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1.
Surgery ; 154(1): 48-57, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23684364

RESUMO

BACKGROUND: We tested the hypotheses that an increase in systemic thrombin activity occurs in both disseminated intravascular coagulation (DIC) with the fibrinolytic phenotype and in acute coagulopathy of trauma shock (ACoTS), and that the patients diagnosed as having ACoTS overlap or are identical with those diagnosed as having DIC. METHODS: We made a prospective study of 57 trauma patients, including 30 patients with DIC and 27 patients without DIC. Patients with ACoTS, defined as a prothrombin time ratio >1.2, were also investigated. We included 12 healthy volunteers as controls. The levels of soluble fibrin, antithrombin, prothrombinase activity, soluble thrombomodulin, and markers of fibrin(ogen)olysis were measured on days 1 and 3 after the trauma. The systemic inflammatory response syndrome and the Sequential Organ Failure Assessment were scored to evaluate the extent of inflammation and organ dysfunction. RESULTS: Patients with DIC showed more systemic inflammation and greater Sequential Organ Failure Assessment scores and were transfused with more blood products than the patients without DIC. On day 1, normal prothrombinase activity, increased soluble fibrin, lesser levels of antithrombin, and increased soluble thrombomodulin were observed in patients with DIC in comparison with controls and non-DIC patients. These changes were more prominent in patients with DIC who met the overt criteria for DIC established by the International Society on Thrombosis and Haemostasis. Multiple regression analysis showed that antithrombin is an independent predictor of high soluble fibrin in DIC patients. Greater levels of fibrin and fibrinogen degradation products, D-dimer, and the fibrin and fibrinogen degradation products/D-dimer ratio indicated increased fibrin(ogen)olysis in DIC patients. Almost all ACoTS patients overlapped with the DIC patients. The changes in the measured variables in ACoTS patients coincided with those in DIC patients. CONCLUSION: Normal prothrombinase activity and insufficient control of coagulation give rise to systemic increase in thrombin generation and its activity in patients with DIC with the fibrinolytic phenotype at an early phase of trauma. The same is true in patients with ACoTS, and shutoff of thrombin generation was not observed.


Assuntos
Antitrombinas/sangue , Transtornos da Coagulação Sanguínea/sangue , Coagulação Intravascular Disseminada/sangue , Choque Traumático/sangue , Trombina/biossíntese , Tromboplastina/metabolismo , Doença Aguda , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Estudos Prospectivos , Protrombina
2.
Shock ; 39(6): 514-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23542400

RESUMO

Trauma-induced tissue factor (TF) release into the systemic circulation is considered to play an important role in the development of disseminated intravascular coagulation (DIC) immediately after severe trauma. However, the relationship between TF and hyperfibrinolysis, especially fibrinogenolysis, has been unclear. A total of 18 rats were divided into three groups: (a) the control group was infused with normal saline; (b) the low-dose group was infused with 4 U/kg TF; and (c) the high-dose group was infused with 16 U/kg TF. Arterial blood was drawn immediately and 2 and 4 h after the start of TF infusion. At each sampling point, arterial blood gases, platelet counts, and coagulation variables were measured. The fibrinogen degradation products were evaluated by a Western blot analysis. Hypotension, hypoxemia, and lactic acidosis were not observed in any of the three groups. In proportion to the doses of TF, the platelet counts, coagulation, and fibrinolysis variables deteriorated in line with DIC. The α2-plasmin inhibitor levels significantly decreased in the high-dose group compared with the other groups. The amounts of fibrinogen degradation products increased in proportion to the doses of TF. The plasmin-α2-plasmin inhibitor complex level in the high-dose group increased more than that of the other groups. In conclusion, TF can induce DIC associated with fibrinolysis and fibrinogenolysis without tissue hypoperfusion. The decrease in the α2-plasmin inhibitor level and the significant increase in the plasmin level may be the two main factors underlying the pathogenesis of hyperfibrin(ogen)olysis after TF administration.


