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1.
J Stroke Cerebrovasc Dis ; 28(10): 104283, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31324409

RESUMO

INTRODUCTION: Administering intravenous IV tissue plasminogen activator (tPA) is the recommended standard of care in acute ischemic stroke (AIS), although it is not recommended to administer intravenous thrombolysis with tPA following heparin reversal with protamine sulfate in patients with AIS. METHODS: We describe a case series of three patients and the most comprehensive literature review published to date in this specific subset of AIS patients undergoing thrombolysis following heparin reversal with protamine sulfate. The literature review was based on a scoping review methodology performed on four databases; PubMed, CINAHL, Web of Science, and Cochrane Library. All sources were searched from the inauguration of the database until February 2019. A total of six articles involving eight patients were identified. RESULTS: The primary safety outcome of no symptomatic intracranial hemorrhage (sICH) was met in all eleven patients, although only seven cases had a good functional outcome at 3 months. CONCLUSIONS: In appropriately selected AIS patients, coagulopathy correction appears to be safe from an sICH standpoint and may be beneficial. However, given the potential for bias with observational databases, case reports and case series, extreme caution is warranted in applying these results to routine clinical practice.


Assuntos
Anticoagulantes/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Antagonistas de Heparina/uso terapêutico , Heparina/uso terapêutico , Protaminas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/administração & dosagem , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Isquemia Encefálica/sangue , Isquemia Encefálica/diagnóstico , Feminino , Fibrinolíticos/efeitos adversos , Heparina/efeitos adversos , Antagonistas de Heparina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Protaminas/efeitos adversos , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento
2.
Br J Neurosurg ; 33(2): 156-160, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29706113

RESUMO

OBJECTIVE: This study was performed to identify risk factors for neck haematoma requiring re-exploration after carotid endarterectomy. Neck haematoma is a well-known complication after carotid endarterectomy, but there has been little discussion about intraoperative techniques for its prevention. We also investigated an intraoperative neck flexion technique for prevention of neck haematoma. METHODS: A retrospective study reviewed 384 carotid endarterectomies performed at our institution from 2003 to 2016. The endpoint was neck haematomas requiring re-exploration after carotid endarterectomy. Endpoint predictors (general factors, preoperative medication, and intraoperative factors) were identified by univariate analysis. Our intraoperative neck flexion technique involved changing the neck and head position from extension to flexion during carotid endarterectomy. In patients with neck haematoma, we assessed the interval from carotid endarterectomy to re-exploration, the source of bleeding, and the method of airway rescue. RESULTS: There was one major and three minor perioperative strokes (1.1%). Neck haematoma occurred in 9 patients (2.4%). Univariate analysis (odds ratio [95% confidence interval]) identified preoperative clopidogrel therapy (4.19 [1.03-17.06], P = .04) and not using protamine sulfate after heparin (4.13 [1.02-25.06], P = .04) as risk factors for haematoma. We used the intraoperative neck flexion technique in 87 patients and no neck haematomas occurred. There was no additional morbidity and no mortality in the patients who required re-exploration. The interval between carotid endarterectomy and re-exploration ranged from 0 to 30 hours. Intubation before re-exploration was often difficult. We recommend using a laryngeal mask and performing minor wound re-exploration under local anesthesia before tracheal intubation for general anesthesia. Haematomas were mainly caused by venous bleeding or capillary oozing. CONCLUSIONS: This study showed that neck haematoma is uncommon after carotid endarterectomy, but requires emergency airway rescue and re-exploration.


Assuntos
Endarterectomia das Carótidas/efeitos adversos , Hematoma/etiologia , Lesões do Pescoço/etiologia , Complicações Pós-Operatórias/terapia , Idoso , Idoso de 80 Anos ou mais , Clopidogrel/efeitos adversos , Clopidogrel/uso terapêutico , Determinação de Ponto Final , Feminino , Antagonistas de Heparina/uso terapêutico , Humanos , Máscaras Laríngeas , Masculino , Pessoa de Meia-Idade , Posicionamento do Paciente , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Protaminas/uso terapêutico , Reoperação/efeitos adversos , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia
3.
Am J Emerg Med ; 37(1): 174.e5-174.e6, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30274763

