Factibilidad del uso de bivalirudina como anticoagulante en soporte vital extracorpóreo / Experience with anticoagulation with bivalirudin during extracorporeal membrane oxygenation

Background: Extracorporeal membrane oxygenation (ECMO) is used with increasing frequency in patients with respiratory and cardiac failure. The achievement of an adequate anticoagulation is critical to avoid patient and circuit complications. Aim: To assess the feasibility and safety of anticoagulation with bivalirudin, as an alternative to unfractionated heparin (UFH), in patient with ECMO. Material and Methods: Observational study, which included all patients receiving anticoagulation with bivalirudin during ECMO, according to a standardized protocol, between august 2015 to May 2016. Results: Bivalirudin was used in 13 out 70 patients connected to ECMO. Ten procedures were for cardiac support and three for respiratory support. Mortality was 43%. ECMO lasted 31 ± 31 days. The time of UFH use before changing to bivalirudin was 7 ± 7 days. The reasons to change to bivalirudin were inadequate levels of partial thromboplastin time (PTT) in nine patients, and heparin induced thrombocytopenia (HIT) in four patients. The time of bivalirudin use was 24 ± 33 days. Per patient, a mean of 2.7 ± 4 oxygenators were changed. These had a useful life of 11.4 and 19.1 days during UFH and bivalirudin use, respectively. The mean bivalirudin dose was 0.08 ± 0.04 mg/kg/h. There was no significant bleeding, thrombosis or circuit obstruction during its use. PTT levels (p < 0.01) and platelet count (p < 0.01) increased significantly after the start of bivalirudin use in patients with UHF resistance and HIT, respectively. Conclusions: Bivalirudin was a safe and efficient drug for anticoagulation during ECMO. It is important to have an alternative drug for anticoagulation in ECMO patients.

Extremely Elevated International Normalized Ratio of Warfarin in a Patient with CYP2C9*1/*3 and Thyrotoxicosis

A 73-yr-old Korean man with permanent atrial fibrillation visited outpatient clinic with severely increased International Normalized Ratio (INR) values after taking a usual starting dosage of warfarin to prevent thromboembolism. We found out later from his blood tests that he had hyperthyroidism at the time of treatment initiation. His genetic analysis showed CYP2C9*1/*3 and VKORC1+1173TT genotypes. We suspect that both hyperthyroidism and genetic variant would have contributed to his extremely increased INR at the beginning of warfarin therapy. From this case, we learned that pharmacogenetic and thyroid function test might be useful when deciding the starting dosage of warfarin in patients with atrial fibrillation.

Changes in Plasma Levels of Natural Anticoagulants in Disseminated Intravascular Coagulation: High Prognostic Value of Antithrombin and Protein C in Patients with Underlying Sepsis or Severe Infection

BACKGROUND: Dysfunctional natural anticoagulant systems enhance intravascular fibrin for mation in disseminated intravascular coagulation (DIC), and plasma levels of natural anti coagulants can be used in the diagnosis and prognosis of DIC. Herein, the diagnostic value of 4 natural anticoagulants was assessed, and the prognostic value of antithrombin and protein C were validated in a large population. METHODS: Part 1 study included 126 patients with clinically suspected DIC and estimated plasma levels of 4 candidate anticoagulant proteins: antithrombin, protein C, protein S, and protein Z. Part 2 comprised 1,846 patients, in whom plasma antithrombin and protein C levels were compared with other well-known DIC markers according to the underlying dis eases. The 28-day mortality rate was used to assess prognostic outcome. RESULTS: Antithrombin and protein C showed higher areas under the ROC curve than pro tein S and protein Z. In part 2 of the study, antithrombin and protein C levels significantly correlated with DIC score, suggesting that these factors are good indicators of DIC severity. Antithrombin and protein C showed significant prognostic power in Kaplan-Meier analyses. In patients with sepsis/severe infection, antithrombin and protein C showed higher hazard ratios than D-dimer. Platelet count showed the highest hazard ratio in patients with hemato logic malignancy. In patients with liver disease, the hazard ratio for antithrombin levels was significantly high. CONCLUSIONS: Decreased plasma anticoagulant levels reflect florid consumption of the phys iologic defense system against DIC-induced hypercoagulation. Plasma antithrombin and protein C levels are powerful prognostic markers of DIC, especially in patients with sepsis/severe infection.

