Combinations of low doses of unfractionated heparin and of low-molecular-weight heparin prevent experimental venous thrombosis

Synergism between low-molecular-weight heparin and low doses of unfractionated heparin (UH) enhancing anti-factor Xa activity and the release of tissue factor pathway inhibitor was observed. The aim of this study was to verify whether this association is effective in preventing experimental venous thrombosis. Seventy rats were allocated into 7 groups: the control group treated with distilled water, the H-350 group treated with UH 350 IU/kg, the E-2 group treated with enoxaparin 2 mg/kg, the H-175 group treated with UH 175 IU/kg, the E-1 group treated with enoxaparin 1 mg/kg, the H-175 + E-1 group treated with UH 175 IU/kg plus enoxaparin 1 mg/kg, and the H-100 + E-0.5 group treated with UH 100 IU/kg plus enoxaparin 0.5 mg/kg. Forty minutes after subcutaneous injection, thrombosis was induced in vena cava. Three hours later, if present, thrombi were withdrawn and weighed. Bleeding time, activated partial thromboplastin time, thrombin time (TT), and anti-factor Xa were measured at the beginning and end of the experiment. Fortyeight other animals were treated, but without inducing thrombus, and tests were performed 40 min after injection. Thrombus developed in 90.9% of control animals, 20% of the H-350 group, 22.2% of the E-2 group, 10% of the H-175 + E-1 group, and 30% of the H-100 + E-0.5 group; there was a difference between group C and the other groups. Only in the H-350 and H-175 + E-1 groups were TT and activated partial thromboplastin time prolonged in relation to control at the end of the experiment. Forty minutes after injection, TT was prolonged in the H-350 and H-175 + E-1 groups. In conclusion, combinations of low doses of low-molecular-weight heparin and low doses of UH were as effective as high doses of each one used alone in preventing thrombus development in rat vena cava. Copyright (c) 2005 S. Karger AG, Basel.

Prophylaxis of deep-vein thrombosis after lower extremity amputation: Comparison of low molecular weight heparin with unfractionated heparin

OBJETIVO: Comparar a eficácia e segurança da profilaxia com heparina de baixo peso molecular (enoxaparina) versus heparina não fracionada (HNF). MÉTODOS: Setenta e cinco pacientes (59 homens e 16 mulheres ), submetidos a amputação maior dos membros inferiores (30 acima do joelho e 45 abaixo do joelho ), foram tratados ao acaso com HNF subcutânea (5,000 IU -2x/dia ) ou enoxaparina subcutânea (40mg/dia ) durante a hospitalização . A profilaxia teve início 12 horas antes da cirurgia ou , em casos emergenciais , no primeiro dia de pós-operatório. RESULTADOS: Os dois grupos de tratamento foram comparáveis em termos de características gerais . A avaliação da TVP foi feita por meio de exame clínico diário e pelo mapeamento dúplex antes e 5-8 dias após a cirurgia . A TVP foi documentada no lado operado em 9,75% dos pacientes tratados com enoxaparina e em 11,76% dos pacientes tratados com HNF (p=0,92) e houve um caso de TVP bilateral em cada grupo . Sangramentos não foram verificados nos 2 grupos . CONCLUSÃO: A enoxaparina e HNF foram igualmente eficientes e seguras para a profilaxia da TVP em pacientes submetidos à amputação de membros inferiores .

An open-label, comparative study of the efficacy and safety of once-daily dose of enoxaparin versus unfractionated heparin in the treatment of proximal lower limb deep-vein thrombosis

