RESUMO
OBJECTIVE: To investigate the effect of natural hirudin on revascularization of ischemic skin flap in rats using Micro-CT and three-dimensional (3D) reconstruction. METHODS: Thirty-two Sprague Dawley rats were prepared a ischemic skin flap (8.0 cm×1.8 cm) model on the back and randomly divided into hirudin group and control group (16 rats in each group). At immediate and within 3 days after operation, the rats were treated with hypodermic injection of natural hirudin 0.3 mL (including natural hirudin 6 ATU) every day in hirudin group and the equal amount of normal saline in control group. At 6 days after operation, the survival rate of skin flap was evaluated, histological changes were observed by HE staining, and the volemia, length of blood vessels, and number of blood vessels were analyzed with Micro-CT 3D reconstruction. RESULTS: Both groups of rats survived to the end of the experiment without infection. Different degrees of necrosis occurred in the distal part of the skin flaps in both groups at 6 days after operation, but the flap survival rate of the hirudin group (72.11%±8.97%) was significantly higher than that of control group (58.94%±4.02%) ( t=3.280, P=0.008). Histological observation showed that the histological hierarchy of the hirudin group was clearer than that of the control group, with more microangiogenesis and less inflammatory response and inflammatory cell infiltration. Micro-CT 3D reconstruction showed that the flap vessels in the hirudin group were more and denser, and the volemia, length of blood vessels, and number of blood vessels were significantly higher than those in the control group ( P<0.05). CONCLUSION: Natural hirudin can reduce the inflammation of tissue, promote the regeneration and recanalization of blood vessels in ischemic skin flap, so as to improve the survival rate of the flap.
Assuntos
Sobrevivência de Enxerto , Terapia com Hirudina , Transplante de Pele , Pele/irrigação sanguínea , Animais , Inflamação , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Microtomografia por Raio-XRESUMO
Bivalirudin, a direct thrombin inhibitor with a fast onset of action and short half-life, is often referred to as an alternative anticoagulant to a heparin/protamine regimen. Bivalirudin demonstrated promising results as an anticoagulant in cardiac surgery with and without cardiopulmonary bypass, postcardiotomy extracorporeal membrane oxygenation, interventional cardiology and endovascular procedures, and particularly in the treatment of patients with heparin-induced thrombocytopenia undergoing high-risk cardiac surgery. Currently, bivalirudin in cardiac surgery with cardiopulmonary bypass has a limited clinical spectrum, likely because the still obvious advantages of its competitor, heparin, outweigh it in terms of medical costs, established point-of-care monitoring systems, and availability of protamine as a reversal agent. The unique pharmacology of the drug also requires adjustment of surgical and perfusion strategy. In contrast, in off-pump coronary artery surgery, established protocols from interventional cardiology can be easily translated into the operating room. In this setting bivalirudin has the potential for a more important role in the future. Through a triple mechanism of action-inhibition of plasma thrombin, clot bound thrombin, and collagen-induced platelet activation-bivalirudin may perform better than heparin by attenuating the immediate postoperative prothrombotic state and thus positively impacting the early coronary graft patency after off-pump coronary artery bypass grafting. Further studies are necessary to better evaluate this niche field and discover further applications for this unique anticoagulant.
Assuntos
Anticoagulantes/uso terapêutico , Terapia com Hirudina , Hirudinas , Fragmentos de Peptídeos/uso terapêutico , Adulto , Heparina/uso terapêutico , Humanos , Proteínas RecombinantesRESUMO
OBJECTIVE: Vascular plug formation by mechanical injury that exposes abundant extracellular matrix is an ideal model to mimic thrombus formation. The objective of this study was to standardize our previously established in vivo mouse model of thrombus formation induced by mechanical injury. RESULTS: The mechanical injury was exerted by pinching the abdominal aorta with hemostatic forceps for either 15 (moderate injury) or 60 (severe injury) seconds. Thrombus formation was monitored for 20min in real time using a fluorescent microscope coupled to a CCD camera. In the moderate injury, thrombus formation peaked at approximately 1min after injury and resolved within 3min, with the mean AUC (area under the curve) of 165.2±17.29mm(2), whereas a larger thrombus was observed upon the severe injury, with the mean AUC of 600.5±37.77mm(2). Using scanning electron microscopy and HE staining, a complete deformation of the endothelium in the moderate injury model and the exposure of the media in the severe injury model were observed. The model was also evaluate for its application on the effects of antithrombotic drugs targeting GP IIb-IIIa (eptifibatide), ADP receptor P2Y1 (MRS2500) and P2Y12 (clopidogrel), and thrombin (hirudin) on thrombus formation. CONCLUSIONS: We have improved a vascular injury model with optimal reproducibility and feasibility that allows evaluating the effect of anti-thrombotic drugs on thrombus formation in vivo.