Determination of Plasma Warfarin Concentrations in Korean Patients and Its Potential for Clinical Application / 대한진단검사의학회지

BACKGROUND: Warfarin is a widely used oral anticoagulant with broad within- and between-individual dose requirements. Warfarin concentrations can be monitored by assessing its pharmacologic effects on International Normalized Ratio (INR). However, this approach has not been applied in the routine clinical management of patients receiving warfarin therapy. We performed a plasma warfarin assay using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) to determine if such an assay can be utilized in routine clinical practice. METHODS: We included a total of 105 patients with atrial fibrillation, and who were receiving warfarin for more than 1 yr. The plasma concentrations of total warfarin and 7-hydroxywarfarin were determined by HPLC-MS/MS (Waters, UK). We assessed the association between warfarin dose, concentration, and INR as well as the effects of these factors on warfarin concentrations. RESULTS: The mean maintenance dose of warfarin in 105 patients was 4.1+/-1.3 mg/day (range, 1.7-8.0 mg/day) and their mean plasma warfarin concentration was 1.3+/-0.5 mg/L. We defined a concentration range of 0.6-2.6 mg/L (corresponding to the 2.5th to 97.5th percentile range of the Plasma warfarin levels in the 74 patients showing INR within target range) as the therapeutic range for warfarin. The correlation of warfarin dose with warfarin concentration (r2=0.259, P<0.001) was higher than that with INR (r2=0.029, P=0.072). CONCLUSIONS: There was a significant correlation between warfarin dose and plasma warfarin concentrations in Korean patients with atrial fibrillation. Hence, plasma warfarin monitoring can help determine dose adjustments and improve our understanding of individual patient response to warfarin treatment.

Controle da qualidade das preparações de heparina disponíveis no Brasil: implicações na cirurgia cardiovascular / Heparin quality control in the Brazilian market: implications in the cardiovascular surgery

INTRODUÇÃO: A mudança na marca da heparina rotineiramente utilizada nas cirurgias cardíacas no Brasil tem sido acompanhada por aumento do número de casos de discrasia sanguínea, aumento de reoperações e efeitos adversos em nossa Instituição e em outras. MÉTODOS: Foram avaliadas no Laboratório de Tecido Conjuntivo do HUCFF/UFRJ, quatro preparações disponíveis e comparadas à heparina retirada do mercado (Liquemine) e ao padrão de controle internacional. As preparações de heparina foram submetidas à ressonância nuclear magnética para avaliação da integridade estrutural, bem como avaliação de sua eficácia anticoagulante. RESULTADOS: Houve diferença significativa quanto à atividade anticoagulante entre as amostras. Também se observou a presença de contaminação com dermatam sulfato, amostras degradadas quimicamente e com significativa alteração do peso molecular. CONCLUSÃO: Das amostras estudadas, nenhuma atendeu aos requisitos de segurança para utilização em cirurgias cardíacas com circulação extracorpórea. Nenhuma delas apresentou a qualidade semelhante ao Liquemine, não mais disponível no mercado brasileiro.

INTRODUCTION: The change in the heparin solution trade mark in Brazil that had been commonly used in cardiac surgery has shown increased number in the coagulopathy, re-exploration and other side effects in our Institution and others. METHODS: All four different heparin solutions available in the Brazilian market were studied in the Connective Tissue Lab, HUCFF, UFRJ and compared to the Liquemine (out of the market) and the international control solution. All samples were evaluated by magnetic nuclear resonance as well as their anticoagulant effectiveness. RESULTS: There were significant differences among them regarding the anticoagulant activity. It was also observed contamination with other dermatan sulfate, samples chemically degraded and with significant change in the molecular weight. CONCLUSION: Among the studied samples, none of them can offer security in cardiac surgeries on pump. None of them has demonstrated similar quality to Liquemine, which is not available in the Brazilian market.

O que evoluir no tratamento da síndrome isquêmica aguda / What will be the future of acute coronary syndrome treatment

A incidência e o risco de infarto agudo do miocárdio com supradesnivelamento do segmento ST têm diminuído nos últimos 25 anos, mas a incidência de síndrome isquêmica aguda tem-se eelvado, com risco comprarável ao do infarto agudo do miocárdio com supradesnivelamento do segmento ST. A utilização das Diretrizes, pelos cardiologistas, diminui a...