Assuntos
Coagulação Intravascular Disseminada/sangue , Fibrinólise/efeitos dos fármacos , Tromboplastina/farmacologia , Animais , Coagulação Sanguínea/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Coagulação Intravascular Disseminada/induzido quimicamente , Relação Dose-Resposta a Droga , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Hemoglobinas/metabolismo , Masculino , Oxigênio/sangue , Pressão Parcial , Contagem de Plaquetas , Ratos , Ratos Wistar , Tromboplastina/administração & dosagem , alfa 2-Antiplasmina/metabolismo
3.
J Crit Care ; 28(4): 534.e1-5, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23337480

RESUMO

PURPOSE: The aim of this study was to determine whether the relative change in the end-expiratory lung volume (EELV) obtained by the recruitment maneuver (RM) can serve as an indicator of the change in the P/F ratio. MATERIALS AND METHODS: The effects of the intermittent stepwise increases in the RM (peak inspiratory pressure, 45, 50, and 55 cm H2O) were compared in 21 patients with atelectasis under mechanical ventilation. The EELV, the ratio of arterial oxygen concentration to the fraction of inspired oxygen P/F ratio, and relative change rate (Δ) in these parameters were evaluated after each RM. RESULTS: A greater improvement in the EELV (1157 ± 344 mL vs 1469 ± 396 mL) and P/F ratio (250 ± 99 vs 320 ± 92) was observed after the RM. The ΔEELV was correlated with the ΔP/F ratio (ρ = 0.73, P < .01) and was identified as an accurate predictor of the improvement of the ΔP/F ratio by the receiver operating characteristic curve (the area under the curve, 0.93; P < .01). CONCLUSIONS: These results suggest that the ΔEELV obtained by intermittent stepwise RM can serve as an indicator of the change in the P/F ratio.


Assuntos
Medidas de Volume Pulmonar , Atelectasia Pulmonar/fisiopatologia , Atelectasia Pulmonar/terapia , Idoso , Análise de Variância , Feminino , Capacidade Residual Funcional , Humanos , Complacência Pulmonar , Masculino , Oxigênio/sangue , Seleção de Pacientes , Curva ROC , Respiração Artificial , Mecânica Respiratória
4.
Shock ; 37(6): 569-73, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22552020

RESUMO

Recombinant human soluble thrombomodulin (TM-α) was recently developed as an anticoagulant for patients with disseminated intravascular coagulation (DIC). However, the pharmacokinetics and pharmacodynamics of TM-α in DIC patients with severe renal impairment have not yet been elucidated. We investigated the pharmacokinetics and pharmacodynamics of TM-α in DIC patients with severe renal impairment. Eleven DIC patients with severe renal impairment (creatinine clearance <30 mL/min) and 10 DIC patients without severe renal impairment (creatinine clearance ≥30 mL/min) were included in this study. In all patients, a dose of 380 U/kg of TM-α was administered during a 30-min infusion. Blood samples were taken before the start of the first TM-α administration, and at 0.5, 2, 4, 8, and 24 h after the start of administration. Although the clearance of TM-α in the patients with renal impairment was 80% of that in the patients without renal impairment, none of the pharmacokinetic values were significantly different between the groups. In the pharmacokinetic simulation, however, the trough levels of TM-α increased gradually in the patients with renal impairment when the same dose of TM-α was repeatedly administered. After the administration of TM-α, the prothrombinase activities in the patients in both groups were sufficiently inhibited during the observation period. Although the pharmacokinetic values in DIC patients with severe renal impairment were only slightly different from those in DIC patients without severe renal impairment, we need to pay attention to the elevation of the trough levels of TM-α when the same dose of TM-α is repeatedly administered.


