RESUMO
Peripheral T cell lymphomas (PTCL) are rare in children and adolescents, and data about outcome and treatment results are scarce. The present study is a joint, international, retrospective analysis of 143 reported cases of non-anaplastic PTCL in patients <19 years of age, with a focus on treatment and outcome features. One hundred forty-three patients, between 0.3 and 18.7 years old, diagnosed between 2000 and 2015 were included in the study. PTCL not otherwise specified was the largest subgroup, followed by extranodal NK/T cell lymphoma, hepatosplenic T cell lymphoma (HS TCL), and subcutaneous panniculitis-like T cell lymphoma (SP TCL). Probability of overall survival (pOS) at 5 years for the whole group was 0.56 ± 0.05, and probability of event-free survival was (pEFS) 0.45 ± 0.05. Patients with SP TCL had a good outcome with 5-year pOS of 0.78 ± 0.1 while patients with HS TCL were reported with 5-year pOS of only 0.13 ± 0.12. Twenty-five percent of the patients were reported to have a pre-existing condition, and this group had a dismal outcome with 5-year pOS of 0.29 ± 0.09. The distribution of non-anaplastic PTCL subtypes in pediatric and adolescent patients differs from what is reported in adult patients. Overall outcome depends on the subtype with some doing better than others. Pre-existing conditions are frequent and associated with poor outcomes. There is a clear need for subtype-based treatment recommendations for children and adolescents with PTCL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma de Células T Periférico/terapia , Avaliação de Resultados em Cuidados de Saúde/métodos , Adolescente , Criança , Pré-Escolar , Terapia Combinada , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , Lactente , Cooperação Internacional , Masculino , Indução de Remissão , Estudos Retrospectivos , Adulto JovemRESUMO
Haematopoietic stem cell transplantation (HSCT) is an immunological treatment that has been used for more than 40 years to cure a variety of diseases. The procedure is associated with serious side effects, due to the severe impairment of the immune system induced by the treatment. After a conditioning regimen with high-dose chemotherapy, sometimes in combination with total body irradiation, haematopoietic stem cells are transferred from a donor, allowing a donor-derived blood system to form. Here, we discuss the current knowledge of humoral problems and B cell development after HSCT, and relate these to the current understanding of human peripheral B cell development. We describe how these studies have aided the identification of subsets of transitional B cells and also a robust memory B cell phenotype.
Assuntos
Subpopulações de Linfócitos B/citologia , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/citologia , Linfopoese/fisiologia , Animais , Formação de Anticorpos , Antígenos de Diferenciação de Linfócitos B/análise , Linhagem da Célula , Sobrevivência de Enxerto , Humanos , Hospedeiro Imunocomprometido , Memória Imunológica , Imunofenotipagem , Infecções/etiologia , Antígenos Comuns de Leucócito/biossíntese , Linfopenia/etiologia , Camundongos , Condicionamento Pré-Transplante/efeitos adversosRESUMO
Viral opportunistic infections remain a threat to survival after stem cell transplantation (SCT). We retrospectively investigated infections caused by cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus type 6 (HHV6), or adenovirus (AdV) during the first 6-12 months after pediatric SCT. Serum samples from 47 consecutive patients were analyzed by quantitative real-time polymerase chain reaction assay. DNAemia at any time point occurred for CMV in 47%, for EBV in 45%, for HHV6 in 28%, and for AdV in 28%. Three patients (6.3%) died of CMV-, EBV-, or AdV-related complications 4, 9, and 24 weeks after SCT, respectively, representing 21% of total mortality. These 3 cases were clearly distinguishable by DNAemia increasing to high levels. Serum positivity for CMV immunoglobulin G in either recipient or donor at the time of SCT, total body irradiation, and anti-thymocyte globulin conditioning were independent risk factors for high CMV or EBV DNA levels. We conclude that DNAemia levels help to distinguish significant viral infections, and that surveillance and prophylactic measures should be focused on patients with risk factors in whom viral complications rapidly can become fatal.
