Compromiso cardíaco en el síndrome inflamatorio multisistémico post SARS-CoV-2 en niños / Cardiac involvement in post-SARS-CoV-2 multisystem inflammatory syndrome in children / Envolvimento cardíaco na síndrome inflamatória multissistêmica pós-SARS-CoV-2 em crianças

Objetivo: describir las características de ocho pacientes pediátricos que se presentaron con síndrome inflamatorio multisistémico (MIS-C) asociado a SARS-CoV-2 y compromiso cardíaco. Material y métodos: estudio descriptivo, retrospectivo de ocho pacientes con edades entre 1 y 13 años, con diagnóstico de MIS-C y compromiso cardíaco, asistidos en el CHPR. Se analiza su historia clínica, evolución y tratamiento. Resultados: los pacientes presentaron fiebre en el 100%, exantema e hiperemia conjuntival en el 88%, síntomas digestivos en el 50%, insuficiencia respiratoria en el 25% y shock en el 50%. Todos requirieron ingreso a cuidados intensivos. La alteración de la contractilidad cardíaca estuvo presente en el 63% de los pacientes, fue leve y segmentaria en el 80%, el 60% requirió soporte inotrópico por 3 días, recuperando una función normal en 7 días. La insuficiencia mitral se presentó en el 25% y el derrame pericárdico en el 38%, ambos de grado leve. Un paciente presentó dilatación de arterias coronarias con Z score < 2. El 85% de los pacientes presentó alteraciones del ECG, en el 29% se trató de alteración en la repolarización, en el 29% intervalo QTc prolongado, en el 15% bloqueo atrioventricular de 1er grado y bloqueo incompleto de rama derecha. Un paciente tuvo fibrilación auricular por 3 días con remisión espontánea a ritmo sinusal. Las troponinas estuvieron altas en el 57% de los pacientes y el ProBNP elevado en el 100%. Todos recibieron inmunoglobulinas, metilprednisolona y aspirina. Conclusiones: se presentaron ocho pacientes pediátricos con MIS-C y compromiso cardíaco, el 50% se presentó en shock, todos requirieron ingreso a cuidados intensivos. El 85% presento alteraciones en el ECG. El 63% presentó compromiso de la contractilidad sectorial y leve, se normalizó en 7 días. El 60% requirió soporte inotrópico por una media de 3 días.

Objective: describe the characteristics of 8 children who presented Multisystem Inflammatory Syndrome associated with SARS-CoV2 infections (MIS-C) and cardiac involvement. Material and methods: descriptive, retrospective study of 8 patients of between 1 and 13 years of age, diagnosed with MIS-C and cardiac involvement, assisted at the Pereira Rossell Children Hospital, analysis of their medical records, evolution and treatment. Results: the patients showed: fever in 100% of the cases, rash and conjunctival hyperemia in 88%, digestive symptoms in 50%, respiratory failure in 25% and shock in 50%. All required admission to Intensive Care. Cardiac contractility alteration was present in 63% of patients, the affectation was mild and segmental in 80%, 60% required inotropic support for 3 days and recovered normal functions in 7 days. Mitral regurgitation was present in 25% of the cases and pericardial effusion in 38%, mild in both cases. One patient had dilated coronary arteries with a Z score <2. 85% of the patients presented ECG abnormalities, 29% present alteration of repolarization, 29% prolonged QTc, 15% 1st degree atrioventricular block and incomplete right bundle branch block. One patient had atrial fibrillation for 3 days with spontaneous remission to sinus rhythm. Troponins were increased in 57% of the patients and ProBNP elevated in 100%. All patients received Immunoglobulins, Methylprednisolone and Aspirin. Conclusions: we present eight pediatric patients with MIS-C and cardiac involvement, 50% suffered shock, all required admission to Intensive Care. ECG abnormalities were found in 85% of the patients. Mild and segmental contractility compromise was found in 63% of the patients and normalized in 7 days. 60% required inotropic support for a mean of 3 days.