Assuntos
Aorta/lesões , Aorta/patologia , Trombose/etiologia , Trombose/patologia , Animais , Aorta/efeitos dos fármacos , Clopidogrel , Modelos Animais de Doenças , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Eptifibatida , Terapia com Hirudina/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peptídeos/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Estresse Mecânico , Trombose/tratamento farmacológico , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêuticoRESUMO
We aim to investigate the effects of locally injected natural and recombinant hirudin on vascular endothelial growth factor (VEGF) expression and flap survival in venous congested skin flaps using a rat model. A dorsal random skin flap (10 × 3 cm) was prepared on each of 30 Wistar rats to establish a venous congested model. The rats were randomly divided into 2 treatment groups [receiving subcutaneous injection of either natural hirudin (6 U) or recombinant hirudin (6 U)] and a control group, which received subcutaneous injection of physiologic saline. After treatment, skin flap survival rates were calculated. VEGF messenger RNA levels and VEGF-positive vessel density as a marker for VEGF levels were measured in the flaps during and after treatment. The skin flap VEGF messenger RNA levels increased in the natural hirudin-treated group. The VEGF-positive vessel density was increased in all 3 groups. Statistically significant increases of VEGF levels were observed in the natural and recombinant hirudin-treated groups compared with the control group (P < 0.05). The skin flap survival rates were improved in both hirudin treated groups. Natural and recombinant hirudin can increase VEGF expression in random skin flaps, which can potentially improve random skin flap survival in rats through angio genic mechanisms. Our results showed that hirudin treatment led to an increase in VEGF expression in the congested skin flaps. Natural hirudin demonstrated more pronounced effects than recombinant hirudin. Further studies are needed to understand the specific mechanisms.
Assuntos
Anticoagulantes/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Hirudinas/farmacologia , Hiperemia/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Retalhos Cirúrgicos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Anticoagulantes/uso terapêutico , Biomarcadores/metabolismo , Sobrevivência de Enxerto/fisiologia , Terapia com Hirudina , Hiperemia/etiologia , Distribuição Aleatória , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Retalhos Cirúrgicos/irrigação sanguínea , Retalhos Cirúrgicos/fisiologia , Resultado do TratamentoRESUMO
OBJECTIVES: To this day, a standardized protocol for medicinal leech therapy does not exist. The purpose of this article was to review literature in the hope of proposing a unified, coherent, feasible, and safe protocol for using medicinal leeches when warranted. STUDY DESIGN: A literature search was conducted in the following databases: PubMed, MDConsult, The Cochrane Library, OMIM, and Google. This was supplemented by a search for selected authors. Keywords used were medicinal leech therapy, leech therapy, leeching, replantation, thromboembolism, venous congestion, Hirudo medicinalis, Hirudotherapy, leech protocol, and Hirudo protocol. RESULTS: Based on titles and abstracts, 26 articles and 1 Web site were identified. CONCLUSIONS: Leech therapy can be an excellent alternative for the treatment of venous congestion in free flaps, pedicled flaps, and replanted tissues. Psychological precounseling, antibiotic therapy, number of leeches to be used, length of therapy, and laboratory checks should be taken into consideration before initiating therapy.