Assuntos
Infecções por Vírus de DNA/etiologia , Infecções por Vírus de DNA/prevenção & controle , DNA Viral/sangue , Transplante de Células-Tronco/efeitos adversos , Irradiação Corporal Total/efeitos adversos , Adolescente , Antibacterianos/uso terapêutico , Anticorpos Antivirais/sangue , Soro Antilinfocitário , Antivirais/uso terapêutico , Criança , Pré-Escolar , Infecções por Vírus de DNA/virologia , Vírus de DNA/genética , Vírus de DNA/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Lactente , Masculino , Estudos Retrospectivos , Fatores de Risco , Viremia/sangueRESUMO
The impact of conditioning regimen prior to hematopoietic cell transplant (HCT) in pediatric AML-patients is not well studied. We retrospectively analyzed the impact of Busulfan-Cyclophosphamide (BuCy), Busulfan-Cyclophosphamide-Melphalan (BuCyMel) and Clofarabine-Fludarabine-Busulfan (CloFluBu) in pediatric AML-patients, with similar upfront leukemia treatment (NOPHO-DBHconsortium), receiving an HCT between 2010 and 2015. Outcomes of interest were LFS, relapse, TRM and GvHD. 103 patients were included; 30 received BuCy, 37 BuCyMel, and 36 CloFluBu. The 5-years LFS was 43.3% (SE ± 9.0) in the BuCy group, 59.2 % (SE ± 8.1) after BuCyMel, and 66.7 % (SE ± 7.9) after CloFluBu. Multivariable Cox regression analysis showed a trend to lower LFS after BuCy compared to CloFluBu (p = 0.07). BuCy was associated with a higher relapse incidence compared to the other regimens (p = 0.06). Younger age was a predictor for relapse (p = 0.02). A strong correlation between Busulfan Therapeutic Drug Monitoring (TDM) and lower incidence of aGvHD (p < 0.001) was found. In conclusion, LFS after BuCyMel and CloFluBu was comparable, lower LFS was found after BuCy, due to higher relapse incidence. CloFluBu was associated with lower incidence of aGvHD, suggesting lower toxicity with this type of conditioning. This finding is also explained by the impact of Busulfan monitoring.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Protocolos de Quimioterapia Combinada Antineoplásica , Bussulfano/uso terapêutico , Criança , Ciclofosfamida/uso terapêutico , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Estudos Retrospectivos , Condicionamento Pré-Transplante , Vidarabina/uso terapêuticoRESUMO
We compared outcome and toxicity in two paediatric groups undergoing SCT and treated with busulphan (BU) by the oral route of administration. One group receiving the standard dose of 1 mg/kg q.i.d. for a total of 16 doses was compared with age- and disease-matched patients receiving 2 mg/kg of BU b.i.d. for a total of eight doses. Seventy-two patients from two Swedish paediatric transplantation centres were included; one centre used a standard q.i.d. administration (n=37) and the second centre used a b.i.d. administration setting (n=35). Our primary objective was to determine the incidence of veno-occlusive disease (VOD), graft-versus-host disease (GVHD), relapse frequency and transplant-related mortality in both cohorts. A total of 17 autologous and 55 allogeneic transplantations was performed for malignant (n=47) and non-malignant (n=25) diseases in the two centres during the period 1990-2005. No significant difference in the incidence of VOD, graft rejection, GVHD, relapse rate or overall survival was observed between the two centres. The clinical outcome of SCT for paediatric patients conditioned with oral BU at a dose of 2 mg/kg for eight doses is comparable to that found for children conditioned using the standard regimen given 1 mg/kg q.i.d. for 16 doses.