RESUMO

Clinical practice guidelines recommend protamine sulfate for reversal of enoxaparin associated bleeds dependent on the time from last administration and dose of enoxaparin. We present a case of a hemodynamically unstable patient with an enoxaparin induced abdominal wall hematoma/hemorrhage and the previous enoxaparin administration 21.5 h prior to presentation with a therapeutic anti-Xa assay (0.8 IU/mL) upon assessment in the emergency department. Along with resuscitative efforts, an interdisciplinary team collaborated to administer protamine sulfate 50 mg intravenous once (0.5 mg per 1 mg of enoxaparin) to reverse the therapeutic anticoagulation. Our case demonstrates the importance of monitoring renal function and the potential for accumulation of enoxaparin in patients with renal dysfunction leading to prolonged therapeutic anti-Xa assays. With the availability of anti-Xa assays, future reversal recommendations of enoxaparin associated bleeds using protamine sulfate should include the initial anti-Xa assay as a guide for the dosing regimen.


Assuntos
Anticoagulantes/efeitos adversos , Enoxaparina/efeitos adversos , Hematoma/induzido quimicamente , Hematoma/tratamento farmacológico , Antagonistas de Heparina/uso terapêutico , Protaminas/uso terapêutico , Parede Abdominal/diagnóstico por imagem , Idoso , Esquema de Medicação , Serviço Hospitalar de Emergência , Feminino , Hematoma/complicações , Hematoma/diagnóstico por imagem , Humanos , Insuficiência Renal Crônica/complicações , Fatores de Tempo , Tomografia Computadorizada por Raios X
4.
Neurologist ; 23(6): 194-196, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30379743

RESUMO

BACKGROUND: Patients with an acute ischemic stroke (AIS) following cardiac catheterization (CC) generally do not receive intravenous thrombolysis [intravenous tissue plasminogen activator (IV-tPA)] as it is contraindicated due to the coagulopathy related to the heparin used during the procedure. We report a case of AIS successfully treated with IV thrombolysis following protamine reversal of heparin effect. CASE REPORT: An 87-year-old man with diabetes mellitus, hypertension, neurofibromatosis, and hyperlipidemia underwent elective transradial CC following an abnormal stress test. He had 2 drug-eluting stents for severe stenosis of mid-circumflex and right coronary arteries and received heparin 13,000 IU during procedure. He developed acute left hemiparesis with initial NIH stroke scale (NIHSS) of 4. Computed tomographic scan of the brain and computed tomographic angiogram of head and neck were unremarkable. Bedside activated clotting time was 181. Protamine 40 mg was administered and 30 minutes later, the activated clotting time level was normalized. IV-tPA was administered at 4 hours 25 minutes from his last known well. Within 15 minutes, his NIHSS was 0. Magnetic resonance imaging of brain showed no acute infarction 24 hours after stroke. CONCLUSIONS: There are limited reports of protamine reversal of heparin before IV-tPA administration. To our knowledge, there are only 6 AIS cases including ours. Three cases received 0.6 mg/kg of tPA dose. All have favorable outcomes and no intracranial hemorrhage was reported. Protamine reversal of heparin for AIS after CC seems to be safe. Further studies are needed to confirm the therapeutic safety and efficacy of this strategy.


Assuntos
Cateterismo Cardíaco/efeitos adversos , Fibrinolíticos/efeitos adversos , Antagonistas de Heparina/uso terapêutico , Heparina/efeitos adversos , Protaminas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Idoso de 80 Anos ou mais , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Humanos , Masculino , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento
5.
PLoS One ; 13(8): e0201647, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30075017

RESUMO

Low plasma fibrinogen level is common after cardiopulmonary bypass (CPB). Current substitution practice with fibrinogen concentrate generally follows a single measurement and cut-off values from the literature, whereas early postoperative endogenous fibrinogen kinetics is incompletely described and widely disregarded. The aim of this study was to determine the short-term recovery pattern of plasma fibrinogen after CPB weaning. Our hypothesis was that in the absence of surgical bleeding, CPB-induced hypofibrinogenemia would resolve spontaneously and predictably within a few hours. In a prospective, observational study of 26 patients undergoing conventional CPB (cCPB) or minimally invasive extracorporeal circulation (MiECC), Clauss fibrinogen level (C-FIB) was determined at 10 closely spaced time points after protamine administration. Primary endpoint was the time to recovery of post-CPB fibrinogen levels to ≥1.5 g/L. C-FIB reached its nadir after protamine administration corresponding to 62 ± 5% (mean ± SD) of the baseline level after cCPB and 68 ± 7% after MiECC (p = 0.027 vs. cCPB). C-FIB recovered spontaneously at a nearly constant rate of approximately 0.08 g/L per hour. In all patients, C-FIB was ≥1.5 g/L at 4 hours and ≥2.0 g/L at 13 hours after CPB weaning. Following cardiac surgery with CPB and in the absence of surgical bleeding, spontaneous recovery of normal endogenous fibrinogen levels can be expected at a rate of 0.08 g/L per hour. Administration of fibrinogen concentrate triggered solely by a single-point measurement of low plasma fibrinogen some time after CPB is not justified.