Objetivo: descrever as características de 8 pacientes pediátricos que apresentaram Síndrome Inflamatória Multissistêmica (MIS-C) associada ao SARS-CoV-2 e comprometimento cardíaco. Material e métodos: estudo descritivo, retrospectivo, de oito pacientes com idade entre 1 e 13 anos, com diagnóstico de MIS-C e comprometimento cardíaco, assistidos pelo CHPR. Seu prontuário médico, evolução e tratamento são analisados. Resultados: os pacientes apresentaram febre em 100%, erupção cutânea e hiperemia conjuntival em 88%, sintomas digestivos em 50%, insuficiência respiratória em 25% e choque em 50%. Todos necessitaram de internação nos cuidados intensivos. A alteração da contratilidade cardíaca esteve presente em 63% dos pacientes, foi leve e segmentar em 80%, 60% necessitaram de suporte inotrópico por 3 dias, recuperando a função normal em 7 dias. A regurgitação mitral ocorreu em 25% dos pacientes e o derrame pericárdico em 38%, ambos de grau leve. Um paciente apresentou dilatação da artéria coronária com escore Z < 2. 85% dos pacientes apresentaram anormalidades no ECG, 29% foram alterações de repolarização, 29% intervalo QTc prolongado em bloqueio atrioventricular de 1º grau a 15% e bloqueio incompleto do ramo direito. Um paciente apresentou fibrilação atrial por 3 dias com remissão espontânea ao ritmo sinusal. As troponinas foram elevadas em 57% dos doentes e ProBNP elevado em 100%. Todos receberam imunoglobulinas, Metilprednisolona e aspirina. Conclusões: houve oito pacientes pediátricos com SMIM-C e comprometimento cardíaco, 50% em choque, todos necessitaram de internação em terapia intensiva. 85% apresentaram elevações no ECG. 63% apresentaram comprometimento setorial e de contratilidade leve, normalizados em 7 dias. 60% necessitaram de suporte inotrópico por uma média de 3 dias.

Sobredosis accidental de enoxaparina en un recién nacido / Enoxaparin overdose in a newborn

La enoxaparina es una heparina de bajo peso molecular utilizada en el período neonatal. Requiere menor monitoreo que la heparina estándar o no fraccionada, si bien es escaso el conocimiento actual acerca de su dosis y de los niveles terapéuticos en los neonatos. Además, existe una información muy limitada respecto del manejo de su sobredosificación en este grupo de edad. Se presenta el primer caso publicado en castellano de un neonato que recibió una dosis de enoxaparina diez veces superior a la terapéutica de forma accidental y en el que se administró una dosis aislada de protamina para revertir su efecto.

Enoxaparin is a low molecular weight heparin used in the neonatal period. It requires less monitoring than standard or unfractionated heparin, although current knowledge about its dose and therapeutic levels in neonates is scarce. In addition, there is very limited information about the management of overdose in this age group. We present the first case published in Spanish of a neonate who accidentally received a dose of enoxaparin ten times higher than the therapeutic one and an isolated dose of protamine to reverse its effect.

Methylene blue to treat protamine-induced anaphylaxis reactions. An experimental study in pigs

ABSTRACT Objective: To examine if methylene blue (MB) can counteract or prevent protamine (P) cardiovascular effects. Methods: The protocol included five heparinized pig groups: Group Sham -without any drug; Group MB - MB 3 mg/kg infusion; Group P - protamine; Group P/MB - MB after protamine; Group MB/P - MB before protamine. Nitric oxide levels were obtained by the nitric oxide/ozone chemiluminescence method, performed using the Nitric Oxide Analizer 280i (Sievers, Boulder, CO, USA). Malondialdehyde plasma levels were estimated using the thiobarbiturate technique. Results: 1) Groups Sham and MB presented unchanged parameters; 2) Group P - a) Intravenous protamine infusion caused mean arterial pressure decrease and recovery trend after 25-30 minutes, b) Cardiac output decreased and remained stable until the end of protamine injection, and c) Sustained systemic vascular resistance increased until the end of protamine injection; 3) Methylene blue infusion after protamine (Group P/MB) - a) Marked mean arterial pressure decreased after protamine, but recovery after methylene blue injection, b) Cardiac output decreased after protamine infusion, recovering after methylene blue infusion, and c) Sustained systemic vascular resistance increased after protamine infusion and methylene blue injections; 4) Methylene blue infusion before protamine (Group MB/P) - a) Mean arterial pressure decrease was less severe with rapid recovery, b) After methylene blue, there was a progressive cardiac output increase up to protamine injection, when cardiac output decreased, and c) Sustained systemic vascular resistance decreased after protamine, followed by immediate Sustained systemic vascular resistance increase; 5) Plasma nitrite/nitrate and malondialdehyde values did not differ among the experimental groups. Conclusion: Reviewing these experimental results and our clinical experience, we suggest methylene blue safely prevents and treats hemodynamic protamine complications, from the endothelium function point of view.

