por pneumonia. CONCLUSÄO: A recanalizaçäo arterial com o rt-PA foi obitida em 4 de 6 pacientes, com melhora funcional. O rt-PA deve ser utilizado em pacientes selecionados com intervalo de até 3h do envento, segundo estudos randomizados.

Purpose - To evaluate thrombolytic therapy with rt-PA for acute stroke within 6h of symptom onset, and assessment of neurologic outcome. Methods - We studied 6 patients, four women, mean age 63±18 years, with severe neurologic deficit within 6h of stroke onset, and with no spontaneous improvement. The stroke was embolic in 3, and thrombotic in the others. All patients were submitted to a head CT scan followed by either a cerebral angiography in 3 patients, or a transcranial Doppler, in the other 3 for assessment of arterial obstruction, and patency after thrombolytic therapy. We used 0.9mg/kg of rt-PA, IV, over 60min in 5 patients, and 0.5mg/kg by intra-arterial infusion, over 60min, in one. At the begining a bolus of 10% of the total dose was dilevered during 1 to 2min. Head scan was repeated 24h and 7 days after treatment to detect ischemic areas and hemorrhagic complications. Results - Middle cerebral artery occlusion was observed in 5 patients and posterior cerebral artery occlusion in one. The obstruction was cleared in 4 patients with persistence of the patency after 24h. A complete neurologic recovery was found in one patient, and a partial recovery in three. In two patients there was failure of arterial recanalization with no neurologic recovery. Only one patient had hemorrhagic transformation of ischemic tissue,without neurologic worsening. Death occured in one patient due to pulmonary infection.Conclusion - Arterial patency with thrombolytictherapy was effective in 4 of our 6 patients. All 4 patientsalso disclosed a certain degree of neurologic improvement, rt-PA can be successfuly used in selected patients upto 3h of the event onset, as shown in randomized studies

Terapia trombolítica em trombose venosa profunda. Experiência clínica inicial / Thrombolytic therapy in deep venous thrombosis. Initial clinical experience

Four cases of proximal deep venous thrombosis treated with streptokinase and tissue plasminogen activator are reported. Therapy monitorization was performed by ultrasonography with color Doppler and thrombolytic agents were used by venous infusion. There was complete lysis in two cases, and the mean rate of venous recanalization was 88. Reversible hemorrhagic complications were observed in two patients, and late ultrasonographic control (after six months) demonstrated venous insufficiency in one case.

Acidente vascular cerebral isquêmico agudo embólico tratado com rt-PA durante cinecoronariografia eletiva / Acute Embolic Ischaemic Stroke Treated with rt-PA during Elective Coronary Angiography

A 56-year-old female with unstable angina, presented an acute embolic ischaemic stroke of right medium cerebral artery during elective coronary angiography. Complete patency was achieved after an intraarterial infusion of rt-PA (60mg/60min) with important functional improvement.

Mulher de 56 anos, portadora de angina instável, apresentou episódio tromboembólico agudo da artéria cerebral média direita, durante cinecoronariografia eletiva. A infusão intra-arterial do rt-PA, na dose de 60mg, durante 60min, promoveu recanalização da artéria com recuperação do déficit neurológico

Thrombolysis utilisation in acute myocardial infarction in Bahrain.

We retrospectively studied 114 consecutive patients of acute myocardial infarction diagnosed in the Accident and Emergency department of our hospital, to determine the percentage of eligible patients who actually received thrombolytic therapy, the number of those excluded from receiving such therapy and the various exclusion criteria. We found that 66 patients (57.9%) received thrombolysis with either streptokinase or tissue plasminogen activator (tPA). The remaining 48 (42.1%) were excluded because of delayed presentation to hospital after the onset of symptoms (23.7%), old age or other contraindications. Although the percentage of thrombolysis utilisation in acute myocardial infarction in our centre is much higher as compared to others in the world, we find that there is a scope for improving these figures by reducing the number of patients excluded because of late presentation through health education and improved utilisation of ambulance services.

Estudo Brasileiro com alteplase no infarto agudo do miocárdio--EBRALT / Brazilian atudy with alteplase in acute myocardial infarction- "Ebralt"

PURPOSE--Prospective evaluation of the effects of the intravenous administration of rt-PA (Alteplase) up to 6 hours after the pain onset on the patency of the AMI related artery, mortality, adverse reactions and complications. METHODS--Open, multicenter, non-comparative study involving 139 patients with diagnosis of AMI, with less than 6h of duration. The rt-PA was intravenously administered, in a dose of 100mg, as follows: 10mg in the 1st 2min, 50mg in 58min and 40mg in 120min. In addition, the patients received intravenous heparin (5000 IU at first and then, 1000 IU/hour, for 24h), aspirin (500mg in the 1st day and then, 100mg/day) and dipyridamole (75mg, three times a day), during the hospitalization period. The angiographic study was performed in 129 (93) patients, within the 1st week of AMI. RESULTS--The age of the patients ranged from 29 to 85 (mean 56.6 +/- 10.3) years. The related artery for the AMI was patent (TIMI II and III flow) in 92/129 (71) patients, with a mean ejection fraction of 50 +/- 14, a value higher than that exhibited by patients with TIMI 0 and I flow (average ejection fraction = 44 +/- 14). Reinfarction was diagnosed in 9 (6.4) patients during the hospitalization period. During this period, there were 9 (6.4) deaths. Minor hemorrhages were observed in 19 (12) patients and major hemorrhages in 3 (2) cases. No patient experienced stroke. CONCLUSION--The administration of the rt-PA therapy in the AMI was associated to a high reperfusion index of the related artery for the infarction, with improved left ventricular function and low incidence of reinfarction and in-hospital mortality, as well as, complications.