Assuntos
Afibrinogenemia/tratamento farmacológico , Ponte Cardiopulmonar/efeitos adversos , Circulação Extracorpórea/efeitos adversos , Fibrinogênio/análise , Protaminas/administração & dosagem , Afibrinogenemia/sangue , Afibrinogenemia/etiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Protaminas/uso terapêutico , Remissão Espontânea , Resultado do Tratamento
6.
Int Heart J ; 59(3): 482-488, 2018 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-29743410

RESUMO

Bleeding complications following percutaneous coronary interventions (PCI) have been closely associated with morbidity and mortality. Although radial arteries have been widely used in current PCI, including primary PCI, transfemoral PCI remains necessary for complex PCI. The purpose of this study was to compare the incidence of complications following elective transfemoral PCI between manual compression with and without protamine. We identified 249 consecutive patients who underwent elective transfemoral PCI from hospital records, and divided them into two groups: patients who used protamine for manual compression (the protamine group; n = 205) and patients who did not (the non-protamine group, n = 44). Complications including acute thrombosis, bleeding requiring blood transfusion, transient hypotension, skin rash, and death within 30 days were compared between groups. The baseline clinical and procedural characteristics were comparable between the protamine and non-protamine groups. The incidences of all complications were not different between the protamine (5.9%) and the non-protamine groups (9.1%) (P = 0.43). While more than 90% of the patients received drug-eluting stent implantation, there was no acute thrombus in either group. The incidence of bleeding requiring blood transfusion was significantly lower in the protamine group (0.5%) than in the non-protamine group (6.8%) (P = 0.002). Multivariate logistic regression analysis revealed the inverse association between protamine use and bleeding requiring blood transfusion (odds ratio 0.08, 95% confidence interval 0.01-0.84, P = 0.04). In conclusion, the use of protamine for manual compression following elective transfemoral PCI was safe and was associated with less bleeding complications.


Assuntos
Anticoagulantes/efeitos adversos , Antagonistas de Heparina/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Protaminas/efeitos adversos , Idoso , Transfusão de Sangue/estatística & dados numéricos , Doença da Artéria Coronariana/cirurgia , Stents Farmacológicos/efeitos adversos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Feminino , Técnicas Hemostáticas , Antagonistas de Heparina/uso terapêutico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Protaminas/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
7.
Ann Thorac Surg ; 106(3): 799-806, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29753821

RESUMO

BACKGROUND: Perioperative bleeding is a common complication in pediatric patients undergoing cardiac operation. Although thromboelastography (TEG) has been used in patients undergoing adult cardiac operation, limited data are available in pediatric patients. We hypothesize that TEG variables may be associated with surrogate end points for postoperative bleeding in pediatric patients undergoing complex cardiac operation. METHODS: In a retrospective study, TEG was obtained after protamine administration and on admission to the intensive care unit (ICU) in pediatric patients (≤18 years) undergoing cardiac operation that required cardiopulmonary bypass. A composite end point of extended blood product transfusion or surgical re-exploration for bleeding was used as a surrogate for perioperative bleeding. TEG variables were compared between patients who did or did not reach the composite end point. RESULTS: The study included 511 pediatric patients undergoing complex cardiac operation. The composite end point was reached in 52% of patients with maximum amplitude (MA) less than 45 mm compared with 31% with MA of 45 mm or more (p < 0.001). With the use of multivariable regression analysis, MA less than 45 mm was independently associated with the composite end point (p < 0.001). Patients with MA less than 45 mm who received platelet transfusion in the operating room (OR) were less likely to reach the composite end point within the subsequent 24 hours (8%) compared with patients who did not receive intraoperative platelet transfusion (24%) (p = 0.02). CONCLUSIONS: Intraoperative TEG MA less than 45 mm is associated with a surrogate end point for intraoperative bleeding in pediatric patients undergoing complex cardiac operation. In patients with MA less than 45 mm, prophylactic platelet transfusion in the OR may be associated with reduction in bleeding end points in the ICU.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Mortalidade Hospitalar , Hemorragia Pós-Operatória/terapia , Protaminas/uso terapêutico , Tromboelastografia/métodos , Transfusão de Sangue/métodos , Procedimentos Cirúrgicos Cardíacos/métodos , Ponte Cardiopulmonar/efeitos adversos , Ponte Cardiopulmonar/métodos , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/cirurgia , Hospitais Pediátricos , Humanos , Lactente , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Transfusão de Plaquetas/métodos , Hemorragia Pós-Operatória/diagnóstico , Hemorragia Pós-Operatória/mortalidade , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Resultado do Tratamento
8.
Perfusion ; 33(6): 445-452, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29544405