Assuntos
Anticoagulantes/farmacocinética , Coagulação Intravascular Disseminada/metabolismo , Nefropatias/complicações , Trombomodulina/metabolismo , Idoso , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Coagulação Intravascular Disseminada/complicações , Feminino , Humanos , Nefropatias/metabolismo , Masculino , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/farmacologia , Trombomodulina/uso terapêutico , Tromboplastina/análise
5.
Clin Appl Thromb Hemost ; 18(4): 364-9, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22275391

RESUMO

The data from 254 patients with severe trauma were retrospectively analyzed. The patients were subdivided into disseminated intravascular coagulation (DIC) and non-DIC. There was a difference in the incidence of the continuous progression from the early to late phase of DIC between the patients with and without DIC on day 0. While 2 of 9 patients who newly developed late-phase DIC were complicated with sepsis, none of the 32 patients who showed a continuous progression of DIC from the early to late phase of trauma developed sepsis. The DIC and Sequential Organ Failure Assessment scores on day 0 were independent factors that predicted the continuous progression of the DIC from the early to late phase of trauma. Trauma itself, but not sepsis, contributes to the continuous progression of DIC from the early to late phase of trauma. The severity of DIC and organ dysfunction are involved in the pathogenesis of this continuous progression.


Assuntos
Coagulação Intravascular Disseminada , Ferimentos e Lesões , Adulto , Idoso , Coagulação Intravascular Disseminada/epidemiologia , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/patologia , Coagulação Intravascular Disseminada/fisiopatologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sepse/epidemiologia , Sepse/etiologia , Sepse/patologia , Sepse/fisiopatologia , Índices de Gravidade do Trauma , Ferimentos e Lesões/complicações , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/patologia , Ferimentos e Lesões/fisiopatologia
6.
Dig Dis Sci ; 56(8): 2361-5, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21384123

RESUMO

BACKGROUND: The gut flora is crucially involved in host homeostasis. However, the changes in the gut flora during the early phase of a critical illness are unknown. AIMS: We investigated the changes in the gut flora at an early phase of severe insult in critically ill patients. METHODS: Fifteen patients who experienced a sudden and severe insult were studied, along with 12 healthy volunteers as the control group. Fecal samples were acquired from the subjects by swabs of the rectum within 6 h after admission to the emergency room (day 0). Samples were serially collected from patients until day 14. Samples were also collected from control subjects. RESULTS: On day 0, total bacterial counts were decreased to one-thousandth the number of the control subjects, in particular, obligate anaerobes and Lactobacillus were significantly decreased. In addition, on day 0, the major short-chain fatty acids of the patients were significantly lower than those of the control subjects. The gut flora and the concentrations of major short-chain fatty acids did not recover to normal levels. In contrast, Enterococcus and Pseudomonas increased during the study period. CONCLUSIONS: The gut flora in critically ill patients changed immediately after a severe insult. The concentrations of the three major short-chain fatty acids were immediately decreased in tandem with the destruction of the gut flora. The gut flora and the concentration of major short-chain fatty acids did not improve during the first 2 weeks after hospital admission. At the same time, the number of harmful bacteria gradually increased.


Assuntos
Estado Terminal , Intestinos/microbiologia , Adulto , Carga Bacteriana , Enterococcus/isolamento & purificação , Ácidos Graxos Voláteis/metabolismo , Fezes/microbiologia , Feminino , Humanos , Lactobacillus/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Pseudomonas/isolamento & purificação
7.
Inflammation ; 34(3): 193-7, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20499270

RESUMO

Migration inhibitory factor (MIF) is associated with multiple organ dysfunction syndrome (MODS) in patients with systemic inflammatory response syndrome (SIRS). Our purposes were to determine the serum MIF, cortisol, and tumor narcosis factor-α (TNF-α) and to investigate the influences of the balance between the levels of MIF and cortisol in patients with blunt trauma. The cortisol levels were identical between the patients with and without MODS. However, the MIF and TNF-α levels in the patients with MODS were statistically higher than those of the patients without MODS. The cortisol/MIF ratios in the patients with MODS were statistically higher than those of the patients without MODS. The results show that MIF and TNF-α play an important role together in posttraumatic inflammatory response. An excessive serum MIF elevation overrides the anti-inflammatory effects of cortisol and leads to persistent SIRS followed by MODS in blunt trauma patients.