Background: Treatment of deep-vein thrombosis (DVT) with a once-daily regimen of enoxaparin, rather than a continuous infusion of unfractionated heparin (UFH) is more convenient and allows for home care in some patients. This study was designed to compare the efficacy and safety of these two regimens for the treatment of patients with proximal lower limb DVT. Methods: 201 patients with proximal lower limb DVT from 13 centers in Brazil were randomized in an open manner to receive either enoxaparin [1.5 mg/kg subcutaneous (s.c.) OD] or intravenous (i.v.) UFH (adjusted to aPTT 1.5-2.5 times control) for 5-10 days. All patients also received warfarin (INR 2-3) for at least 3 months. The primary efficacy endpoint Was recurrent DVT (confirmed by venography or ultrasonography), and safety endpoints included bleeding and serious adverse events. The rate of pulmonary embolism (PE) was also collected. Hospitalization was at the physician's discretion. Results: Baseline patient characteristics were comparable between groups. The duration of hospital stay was significantly shorter with enoxaparin than with UFH (3 versus 7 days). In addition, 36% of patients receiving enoxaparin did not need to be hospitalized, whereas all of the patients receiving UFH were! hospitalized. The treatment duration was slightly longer with enoxaparin (8 versus 7 days). There was a nonsignificant trend toward a reduction in the rate of recurrent DVT with enoxaparin versus UFH, and similar safety. Conclusions: A once-daily regimen of enoxaparin 1.5 mg/kg subcutaneous is at least as effective and safe as conventional treatment with a continuous intravenous infusion of UFH. However, the once daily enoxaparin regimen is easier to administer (subcutaneous versus intravenous), does not require aPTT monitoring, and leads to both a reduced number of hospital admissions and an average 4-day-shorter hospital stay. (C) 2004 Elsevier Ltd. All rights reserved.

Chemical reduction of carboxyl groups in heparin abolishes its vasodilatory activity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Trombose venosa profunda de membros superiores: estudo coorte retrospectivo de 52 casos

OBJETIVO: Rever os fatores predisponentes e a evolução em série de casos de trombose venosa profunda dos membros superiores de nossa instituição. MÉTODOS: Cinqüenta e dois pacientes consecutivos, com trombose venosa profunda dos membros superiores (29 homens e 23 mulheres), idade média de 52,3 anos, documentados por mapeamento dúplex (71,1%), flebografia (11,1%) ou clinicamente (15,6%), foram incluídos no presente estudo. RESULTADOS: As manifestações clínicas foram: dor no antebraço (24 casos - 46,1%), dor no braço (27 casos - 51,9%), edema do membro superior (45 casos - 86,5%), dor à compressão do membro superior (36 casos - 70,2%) e dor à movimentação do mesmo (32 casos - 61,7%). Os principais fatores de risco foram: punção ou acesso venoso (20 casos - 39,1%) e câncer (16 casos - 32,6%). As veias envolvidas foram: umeral (n = 18), axilar (n = 27), subclávia (n = 15) e jugular (n = 11). A embolia pulmonar estava inicialmente presente em quatro casos (7,6%). O tratamento inicial foi feito com heparina não-fracionada intravenosa (64,3%), subcutânea (16,7%), ou heparina de baixo peso molecular (17,1%), seguido de varfarina. Doze pacientes morreram antes da alta, em função de causas não relacionadas à embolia pulmonar. Foram acompanhados os 40 pacientes restantes por período de 3 meses a 10 anos, sendo que dois morreram de causas não relacionadas à embolia pulmonar, um paciente desenvolveu seqüelas pós-trombóticas, como edema residual e limitações aos movimentos, e seis ficaram com discretos sintomas residuais (edema e dor). CONCLUSÕES: A trombose venosa profunda dos membros superiores foi mais freqüente em pacientes submetidos a acessos venosos e com neoplasia em atividade. Comparando com dados da literatura, a evolução dos pacientes sob tratamento exclusivo com anticoagulantes foi, no mínimo, similar a outros tratamentos propostos.

Novos anticoagulantes para a profilaxia do tromboembolismo venoso em cirurgias ortopédicas de grande porte

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.