Assuntos
Bussulfano/efeitos adversos , Leucemia/terapia , Agonistas Mieloablativos/efeitos adversos , Condicionamento Pré-Transplante/métodos , Administração Oral , Bussulfano/administração & dosagem , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/métodos , Hepatopatia Veno-Oclusiva , Humanos , Lactente , Masculino , Agonistas Mieloablativos/administração & dosagem , Análise de Sobrevida , Transplante Autólogo , Transplante HomólogoRESUMO
INTRODUCTION: During extracorporeal circulation the contact between blood and the artificial surface of the circuit induces several changes in the hemostatic system. The objective of the present study was to assess the effect of a serine protease inhibitor--Nafamostat mesilate (FUT-175)--on coagulation and on platelets during experimental extracorporeal circulation. METHODS: Two identical Extra Corporeal Life Support (ECLS) circuits were primed with fresh, heparinized human blood and circulated for 24 h. FUT-175 was added to one of the paired circuits and the other was used as a control. The following FUT-175 concentrations were employed: (1) 7.1 mg/l/h, (2) 14.2 mg/l/h, (3) 14.2 mg/l/h + 85.5 mg given as an initial bolus, (4) 28.5 mg/l/h + 171 mg given as an initial bolus. Blood samples were collected from the circuits before the start of the perfusion and at 0.5, 1, 3, 12, and 24 h of perfusion, and analysed for platelet count, plasma betathromboglobulin (beta-TG), platelet membrane glycoprotein (GP) Ib and GPIIb/IIIa expression, thrombin/antithrombin III complex (TAT), prothrombin fragment 1+2 (F1+2), fibrinogen, D-dimer, and plasminogen activator inhibitor 1 activity (PAI-1). RESULTS: Significantly higher platelet membrane GPIb expression and lower plasma beta-thromboglobulin levels were observed in the circuits holding FUT-175, suggesting a lower degree of platelet activation. Also, a reduced activation of the coagulation system was observed in the "FUT-circuits", as reflected by the levels of F1+2 and TAT, and the PAI-1 activity that was rapidly inactivated. CONCLUSION: FUT-175 reduces the activation of platelets and plasma coagulation in an in vitro ECLS model.
Assuntos
Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Circulação Extracorpórea , Guanidinas/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Inibidores de Serina Proteinase/farmacologia , Benzamidinas , HumanosRESUMO
BACKGROUND: The increased bleeding tendency observed after cardiopulmonary bypass is caused in part by thrombocytopenia and impaired platelet function induced by the procedure. Previous in vitro studies have shown that nitric oxide (NO) added to the oxygenator sweep gas reduces platelet activation during experimental perfusion. We evaluated the effect of 40 ppm of NO, added to the oxygenator sweep gas, on platelet consumption and activation in patients undergoing cardiopulmonary bypass. METHODS: Twenty patients scheduled to undergo cardiopulmonary bypass were randomized to either the control or the NO arm of the study. Their platelet count, plasma beta-thromboglobulin level, platelet membrane glycoprotein Ib and IIb/IIIa levels, adenosine diphosphate-induced platelet aggregation, plasma nitrate level, and plasma hemoglobin were assayed before, during, and after cardiopulmonary bypass. RESULTS: After operation, slightly higher platelet counts were observed in the NO-treated patients than in the control patients, which might indicate a lower degree of platelet adhesion to the artificial surfaces of the extracorporeal circuit. However, this difference did not reach statistical significance. In addition, a difference in platelet membrane expression of glycoprotein Ib was seen between the NO and control groups after operation; the platelets of the control patients had significantly higher glycoprotein Ib expression than those of the NO-treated patients. The results of platelet aggregometry indicated preserved platelet function in both the NO-treated and control patients. The blood methemoglobin levels also were low in both groups. CONCLUSIONS: Nitric oxide might reduce the platelet consumption encountered during cardiopulmonary bypass without having any adverse effect on platelet function, as reflected by the preserved aggregation response seen in our patients. However, the best route of NO administration and the optimum dose remain to be established.
