Mechanical heart valve thrombosis during pregnancy under non / 中南大学学报(医学版)

Anticoagulation drugs should be used for patients with mechanical heart valve (MHV) in case of potential risk of thrombosis. Pregnant women with MHV have to change therapies due to teratogenic effect of some anti-coagulation drugs. European Society of Cardiology clinical guidelines for the management of cardiovascular diseases during pregnancy gives specific suggestions for anticoagulation therapy.We have treated 2 patients with mechanical heart valve thrombosis (MVT) during pregnancy: One received low molecular weight heparin (LMWH) throughout the pregnancy and developed MVT at the third trimester of pregnancy; one developed MVT at the first trimester when replacing vitamin K antagonists (VKA) with LMWH. These patients raised secondary reflection on the balance between clinical guideline and personalized medicine. During LMWH therapy, we should dynamically monitor patients' anti-activated factor X (anti-Xa) level to evaluate coagulation function during pregnancy. When a pregnant woman with MHV develops symptoms of acute heart failure, stuck mechanical valve should be paid attention to and surgery should be promptly performed if necessary.

Caracterización de neonatos de madres con hipercoagulabilidad en régimen tromboprofiláctico / Characterization of neonates of mothers with hypercoagulability in thromboprophylactic regimen

Introducción: Hace una década, en el Instituto de Hematología e Inmunología se comenzó la tratamiento de mujeres con pérdidas recurrentes de embarazos por trastornos de hipercoagulabilidad. Objetivo: Caracterizar clínicamente a estos neonatos e identificar los efectos adversos de la terapia tromboprofiláctica en los recién nacidos. Métodos: Se realizó estudio descriptivo, de corte transversal entre enero de 2014 y agosto de 2017, que incluyó 62 recién nacidos, hijos de madres con diagnóstico de trombofilia que utilizaron durante la gestación, régimen de tromboprofilaxis con heparinas de bajo peso molecular y aspirina. Todas las gestantes fueron evaluadas con sistematicidad en las consultas de Hemostasia y Obstetricia, del Instituto de Hematología e Inmunología y Hospital Enrique Cabrera, respectivamente. Resultados: La mayoría de los neonatos nacieron a término, con apgar normal y pesos superiores a 2 500 g. El 82,3 por ciento de las gestantes comenzaron la tromboprofilaxis con menos de 5 semanas de gestación. Hubo diferencias significativas cuando se compararon los pesos de los neonatos de las madres que comenzaron el tratamiento temprano con aquellas que lo iniciaron tardíamente. El tipo de trombofilia y la edad materna no influyeron en los pesos de los neonatos, pero aquellas gestantes con sintomatología más grave tuvieron hijos de menor peso que, aunque no fue significativo, requiere una observación. Ningún recién nacido presentó efectos secundarios a la terapia tromboprofiláctica. Conclusiones: Los neonatos nacidos de madres con trombofilia que iniciaron tromboprofilaxis de forma temprana no fueron diferentes a los recién nacidos de madres sin hipercoagulabilidad(AU)

Introduction: A decade ago, at the Institute of Hematology and Immunology, treatment of women with recurrent pregnancy losses due to hypercoagulability disorders began. Objective: Clinically characterize these infants and identify the adverse effects of thromboprophylactic therapy in newborns. Methods: A descriptive and transversal study was carried out between January 2014 and August 2017, which included 62 children of mothers with a diagnosis of thrombophilia who used during pregnancy, a thromboprophylaxis regimen with low molecular weight heparins and aspirin. All pregnant women were systematically evaluated in the Hemostasis and Obstetrics consultations of the Institute of Hematology and Immunology and Hospital Enrique Cabrera. Results: The majority of the neonates were born at term, with normal apgar and weights above 2,500 g. 82.3 percent of pregnant women started thromboprophylaxis with less than 5 weeks of gestational age. There were significant differences when the weights of the infants of the mothers who started the treatment early were compared with those who started it late. The type of thrombophilia and maternal age did not influence the weights of the neonates, but those cases with more severe symptoms had children of lower weight, which although it was not significant, requires observation. No newborn presented side effects to thromboprophylactic therapy. Conclusions: Infants born to mothers with thrombophilia who started thromboprophylaxis early were not different from those born to mothers without hypercoagulability(AU)

Segurança da ablação de fibrilação atrial com RNI terapêutico: comparação com a transição com heparina de baixo peso / Safety of ablation for atrial fibrillation with therapeutic INR: comparison with transition to low-molecular-weight heparin