Assuntos
Hidrocortisona/sangue , Oxirredutases Intramoleculares/sangue , Fatores Inibidores da Migração de Macrófagos/sangue , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/etiologia , Ferimentos não Penetrantes/sangue , Ferimentos não Penetrantes/complicações , Adulto , Feminino , Traumatismos Cranianos Fechados/sangue , Traumatismos Cranianos Fechados/complicações , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangue , Ferimentos não Penetrantes/fisiopatologia , Adulto Jovem
8.
Surgery ; 149(2): 221-30, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20655560

RESUMO

BACKGROUND: The aims of the present study were to confirm the consumption coagulopathy of disseminated intravascular coagulation with the fibrinolytic phenotype at an early phase of trauma and to test the hypothesis that thrombin-activatable fibrinolysis inhibitor, neutrophil elastase, and plasmin contribute to the increased fibrinolysis of this type of disseminated intravascular coagulation. Furthermore, we hypothesized that disseminated intravascular coagulation at an early phase of trauma progresses dependently to disseminated intravascular coagulation with a thorombotic phenotype from 3 to 5 days after injury. METHODS: Fifty-seven trauma patients, including 30 patients with disseminated intravascular coagulation and 27 patients without disseminated intravascular coagulation, were studied prospectively. Levels of thrombin-activatable fibrinolysis inhibitor, tissue-type plasminogen activator plasminogen activator inhibitor-1 complex, plasmin alpha2 plasmin inhibitor complex, D-dimer, neutrophil elastase, and fibrin degradation product by neutrophil elastase were measured on days 1, 3, and 5 after trauma. The prothrombin time, fibrinogen, fibrin/fibrinogen degradation product, antithrombin, and lactate also were measured. RESULTS: Independent of the lactate levels, disseminated intravascular coagulation patients showed a prolonged prothrombin time, lesser fibrinogen and antithrombin levels, and increased levels of fibrin/fibrinogen degradation product on day 1. Disseminated intravascular coagulation diagnosed on day 1 continued to late-phase disseminated intravascular coagulation on days 3 and 5 after trauma. Increased levels of tissue-type plasminogen activator plasminogen activator inhibitor-1 complex, plasmin alpha2 plasmin inhibitor complex, D-dimer, neutrophil elastase, and fibrin degradation product by neutrophil elastase but not thrombin-activatable fibrinolysis inhibitor were observed in the disseminated intravascular coagulation patients. No correlation was observed between plasmin alpha2 plasmin inhibitor complex and fibrin degradation product by neutrophil elastase in disseminated intravascular coagulation patients. Multiple regression analysis showed the disseminated intravascular coagulation score and the tissue-type plasminogen activator plasminogen activator inhibitor-1 complex levels on day 1 to correlate with the total volume of transfused blood. Patient prognosis deteriorated in accordance with the increasing disseminated intravascular coagulation severity. CONCLUSION: Disseminated intravascular coagulation at an early phase of trauma is associated with consumption coagulopathy and excessive fibrinolysis both by plasmin and neutrophil elastase independent of hypoperfusion and continues to disseminated intravascular coagulation at a late phase of trauma. Increased fibrinolysis requires more blood transfusions, contributing to a poor patient outcome.