Assuntos
Plaquetas/efeitos dos fármacos , Ponte de Artéria Coronária , Implante de Prótese de Valva Cardíaca , Óxido Nítrico/uso terapêutico , Difosfato de Adenosina/farmacologia , Idoso , Plaquetas/fisiologia , Ponte Cardiopulmonar/efeitos adversos , Ponte Cardiopulmonar/instrumentação , Feminino , Seguimentos , Hemoglobinas/análise , Humanos , Masculino , Metemoglobina/análise , Pessoa de Meia-Idade , Nitratos/sangue , Óxido Nítrico/administração & dosagem , Oxigenadores , Ativação Plaquetária/efeitos dos fármacos , Adesividade Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Contagem de Plaquetas/efeitos dos fármacos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/análise , Complexo Glicoproteico GPIb-IX de Plaquetas/análise , Complexo Glicoproteico GPIb-IX de Plaquetas/efeitos dos fármacos , Hemorragia Pós-Operatória/prevenção & controle , Trombocitopenia/prevenção & controle , beta-Tromboglobulina/análiseRESUMO
BACKGROUND: Hemorrhage is a major complication experienced in 10% to 35% of neonates treated with extracorporeal life support (ECLS). The increased bleeding tendency is partly due to an ECLS-induced thrombocytopenia and impaired platelet function. In the present study, we evaluated the effect of nitric oxide on the ECLS-induced platelet consumption and activation. METHODS: Two identical in vitro ECLS circuits were primed with fresh, heparin-treated human blood and circulated for 24 hours. Nitric oxide (15, 40, or 77 ppm) was added to one of the oxygenators in each pair. Eight paired experiments were performed. Platelet count, plasma beta-thromboglobulin, platelet serotonin content, plasma nitrate, plasma cyclic guanosine monophosphate, and platelet membrane glycoprotein Ib were assayed before the start and at 0.5, 1, 3, 12, and 24 hours of perfusion. RESULTS: Plasma nitrate and plasma cyclic guanosine monophosphate levels were significantly higher in the nitric oxide circuits than in the control circuits (p < 0.01). Higher platelet counts (p < 0.01) and lower beta-thromboglobulin levels (p < 0.01) were observed in the nitric oxide circuits compared with the control circuits. However, no significant differences in platelet serotonin content or platelet membrane glycoprotein Ib density were noted between the circuits. CONCLUSIONS: Nitric oxide probably reduces platelet consumption and platelet activation during ECLS.
Assuntos
Oxigenação por Membrana Extracorpórea , Óxido Nítrico/administração & dosagem , Ativação Plaquetária/efeitos dos fármacos , Análise de Variância , Plaquetas/química , Plaquetas/efeitos dos fármacos , Relação Dose-Resposta a Droga , Oxigenação por Membrana Extracorpórea/instrumentação , Oxigenação por Membrana Extracorpórea/métodos , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Humanos , Técnicas In Vitro , Plasma/química , Plasma/efeitos dos fármacos , Fatores de TempoRESUMO
The aim of this study was to evaluate an in vitro model for investigation of platelet function parameters in an extracorporeal system. Two different perfusion pumps were compared, a roller pump (Polystan) and a centrifugal pump (Biomedicus). A continuous increase in glycoprotein (GP)1b-negative platelets was observed in both circuits. A marked increase of plasma beta-thromboglobulin thromboglobulin concentration and a decrease of the intracellular pool of serotonin was observed, indicating a marked release of alpha as well as of dense granules. The plasma concentration of glycocalicin increased in parallel with a reduced platelet surface expression of GP1b, suggesting that the loss of GP1b is caused by proteolysis rather than by a downregulation of this receptor protein. It is concluded that ECLS results in a pronounced platelet degranulation and causes changes of important membrane receptors which might explain some of the bleeding problems observed in patients treated with ECLS. No significant difference was noted between the roller pump and the centrifugal pump. Trial of strategies, e.g., protease inhibitors and nitric oxide to revert this untoward effect of ECLS are highly warranted.