Recanalization after acute deep vein thrombosis / Recanalizacao apos trombose venosa profunda aguda

The process of recanalization of the veins of the lower limbs after an episode of acute deep venous thrombosis is part of the natural evolution of the remodeling of the venous thrombus in patients on anticoagulation with heparin and vitamin K inhibitors. This remodeling involves the complex process of adhesion of thrombus to the wall of the vein, the inflammatory response of the vessel wall leading to organization and subsequent contraction of the thrombus, neovascularization and spontaneous lysis of areas within the thrombus. The occurrence of spontaneous arterial flow in recanalized thrombosed veins has been described as secondary to neovascularization and is characterized by the development of flow patterns characteristic of arteriovenous fistulae that can be identified by color duplex scanning. In this review, we discuss some controversial aspects of the natural history of deep vein thrombosis to provide a better understanding of its course and its impact on venous disease.

O processo de recanalização das veias dos membros inferiores, após um episódio de trombose venosa profunda aguda em pacientes anticoagulados com heparina e inibidores da vitamina K, faz parte da evolução natural da remodelagem do trombo venoso. Esse complexo processo de remodelagem envolve a adesão do trombo à parede da veia, à resposta inflamatória da parede do vaso, levando à organização e subsequente contração do trombo, à neovascularização e à lise espontânea de áreas no interior do trombo. A presença de fluxo arterial espontâneo em veias com trombose recanalizada tem sido descrita como secundária à neovascularização e se caracteriza pelo desenvolvimento de fluxo com padrão de fístulas arteriovenosas, identificadas por meio de mapeamento dúplex colorido. Nesta revisão, são discutidos alguns aspectos controversos da história natural da trombose venosa profunda, para uma melhor compreensão da sua evolução e do seu impacto sobre a doença venosa.

Reversal of the anticoagulant and anti-hemostatic effect of low molecular weight heparin by direct prothrombin activation

Lopap, found in the bristles of Lonomia obliqua caterpillar, is the first exogenous prothrombin activator that shows serine protease-like activity, independent of prothrombinase components and unique lipocalin reported to interfere with hemostasis mechanisms. To assess the action of an exogenous prothrombin activator reversing the anticoagulant and antihemostatic effect induced by low molecular weight heparin (LMWH), male New Zealand rabbits (N = 20, weighing 3.8-4.0 kg) allocated to 4 groups were anticoagulated with 1800 IU/kg LMWH (iv) over 2 min, followed by iv administration of saline (SG) or recombinant Lopap (rLopap) at 1 µg/kg (LG1) or 10 µg/kg (LG10), 10 min after the injection of LMWH, in a blind manner. Control animals (CG) were treated only with saline. The action of rLopap was assessed in terms of activated partial thromboplastin time (aPTT), prothrombin fragment F1+2, fibrinogen, and ear puncture bleeding time (BT) at 5, 10, 15, 17, 20, 30, 40, 60, and 90 min after initiation of LMWH infusion. LG10 animals showed a decrease of aPTT in more than 50% and BT near to normal baseline. The level of prothrombin fragment F1+2 measured by ELISA had a 6-fold increase with rLopap treatment (10 µg/kg) and was inversely proportional to BT in LMWH-treated animals. Thus, Lopap, obtained in recombinant form using E. coli expression system, was useful in antagonizing the effect of LMWH through direct prothrombin activation, which can be a possible strategy for the reversal of bleeding and anticoagulant events.