Assuntos
Coagulação Intravascular Disseminada/sangue , Fibrinolisina/fisiologia , Fibrinólise , Elastase de Leucócito/fisiologia , Ferimentos e Lesões/sangue , Adulto , Idoso , Transfusão de Sangue , Coagulação Intravascular Disseminada/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Prospectivos , Ferimentos e Lesões/complicações
9.
Biochem Biophys Res Commun ; 391(3): 1421-6, 2010 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-20026056

RESUMO

Foxp3(+)CD4(+) regulatory T cells (Treg) control not only autoimmunity but also the effective immune response against RNA virus infections, which produces virus-derived double-stranded RNA (dsRNA). To induce effective anti-viral immunity, it is a key issue to learn how Treg respond to dsRNA in vitro and in vivo. We here showed that synthetic dsRNA, polyI:C, caused peripheral expansion of functional Treg in a TICAM-1- and IL-6-dependent manner in vivo. PolyI:C did not expand Treg directly, but promoted the expansion of naturally occurring Treg indirectly through IL-6 produced from dendritic cells (DCs). In addition, the expansion of Treg by IL-6 was inhibited by IFN-alpha from polyI:C-stimulated DCs. These data suggest that the balance of IL-6 and IFN-alpha in the region of RNA virus infection may determine the number of peripheral Treg, which affects the effective immune responses against viruses.


Assuntos
Células Dendríticas/imunologia , Interferon-alfa/metabolismo , Interleucina-6/metabolismo , Ativação Linfocitária , RNA de Cadeia Dupla/imunologia , RNA Viral/imunologia , Linfócitos T Reguladores/imunologia , Proteínas Adaptadoras de Transporte Vesicular/genética , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/imunologia , Proliferação de Células , Células Cultivadas , Interferon-alfa/genética , Interleucina-6/genética , Camundongos , Camundongos Mutantes , Poli C/imunologia , Poli C/farmacologia , RNA de Cadeia Dupla/farmacologia , Ratos , Linfócitos T Reguladores/efeitos dos fármacos
10.
Thromb Res ; 124(6): 706-10, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19651430

RESUMO

INTRODUCTION: To validate the diagnostic criteria for disseminated intravascular coagulation (DIC) established by the Japanese Association for Acute Medicine (JAAM) at an early stage of trauma and to evaluate the hypothesis that the JAAM criteria can diagnose DIC with a higher sensitivity than the International Society on Thrombosis and Haemostasis (ISTH) overt DIC criteria. MATERIALS AND METHODS: Based on a review of medical records, the data of 314 trauma patients were retrospectively obtained at 4 time points within 24 hr after arrival to the Emergency Department. RESULTS: One hundred and forty-one JAAM DIC patients (44.9%) showed differences in the prevalence of massive bleeding and multiple organ dysfunction syndrome (MODS), and the outcome in comparison to the non-DIC patients. A stepwise logistic regression analysis showed that the maximum JAAM DIC scores independently predicted the patient death. All of the patients who developed ISTH overt DIC could be identified by the JAAM DIC criteria at early time points. The mortality rate and the incidence of massive bleeding and MODS of the patients with the ISTH overt DIC were higher than those only met the JAAM DIC criteria. Stepwise increases in the ISTH overt DIC scores and the incidence of the overt DIC were observed in accordance with the increases in the JAAM DIC scores. While the mortality rates were identical, there were marked differences in the incidence of MODS and Sequential Organ Failure Assessment scores between the DIC patients associated with trauma and sepsis. CONCLUSIONS: The results show that the JAAM scoring system has acceptable validity for the DIC diagnosis at an early phase of trauma, and also that the scoring system can diagnose DIC with a higher sensitivity than the criteria of the ISTH overt DIC. Bleeding as well as MODS may affect the prognosis of the patients associated with DIC.


Assuntos
Coagulação Intravascular Disseminada/classificação , Coagulação Intravascular Disseminada/diagnóstico , Adulto , Idoso , Cardiologia/métodos , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sepse/classificação , Sepse/diagnóstico , Fatores de Tempo , Ferimentos e Lesões/classificação , Ferimentos e Lesões/diagnóstico
11.
Thromb Res ; 124(5): 608-13, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19660788