Assuntos
Órgãos Artificiais , Circulação Extracorpórea , Ativação Plaquetária , Glicoproteínas da Membrana de Plaquetas/análise , Centrifugação/efeitos adversos , Circulação Extracorpórea/efeitos adversos , Circulação Extracorpórea/instrumentação , Hemoglobinas/análise , Humanos , Técnicas In Vitro , Contagem de Plaquetas , Complexo Glicoproteico GPIb-IX de Plaquetas/análise , Serotonina/sangue , beta-Tromboglobulina/análiseRESUMO
OBJECTIVE: During extracorporeal circulation, initial contact between blood and the artificial surface of the circuit induces an overall activation of the hemostatic system. The objective of this study was to investigate the combined effect of epoprostenol (PGI (2) ), nitric oxide (NO) and nafamostat mesilate (FUT-175, a serine protease inhibitor), on plasma coagulation and platelet activation during experimental long-term perfusion. DESIGN: Two identical extracorporeal life support (ECLS) circuits were primed with fresh, heparinized human blood, and circulated for 24 h. FUT was given with a bolus dose of 85 mg/l blood at the initiation of the experiment and thereafter as a continuous infusion of 14 mg/l/h. PGI (2), at a rate of 2.4 microg/l/h, was also administered to the experimental circuit, and 120 ppm NO gas was added to the oxygenator sweep gas. The other circuit was used as a control. RESULTS: Higher platelet count and platelet membrane expression of GPIb were found in the experimental circuits as compared with control circuits. The levels of thrombin/antithrombin III complex (TAT) and prothrombin fragment 1 + 2 (F1 + 2) increased significantly over time in the control circuits but remained low in the experimental circuits. Plasma levels of plasminogen activator inhibitor 1 (PAI-1) decreased rapidly in both circuits but were higher in the control circuits at each time point studied. CONCLUSION: The activation of platelets and of the coagulation system encountered during extracorporeal perfusion is consistently inhibited by a combination of PGI (2), NO and FUT-175. The combination of these drugs appears to be more effective than each drug separately.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Perfusão , Ativação Plaquetária/efeitos dos fármacos , Glicoproteínas da Membrana de Plaquetas , Antitrombina III/metabolismo , Biomarcadores/sangue , AMP Cíclico/sangue , GMP Cíclico/sangue , Hemoglobinas/metabolismo , Humanos , Integrina beta3/sangue , Metemoglobina/metabolismo , Fragmentos de Peptídeos/sangue , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Contagem de Plaquetas , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Glicoproteína IIb da Membrana de Plaquetas/sangue , Precursores de Proteínas/sangue , Protrombina , Trombina/metabolismo , Tempo , Fatores de Tempo , Resultado do Tratamento , beta-Tromboglobulina/metabolismoRESUMO
Hemorrhages are major complications experienced in 10-35% of neonates treated with extracorporeal life support (ECLS). The increased bleeding tendency is partly due to an ECLS induced thrombocytopenia and impaired platelet function. In the present study, we evaluated the effect of epoprostenol on the ECLS induced platelet consumption and activation. In terms of the methods, identical in vitro ECLS circuits were primed with fresh heparinized human blood and circulated for 24 h. Epoprostenol (2.4 microg/L blood/h) was added to one of the circuits in each pair. In total, 6 paired experiments were performed. The platelet count, neutrophil count, plasma concentration of hemoglobin, and platelet membrane expression of glycoproteins (GP) Ib and IIb/IIIa were assayed before the start and at 0.5, 1, 3, 12 and 24 h of perfusion. Higher platelet counts were observed in the experimental circuits. However, no difference in the platelet membrane expression of GPIb and GPIIb/IIIa could be observed between the circuits. In conclusion, epoprostenol reduces platelet consumption during ECLS without affecting the membrane expression of GPIb and GPIIb/IIIa.