RESUMO

INTRODUCTION: Accurate dosing of protamine reversal following on-pump cardiac surgical procedures is challenging, with both excessive and inadequate administration recognised to increase bleeding risk. We aimed to examine the relationship between three ratios for heparin reversal and markers of haemostasis. METHODS: A retrospective analysis of a prospectively collected database was undertaken at a single tertiary cardiac unit, reviewing all cases of on-pump coronary artery bypass grafts and single valve replacements from 01/01/2011 to 31/12/2015. The ratio between total intra-operative heparin and protamine was stratified to three groups (low: ≤0.6 mg per 100 IU of heparin, moderate: 0.6-1.0 and high: >1.0) and related to the primary outcome of red blood cell (RBC) transfusion, with secondary outcomes being the number of units transfused, the haemoglobin differential and mediastinal drain output at 4 hours. RESULTS: Of the 803 patients identified, 338 received a blood transfusion, with 1035 units being used. Eighteen percent of individuals (145) received a low ratio, 50% (404) received a moderate ratio and 32% (254) a high ratio. Using the moderate group as a reference, the low dose group was 56.5% less likely to have received a RBC transfusion (OR 0.435; 95% CI 0.270:0.703 p=0.001) while the high dose group carried a 241% increased association with transfusion (OR 3.412; 95% CI 2.399:4.853 p<0.001). For those transfused, a lower protamine:heparin ratio was associated with a lower number of units transfused, lesser haemoglobin differential and less mediastinal drain output. CONCLUSION: Higher doses of intra-operative protamine relative to heparin are associated with greater risk of transfusion and post-operative bleeding.


Assuntos
Anticoagulantes/uso terapêutico , Ponte Cardiopulmonar/métodos , Ponte de Artéria Coronária/métodos , Antagonistas de Heparina/uso terapêutico , Heparina/uso terapêutico , Hemorragia Pós-Operatória/terapia , Protaminas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Transfusão de Sangue , Ponte Cardiopulmonar/efeitos adversos , Ponte de Artéria Coronária/efeitos adversos , Feminino , Heparina/administração & dosagem , Antagonistas de Heparina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/etiologia , Protaminas/administração & dosagem , Estudos Retrospectivos , Adulto Jovem
9.
J Extra Corpor Technol ; 50(1): 5-18, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29559750