Avaliação comparativa da atividade biológica de heparinas não fracionadas pelas metodologias de inibição da coagulação do plasma ovino (ICPO) e de tempo de tromboplastina parcial ativada (TTPA) / Comparative study on the biological activity of non-fractionated heparin by using sheep plasma coagulation inhibition assay (SPCIA) and activated partial thromboplastin time (APTT) methodologies

O objetivo deste trabalho foi realizar o estudo comparativo entre os métodos ICPO e TTPA, para avaliar a eficácia da implantação do TTPA como método para a avaliação da segurança e eficácia de heparinas não fracionadas em produtos farmacêuticos. Foram avaliados, comparativamente, cinco lotes de diferentes fabricantes de heparinas não fracionadas (polissacarídeo sulfatado usado como droga anticoagulante), de origem suína ou bovina, testadas com base no 5º Padrão Internacional de Heparina. Esses produtos foram provenientes de coletas efetuadas pelas autoridades sanitárias para análise no Instituto Nacional de Controle de Qualidade em Saúde (INCQS). As amostras foram analisadas quanto à pureza e potência anticoagulante, por meio de duas metodologias: inibição da coagulação do plasma ovino (ICPO) e tempo de trombo plastina parcial ativada (TTPA). Houve boa concordância entre as duas metodologias, sendo que a técnica TTPA apresentou ser mais simples, rápida e objetiva, quando da utilização do coagulômetro para a medição do tempo de formação de coágulos, em detrimento da leitura subjetiva dos graus de coagulação no ensaio de ICPO. A implantação e a execução do TTPA em paralelo à utilização do ICPO garantirão o aumento de sensibilidade técnica na avaliação da segurança e eficácia de heparinas não fracionadas.

Reversión de la anticoagulación en pacientes con dosis altas de heparina: protamina en dosis standard versus dosis reducidas / Reversal anticoagulation in patients with high doses heparin: protamine in standard doses versus small doses

Evaluar y comparar, en pacientes sometidos a circulación extracorpórea (CEC), la reversión de la anticoagulación con dos dosis distintas de protamina: una dada en forma proporcional a la heparina usada versus una dosis calculada según peso del paciente, independiente de la heparina administrada. Material y Método: Se incorporaron los pacientes que para la CEC requirieron una dosis de heparina superior a 300 U•kg-1. Los criterios de exclusión fueron: alteraciones de las pruebas de coagulación preoperatorias y paro circulatorio hipotérmico. La técnica anestésica, el uso de fármacos y el uso de hemoderivados fue de decisión del anestesista. Para la reversión con protamina los pacientes fueron aleatorizados en dos grupos: Grupo A o dosis estándar: Reversión con 0,8 mg protamina por cada 100 U de heparina usada. Grupo B o dosis reducida: Reversión con 2,4 mg protamina•kg-1, independiente de la dosis de heparina usada. La protamina fue preparada por una persona ajena al pabellón y el equipo tratante era ciego al grupo del paciente. El seguimiento de los pacientes las primeras 24 h en UTI fue realizado por una persona ciega al grupo del paciente. Resultados: Hubo solamente una diferencia demográfica: más mujeres en el grupo B (p = 0,029). En el preoperatorio no hubo diferencias en hematocrito, recuento de plaquetas, tratamiento anticoagulante oral (TACO) y heparina preoperatoria, tipo de cirugía y uso de aspirina. En el intraoperatoriono hubo diferencias en el tiempo de coagulación activada (TCA) basal, hematocritos en CEC, TCA en CEC y duración de CEC. La dosis de heparina por kg de peso fue mayor en el grupo B (p = 0,0433). La relación protamina/heparina total fue 0,81 para el Grupo A y 0,44 para el Grupo B, las que fueron diferentes (por el diseño del estudio)...