Assuntos
Plaquetas/efeitos dos fármacos , Epoprostenol/farmacologia , Oxigenação por Membrana Extracorpórea , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Análise de Variância , Seguimentos , Hemoglobinas/análise , Hemorragia/prevenção & controle , Humanos , Contagem de Leucócitos , Neutrófilos/patologia , Contagem de Plaquetas , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/análise , Complexo Glicoproteico GPIb-IX de Plaquetas/análise , Trombocitopenia/fisiopatologiaRESUMO
Blood platelets are rapidly activated in contact with biomaterials and, therefore, can be used as markers of the biocompatibility of various components in an extracorporeal system. In the present work two different oxygenators, one membrane oxygenator (Avecor) and one hollow-fibre oxygenator ("Lilliput', Dideco) were compared. Complete in vitro extracorporeal membrane oxygenation circuits were perfused with fresh, heparinized human blood for 24 h. Eight experiments were performed with the hollow-fibre oxygenator and five experiments with the membrane oxygenator. Blood gases, electrolytes, glucose and haematocrit were kept within physiological limits. Platelet count, plasma concentration of beta-thromboglobulin, platelet serotonin content, platelet membrane glycoprotein lb and its degradation product glycocalicin, as well as plasma haemoglobin concentration were assayed. As regards most of these variables, significant differences in favour of the hollow-fibre oxygenator were observed.
Assuntos
Oxigenação por Membrana Extracorpórea/instrumentação , Membranas Artificiais , Ativação Plaquetária , Humanos , Técnicas In Vitro , Cloreto de Polivinila , SiliconesRESUMO
OBJECTIVE: Extra corporeal circulation of human blood is used daily in lifesaving procedures such as open-heart surgery and extracorporeal membrane oxygenation (ECMO). But extracorporeal circulation also induces activation of various cascade reactions in the blood. The objective of this study was to evaluate the effects of hemofiltration on cytokine release and removal as well as on platelet activation and consumption. MATERIAL AND METHODS: Two complete ECMO systems, each of them holding a hollow fiber oxygenator, a bladder box, PVC tubing and a roller pump were perfused for 24 h with fresh, heparinized human blood. A hemofilter was added to one of the paired systems. Blood samples were collected from both circuits before start, and at 0.5, 1, 3, 12 and 24 h of perfusion. A total of 8 paired experiments was performed. RESULTS: The plasma concentration of interleukin (IL)1beta, IL-6 and IL-8, as well as of IL-1 receptor antagonist (IL-1ra) increased over time in both systems, but consistently lower levels were observed in the filter circuits compared to the controls. Only minor parts of these cytokines could be assayed in the ultrafiltrate. No significant difference in platelet count and platelet membrane expression of glycoprotein Ib was observed between the circuits. CONCLUSIONS: By adding a hemofilter to the ECMO circuit, it is possible to reduce the plasma concentration of interleukins without significantly affecting platelet activation and consumption.
Assuntos
Citocinas/sangue , Oxigenação por Membrana Extracorpórea , Hemofiltração , Ativação Plaquetária/fisiologia , Hemoglobinometria , Humanos , Técnicas In Vitro , Contagem de Leucócitos , Neutrófilos/imunologia , Contagem de Plaquetas , Glicoproteínas da Membrana de Plaquetas/metabolismo , beta-Tromboglobulina/metabolismoRESUMO
The objective of this study was to evaluate the effect of albumin priming on platelet consumption and activation during long-term perfusion. Two identical in vitro extracorporeal membrane oxygenation circuits were used; one was primed with Ringer's solution containing human serum albumin, the other with Ringer's solution only. Fresh heparinized human blood was pooled, divided between the two systems and circulated for 24 h at 37 degrees C. Platelet count, plasma concentration of betathromboglobulin (BTG), platelet membrane density of glycoprotein (GP) Ib and of GPIIb/IIIa were assayed before the start and at 0.5, 1, 3, 12 and 24 h of perfusion. In total, seven experiments were performed. We found that during the first hour of perfusion, slightly higher platelet counts (p = 0.058) and lower BTG values (p = 0.0005) were observed in the circuits primed with albumin, compared to the control circuits. No statistically significant differences were observed for the platelet membrane expression of GPIb and GPIIb/IIIa. We conclude that albumin priming appears to transiently prevent platelet consumption and activation during long-term perfusion.