RESUMO

Despite more than a half century of "safe" cardiopulmonary bypass (CPB), the evidence base surrounding the conduct of anticoagulation for CPB has not been organized into a succinct guideline. For this and other reasons, there is enormous practice variability relating to the use and dosing of heparin, monitoring heparin anticoagulation, reversal of anticoagulation, and the use of alternative anticoagulants. To address this and other gaps, the Society of Thoracic Surgeons (STS), the Society of Cardiovascular Anesthesiologists (SCA), and the American Society of Extracorporeal Technology (AmSECT) developed an Evidence Based Workgroup. This was a group of interdisciplinary professionals gathered together to summarize the evidence and create practice recommendations for various aspects of CPB. To date, anticoagulation practices in CPB have not been standardized in accordance with the evidence base. This clinical practice guideline was written with the intent to fill the evidence gap and to establish best practices in anticoagulation for CPB using the available evidence. To identify relevant evidence a systematic review was outlined and literature searches were conducted in PubMed® using standardized MeSH terms from the National Library of Medicine list of search terms. Search dates were inclusive of January 2000 to December 2015. The search yielded 833 abstracts which were reviewed by two independent reviewers. Once accepted into the full manuscript review stage, two members of the writing group evaluated each of 286 full papers for inclusion eligibility into the guideline document. Ninety-six manuscripts were included in the final review. In addition, 17 manuscripts published prior to 2000 were included to provide method, context, or additional supporting evidence for the recommendations as these papers were considered sentinel publications. Members of the writing group wrote and developed recommendations based on review of the articles obtained and achieved more than two thirds agreement on each recommendation. The quality of information for a given recommendation allowed assessment of the level of evidence as recommended by the AHA/ACCF Task Force on Practice Guidelines. Recommendations were written in the three following areas 1) Heparin dosing and monitoring for initiation and maintenance of CPB, 2) Heparin contraindications and heparin alternatives, 3) Reversal of anticoagulation during cardiac operations. It is hoped that this guideline will serve as a resource and will stimulate investigators to conduct more research and expand upon the evidence base on the topic of anticoagulation for CPB.


Assuntos
Anticoagulantes/uso terapêutico , Ponte Cardiopulmonar/métodos , Heparina/uso terapêutico , Hirudinas , Humanos , Fragmentos de Peptídeos/uso terapêutico , Protaminas/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Sociedades Médicas/organização & administração
10.
11.
J Int Med Res ; 46(2): 873-882, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28974132

RESUMO

Objective This study compared the activated clotting time (ACT) measured using the Hemochron Jr. Signature (HACT) with the ACT measured using the Medtronic ACT Plus (MACT) during cardiopulmonary bypass (CPB) with acute normovolemic haemodilution (ANH) in patients undergoing cardiac surgery. Methods The ACT was checked at baseline with both devices after inducing anaesthesia, and 400 to 800 mL of whole blood was withdrawn to induce moderate ANH. Before initiating CPB, a 300-IU/kg bolus dose of heparin was administered to maintain the HACT at >400 s; protamine was later given to reverse the anticoagulation. The ACT was checked using both devices at baseline, during heparinisation, and after protamine administration. Results In total, 106 pairs of samples from 29 patients were analysed. The ACT showed a good correlation between the two devices (r = 0.956). However, Bland-Altman analysis showed that the MACT was higher, particularly at baseline and during heparinisation. Multiple regression analysis showed that the blood glucose concentration significantly influenced the differences between the two ACT devices. Conclusions The HACT was lower than the MACT during CPB with ANH in patients undergoing cardiac surgery. Clinicians should be cautious when using each ACT device within generally accepted reference ACT values.


Assuntos
Automação Laboratorial/instrumentação , Ponte Cardiopulmonar , Hemodiluição/métodos , Flebotomia/métodos , Tempo de Coagulação do Sangue Total/instrumentação , Idoso , Anestesia Geral , Anticoagulantes/uso terapêutico , Artefatos , Automação Laboratorial/normas , Glicemia/metabolismo , Viscosidade Sanguínea , Feminino , Heparina/uso terapêutico , Antagonistas de Heparina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Protaminas/uso terapêutico , Análise de Regressão , Tempo de Coagulação do Sangue Total/normas
12.
J Radiat Res ; 59(1): 27-34, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29121251

RESUMO

We examined the effectiveness of localized administration of fibroblast growth factor-2 containing low-molecular-weight heparin/protamine nanoparticles (FGF-2&LMWH/P NPs) on apoptosis in vivo and on healing of radiation-induced skin injury in a rat model. FGF-2 binds onto LMWH/P NPs, which can significantly enhance and stabilize FGF-2 as a local carrier. X-irradiation at a dose of 25 Gy was administered to the lower part of the back (using a lead sheet with two holes) 1 h before the administration of FGF-2&LMWH/P NPs. Cutaneous full-thickness defect wounds were then formed in X-irradiated areas to examine the time-course of wound healing, and the wound tissues were microscopically and histologically compared and examined. Wound healing was significantly delayed by X-irradiation, but FGF-2&LMWH/P NPs administration prior to irradiation led to a significantly shorter delay compared with FGF-2 alone, LMWH/P NPs alone, and controls. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining showed that the proportions of apoptotic dermal fibroblasts in X-irradiated skin were significantly lower in rats administered FGF-2&LMWH/P NPs than in controls. However, 8-hydroxy-2'-deoxyguanosine (8-OHdG) staining showed no differences. Thus, localized administration of FGF-2&LMWH/P NPs prior to irradiation may alleviate X-irradiation-induced healing-impaired wound repair in normal tissue.