Objetivo - Avaliar prospectivamente os efeitos dort-PA (alteplase), administrado por via intravenosa (IV) até 6h após início da dor, na perviabilidade da artéria responsável pelo infarto agúdo do miocárdio (IAM), na morbimortalidade, nas reações adversas e nas complicações. Métodos - Estudo multicêntrico, aberto, não comparativo, envolvendo 139 pacientes com diagnóstico de IAM, com menos de 6h de duração. O rt-PA foi administrado por via IV, na dose de 100mg, assim distribuída: 10mg nos 2min iniciais, 50mg em 58min e 40mg em 120min. Os pacientes receberam, ademais, heparina via IV (5.000UI iniciais e 1.000UI/h, durante 24h), aspirina (500mg no 1º dia e, a seguir, 100mg/dia) e dipiridamol (75mg, 3 vezes ao dia), durante período de internação. Estudo cinecoronariográfico foi realizado em 129 (93%) pacientes, dentro da Iª semana do IAM. Resultados - As idades dos pacientes variaram de 29 a 85 (média 56,6 10,3) anos, sendo 80% do sexo masculino. A artéria responsável pelo IAM estava pérvia (fluxo TIMI II e III) em 92/129 (71%) pacientes, os quais apresentaram fração de ejeção média (FEm) =50 14%, valor esse maior do que o dos pacientes com fluxo TIMI 0 e I (FEm = 4414%). Reinfarto foi diagnosticado em 9 (6,4%) pacientes durante o período de internação hospitalar. Nesse período, ocorreram 9 (6,4%) óbitos. Hemorragias menores foram observadas em 19 (12%) pacientes e hemorragias maiores em 3 (2%) casos. Nenhum paciente apresentou acidente vascular cerebral. Conclusão - A terapêutica com rt-PA no IAM associou-se a elevado índice de reperfusão da artéria responsável pelo infarto, com melhora da função ventricular esquerda e baixa incidência de reinfarto e de mortalidade hospitalar, bem como de complicações

Estado lítico sistêmico como marcador do sucesso terapêutico após rt-PA em bolo no infarto do miocárdio / lytic state as marker of therapeutic success after rt-PA in bolus in myocardial infarction

Avaliar o estado lítico sistêmico (ELS) através do nível de fibrinogênio sérico (FS) após tratamento com rt-PA em bolo no infarto do miocárdio (IM) e sua relaçäo com recanalizaçäo coronária. Cinqüenta e um pacientes (38 homens, média de idade de 53 ñ 9,8 anos) com IM submetidos a terapêutica com 70 mg de rt-PA em bolo por via venosa após demonstraçäo de oclusäo da artéria relacionada ao infarto (ARI). Foram feitas dosagens de FS pré-tratamento e após 90 minutos e comparados seus níveis no grupo de pacientes recanalizados (grupo 1) com os do grupo de pacientes com falha terapêutica (grupo 2). Todos os pacientes tinham níveis normais de FS e pré-tratamento. Após 90 minutos a média do FS diminuiu em 35,1% (276,8 ñ 55,5 mg/dl para 168,9 ñ 78,2 mg/dl). Os grupos 1 e 2 aos 90 minutos apresentaram níveis de FS semelhantes (145,1 ñ 96,7 mg/dl contra 187,0 + 53,7 mg/dl). A terapêutica com rt-PA em bolo no IM reduz de maneira significativa o FS, mas o ELS atingido foi semelhante nos grupos com ou sem recanalizaçäo da ARI

Purpose: Evaluate the lytic state (LS) expressed by the level of plasmatic fibrinogen (PF) after rt-PA in bolus tn,fusion for acute myocardial infarction (MI) and its relation to coronary reperfusion. Patients and methods: Fifty-one patients (38 men, mean age of 53.0 ± 9.8 years) with demonstrated occlusion of the infarct related artery (IRA) received an intravenous bolus infusion of 70 mg of rt-PA, PF was assessed before and 90 minutes after the treatment and the levels were compared in patients with (group 1) and without (group 2) reperfusion of the IRA. Results: Basal levels of PF were within the normal range in all patients. There was a decrement of 35.1% in the PF dosed at 90 minutes, from 276.8 ± 55.5 mg/al to 168.0 ± 68.2 mg/dl. Both groups were similar in the levels of PF 90 after treatment (145.1 ± 95.7 mg/dl in group I versus 187.0 ± 53.7 mg/dl in group 2). Conclusion: In bolus rt-PA treatment for MI significantly reduces the PF, but the LS obtained was similar in patients with or without reperfusion of the IRA.

Ativadores do plasminogênio como agentes trombolíticos no infarto do miocardio / Plasminogen activators as thrombolytic agents in myocardical infarction

O tratamento atual do oclusäo aguda das coronárias inclui o uso de agentes trombolíticos. A experiência do Instituto do Coraçäo (HCFMUSP) num período entre 1981 e 1985, demonstrou que a infusäo intracoronária de estreptoquinase em 117 pacientes com infarto do miocárdio, foi capaz de recanalizar 87% das artérias coronárias. Várias drogas com especificidade para a fibrina foram desenvolvidas recentemente: 1) Ativador tecidual do plasminogênio (t-PA); 2) Ativador tipo uroquinase de cadeia simples (scuPA); 3) Complexo Plasminogênio-Estreptoquinase acilado (APSAC). Os autores discutem as propriedades dos agentes trombolíticos no tratamento do infarto do miocárdio