Objective: To evaluate and compare reversal of anticoagulation with different dose regimens of protamine in patients undergoing to CPB (cardiopulmonary bypass), one given according to the heparin dose administered and another calculated according to patient’s weight. Patients y Methods: Patients subjected to CPB and receiving a heparin dose greater than 300 IU/kg were enrolled. Exclusion criterias were: preoperative coagulopathy and hypothermic circulatory arrest. The anesthetic technic, drugs given and blood products transfusion were decided by the attending anesthesiologist. Patients were randomized to: Group A or standard dose: Reversal with 0.8 mg of protamine for each 100 IU of heparin given. Group B or reduced dose: Reversal with 2.4 mg of protamine per kilogram of patient’s weight, independent of heparin dose used. The protamine was prepared for a person blinded to group allocation, same as the team taking care of the patient. The patient’s follow up in the ICU during the first 24 hours was also done by someone blinded to group allocation. Results: There was only one demographic difference at baseline: more women in Group B (p = 0.029). There were no differences among the preoperative: hematocrit, platelets count, oral anticoagulant treatment, heparin administration, aspirin consumption and surgical plan. In the intraoperative course there were no differences in the baseline ACT, hematocrit during CBP, ACT in CBP and CBP duration. The average heparin dose (adjusted per kilogram) was greater in Group B (p = 0.0433).The protamine/heparin ratios were different among groups (Group A 0.81; Group B 0.44), as expected in this study design. The activated coagulation time (ACT)...

Guías para la prevención de enfermedad tromboembólica en pacientes pediátricos: (IV Consenso Venezolano sobre Enfermedad Tromboembólica 2008-2009): [revisión] / Guidelines for the prevention of thromboembolic disease in pediatric patients (IV Consensus on thromboembolic disease Venezuelan 2008-2009): [review]

La Enfermedad Tromboembólica (ETE) en la edad pediátrica ha adquirido mayor importancia, debido al aumento de su incidencia derivada de la optimización de técnicas diagnósticas y terapéuticas. Los episodios de ETE en los niños aparecen de forma brusca y el diagnóstico se hace con métodos incruentos como ecografía doppler, resonancia magnética y estudios angiográficos. Hasta hace poco no se disponía de recomendaciones específicas para el tratamiento de la ETE en el niño; en la actualidad se cuenta con esquemas terapéuticos desarrollados con base en la experiencia con adultos, adaptados a la edad pediátrica. Se revisan las principales patologías y procedimientos susceptibles de producir enfermedad tromboembólica así como las indicaciones de los principales agentes terapéuticos, incluyendo las heparinas, los anticoagulantes orales, antiagregantes y fibrinolíticos y se dan recomendaciones de uso. Dada la morbimortalidad observada en niños afectados por ETE, hay sobradas justificaciones para tomar una actitud activa que intente controlar el proceso y procurar que el beneficio esperado sea siempre superior al riesgo inherente al tratamiento.

Thromboembolic disease (TD) in pediatric patients has gained relevance, due to an increase in its incidence, as a result of the optimization of diagnostic and therapeutic techniques. Episodes of TD in children appear abruptly and diagnosis is carried out through non-invasive methods such as doppler ecography, magnetic resonance imaging and angiography. Until recently, specific recommendations for the treatment of TD in children were unavailable; nowadays, therapeutic schemes developed on the basis of experience with adults adapted to pediatric patients are available. The main pathologies and procedures capable of causing thromboembolic disease were reviewed, as well as the indications of main therapeutic agents, including heparins, oral anticoagulants, platelet antiagregant and fibrinolytic agents. Use recommendations are given. Considering the morbimortality rate observed in children affected by TD, there are plenty of reasons to take an active role to control the process, and seek that expected benefits outweigh the inherent risks of treatment.