Risk-assessment algorithm and recommendations for venous thromboembolism prophylaxis in medical patients

The risk for venous thromboembolism (VTE) in medical patients is high, but risk assessment is rarely performed because there is not yet a good method to identify candidates for prophylaxis. Purpose: To perform a systematic review about VTE risk factors (RFs) in hospitalized medical patients and generate recommendations (RECs) for prophylaxis that can be implemented into practice. Data sources: A multidisciplinary group of experts from 12 Brazilian Medical Societies searched MEDLINE, Cochrane, and LILACS. Study selection: Two experts independently classified the evidence for each RF by its scientific quality in a standardized manner. A risk-assessment algorithm was created based on the results of the review. Data synthesis: Several VTE RFs have enough evidence to support RECs for prophylaxis in hospitalized medical patients (eg, increasing age, heart failure, and stroke). Other factors are considered adjuncts of risk (eg, varices, obesity, and infections). According to the algorithm, hospitalized medical patients ≥40 years-old with decreased mobility, and ≥1 RFs should receive chemoprophylaxis with heparin, provided they don't have contraindications. High prophylactic doses of unfractionated heparin or low-molecular-weight-heparin must be administered and maintained for 6-14 days. Conclusions: A multidisciplinary group generated evidence-based RECs and an easy-to-use algorithm to facilitate VTE prophylaxis in medical patients. © 2007 Rocha et al, publisher and licensee Dove Medical Press Ltd.

Fondaparinux em intervenção coronária percutânea no tratamento da síndrome coronária aguda

Background: Fondaparinux is considered an agent with a well-established safety and efficacy profile in the treatment of non-ST segment elevation acute coronary syndromes, but when used alone, is associated to a higher incidence of thrombotic complications during invasive coronary procedures, requiring the supplementation of an anti-IIa agent. This study aimed to evaluate the efficacy and safety of percutaneous coronary intervention (PCI) in patients with non-ST segment elevation acute coronary syndromes previously treated with fondaparinux. Methods: Prospective, controlled registry enrolling 127 consecutive patients submitted to an early invasive stratification during treatment with fondaparinux, with supplementation of intravenous unfractionated heparin at a dose of 85 U/kg at the time of PCI. Results: The rate of the composite primary endpoint including death, acute myocardial infarction, stroke, stent thrombosis or emergency myocardial revascularization was 3.2%. The cumulative incidence of major bleeding and vascular complications was 3.2%. There were no cases of guidecatheter thrombosis or abrupt vessel closure. Conclusions: PCI in patients with acute coronary syndromes receiving fondaparinux is associated with a low rate of major adverse cardiovascular ischemic events and severe hemorrhagic complications. Supplementation of unfractionated heparin during the invasive procedures eliminates the risk of catheter-related thrombosis.

Associação de doses baixas de heparina não fracionada e de heparina de baixo peso molecular na prevenção de trombose venosa experimental

Pós-graduação em Bases Gerais da Cirurgia - FMB

Trombose venosa profunda aguda: avaliação prospectiva do início do processo de revanalização das veias dos membros inferiores pelo mapeamento dúplex em cores

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Novos anticoagulantes para a profilaxia do tromboembolismo venoso em cirurgias ortopédicas de grande porte: revisão sistemática de ensaios clínicos randonizados

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Heparin-binding proteins of canine seminal plasma

Heparin-binding proteins (HBP) from seminal plasma have been expected to participate in modulation of the acrosomal reaction, and have been correlated with fertility in some species. However, they have not been described in the dog. The aim of this study was to document the HBPs of canine seminal plasma. Six pooled samples of seminal plasma from three crossbred dogs were used. The HBPs were isolated by heparin affinity chromatography and the fractions recovered were pooled. One-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) was carried out on 12 and 18% vertical minigels. The stained gels were scanned and the molecular weight (kDa) values for each band within a lane were calculated by image analysis software. The electrophoresis analysis of the pooled eluded fractions identified 19 bands, with molecular weights varying from 61.5 to 5.2 kDa. Previous studies, using one-dimensional SDS-PAGE, identified two bands (67 and 58.6 kDa), which were positively correlated with some semen parameters (sperm motility, sperm vigor, percentage of morphologically normal sperm and plasma membrane integrity). The 61.5 kDa band detected in the present study apparently corresponded to the 58.6 kDa band identified previously. Canine seminal plasma contained HBP; since HBP modulate the acrosome reaction in other species, they may have the same function in the dog. Further studies are necessary to better characterize this protein and determine if it is associated with fertility in the dog. (c) 2006 Elsevier B.V. All rights reserved.

DNA and heparin chaperone the refolding of purified recombinant replication protein A subunit 1 from Leishmania amazonensis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)