Qualidade da anticoagulação oral em ambulatório especializado de hospital terciário: um estudo piloto / Quality of oral anticoagulation in a specialized outpatient clinic of a terciary care center: a pilot study

Introdução: A anticoagulação oral constitui prática complexa, requerendo monitorização contínua de INR, educação do paciente e da equipe assistente, que deve dispor, ainda, de estrutura para manejo das complicações do tratamento.Objetivo: Descrever o perfil dos pacientes em acompanhamento no Ambulatório de Anticoagulação Oral do Serviço de Cardiologia do Hospital de Clínicas de Porto Alegre e identificar a porcentagem de pacientes dentro do INR alvo determinado.Material e métodos: Estudo descritivo, retrospectivo com a análise das fichas de acompanhamento ambulatorial dos pacientes vinculados ao Ambulatório de Anticoagulação Oral do Serviço de Cardiologia do Hospital de Clínicas de Porto Alegre. Foram registrados características dos pacientes, doenças associadas, medicamentos em uso, indicação da anticoagulação, INR alvo, eventos embólicos e sangramentos e porcentagem de pacientes dentro do INR alvo ao longo das consultas, entre outros. Resultados: Foram analisados 189 pacientes (60 mais ou menos 16 anos), com tempo de acompanhamento médio de 15 mais ou menos 10 meses e média de consultas por paciente de 10,3 mais ou menos 6,3. A média de consultas até ser atingindo o INR alvo foi de 3 mais ou menos 2,3. As indicações mais freqüentes de anticoagulação crônica foram a presença de fibrilação atrial em 95 (50,3 por cento) pacientes e as próteses valvulares mecânicas em 119 (63 por cento) pacientes. Os anticoagulantes em uso foram varfarina em 80 por cento dos casos e femprocumona em 20 por cento. Em relação à porcentagem de consultas em que os pacientes se mantiveram dentro do INR alvo observou-se que apenas 7 por cento dos pacientes estiveram dentro do INR alvo em 81-100 por cento das consultas. Considerando a primeira,décima e vigésima consultas, 63 por cento, 40 por cento e 25 por cento dos pacientes encontravam-se fora do INR alvo (P<0,01). Sangramentos ocorreram em 65 (34.4 por cento) pacientes, e eventos tromboembólicos ocorreram em apenas 3 pacientes...

Anticoagulação nas disfunções valvares / Anticoagulation of dysfunction valves

A doença valvar está associada a duas importantes ocorrências: tromboembolismo e desadaptação hemodinâmica. Ambas modificam a qualidade de vida. Desadaptação hemodinâmica altera a capacidade funcional...

Aféresis con una máquina de recuperación intraquirúrgica de sangre / Apheresis using a red blood cell saver device

Algunos autores han propuesto que una máquina de recuperación intraoperatoria de sangre, que posea la capacidad de modificar su velocidad de centrifugación a fin de ajustarla a la requisitoria de la separación de componentes sanguíneos, puede ser utilzada con este fin. La Stat-Compact de Dideco cumple con este requisito, por lo que analizamos sus posibilidades como procesador celular. Plasmaféresis terapéutica : dos pacientes con esclerosis en placa fueron tratados con 3 y 5 recambios plasmáticos respectivamente, obteniendo una disminución de la IgG en LCR (de 30,9 a 2,3 µg por ciento y de 38,9 µg por ciento a "no dosable") y evolución clínica muy favorable. Una paciente embarazada, portadora de un anticuerpo anti-D con un dosaje ponderal de 40,28 mg/ml, fue sometida a 6 recambios plasmáticos (con disminución de 28,5 mg/ml), interrumpiéndose el tratamiento por muerte fetal intraútero. En este aspecto, consideramos que, a pesar de obtener resultados auspiciosos (de acuerdo con la indicación), el número de casos no es suficiente para obtener conclusiones.

Controle laboratorial da anticoagulaçäo oral / Laboratory control of the oral anticoagulation

Objetivo. Foram testadas seis preparaçöes de tromboplastina na realizaçäo do controle laboratorial da anticoagulaçäo oral. Material e Métodos. Os reagentes testados foram: Labtest, lote n§ 0301, ISI = 1,50; Biolab, lote n§ 10252, ISI = 1,60; Baxter TPCD, lote n§ 502A, ISI = 2,55; Baxter TPC, lote n§ 13, ISI = 1,97; Baxter TPS, lote n§ 27, ISI = 1,18; e Behring, lote n§ 505771A, ISI = 1,11. Foram avaliados 31 pacientes portadores de doença tromboembólica, em uso da mesma dose de drogas antivitamina K há mais de dez dias, mediante medida do tempo de protrombina (TP). Para cada reagente foi construída curva-padräo, utilizando-se pool de plasmas normais diluído em tampäo Veronal. Os resultados obtidos em segundos foram expressos em atividade de protrombina (AP), deduzindo-se o valor na curva-padräo. Foram também expressos em RNI, calculada a partir do resultado do TP para cada paciente, e do índice de sensibilidade internacional (ISI) de cada preparaçäo de tromboplastina, fornecido pelo fabricante. Resultados. Existe discrepância entre os resultados obtidos com preparaçöes diferentes, quando se expressa o resultado em AP (p < 0,01), mas esta discrepância desaparece ao se exprimi-lo em RNI. Conclusöes. Demonstra-se a necessidade de se exprimir o resultado do TP em RNI quando do controle laboratorial das drogas antivitamina K, permitindo o ajuste de dose do medicamento com segurança, sem interferência das variaçöes de sensibilidade dos reagentes utilizados por vários laboratórios