Evaluation of hemodynamic changes due to protamine administration by calcium gluconate after coronary artery bypass grafting surgery

Administration of Protamine sulfate for heparin neutralization after cardiopulmonary bypass may be associated with adverse reactions such as transient hypotension to cardiovascular collapse. Although catastrophic events are rare and occur only in 2.6% of cardiac surgeries, it is associated with adverse postoperative outcome. The aim of this study is to investigate whether bolus administration of calcium gluconate can minimize the adverse hemodynamic effects of protamine. This randomized clinical trial [RCT] prospective study was conducted between Feb. 2006 to Dec. 2008. The patients were randomly allocated into three groups including group A [42 patients] who received only protamine after weaning from cardiopulmonary, group B [44 patients] concomitantly treated with protamine sulfate and calcium gluconate, and group C [40 patients] receiving calcium gluconate 5 minutes before administration of protamine. Hemodynamic variables such as systolic and diastolic blood pressures, mean of arterial pressure, central venous pressure and heart rate were obtained 0, 2, 4, 6, 8 and 10 minutes after protamine administration from each group. Systolic blood pressure in groups A [control] and C [calcium administration before protamine] 0,2,4,6,8 and 10 minutes after protamine administration initially decreased and increased subsequently [P=0.228]. Also no statistically significant difference was found in diastolic blood pressure [DBP], mean arterial pressure [MAP], central venous pressure [CVP], and heart rate [HR] in 0,2,4,6,8, and 10 minutes in any of the three groups. In our study, hemodynamic changes in 10 minutes after protamine administration for heparin neutralization in patients with good left ventricular systolic function after coronary artery bypass grafting surgery were mild, and prophylactic calcium gluconate administration concurrent with or before protamine injection was not recommended

Assessment of a DNA vaccine encoding an anchored-glycosylphosphatidylinositol tegumental antigen complexed to protamine sulphate on immunoprotection against murine schistosomiasis

Protamine sulphate/DNA complexes have been shown to protect DNA from DNase digestion in a lipid system for gene transfer. A DNA-based vaccine complexed to protamine sulphate was used to induce an immune response against Schistosoma mansoni anchored-glycosylphosphatidylinositol tegumental antigen in BALB/c mice. The protection elicited ranged from 33 to 44 percent. The spectrum of the elicited immune response induced by the vaccine formulation without protamine was characterized by a high level of IgG (IgG1> IgG2a). Protamine sulphate added to the DNA vaccine formulation retained the green fluorescent protein encoding-plasmid longer in muscle and spleen. The experiments in vivo showed that under protamine sulphate effect, the scope of protection remained unchanged, but a modulation in antibody production (IgG1= IgG2a) was observed.

Measurement of activated clotting time during cardiopulmonary bypass in infective endocarditis patients / 中南大学学报(医学版)

OBJECTIVE@#To investigate the proper dosage of heparin and protamin in treating the patients with infective endocarditis (IE) during the operation.@*METHODS@#Activated clotting time (ACT) was measured during and after cardiopulmonary bypass (CPB) in 30 patients with IE and 30 patients with rheumatic heart disease (RHD) respectively.@*RESULTS@#The dosage of heparin before bypass in IE group was significantly higher than that of RHD group (P0.05).@*CONCLUSION@#The dosage of protamin should be increased to 3 mg/kg as the heparin is over 400 U/kg before CPB in the patient with IE, but the ratio of protamin and heparin will not be obviously changed.

Inhibition of three alphaherpesviruses (Herpes simplex 1 and 2 and pseudorabies virus) by heparin, heparan and other sulfated polyelectrolytes

The first step of the herpes virus infection is the attachment to heparan sulfate molecules on the cellular membrane. In order to improve the characterization of this phenomenon, we compared the inhibitory effect of six sulfated polyelectrolytes (PE): heparin, heparan, low molecular wight heparin, chondroitin, dextran and protamine on plaque formation by pseudorabies virus (PRV) were compared. The PE with the highest antiherpetic effect was heparin, followed by dextran sulfate. Heparan sulfate, which has been proposed as the initial receptor of herpes virus on the cell surface showed and effect 100-fold lower than heparin. Comparative inhibition curves of heparin and heparan sulfate against three herpes viruses: herpes simplex virus 1 (HSV-1), HSV 2 and PRV showed similar kinetics of inhibition of plaque formation, suggesting these viruses could share similar cell adsorption mechanisms

Effects of heparin protamine and heparin-protamine complex on cardiovascular system