RESUMO

INTRODUCTION: Disseminated intravascular coagulation (DIC) with an antifibrinolytic phenotype is characterized by microvascular thrombosis leading to poor outcome at the late-stage of trauma. To test the hypothesis that DIC with a fibrinolytic phenotype at an early stage of trauma also contributes to a poor outcome due to severe bleeding, we conducted a retrospective, cohort study. MATERIALS AND METHODS: The subjects included 314 consecutive severe trauma patients. A systematic review of medical records of the patients was conducted to provide the base line characteristics and DIC-related variables. The data of these variables were obtained at 4 time points within 24 hr after arrival to the emergency department (ED); Time Point 1, immediately after arrival to the ED to 4 hr after arrival; Time Point 2, 4 to 8 hr after arrival; Time Point 3, 8 to 16 hr after arrival; Time Point 4, 16 to 24 hr after arrival. RESULTS: Nonsurvivors (87.3%, 48/55) met the Japanese Association for Acute Medicine (JAAM) DIC criteria showing lower fibrinogen levels, a prolonged prothrombin time, and higher fibrin/fibrinogen degradation products (FDP) and D-dimer levels in comparison to those of the 289 survivors. The FDP/D-dimer ratio and lactate level were significantly higher in the nonsurvivors than those of the survivors. Lower fibrinogen levels and higher FDP/D-dimer ratio suggest fibrinogenolysis in DIC of the nonsurvivors. Furthermore a stepwise logistic regression analysis showed that the JAAM DIC score, levels of fibrinogen, FDP and lactate at Time Point 1 are independent predictors of death. Low levels of fibrinogen and high FDP but not D-dimer predict massive bleeding at an early stage of trauma. The optimal cutoff points for the prediction of death and massive bleeding were fibrinogen (1.90, 1.90 g/L) and FDP (35.2, 68.7 mg/L), respectively. CONCLUSIONS: DIC with a fibrinolytic phenotype modified through fibrinogenolysis at an early phase of trauma contributes to poor prognosis due to massive bleeding. Tissue hypoperfusion may be involved in the pathogenesis of this type of DIC.


Assuntos
Coagulação Intravascular Disseminada/sangue , Ferimentos e Lesões/sangue , Adulto , Coagulação Sanguínea , Plaquetas/fisiologia , Coagulação Intravascular Disseminada/etiologia , Feminino , Fibrinólise , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Curva ROC , Análise de Regressão , Índice de Gravidade de Doença , Resultado do Tratamento
12.
Clin Appl Thromb Hemost ; 15(5): 561-6, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18840625

RESUMO

A study was conducted to test the hypotheses that antithrombin III (antithrombin) improves disseminated intravascular coagulation (DIC) when applied to DIC patients diagnosed by sensitive criteria and that the administration of high-dose antithrombin is a beneficial treatment for DIC. Twenty-three DIC patients diagnosed based on the Japanese Association for Acute Medicine (JAAM) DIC diagnostic criteria were treated with either high-dose (60 IU/kg/day) or low-dose (30 IU/kg/day) antithrombin concentrates for 3 days. The clinical conditions that cause DIC were restricted to systemic inflammatory response syndrome (SIRS) and sepsis. Data of antithrombin activity, platelet counts, coagulation and fibrinolytic markers, and DIC scores before antithrombin administration (day 0), on days 1 to 3, and on day 7 were retrospectively collected from computer-based records. Patients who met the JAAM DIC criteria were administered either high-dose (12 patients) or low-dose (11 patients) antithrombin. The patients' backgrounds and antithrombin activity (high dose, 51.5 +/- 14.5%; low dose, 62.6 +/- 19.3%; P = .153) on day 0 were identical in the 2 groups. The JAAM DIC score and prothrombin time ratio on day 7 significantly improved when compared with those on day 0. However, mortality at 28 days as well as interaction within the antithrombin doses administered showed no difference. There were also no differences in the time course of the platelet counts, coagulation and fibrinolytic markers, and DIC scores in the 2 groups. The authors conclude that the effects of antithrombin on prognosis and coagulation and fibrinolytic parameters are independent of the doses administered in patients with SIRS/sepsis-associated DIC.