FUNDAMENTO: O manejo ideal da anticoagulação oral (ACO) no período pré- e pós-ablação de fibrilação atrial (FA) ainda é motivo de controvérsia. OBJETIVO: Comparar duas estratégias de anticoagulação: suspensão da warfarina com a utilização de heparina de baixo peso molecular (HBPM) e a realização da ablação sem a suspensão da warfarina, mantendo o RNI terapêutico (entre 2,0 e 3,0). MÉTODOS: 140 pacientes (pt) portadores de FA persistente/ permanente submetidos à ablação por cateter de FA foram divididos em dois grupos: no grupo I (70 pt), a warfarina foi suspensa cinco dias antes do procedimento e utilizada terapia de transição com HBPM (enoxaparina 1 mg/kg 2x/dia pré-ablação e 0,5 mg/kg 2x/dia após o procedimento); no grupo II (70 pt), a warfarina não foi suspensa e o procedimento foi realizado com RNI terapêutico. Ambos os grupos receberam heparina intravenosa (TCA > 350 seg) durante o procedimento. RESULTADOS: No Grupo I, observou-se complicação hemorrágica maior (1,4 por cento) e 4 pt (5,7 por cento) com complicações hemorrágicas menores. No Grupo II, 2 pt (2,8 por cento) apresentaram complicações hemorrágicas menores e 1 pt apresentou sangramento maior; porém, este ocorreu após uso de HBPM por RNI < 2,0. Não houve complicação tromboembólica ou morte cardiovascular nos dois grupos após 16 ± 8 meses. CONCLUSÃO: A realização de ablação por cateter de FA sem a suspensão de ACO e RNI terapêutico é uma estratégia semelhante em segurança e eficácia quando comparada à tradicional transição com HBPM, evitando um período inicial pós-ablação de anticoagulação potencialmente inadequada.

BACKGROUND: The ideal management of oral anticoagulation (OAC) before and after catheter ablation for atrial fibrillation (AF) is still controversial. OBJECTIVE: To compare two anticoagulation strategies for catheter ablation for AF: warfarin withholding and use of low-molecular-weight heparin (LMWH); and maintenance of warfarin and therapeutic INR (between 2.0 and 3.0). METHODS: 140 patients (pt) with persistent/permanent AF undergoing catheter ablation for AF were divided into two groups: Group I (70 pt), in which warfarin was withheld five days prior to the procedure and transition to LMWH was used (enoxaparin: 1 mg/kg 2x/day before ablation, and 0.5 mg/kg 2x/day after ablation); Group II (70 pt), in which warfarin was not withheld and the procedure was performed with therapeutic INR. Both groups received intravenous heparin (ACT > 350 seconds) during ablation. RESULTS: In Group I, one pt (1.4 percent) had a major hemorrhagic complication and four pts (5.7 percent) had minor hemorrhagic complications. In Group II, two pts (2.8 percent) had minor hemorrhagic complications and one pt had a major bleeding, which occurred after using LMWH due to INR < 2.0. None of the groups had thromboembolic complications or cardiovascular death over a period of 16 ± 8 months. CONCLUSION: Catheter ablation for AF without withholding OAC and with therapeutic INR is a strategy that has similar safety and efficacy when compared with the traditional transition to LMWH, avoiding the potentially inadequate anticoagulation of the initial post-ablation period.

Novos anticoagulantes para a profilaxia do tromboembolismo venoso em cirurgias ortopédicas de grande porte / New anticoagulants for the prophylaxis of venous thromboembolism