The cardiovascular effects of heparin and protamine sulphate were studied in the in vitro isolated perfused heart and aortic spiral strips of rabbits and in the in vitro arterial blood pressure and ECG of anesthetized cats. Heparin and protamine sulphate, in therapeutic doses, induced a dose dependent cardioinhibitory effect which was reversible and might be through a direct myocardial depressant action. Combined administration of both drugs showed an effect lesser than the summation effect of each drug separately. Protamine [32-256 ug/ml] and only high concentration of heparin [25.6 units/ml] reduced the response of aortic strip to noradrenaline. The combined effect of both drugs together was lesser than expected. In vivo, I.V. injection of heparin did not produce any change in the arterial blood pressure or ECG of anesthetized cats. But rapid I.V. injection of protamine in periods less than 30 seconds, revealed dose dependent reductions of heart rates and decreased the blood pressure suddenly and transient in only 25% of the cases studied. This drop of blood pressure and negative chromotropic effect occurred even after preheparinization of the cats. These data demonstrate that cardiovascular effects, previously attributed to heparin-protamine complex, are due to heparin and protamine themselves separately and circulating heparin does not aggravate these effects of protamine alone

Diminuiçäo do sangramento pós-operatório produzido pela heparina, após aplicaçäo tópica de adenosina trifosfato (ATP) em cirurgia cardíaca com circulaçäo extracorpórea / Reduction of postoperative bleeding produced by heparin, before topical application of adenosine triphosphate in cardiac surgery with extracorporeal circulation

A concentraçäo de heparina foi determinada no sangue de pacientes submetidos a cirurgia cardíaca com circulaçäo extracorpórea, antes e depois da sua neutralizaçäo com protamina. Determinou-se também a quantidade de heparina no sangue coletado dos drenos da cavidade torácica 12 horas após a operaçäo. Cerca de 15 por cento da heparina, a despeito de um tempo de coagulaçäo normal, permanece na circulaçäo após a administraçäo de protamina, e também é encontrada no sangue coletado dos drenos da cavidade torácica. O peso molecular médio dessa heparina circulante, bem como da encontrada nos drenos torácicos, foi ao redor de 7 KiloDaltons (KDa), comparando ao de 15 KDa da heparina dosada no sangue antes da sua neutralizaçäo pela protamina. Graças a achados anteriores de que as heparinas de baixo peso molecular, responsáveis pelo sangramento da ferida operatória, podem ser neutralizadas por trifosfato de adenosina (ATP), a cavidade torácica de pacientes consecutivos e näo selecionados, divididos em 3 grupos de 15, foi lavada com diferentes concentraçöes, ou de ATP (10 elevado a -5, 5 x 10 elevado a -4 M) ou com protamina, ou, ainda, apenas com soluçäo fisiológica (grupo controle). Observou-se uma curva dose-resposta linear entre a diminuiçäo do sangramento com o aumento da dose da ATP utilizada. ATP, numa concentraçäo de 10 elevado a -4 M, diminuiu significativamente o volume de sangue drenado da cavidade torácica dos pacientes (média de 288 + ou - 188 ml), quando comparado ao grupo que recebeu protamina (média de 496 + ou - 210 ml), e ao grupo controle (média 564 + ou - 288 ml) (p<0,05). ATP numa concentraçäo de 5 x 10 elevado a -5 M reduziu as perdas sanguíneas a 370 + ou - 155 ml dos pacientes (p<0,08). A média de sangramento, no total dos pacientes que receberam ATP, foi de 314 + ou - 170 ml(p<0,08).

Uso de anticoagulantes em doenças cardiovasculares / Anticoagulant drugs in cardiovascular diseases

Os autores revisaram as principais características dos dois grupos de fármacos anticoagulantes (heparina e anticoagulantes orais), bem como os respectivos esquemas terapêuticos, a incidência de complicaçöes e seu controle clínico. Por fim, säo discutidas as particularidades da anticoagulaçäo em diversas situaçöes clínicas, com realce para as afecçöes cardiovasculares e a embolia pulmonar