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.

Terapia antitrombótica na fase aguda das síndromes coronarianas aguda / Antithrombotic therapy in acute phase of acute coronary syndrome

A morbidade e a mortalidade nas síndromes coronarianas agudas – causadas principalmente pela instabilidade da placa aterosclerótica, levando à formação de trombos – foi bastante reduzida com o advento de antiplaquetários, antitrombóticos e revascularização precoce. Hoje, dispomos de quatro antitrombóticos para uso nestas condições: a heparina não fracionada, a de baixo peso molecular, o fondaparinux e a bivalirudina – sendo apenas as três primeiras disponíveis no Brasil. Como são agentes antiocoagulantes, o risco de sangramento não é desprezível e deve ser apropriadamente dosado com o fim de trazer o máximo benefício antitrombótico, sem grande risco hemorrágico. Nesta revisão sumarizamos o atual estado da arteno uso de antitrombóticos no Brasil...

Morbidity and mortality in the acute coronary syndromes – caused in the majorly by atherosclerotic plaque instability, with consequent thrombus formation – was drastically reduced by the advent of antiplatelet and antithrombotic agents, and by early revascularization. Nowadays, we have 4 antithrombotic agents: unfractionated heparin, low molecular weight heparin, fondaparinux and bivalirudin – with only the first 3 available in Brazil. As they comprise anticoagulant effects, the risk of bleedingis high and must be taken into account when prescribed, in order to bring the greater benefits without higher bleeding risk. In this review we summarized the current state of the art about the use of these agents in our country...

Comparison of topical use of protamine and tranexamic acid in surgical patients requiring cardio-pulmonary bypass

To determine the effectiveness of local protamine in reducing post-operative blood loss compared to loca1 tranexamic acid. Randomized controlled trial. Armed Forces Institute of Cardiology/National Institute of Heart Diseases Rawalpindi from January 2011 to September 2011. One hundred and twenty cardiac surgrcal patients were randomly divided into two equal groups, one receiving local protamine while the other group receiving local tranexamic acid before chest closure. The efficiency was measured as post-operative blood loss and requirement of blood and blood products in the post-surgical ICU. RAverage blood loss in protamine group was significantly less [252.97 ml] compared to tranexamic acie group [680.67 ml]. hTumber of patients requiring no post-operative blood transfusion was sigruficantly higher in protamine group [76.7%] compared to tranexamic acid group [53.3%]. Local protamine is more effective in reducing post-operative blood loss than local tranexamic acid

Remoção Precoce do Introdutor Arterial Após Intervenção Coronária Percutânea por Via Femoral: Estudo de Segurança e Eficácia / Early Removal of the Arterial Sheath After Percutaneous Coronary Intervention Using the Femoral Approach: Safety and Efficacy Study

Introdução: Avaliamos a segurança e eficácia do uso de protamina, guiada pelo tempo de coagulação ativado, para a remoção imediata do introdutor arterial femoral em pacientes submetidos à intervenção coronária percutânea com heparina não fracionada, com o objetivo de propor um algoritmo para a prática clínica. Métodos: Estudo prospectivo, com pacientes consecutivos, com angina estável ou com síndrome coronariana aguda de baixo ou moderado risco. Comparamos os pacientes com a retirada precoce do introdutor arterial àqueles nos quais o introdutor foi retirado de acordo com o protocolo convencional. A decisão pela remoção precoce ou convencional do introdutor foi deixada a critério do operador. Resultados: O grupo de remoção precoce (n = 149) apresentou menor tempo de manuseio do sítio de punção que o grupo de remoção convencional (58,3 ± 21,4 minutos vs. 355 ± 62,9 minutos; p < 0,01), principalmente devido à redução do tempo até a retirada do introdutor (42,3 ± 21,1 minutos vs. 338,6 ± 61,5 minutos; p < 0,01), sem impacto sobre a duração da compressão femoral (16,0 ± 3,6 minutos vs. 16,4 ± 5,1 minutos; p = 0,49). Não houve trombose hospitalar de stent e nem diferença significativa na incidência de eventos vasculares ou hemorrágicos. A incidência de outras hemorragias, que levaram à hospitalização prolongada, foi menor no grupo de remoção precoce (1,3% vs. 5,1%; p = 0,05). Conclusões: O uso seletivo de uma abordagem, para a remoção imediata do introdutor femoral guiada pelo tempo de coagulação ativado e a administração de protamina, é seguro e eficaz em pacientes submetidos à intervenção coronária...