Após cerca de 50 anos de experiência com a heparina e antagonistas da vitamina K (AVK), pesquisas e estudos com novos anticoagulantes vêm evoluindo de forma crescente nos últimos anos. Embora consagrados pelo uso, os anticoagulantes tradicionais têm limitações importantes em termos de controle laboratorial, complicações, efeitos colaterais, interações com medicamentos e dieta. A heparina não fracionada (HNF) tem interação com proteínas plasmáticas e parede vascular, pode desencadear trombocitopenia induzida pela heparina (TIH), só pode ser administrada por via parenteral, exige controle laboratorial pelo teste da tromboplastina parcial ativada (TTPa), pode provocar osteoporose e alopecia quando usada por períodos prolongados e sua produção tem origem biológica. A AVK tem a vantagem de poder ser ministrada por via oral, mas o controle (feito pela razão normatizada internacional) pode ser difícil em alguns casos, já que tem início de ação demorado, janela terapêutica estreita, interação com dieta e grande número de medicamentos, pode provocar necrose de pele em portadores de deficiência de antitrombina e de proteínas C e S, e pode induzir alterações fetais quando usada na gravidez. Na década de 1980, surgiram as heparinas de baixo peso molecular, que foram uma evolução da heparina não fracionada, pois apresentaram maior biodisponibilidade, dosagem por peso corporal, sem necessidade de controle laboratorial, administração por via subcutânea, menor risco de trombocitopenia induzida pela heparina, e eficácia e segurança similares à heparina não fracionada. Na última década surgiram, então, uma série de novos anticoagulantes no mercado, os quais têm apresentado resultados promissores em várias situações de profilaxia e tratamento do tromboembolismo venoso. Nesta revisão, são apresentados as novas heparinas de baixo peso molecular, as heparinas de ultrabaixo peso molecular, os pentassacarídeos, os novos inibidores diretos do fator Xa e inibidores do fator IIa.

After about 50 years of experience with heparin and vitamin K antagonists (VKA), research and clinical studies of new anticoagulants have recently evolved . Although traditional anticoagulants have proven to be clinically useful, they have important limitations in terms of laboratory control, complications, side effects and interactions with medications and food. .Unfractionated heparin interacts with plasma proteins and the vascular wall, may trigger thrombocytopenia, can only be administered parenterally, requires control by the laboratory test of partial thromboplastin time, may cause osteoporosis and alopecia when used for long periods and it is produced from biological sources. VKA have the advantage of being administered orally, but the control (made by the international normalized ratio) can be difficult in some cases, since they have delayed onset of action and metabolism and a narrow therapeutic window. They also interact with foods and with a large number of medications, can cause skin necrosis in patients with antithrombin and protein C and S deficiencies and may induce fetal changes when prescribed in pregnancy. In the 1980ïs the low-molecular-weight heparins were developed and proved to be an evolution over unfractionated heparin, because of their greater bio-availability, fixed dose per body weight, no need for laboratory control, subcutaneous administration, lower risk of heparin-induced thrombocytopenia, and efficacy and safety similar to unfractionated heparin. Over the last decade, a series of new anticoagulants have appeared in the market and shown promising results in several situations of venous thromboembolism prophylaxis and treatment. In the present review, the new low-molecular-weight heparins, ultra-low molecular weight heparin, pentasaccharides and the new direct inhibitors of factor Xa and factor IIa.are addressed.

Inadequação de tromboprofilaxia venosa em pacientes clínicos hospitalizados / Inadequacy of thromboprophylaxis in hospitalized medical patients

O risco de tromboembolismo venoso (TEV) é alto em pacientes internados, mas pode ser reduzido com a utilização adequada de profilaxia. OBJETIVO: Avaliar a utilização e adequação de profilaxia para TEV em pacientes clínicos internados. MÉTODOS: Estudo de coorte transversal em pacientes internados por doenças clínicas em quatro hospitais de Salvador. RESULTADOS: Foram avaliados 226 pacientes: 15,5 por cento em UTIs clínicas, 79 por cento tinham idade > 40 anos e 48 por cento eram homens. A maioria (97 por cento) apresentava pelo menos um fator de risco (FR) para TEV: mobilidade reduzida em 79 por cento e diagnóstico principal como FR em 62 por cento. Dos 208 candidatos a profilaxia, 54 por cento receberam alguma forma: heparina não fracionada (HNF) em 44 por cento, heparina de baixo peso molecular (HBPM) em 56 por cento e métodos mecânicos em dois pacientes. A taxa de utilização foi semelhante entre hospitais privados e públicos (51 por cento versus 49 por cento), mas HBPM predominou em privados (97 por cento) e sem residência médica e HNF em públicos (86 por cento). HBPM foi usada mais freqüentemente que HNF em pacientes > 40 anos, em brancos que em negros ou mulatos, e menos freqüentemente em pacientes com contra-indicações para heparina. Dos 112 pacientes com profilaxia, 63 por cento receberam dosagem adequada: HBPM em 95,2 por cento e HNF em 20,4 por cento. Profilaxia para TEV foi adequada em apenas 33,6 por cento (70/208) dos pacientes. CONCLUSÃO: FR para TEV são freqüentes em pacientes clínicos. Existe ampla variabilidade da profilaxia prescrita em hospitais públicos e privados. HBPM é utilizada mais adequadamente que HNF, entretanto, apenas a minoria dos pacientes clínicos hospitalizados e candidatos a profilaxia recebem dosagem adequada.