Assuntos
Protocolos Clínicos , Traumatismos Cranianos Fechados/terapia , Terapia com Hirudina/métodos , Hirudo medicinalis , Hiperemia/terapia , Aplicação de Sanguessugas/métodos , Lesões do Pescoço/terapia , Animais , Feminino , Humanos , Masculino , Neovascularização Fisiológica/fisiologiaRESUMO
Recombinant hirudins (desirudin, lepirudin) are direct thrombin inhibitors administered as anticoagulants for heparin-induced thrombocytopenia (HIT) and venous thromboembolism (VTE) prophylaxis. Although these small polypeptides are widely used, concern exists over reports of antigenicity. In the largest study of r-hirudin immunogenicity to-date, we evaluated the prevalence, quantity and specificity of IgG immune responses to desirudin (15 mg SC q12h for as long as clinically required) in 245 surgical and medically-ill subjects enrolled in DESIRABLE, a multicenter, open-label, clinical trial of hospitalized patients requiring VTE prophylaxis. Sera obtained before and 30 days after desirudin administration were analyzed for IgG anti-desirudin by immunoenzymetric assay using immobilized desirudin to bind desirudin-reactive antibody and peroxidase conjugated monoclonal-anti-human IgG Fc to detect bound IgG antibody. Of 245 study subjects, 19 (7.7%) were antibody "responders" (>2-fold increase in IgG antibody levels with >50% inhibition by desirudin 30 days post-treatment). There were no differences between responders and non-responders in incidence of clinical outcomes or bleeding-related adverse events. Forty-six patients had detectable desirudin-reactive IgG antibody prior to treatment, with no significant increase in antibody levels after exposure and no increase in clinical events. The origin of pre-existing hirudin-reactive IgG antibody requires further investigation involving suspected anti-thrombin-thrombin interactions. These results indicate a low potential for immunogenicity, with <8% of patients developing IgG antibodies after desirudin administration for VTE prophylaxis. In contrast to reports on lepirudin, production of anti-hirudin antibodies to desirudin has no apparent effect on clinical events.
Assuntos
Anticorpos/imunologia , Hirudinas/imunologia , Técnicas Imunoenzimáticas/métodos , Trombina/imunologia , Idoso , Anticorpos/sangue , Anticorpos Monoclonais/imunologia , Especificidade de Anticorpos , Antitrombinas/administração & dosagem , Antitrombinas/imunologia , Feminino , Heparina/efeitos adversos , Terapia com Hirudina , Hirudinas/administração & dosagem , Hirudinas/genética , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Reprodutibilidade dos Testes , Trombocitopenia/induzido quimicamente , Trombocitopenia/prevenção & controle , Fatores de Tempo , Tromboembolia Venosa/induzido quimicamente , Tromboembolia Venosa/prevenção & controleRESUMO
The aim of this study was to observe the effect of hirudin on the expression of lung tissue protease activated receptor-1 (PAR-1) and the correlation between inflammation factors and the expression of PAR-1 after hirudin pre-treatment and to provide the theoretical basis for the treatment of lung injury by hirudin. Wistar rats of the model group were intraperitoneally administered endotoxin by injection (LPS 10 mg/kg) to copy acute lung injury (ALI) animal models, while the rats of the control group were injected with an equal amount of physiological saline. The rats of the hirudin groups were injected with hirudin and endotoxin intraperitoneally at the same time. The lung tissue was stained by HE dye to detect tumor necrosis factor α (TNF-α) and matrix metallo-proteinase 12 (MMP12) content. RT-PCR was applied to test PAR-1 mRNA expression. The results showed that the expression of PAR-1 mRNA of lung tissue increased significantly, but declined with the increased doses of hirudin when lung injury due to endotoxin occurred. The content of TNF-α and MMP12 was significantly lower compared to that of the endotoxin group. The difference was statistically significant (p<0.05). Hirudin reduced the release of TNF-α and MMP12 in mice by inhibiting the production of PAR-1 and reduced the content of TNF-α and MMP12. Thus, we deduced that hirudin inhibits the inflammation and fibrosis caused by lung injury and plays a role in lung protection as an anti-inflammatory mediator.