Platelet function in patients with lupus anticoagulant and thrombosis / Función plaquetaría en pacientes con anticoagulante lúpico y trombosis

In a group of 337 patients with a history of thrombotic episodes, pregnancy losses and/or thombocytopenia, 66 cases of lupus anticoagulant (LA) were found. Spontaneous platelet aggregation and the aggregatory responses of platelet rich plasmas (PRP) from 14 patients, with a history of thrombotic episodes, with anticardiolipin (ACA) levels above 21 IgGantiphospholipid antibodies units and normal platelet counts were studied and compared with those of 8 patients with history of thrombosis and negative LA and ACA (controls). Epinephrine, adenosine diphosphate, collage and ristocetin were used as platelec aggregation inducers

Manual para pacientes con terapia anticoagulante oral / Manual by patients with oral anticoagulants therapy

Los anticoagulantes orales son farmacos utilizados en la prolilaxis y tratamiento de la enfermedad tromboembólica. Una adecuada educación del paciente es muy importante en en control de la terapia anticoagulante. El presente manual tiene la finalidad de orientar a los pacientes acerca de las indicaciones y riesgos del tratamiento con anticoagulantes orales para tratar complicaciones

Levels of natural anticoagulants, antithrombin III and protein C in diabetic vascular disease

Accelerated micro and macro vascular thrombotic disease is characteristic of diabetes mellitus. A hypercoagulable state is appreciated in this disease. We studied levels of natural anticoagulants such as Antithrombin III[AT III] and protein C which are factors to counteract the effects of hypercoagulable state. Both AT III and protein C levels were found decreased in diabetics with macrovascular disease suggesting that natural mechanism of anticlot formation are also affected in these patients, thus may be contributing to the thrombotic complications

Successful pregnancies in patients with the antiphospholipid syndrome treated with low-dose aspirin

Four patients with bad obstetrical and with positive lupus anticoagulant tests were treated with low-dose aspirin, prednisone or heparin. They had pre-term deliveries of live babies who all survived.

Sulphatide as a major glycosphingolipid in WHHL rabbit serum lipoproteins and its anticoagulant activity.

Sulphatide is found to be a major glycosphingolipid in serum lipoproteins of rabbit and its content is markedly elevated in serum of WHHL rabbit, an animal model for human familial hypercholesterolemia. On analysis of tissue sulphatide contents, serum appears to derive its sulphatide from liver (90%) and small intestine (10%) and passes on to aorta of WHHL rabbit which is found to have a large amount of sulphatide while none is found in normal aorta. Thus it seems that sulphatide finally accumulates in arterial walls along with the progression of atherosclerosis in WHHL rabbit. Since sulphatide at median concentration (8 nmole/ml serum) in various mammals is found to increase activated partial thromboplastin time by 25%, it is suggested that anticoagulant activity may be one of the physiological functions of sulphatide in serum. The observation of an increase in activated partial thromboplastin time by 2.5-fold on injection of sulphatide (10 mg/kg body wt) into rabbit suggests that sulphatide may be an effective and safe antithrombotic agent.

Estabilidad de algunos indicadores hematológicos en sangre refrigerada / Stability of some hematologic indicators in refrigerated blood

Se estudia la estabilidad de 4 indicadores hematológicos: hemoglobina, eritrocito fracción de volumen (EFV), leucocitos concentración numérica (cnum) y eritrocitos concentración numérica (cnum), en sangre almacenada en refrigeración a 4§C, utilizando 3 anticoagulantes diferentes: haparina sódica, etilendiaminotetraacético (EDTA) sal sódica y EDTA sal dipotásica. Se comparan los resultados estadísticamente y se concluye que el EDTA dipotásico es el anticoagulante con el cual se logra mayor estabilidad, además de ser más económico que la heparina sódica. Se sugiere ampliar el uso del EDTA dipotásico como anticoagulante y emplear las muestras tomadas con el mismo como elemento para el control de la calidad en Hematología y para optimizar la atención a los pacientes