Assuntos
Fator 2 de Crescimento de Fibroblastos/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Nanopartículas/química , Protaminas/uso terapêutico , Substâncias Protetoras/uso terapêutico , Lesões por Radiação/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Animais , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Fator 2 de Crescimento de Fibroblastos/farmacologia , Heparina de Baixo Peso Molecular/farmacologia , Humanos , Masculino , Protaminas/farmacologia , Substâncias Protetoras/farmacologia , Ratos Sprague-Dawley , Pele/patologia , Pele/efeitos da radiação , Raios X
13.
Perfusion ; 32(6): 481-488, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28820026

RESUMO

INTRODUCTION: This manuscript represents a pilot study assessing the feasibility of a single-compartment, individualised, pharmacokinetic algorithm for protamine dosing after cardiopulmonary bypass. METHODS: A pilot cohort study in a specialist NHS cardiothoracic hospital targeting patients undergoing elective cardiac surgery using cardiopulmonary bypass. Patients received protamine doses according to a pharmacokinetic algorithm (n = 30) or using an empirical, fixed-dose model (n = 30). Categorical differences between the groups were evaluated using the Chi-squared test or Fisher's exact test. Continuous data was analysed using a paired Student's t-test for parametric data and the paired samples Wilcoxon test for non-parametric data. RESULTS: Patients who had protamine dosing according to the algorithm demonstrated a lower protamine requirement post-bypass relative to empirical management as measured by absolute dose (243 ± 49mg vs. 305 ± 34.7mg; p<0.001) and the heparin to protamine ratio (0.79 ± 0.12 vs. 1.1 ± 0.15; p<0.001). There was no difference in the pre- to post-bypass activated clotting time (ACT) ratio (1.05 ± 0.12 vs. 1.02 ± 0.15; p=0.9). Patients who received protamine according to the algorithm had no significant difference in transfusion requirement (13.3% vs. 30.0%; p=0.21). CONCLUSIONS: This study showed that an individualized pharmacokinetic algorithm for the reversal of heparin after cardiopulmonary bypass is feasible in comparison with a fixed dosing strategy and may reduce the protamine requirement following on-pump cardiac surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Ponte Cardiopulmonar/métodos , Antagonistas de Heparina/uso terapêutico , Heparina/uso terapêutico , Protaminas/uso terapêutico , Idoso , Feminino , Heparina/farmacologia , Antagonistas de Heparina/farmacologia , Humanos , Masculino , Projetos Piloto , Protaminas/farmacocinética
14.
Pharmacotherapy ; 37(10): e103-e106, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28741720

RESUMO

Few patients presenting with acute ischemic stroke (AIS) are eligible for alteplase, especially those receiving ongoing anticoagulation. We describe the first reported case of a patient receiving full-dose intravenous (IV) alteplase for AIS after heparin reversal with protamine. A 73-year-old man presented with AIS. He was treated with IV heparin, tirofiban, loading-dose prasugrel, and aspirin before percutaneous coronary intervention (PCI) for placement of a right coronary artery stent. One hour following PCI, he abruptly developed left hemiparesis and dysphagia. The National Institutes of Health Stroke Scale was 12, and activated partial thromboplastin time (aPTT) was longer than 150 seconds. Head computed tomography (CT) showed no acute pathology, and CT angiogram showed no large-vessel occlusion amenable to mechanical thrombectomy. Repeat aPTT, obtained 45 minutes later, was 110 seconds, at which time protamine 40 mg IV was administered. At 144 minutes from last known well time, full-dose IV alteplase (0.9 mg/kg) was administered. Follow-up head imaging at 25 hours showed right pontine and cerebellar AIS with no evidence of hemorrhage. The patient was discharged to inpatient rehabilitation 2 days later. Modified Rankin Scale at 3 months was 3, improved from 5 at discharge. Given the lack of adverse events associated with IV alteplase in our patient, we advocate cautious evaluation for potential reversal of acutely administered anticoagulation to facilitate alteplase administration in severely disabled patients who are not eligible for mechanical intervention and would have been excluded from definitive AIS treatment.