Assuntos
Fibrinolíticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hirudinas/farmacologia , Metaloproteinase 12 da Matriz/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Animais , Modelos Animais de Doenças , Fibrinolíticos/administração & dosagem , Terapia com Hirudina , Hirudinas/administração & dosagem , Lipopolissacarídeos/toxicidade , Ratos , Ratos Wistar , Receptor PAR-1/genética , Receptor PAR-1/metabolismoRESUMO
The medicinal leech, Hirudo medicinalis, is an excellent example of the use of invertebrates in the treatment of human disease. Utilized for various medical indications since the ancient times, the medicinal leech is currently being used in a narrow range of well-defined and scientifically-grounded clinical applications. Hirudotherapy is most commonly used in the setting of venous congestion associated with soft tissue replantations and free flap-based reconstructive surgery. This is a comprehensive review of current clinical applications of hirudotherapy, featuring a comprehensive search of all major medical search engines (i.e. PubMed, Google Scholar, ScientificCommons) and other cross-referenced sources. The authors focus on indications, contraindications, practical application/handling of the leech, and therapy-related complications.
Assuntos
Hirudo medicinalis , Hiperemia/terapia , Aplicação de Sanguessugas , Animais , Terapia com Hirudina , Humanos , Reimplante , Retalhos Cirúrgicos/irrigação sanguíneaRESUMO
Thrombin inhibition is an important objective in the prevention and treatment of thrombosis. A new molecule, dabigatran etexilate or Pradaxa(®), has been recently licensed for thromboprophylaxis in major orthopedic surgery in several countries but not in the USA. In contrast, the FDA has approved it for prevention in patients with non-valvular atrial fibrillation. This new orally active anticoagulant is being developed for the treatment of venous thromboembolism and acute coronary syndromes in patients with non-valvular atrial fibrillation. Dabigatran is a reversible inhibitor of free thrombin and clot-bound thrombin. An oral thrombin inhibitor melagatran is no longer available due to hepatic toxicity. Several other thrombin inhibitors are used via parenteral administration: lepirudine and desirudine, bivalirudine and argatroban. They are mostly given to patients with heparin-induced thrombocytopenia (HIT). Bivalirudine is used for acute coronary syndrome in patients undergoing percutaneous interventions. The main pharmacologic characteristics of thrombin inhibitor agents are presented focusing on dabigatran etexilate and including the main results of clinical trials.
Assuntos
Antitrombinas/uso terapêutico , Benzimidazóis/uso terapêutico , Terapia com Hirudina , Fragmentos de Peptídeos/uso terapêutico , Piridinas/uso terapêutico , Trombose/prevenção & controle , Anticoagulantes/uso terapêutico , Benzimidazóis/efeitos adversos , Contraindicações , Dabigatrana , Interações Medicamentosas , Heparina/efeitos adversos , Hirudinas , Humanos , Procedimentos Ortopédicos/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Piridinas/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Trombocitopenia/induzido quimicamente , Trombose/etiologia , Trombose Venosa/tratamento farmacológicoRESUMO
BACKGROUND: Ischemia-reperfusion injury impairs lung transplant outcomes. The transcription factors, activator protein-1, and nuclear factor kappa B, are activated early in reperfusion and drive the development of injury. Thrombin inhibition with hirudin, and calcineurin inhibition with tacrolimus have independently been shown to ameliorate lung ischemia-reperfusion injury by reducing activator protein-1 and nuclear factor kappa B activation, respectively. However, high doses were required to achieve protection using individual agents, raising concerns about potential toxicities. We sought to determine if low-dose combination therapy reduced injury through synergistic inhibition of pretranscriptional signaling events. METHODS: Rats were pretreated with either intravenous hirudin or tacrolimus at low doses or high doses, or both at low doses, prior to undergoing left lung ischemia and reperfusion. Lungs were assessed for markers of lung injury, including bronchoalveolar lavage cytokine-chemokine content and transcription factor transactivation of activator protein-1 and nuclear factor kappa B. RESULTS: High-dose monotherapy with hirudin or tacrolimus reduced lung injury and transactivation of activator protein-1 and nuclear factor kappa B activation, respectively, whereas low-dose monotherapy with either agent did not alter transcription factor activation or lung injury compared with positive controls. Low-dose combination therapy was more protective than high-dose monotherapy with either drug, and correlated with a reduction in activation of both transcription factors and their associated cytokines. CONCLUSIONS: The significant decrease in lung injury severity and transcription factor activation with combined pathway inhibition suggests pretranscriptional signaling redundancy between the calcineurin and thrombin dependent pathways in lung reperfusion injury.