BACKGROUND: The risk of venous thromboembolism (VTE) is high in hospitalized patients, however it can be reduced by adequate prophylaxis. OBJECTIVE: To evaluate the adequacy of VTE prophylaxis in hospitalized medical patients. METHODS: A cross-sectional study was performed in hospitalized patients with acute medical illnesses in 4 hospitals of Salvador. RESULTS: We evaluated 226 consecutive patients: 15.5 percent in medical ICU, 79 percent > 40 years of age and 48 percent male. The majority (97 percent) had a least 1 risk factor (RF) for VTE, 79 percent had reduced mobility and 62 percent were diagnosed as having a RF at admission. Of the 208 prophylaxis candidates, 54 percent received some form of prophylaxis: unfractionated heparin (UFH) in 44 percent, low molecular weight heparin (LMWH) in 56 percent and mechanical methods in 2 patients. The utilization rate was similar in private and public hospitals. (51 percent vs. 49 percent), but LMWH was more common in private hospitals, without a residence program (97 percent), and UFH in the public ones (86 percent). LMWH was more frequently used than UFH in patients > 40 years of age, more often in Caucasian than in Black patients, and less frequently in those with contraindications for heparin. Of the 112 patients receiving prophylaxis, 63 percent received adequate dosages: LMWH in 95.2 percent and UFH in 20.4 percent. VTE prophylaxis was adequate in only 33.6 percent (70/208) of the patients. CONCLUSION: Risk Factors for VTE were frequent in medical patients. There was considerable variability of the VTE prophylaxis prescribed in private and public hospitals. LMWH was used more appropriately than UFH. However, only a minority of patients candidates for prophylaxis, received adequate dosages.

Comparison of unfractionated heparin vs low molecular weight heparin in the treatment of acute deep vein thrombosis

To compare the results of unfractionated heparin [UFH] with low molecular weight heparin in the treatment of acute deep vein thrombosis of lower limb. Randomized control trial. Bolan Medical Complex Hospital, Quetta from January 2002 to July 2003. Thirty patients who presented with acute deep vein thrombosis of lower limb, confirmed by either Doppler ultrasonography or venography, were selected for the study. Patients were divided randomly into two groups for treatment. Group 1 was started with unfractionated heparin while group 2 with low molecular weight heparin. Comparison of two treatments to determine the efficacy was done by certain criteria like pain improvement, reduction in swelling, alteration in bleeding profile, complications of therapy, recurrence, morbidity and mortality. The age of the patients ranged from 16-82 years. There were 15 females [50.00%] and 15 males [50.00%]. Pain and swelling were present in all patients [100%], while temperature and superficial vein dilation in 43.3% and 30% respectively. The distribution of DVT in left lower limb was in 13 patients [43.33%], right lower limb involvement in 12 patients [40.00%] and both limbs involvement in 5 patients [16.67%]. In group 1 improvement in pain occurred after 4th day in 13 patients, while in group 2 before 4th day in 8 patients [p-value=0.068]. Improvement in swelling was observed after 6th day in 11 patients [group 1], while before 6th day in 8 patients [group 2] [p-value=0.171]. Bleeding time was prolonged in 5 patients in group1and statistically found significant [p-value=0.014], while in group 2 it was normal. Thromboembolism in 3 patients and major bleeding was observed in 2 patients in group 1, while in group 2 it was normal. Recurrence was reported in 2 patients in group 1 and 1 patient in group 2 [p-value 0.0815]. The hospital stay was more than 10 days in group1 [12 patients], and less than 10 days in group 2 [13 patients]. It was found statistically significant [p-value=0.001]. Three patients died in group 1, while no mortality was observed in group 2. Treatment with low melecular weight heparin [LMWH] has good patient compliance and is easy to administer. LMWH has an advantage over UFH due to its normal bleeding profile and significantly less hospital stay

Thrombolytic therapy in acute pulmonary embolism due to heparin-induced thrombocytopenia type II

Hospitalized patients are in danger of deep venous thrombosis either due to a genetic tendency, immobilization or the underlying medical condition. Paradoxically heparin, the substance used to prevent this complication, can lead to thrombo-embolic phenomena, which can be life threatening. We report a case of heparin-induced thrombocytopenia, which caused a massive pulmonary embolism, and its management by administering a thrombolytic agent in a situation where bleeding seems inevitable