Assuntos
Anticoagulantes/uso terapêutico , Antagonistas de Heparina/uso terapêutico , Heparina/uso terapêutico , Protaminas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Heparina/administração & dosagem , Heparina/efeitos adversos , Antagonistas de Heparina/administração & dosagem , Humanos , Masculino , Tempo de Tromboplastina Parcial , Protaminas/administração & dosagem , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Ativador de Plasminogênio Tecidual/administração & dosagem , Resultado do Tratamento
16.
Semin Cardiothorac Vasc Anesth ; 21(4): 312-320, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28388863

RESUMO

Perioperative management of cardiovascular surgical procedures requiring cardiopulmonary bypass (CPB) in patients with hemophilia A poses a clinical challenge in coagulation management. Use of CPB requires the administration of an anticoagulant, usually unfractionated heparin, and also causes dilutional coagulopathy, platelet dysfunction or platelet consumption coagulopathy. Hypothermia and activation of the inflammatory cascade also affect coagulation. The effects of CPB on circulating levels of factor VIII have not been clearly defined. In this review, the effects of CPB and hemodilution on FVIII are shown in a case presentation, and perioperative laboratory testing in patients with hemophilia A having cardiac surgery is discussed along with perioperative and postoperative coagulation management.


Assuntos
Anticoagulantes/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Ponte Cardiopulmonar/métodos , Hemofilia A/complicações , Assistência Perioperatória/métodos , Ácido Aminocaproico/uso terapêutico , Procedimentos Cirúrgicos Cardíacos/métodos , Fator VIII/efeitos dos fármacos , Hemodiluição/métodos , Heparina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Protaminas/uso terapêutico
17.
Blood Coagul Fibrinolysis ; 28(3): 261-263, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27214037

RESUMO

: Intravenous thrombolysis is the preferred treatment for acute ischemic stroke; however, it remains unestablished in the area of cardiac catheterization. We report three patients with acute ischemic stroke after cardiac catheterization. After reversing the anticoagulant effect of unfractionated heparin with protamine, all of the patients were successfully off-label thrombolyzed with reduced doses of intravenous recombinant tissue plasminogen activator (0.6 mg/kg). This dose was preferred to reduce the risk of symptomatic cerebral or systemic bleeding. The sequential pathway of protamine recombinant tissue plasminogen activator at reduced doses may be safer for reducing intracranial or systemic bleeding events, whereas remaining efficacious for the treatment of acute ischemic stroke after cardiac catheterization.


Assuntos
Cateterismo Cardíaco/efeitos adversos , Antagonistas de Heparina/uso terapêutico , Protaminas/uso terapêutico , Acidente Vascular Cerebral/etiologia , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/administração & dosagem , Resultado do Tratamento
18.
Blood Coagul Fibrinolysis ; 28(4): 329-333, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27273141

RESUMO

: Coronary artery bypass grafting surgery (CABG) in hemophilia patients is challenging. Thromboelastography (TEG) is useful to assess hemostasis perioperatively. A patient with severe hemophilia A underwent CABG with TEG studies. After factor VIII (FVIII) bolus dose, TEG was normalized. Following 'on-pump' heparinization, protamine administration revealed prolonged TEG-R and TEG-R with heparinase confirming it, whereas the activated clotting time was normal, suggesting low FVIII activity rather than excess of heparin. Another FVIII bolus yielded complete normalization of all TEG parameters. Data are compatible with in-vitro assays performed in our laboratory, showing that both heparin and protamine may impair measurable FVIII activity. The rational use of TEG measurements enabled more accurate hemostatic therapy application with regard to FVIII, heparin and protamine administration. Adopting this approach may lead to a better therapy tailoring for hemophilia patients undergoing CABG surgery.