Assuntos
Inibidores de Calcineurina , Terapia com Hirudina , Pulmão/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Tacrolimo/uso terapêutico , Trombina/antagonistas & inibidores , Animais , Sinergismo Farmacológico , Quimioterapia Combinada , Ratos , Ratos Long-EvansRESUMO
The clinical observation that thrombosis in some patients heralds the onset of malignancy has been recognized for over a century. Thrombin the key terminal enzyme of coagulation also promotes angiogenesis and stimulates tumor-platelet adhesion, adhesion to endothelium, tumor implantation, tumor cell growth and metastasis. The thrombin receptor, a member of the protease-activated receptor family, is expressed on many tumor cell lines and on breast tumor biopsy specimens. In addition to mitogenic effects on fibroblast, smooth muscle cells and endothelial cells, thrombin also exerts direct effects on cancer cells by activation of the cell cycle through downregulation of p27(Kip1) and induction of Skp2, and cyclins D and A. MicroRNA 222, which inhibits p27(Kip1), is upregulated by thrombin. In the transgenic TRAMP mouse model of prostate cancer inhibition of endogenous thrombin by hirudin retards spontaneous tumor growth. Inhibition of thrombin may lead to tumor dormancy and could explain inhibition of tumor growth and metastasis by anticoagulants observed in animal models and a beneficial effect on survival observed in some clinical trials of anticoagulants in cancer patients.
Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Neoplasias da Próstata/etiologia , Trombina/fisiologia , Animais , Linhagem Celular , Ciclina A/metabolismo , Ciclina D/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Terapia com Hirudina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , MicroRNAs/metabolismo , Oligopeptídeos/uso terapêutico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Receptores de Trombina/metabolismo , Membro 25 de Receptores de Fatores de Necrose Tumoral/genética , Membro 25 de Receptores de Fatores de Necrose Tumoral/metabolismo , Proteínas Quinases Associadas a Fase S/genética , Proteínas Quinases Associadas a Fase S/metabolismoRESUMO
(1) The standard anticoagulant for preventing thromboembolic events after hip or knee replacement surgery is a subcutaneous low-molecular-weight heparin such as enoxaparin; (2) Dabigatran, a specific thrombin inhibitor, was recently licensed for oral prophylaxis in this setting, as dabigatran etexilate (mesilate), a prodrug; (3) The clinical evaluation of dabigatran in this indication is based on two comparative double-blind trials with similar protocols, comparing dabigatran 150 mg or 220 mg/day versus enoxaparin in 3494 patients undergoing hip replacement surgery and 2101 patients undergoing knee replacement surgery. The results were virtually identical: compared with enoxaparin, dabigatran did not reduce overall mortality (almost zero in the different groups), the frequency of symptomatic pulmonary embolism (almost zero in the different groups), or the frequency of symptomatic deep venous thrombosis (0.1% to 1.2%); (4) There was no difference between the groups with respect to the frequency of severe bleeding (about 1.5%), hepatic disorders (about 4%), or acute coronary events (a few cases). But dabigatran was associated with surgical wound seepage in 7% of patients, versus 4.7% with enoxaparin; (5) The anticoagulant effect of dabigatran, and therefore the frequency of haemorrhage, increases with age and in cases of renal failure. However, clinical trials included relatively few elderly patients and/or patients with renal failure, who nonetheless represent a large proportion of the candidates for hip or knee replacement; (6) Dabigatran becomes more potent when combined with P-glycoprotein inhibitors or with drugs that impair renal function. Combination with other antithrombotic drugs should be avoided. (7) Dabigatran is administered orally, while enoxaparin requires daily subcutaneous injections. Dabigatran therapy does not necessitate laboratory monitoring, while the platelet count must be monitored with enoxaparin. There is no known antidote for dabigatran overdose; (8) In summary, for the prevention of venous thromboembolic events after orthopaedic surgery, it is better to continue to use heparins, at least pending more thorough evaluation of dabigatran.