Evaluación de factores predisponentes para el sangrado mediastinal en cirugía de revascularización miocárdica: Papel del ácido acetilsalicílico, otros antiagregantes plaquetarios, y anticoagulantes / Evaluation of Predisposing Factors for Mediastinal Bleeding in Myocardial Revascularization Surgery: Role of Acetylsalicylic Acid, Other Platelet Adhesion Inhibitors, and Anticoagulants

Propósito del trabajo: Determinar los factores predisponentes para sangrados perioperatorios en cirugía de revascularización miocárdica y establecer el papel de ácido acetilsalicílico, otros antiagregantes plaquetarios, y anticoagulantes, en la ocurrencia de estos sangrados. Método: Se realizó un análisis multivariado de 251 pacientes sometidos a cirugía de revascularización miocárdica en el año 2002. Resultados: En la administración prequirúrgica de ácido acetilsalicílico no se encontró diferencia significativa para la ocurrencia de sangrado perioperatorio importante. No existió incremento significativo en la transfusión de unidades de paquetes globulares, plaquetas, crioprecipitados. Los pacientes con administración de heparina no fraccionada y de bajo peso molecular, tuvieron un sangrado transoperatorio significativamente mayor (p < 0.001) que los pacientes sin este fármaco. El empleo del resto de los fármacos estudiados, no incrementó la cantidad de sangrado ni la administración de hemoderivados. Conclusiones: No existe evidencia estadística que justifique suspender la administración de antiagregantes plaquetarios en los pacientes con síndromes coronarios urgentes o electivos, a quienes se les someta a cirugía de revascularización miocárdica. Sin embargo, resultaría conveniente suspender la administración de heparina no fraccionada y de bajo peso molecular, a pacientes sometidos a cirugía de revascularización miocárdica en forma electiva.

Objective: To determine the main factors for perioperative mediastinal bleeding during coronary artery by-pass grafting and to establish the role of acetylsalicylic acid, other inhibitors of platelet adhesion, and anticoagulants in its occurrence. Methods: A multivariate analysis was performed to the data obtained from 251 patients subjected to coronary artery by-pass grafting in the year 2002. Results: There were no significant differences for the occurrence of perioperative bleeding induced by the preoperative administration of acetylsalicylic acid. No significant increment in the need for blood, platelet, or cryoprecipitates transfusion existed. Patients receiving non-fractionated or low molecular weight heparin had a significantly greater (p < 0.001) transoperative bleeding than patients without this drug. Administration of the other studied drugs did not increase either mediastinal bleeding or the need for blood derivatives. Conclusions: No statistical evidence was found to suspend administration of inhibitors of platelet adhesion in patients with coronary syndromes, subjected to coronary artery by-pass grafting. However, data obtained suggest the convenience of suspending administration of low molecular weight or non-fractionated heparin to patients subjected electively to coronary artery by-pass grafting.

Pentasaccharides: the new anticoagulants

Venous thromboembolism VTE remains a common but preventable disease. The last decade has witnessed major advances in VTE treatment and prophylaxis. Low molecular weight heparins LMWH became the agents of choice in the treatment of deep venous thrombosis DVT and are increasingly used in the treatment of stable pulmonary embolism PE. Increasing focus on simplicity and efficacy has led to the discovery of the synthetic pentasaccharides, substances that specifically inhibit factor Xa activity, producing an antithrombotic effect without affecting other coagulation factors or platelets. Fondaparinux, the first pentasaccharide introduced into the market, was first tried as a prophylactic agent against VTE in patients undergoing major orthopedic procedures, such as hip fracture, total hip and knee replacements, such approach appeared to be more effective than LMWH. Fondaparinux was also used, with promising results, in prophylaxis in patients undergoing major abdominal surgery and high risk medical patients. Pentasaccharides were recently tried in the treatment of both DVT and PE. The largest clinical investigation program ever undertaken in this therapeutic area, has shown that pentasaccharides are as safe and as effective as either unfractionated heparin UFH or LMWH, with the added convenience of once daily injection, no need for monitoring the anticoagulant effect and no major side effects such as thrombocytopenia. Therefore, the efficacy, the safety profile and the added convenience for both patients and physicians alike, will probably keep pentasaccharides as the front runner among new anticoagulants of the future. This article focuses on the use of fondaparinux as a prophylactic agent against VTE in patients undergoing major orthopedic and abdominal surgery along with high risk medical patients; it will also discuss the recent promising data on its use to treat active DVT and PE