Introduction: We evaluated the safety and efficacy of protamine administration, guided by activated clotting time, for the immediate femoral arterial sheath removal in patients undergoing percutaneous coronary intervention with unfractionated heparin in order to propose an algorithm for clinical practice. Methods: Prospective study with consecutive patients with stable angina or low-to-moderate risk acute coronary syndrome. We compared patients with an early removal of the arterial sheath to those whose sheath removal was based on a standard protocol. Results: The early removal group (n = 149) had lower access manipulation time than the conventional group (58.3 ± 21.4 minutes vs. 355.0 ± 62.9 minutes; p < 0.01), mainly due to a reduced time to sheath removal (42.3 ± 21.1 minutes vs. 338.6 ± 61.5 minutes; p < 0.01), with no impact on the duration of femoral compression (16.0 ± 3.6 minutes vs. 16.4 ± 5.1 minutes; p = 0.49). There was no stent thrombosis during hospitalization and no significant differences in the incidence of major vascular or bleeding events. The incidence of other bleeding events leading to a prolonged in-hospital length of stay was lower in the early removal group (1.3% vs. 5.1%; p = 0.05). Conclusions: The selective use of an approach for immediate femoral sheath removal, based on activated clotting time guidance and protamine administration, is a safe and effective option in patients undergoing percutaneous coronary intervention by femoral access...

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)...

Effects of Twice-Daily Injections of Premixed Insulin Analog on Glycemic Control in Type 2 Diabetic Patients

PURPOSE: Premixed insulin is effective to improve glycemic control; however, clinicians may be less likely to know which premixed insulin is appropriate for which patients. This study aimed to evaluate the effects of twice-daily injections of premixed insulin lispro on glycemic control in type 2 diabetic patients. MATERIALS AND METHODS: Forty type 2 diabetic patients, who had been treated with twice-daily injections of human protamine mixture 30/70 insulin for at least 12 months, were divided into two groups; one group whose blood glucose 2 hours after breakfast was greater than 200 mg/dL, was switched to lispro mix50, and the other group whose blood glucose 2 hours after breakfast < 200 was switched to lispro mix25. RESULTS: Glycated haemoglobin (HbA1c) significantly improved in the Mix50 group from 8.3% to 7.5% (at 12 weeks; p < 0.05), and to 7.5% (at 24 weeks; p < 0.05). On the other hand, HbA1c levels in the Mix25 group were slightly decreased from 8.1% to 7.7% at 12 weeks (p < 0.05), and to 7.9% at 24 weeks (not significant). Both postprandial plasma glucose and fasting plasma glucose levels were significantly improved in the Mix50 group, but not in the Mix25 group. Overall, 95% of subjects preferred premixed lispro insulin from human insulin in the viewpoint of the timing of insulin injection by questionnaire analysis. CONCLUSION: Switching from human protamine mixture 30/70 insulin to lispro mix50 twice-daily injection therapy in patients with high postprandial plasma glucose could improve their glycemic control and quality of life.

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.