Assuntos
Benzimidazóis/uso terapêutico , Enoxaparina/uso terapêutico , Inibidores do Fator Xa , Pró-Fármacos/uso terapêutico , Piridinas/uso terapêutico , Trombina/antagonistas & inibidores , Tromboembolia/prevenção & controle , Trombose Venosa/prevenção & controle , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Dabigatrana , Aprovação de Drogas , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Fibrinolíticos/administração & dosagem , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , França , Hemorragia/induzido quimicamente , Heparina/administração & dosagem , Heparina/efeitos adversos , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Terapia com Hirudina , Humanos , Pró-Fármacos/administração & dosagem , Pró-Fármacos/efeitos adversos , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Trombose Venosa/tratamento farmacológico , Trombose Venosa/etiologia , Vitamina K/antagonistas & inibidoresRESUMO
The prothrombotic and hemostatic-altering environment that characterizes cardiac surgery in general and cardiopulmonary bypass (CPB) in particular is unparalleled in medicine, causing, in an alarming number of patients, both thrombotic and hemorrhagic events. Fundamentally, the primary objective of anticoagulant therapy during CPB is to prevent thrombin generation and its attendant prothrombotic, proinflammatory, and vascular effects. Though anticoagulation with unfractionated heparin has been the standard of care for more than a half-century for patients undergoing cardiac surgery, inherent limitations, and an unfavorable safety profile will increasingly stimulate the investigation and development of more safe and effective therapies.
Assuntos
Anticoagulantes/uso terapêutico , Ponte Cardiopulmonar , Heparina de Baixo Peso Molecular/uso terapêutico , Heparina/análogos & derivados , Heparina/uso terapêutico , Antagonistas de Heparina/uso terapêutico , Terapia com Hirudina , Humanos , Protaminas/uso terapêuticoRESUMO
UNLABELLED: The authors present the case of a patient with heparin induced thrombocytopaenia who needed anticoagulation during the perioperative period of a third repeat cardiac operation without transfusions. Prostacyclin pretreatment was contraindicated because of critical aortic stenosis, heparinoids could not have been used due to necessity of postoperative anticoagulation. Recombinant hirudin was applied and its effect was monitored with ekarin coagulation time. Hirudin anticoagulation was continued until the proper INR was reached in the postoperative period. There were no intra- and postoperative complications detected, and there was no need for transfusion either. On his long-term follow-up, 6.5 years after the last cardiac surgery the patients was feeling well and had no complaints. CONCLUSION: Open heart operation of a patient with heparin induced thrombocythopenia can be performed safely by total anticoagulation with lepirudin if it is conducted by ecarin clotting time.
Assuntos
Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Heparina/efeitos adversos , Terapia com Hirudina , Hirudinas/administração & dosagem , Trombocitopenia/induzido quimicamente , Testes de Coagulação Sanguínea/métodos , Endopeptidases , Heparina/administração & dosagem , Terapia com Hirudina/métodos , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Proteínas Recombinantes/administração & dosagem , Reoperação , Resultado do TratamentoRESUMO
This review discusses the pharmacology and clinical applications of hirudin, a bivalent direct thrombin inhibitor (DTI). Besides the current major indication for hirudin--anticoagulation of patients with heparin-induced thrombocytopenia (HIT)--the experience with hirudin in other indications, especially acute coronary syndromes, are briefly presented. Hirudins have been formally studied prior to their regulatory approval; however, important information on their side effects and relevant preventative measures only became available later. Therefore, current recommendations and dosing schedules for hirudin differ considerably from the information given in the package inserts. Drawbacks of hirudin and important precautions for avoiding potential adverse effects are discussed in detail in the third part of this review.