Assuntos
Ponte de Artéria Coronária , Hemofilia A/cirurgia , Hemostasia/efeitos dos fármacos , Assistência Perioperatória/métodos , Tromboelastografia , Anticoagulantes/uso terapêutico , Coagulantes/uso terapêutico , Fator VIII/uso terapêutico , Heparina/uso terapêutico , Antagonistas de Heparina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Protaminas/uso terapêutico
19.
Clin Appl Thromb Hemost ; 23(5): 410-415, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27789605

RESUMO

Bleeding is the most common complication of all anticoagulants. Any bleeding patient on an anticoagulant should be risk-stratified based on hemodynamic instability, source of bleeding, and degree of blood loss. Although minor bleed may be managed with discontinuation of anticoagulant, major bleed may require transfusion of blood products and use of specific antidote. The residual effects of each anticoagulant may be monitored with distinct coagulation assay. Intravenous or oral vitamin K can reverse the effect of warfarin within 24 to 48 hours and is indicated for any bleeding, international normalized ratio of >10 or 4.5 to 10 in patients with other risk factors for bleeding. Fresh frozen plasma or prothrombin complex concentrate (PCC) may be necessary in major bleeding related to warfarin. Protamine sulfate reverses the effect of unfractionated heparin completely and of low-molecular-weight heparin (LMWH) partially. Idarucizumab has recently been approved in United States for dabigatran reversal, whereas andexanet alfa is expected to get approved in the near future for reversal of oral factor Xa inhibitors. The PCC may reverse the effect of rivaroxaban to some extent, but no data are available regarding reversal of apixaban and edoxaban. Aripazine has shown promising results to reverse the effects of LMWH, fondaparinux, and direct oral anticoagulants but is still in the developmental phase.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticoagulantes/efeitos adversos , Antídotos/uso terapêutico , Fatores de Coagulação Sanguínea/uso terapêutico , Hemorragia , Plasma , Protaminas/uso terapêutico , Anticoagulantes/uso terapêutico , Testes de Coagulação Sanguínea , Hemorragia/sangue , Hemorragia/induzido quimicamente , Hemorragia/terapia , Humanos , Coeficiente Internacional Normatizado
20.
Perfusion ; 32(3): 200-205, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27765895

RESUMO

INTRODUCTION: Intestinal fatty acid-binding protein (I-FABP) is increasingly employed as a highly specific marker of intestinal necrosis. However, the value of this marker associated with cardiovascular surgery with hypothermic circulatory arrest is unclear. The aim of this study was to measure serum I-FABP levels and provide the transition of I-FABP levels with hypothermic circulatory arrest to help in the management of intestinal perfusion. METHODS: From August 2011 to September 2013, 33 consecutive patients who had aortic arch surgery with hypothermic circulatory arrest or heart valve surgery performed were enrolled in the study. Twenty patients had aortic surgery with hypothermic (23-29°C) circulatory arrest and 13 patients had heart valve surgery with cardiopulmonary bypass (33°C). RESULTS: I-FABP levels increased, both in patients undergoing aortic surgery with hypothermic circulatory arrest and heart valve surgery with cardiopulmonary bypass, reaching peak levels shortly after the administration of protamine. I-FABP levels in patients with aortic surgery were significantly higher with circulatory arrest. They reached peak levels immediately after recirculation and there was a significant drop at the end of surgery (p<0.001). I-FABP levels in heart valve surgery were gradually increased, with the highest at the administration of protamine; they gradually decreased. Peak I-FABP levels were significantly higher in patients undergoing aortic surgery with hypothermic circulatory arrest than in patients with heart valve surgery. However, no postoperative reperfusion injury occurred in the intestinal tract due to the use of hypothermic organ protection. CONCLUSION: Plasma I-FABP monitoring could be a valuable method for finding an intestinal ischemia in patients with cardiovascular surgery.


Assuntos
Aorta Torácica/cirurgia , Ponte Cardiopulmonar , Proteínas de Ligação a Ácido Graxo/sangue , Parada Cardíaca Induzida , Valvas Cardíacas/cirurgia , Hipotermia Induzida , Traumatismo por Reperfusão/sangue , Idoso , Idoso de 80 Anos ou mais , Ponte Cardiopulmonar/efeitos adversos , Ponte Cardiopulmonar/métodos , Feminino , Parada Cardíaca/sangue , Parada Cardíaca Induzida/efeitos adversos , Parada Cardíaca Induzida/métodos , Humanos , Hipotermia Induzida/efeitos adversos , Hipotermia Induzida/métodos , Intestinos/irrigação sanguínea , Masculino , Período Pós-Operatório , Protaminas/uso terapêutico , Traumatismo por Reperfusão/etiologia
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