Relación costo beneficio del uso del tiempo de coagulación activado durante circulación extracorpórea / Cost-benefit ratio of the activated coagulation time useful during extracorporeal circulation

Analizamos retrospectivamente la relación costo-beneficio de dos métodos de anticoagulación sistémica utilizados durante cirugía cardíaca con circulación extracorpórea: dosis protocolizadas de heparina y protamina (Grupo I, n=87) y la determinación seriada de tiempo de coagulación activado (TCA) (Grupo II, n=123). Las dosis totales de heparina y protamina y el gasto en drogas fueron menores en el grupo II, el costo total de la anticoagulación por paciente fue similar en ambos grupos; en el grupo I un mayor porcentaje de pacientes recibió transfusiones de productos sanguíneos; 26,4 por ciento de los pacientes tuvo TCA considerados insuficientes para iniciar la canulación arterial y circulación extracorpórea. El TCA para monitorizar anticoagulación sistémica no aumentó nuestros costos, nos permitió disminuir las dosis de drogas y objetivar y cuantificar la heparinización y su reversión

Comparison of the hemodynamic changes following left atrial and peripheral venous administration of protamine during cardiac surgery.

The hemodynamic effects of left atrial administration of protamine for heparin reversal were compared with the peripheral venous route. One hundred patients, undergoing cardiac surgery, using cardiopulmonary bypass (CPB) at Siriraj hospital were randomly allocated into two equal groups of fifty. The preoperative and operative characteristics of the two groups were comparable. After the termination of CPB, protamine sulfate was administered over 3 minutes via the left atrium in group I, and via the peripheral vein in group II. The hemodynamics were measured before and 5, 15 and 30 minutes after protamine administration. There were no statistically significant differences in heart rate (HR), arterial blood pressure (BP), and central venous pressure (CVP) between the groups. After administrating protamine and adequate maintaining the preload in both groups of patients within the normal range, the HR did not change from immediate post CBP control values. The arterial BP was not changed for 5 minutes, thereafter, significantly elevated toward the preoperative baseline values. This data indicates that the left atrial injection of protamine does not provide any hemodynamic advantages over the peripheral venous administration.

Controle da heparinizaçäo através do tempo de coagulaçäo ativado em cirurgia cardíaca com circulaçäo extracorpórea / Heparinization control by activated coagulation time in cardiac surgery with extracorporeal circulation

Os autores estudaram 20 pacientes submetidos a cirurgia cardíaca com circulaçäo extracorpórea utilizando um protocolo de controle da heparinizaçäo através do tempo de coagulaçäo ativado (TCA). Avaliaram as variaçöes na série vermelha e no sistema de coagulaçäo entre os períodos pré e pós-operatório, bem como a variaçäo do TCA nos diversos tempos. As doses totais de heparina e protamina foram, respectivamente, 5,85 mg e 4,34 mg/kg de peso. Houve variaçäo significativa entre os eritrócitos, a hemoglobina e as plaquetas (p < 0,001). As variáveis referentes ao tempo de coagulaçäo, tempo de protrombina, tempo de tromboplastina parcial e fibrinogénio näo mostraram variaçäo significativa. O TCA näo mostrou variaçäo significativa entre os valores durante a perfusäo, e nem entre os valores basal e pós-protamina, basal e 30 min pós-protamina. Näo ocorreram complicaçöes hemorrágicas pós-operatórias que pudessem ser atribuídas ao sistema de coagulaçäo. Concluem ser o método excelente para a monitorizaçäo da heparinizaçäo com o sulfato de protamina, que foi utilizado em doses mais baixas

Uso racional de la ecuación heparina-protamina en cirugía con circulación extracorporea / Rational use of the heparin-protamine equation in surgery with extracoporeal circulation

El objetivo de este trabajo es demostrar la utilidad del cálculo del tiempo de coagulación activado para la dosificación y neutralización de heparina durante cirugía con circulación extracorpórea. Se midieron en forma prospectiva los volúmenes de sangrado en ml, en 30 pacienes sometidos a esta cirugía, sus parámetros fueron: 861, 33 ñ 87,4419 (X ñ ES). La comparación se realizó con un grupo histórico de 30 individuos cuyos datos fueron: 1286,66 ñ 127,2939 (X ñ ES). Se demostró diferencia altamente significativa utilizando análisis de varianza (F = 7,58; F0,01 = 7,10 para 1 y 58 grados de libertad) entre ambos métodos a favor del cálculo del tiempo de coagulación activado