Assuntos
Anticoagulantes/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Fibrinolíticos/uso terapêutico , Terapia com Hirudina , Hirudinas , Trombina/antagonistas & inibidores , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/terapia , Angioplastia Coronária com Balão/efeitos adversos , Animais , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/imunologia , Anticoagulantes/farmacocinética , Testes de Coagulação Sanguínea , Ponte Cardiopulmonar , Monitoramento de Medicamentos , Fibrinolíticos/administração & dosagem , Fibrinolíticos/efeitos adversos , Fibrinolíticos/imunologia , Fibrinolíticos/farmacocinética , Hemorragia/induzido quimicamente , Hemostasia Cirúrgica/métodos , Heparina/efeitos adversos , Hirudinas/administração & dosagem , Hirudinas/efeitos adversos , Hirudinas/imunologia , Hirudinas/farmacocinética , Humanos , Protrombina/metabolismo , Diálise Renal , Trombina/metabolismo , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológico , Trombose/sangue , Trombose/tratamento farmacológico , Trombose/etiologia , Procedimentos Cirúrgicos VascularesRESUMO
BACKGROUND: Lepirudin, a recombinant hirudin, is a direct acting thrombin inhibitor that has been used as a heparin alternative in patients with heparin-induced thrombocytopenia requiring on-pump cardiac surgery. To evaluate the efficacy, safety, and clinical utility of lepirudin as a cardiopulmonary bypass (CPB) anticoagulant, we compared lepirudin with heparin in a routine CPB setting. METHODS: Twenty patients were randomly assigned to receive lepirudin (0.25 mg/kg b. w. bolus and 0.2 mg/kg b. w. added to the CPB priming) or heparin (400 U/kg b. w. bolus) with protamine reversal. Lepirudin and heparin anticoagulation during CPB was monitored using the ecarin clotting time or ACT, respectively and additional lepirudin (5 mg) or heparin (5000 U) boluses were administered. RESULTS: The CPB circuit was performed in both groups without thromboembolic complications. Median blood loss during the first 36 hours was statistically higher ( P = 0.007) in the lepirudin group (1.226 +/- 316 ml) compared to the heparin group (869 +/- 189 ml). One patient of the lepirudin group developed pulmonary embolism 24 hours after surgery. This patient was tested homozygous for the FV-Leiden mutation. CONCLUSION: Lepirudin provides effective CPB anticoagulation but induces a higher postoperative blood loss than heparin. Lepirudin should be restricted to patients undergoing CPB who cannot be exposed to heparin.
Assuntos
Anticoagulantes/uso terapêutico , Ponte Cardiopulmonar , Ponte de Artéria Coronária , Heparina/uso terapêutico , Terapia com Hirudina , Perda Sanguínea Cirúrgica , Doença da Artéria Coronariana/cirurgia , Hirudinas/sangue , Humanos , Período Intraoperatório , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/induzido quimicamente , Proteínas Recombinantes/sangue , Proteínas Recombinantes/uso terapêuticoRESUMO
Medical leech therapy has enjoyed a renaissance in the world of reconstructive microsurgery during recent years. Especially venous congestion is decreased using hirudo medicinalis application such as following replantation of amputated fingers or congested flaps. They provide a temporary relief to venous engorgement whilst venous drainage is re-established. Living in symbiosis with Aeromonas hydrophila, who can digest the sixfold blood meal related to their body weight, and a broad number of anticoagulant agents such as the thrombin inhibitor hirudin, apyrase as well as collagenase, hyaluronidase, Factor Xa inhibitor and fibrinase I and II, leeches decrease venous congestion. Laser Doppler flowmetry could demonstrate a significant increase in superficial skin perfusion following leech application 16 mm around the biting zone. Following the initial blood meal accounting for about 2.5 ml, the anticoagulant effect of the various leeches enzymes follows within the next 5-6 hours, which both account for the beneficial effects. Infection associated with leech therapy is a documented complication of leech application, with reported incidences ranging from 2.4 to 20 % and a chinolone antibiotic is currently recommended to face the potential Aeromonas hydrophila infection. Anemia is a second adverse effect during medicinal leech application which has to be taken account with repetitive blood samples. Besides the successful applications of leeches in various applications in plastic and reconstructive microsurgery, randomized-controlled trials are pending to elucidate the value of hirudo medicinalis according to evidence-based criteria above from case series and case studies.