Assuntos
Oxigenação por Membrana Extracorpórea , Perfusão , Ativação Plaquetária/efeitos dos fármacos , Albumina Sérica/farmacologia , Humanos , Contagem de Plaquetas/efeitos dos fármacos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/análise , Complexo Glicoproteico GPIb-IX de Plaquetas/análise , Soluções/farmacologia , beta-Tromboglobulina/análiseRESUMO
The purpose of this study was to compare blood cell activation during in vitro long-term perfusion using 2 parallel in vitro extracorporeal membrane oxygenation (ECMO) systems. We compared two substantially different perfusion systems, an assistance respiratoire extra corporelle (AREC) system on one hand, containing an AREC pump, silicon tubing, and a hollow-fiber oxygenator, and a centrifugal pump system, on the other hand, containing a Biomedicus centrifugal pump, PVC tubing, and a membrane oxygenator. We measured the platelet count using an automated blood cell counter. Platelet activation was evaluated using a flow cytometric technique for the platelet membrane expression of glycoproteins and ELISA for the plasma concentration of beta-thromboglobulin (beta-TG), a platelet specific protein released into the blood upon platelet activation. The neutrophil count was assayed using an automated blood cell counter and the plasma concentration of cytokines using an ELISA kit. A significant difference between the two systems was observed in terms of the platelet membrane expression of glycoprotein (GP)Ib (p=0.0001) and GPIIb/IIIa (p=0.0037), indicating a lower degree of platelet activation in the AREC system. The concentration of neutrophils was significantly lower in the centrifugal system (p=0.002) compared to the AREC system. The neutrophil membrane expression of CD11b was significantly lower (p=0.0067) in the AREC system, indicating a lower degree of neutrophil activation compared to the centrifugal pump system. A significantly lower degree of hemolysis, as expressed by plasma hemoglobin, was observed in the AREC pump system (p=0.0491). In conclusion, lower degrees of the platelet membrane expression of GPIb and GPIIb/IIIa and of the neutrophil membrane expression of CD11b were observed in the AREC system, indicating a lower degree of platelet and neutrophil activation in this system. No significant difference between the two systems as to the plasma concentration of interleukin (IL)-1beta, IL-6, or IL-8 could be recorded. Further studies are warranted to specify the role of each individual component of the two systems.
Assuntos
Plaquetas/fisiologia , Oxigenação por Membrana Extracorpórea/instrumentação , Neutrófilos/fisiologia , Antígenos CD11/análise , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Hemoglobinas/análise , Humanos , Técnicas In Vitro , Interleucinas/sangue , Contagem de Leucócitos , Ativação Plaquetária , Contagem de Plaquetas , Glicoproteínas da Membrana de Plaquetas/metabolismo , beta-Tromboglobulina/análiseRESUMO
The objective of this study was to determine the degree of leukocyte activation, as measured by cytokine release, in circulating blood during experimental extracorporeal circulation. Complete in vitro extracorporeal membrane oxygenation (ECMO) circuits were used, and 9 experiments were performed. Whole blood stored at 37 degrees C was used as the control. Blood samples were withdrawn before the start of perfusion and at 24 h of perfusion. Statistically significant releases of interleukin (IL)-1beta, IL-8, and IL-1 receptor antagonist were observed in the perfusion circuits compared to both the control blood and baseline values. Also, increases in plasma tumor necrosis factor (TNF)alpha and IL-6 were seen after 24 h of perfusion although these changes did not reach statistical significance. These results indicate that extracorporeal circulation induced leukocyte activation and cytokine release. These reactions might, as an additional trauma, deteriorate the situation in an already severely ill patient. A search for methods to counteract this untoward activation seems warranted.