Assuntos
Antitrombina III/administração & dosagem , Coagulação Intravascular Disseminada/tratamento farmacológico , Antitrombina III/efeitos adversos , Estado Terminal , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/diagnóstico , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
13.
Shock ; 29(5): 549-52, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-17998887

RESUMO

To investigate the relationship between the inflammatory responses and postresuscitation syndrome, we prospectively examined the serial changes of neutrophil elastase (NE), urinary trypsin inhibitor (UTI), and TNF-alpha) in successfully resuscitated patients after out-of-hospital cardiac arrest. This study included 36 patients with out-of-hospital cardiac arrests who were admitted to our intensive care unit after return of spontaneous circulation (ROSC). The 11 patients who restored to spontaneous circulation within 30 min after cardiac arrest were defined as the short cardiac arrest group. The 25 patients who restored to spontaneous circulation more than 30 min after cardiac arrest were defined as the long cardiac arrest group. Eight healthy volunteers served as control group. Daily plasma levels of NE, UTI, and TNF-alpha were measured from days 1 to 5 after ROSC. The releases of NE from activated neutrophil just after ROSC in the patients with long cardiac arrest were statistically higher than those of the short cardiac arrest group. There was a significant correlation between the NE levels and the duration of cardiac arrest. A high but insufficient production of UTI for NE release was observed on day 1, especially in the patients with a long duration of cardiac arrest. The cerebral performance category of the short cardiac arrest group was better than that of the long cardiac arrest group. Although high levels of TNF-alpha were sustained in the postresuscitation period, the levels of TNF-alpha were unrelated to the duration of cardiac arrest. In conclusion, a massive release of NE in proportion to the duration of cardiac arrest and an insufficient production of UTI for the NE release may contribute to the pathogenesis of postresuscitation syndrome after out-of-hospital cardiac arrest.


Assuntos
Regulação da Expressão Gênica , Glicoproteínas/biossíntese , Parada Cardíaca/metabolismo , Elastase de Leucócito/metabolismo , Idoso , Cuidados Críticos , Feminino , Glicoproteínas/metabolismo , Humanos , Isquemia , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Ressuscitação , Fator de Necrose Tumoral alfa/metabolismo
14.
Inflammation ; 30(3-4): 118-24, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17534704

RESUMO

To determine the relationship between macrophage migration inhibitory factor (MIF) and disseminated intravascular coagulation (DIC) in patients with systemic inflammatory response syndrome (SIRS) and sepsis, and their relationship to multiple organ dysfunction syndrome (MODS) and prognosis, we conducted a prospective cohort study. Forty-eight patients with SIRS or sepsis were classified as 20 DIC and 28 non-DIC patients. MIF, tumor necrosis factor-alpha (TNF-alpha), soluble fibrin, protein C activity (protein C), and plasminogen activator inhibitor-1 (PAI-1) were all measured within 24 h after the patients met the criteria of SIRS or sepsis (day 0), and on days 1 to 4. The number of SIRS criteria that the patients met and the DIC scores were determined simultaneously. In DIC patients, significantly higher levels of MIF, TNF-alpha, soluble fibrin, PAI-1 were found compared with non-DIC patients. We also found significantly lower protein C levels in the DIC patients than in the non-DIC patients. Significant correlations were found between the peak levels of MIF and soluble fibrin in the DIC patients (rs = 0.496, p < 0.0407). All DIC patients had MODS and also showed a higher number of dysfunctioning organs and a poorer prognosis than the non-DIC patients. A simple logistic regression analysis showed the peak MIF levels and DIC significantly to be related to the patients' death (odds ratio 1.016 and 40.5; p < 0.0409, p < 0.0009, respectively). In conclusion, DIC patients with elevated levels of MIF and TNF-alpha had more organ dysfunctions leading to a poor prognosis in a population of SIRS and sepsis patients. MIF may therefore play a role in the inflammatory and thrombotic processes in DIC patients.


Assuntos
Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/imunologia , Oxirredutases Intramoleculares/sangue , Fatores Inibidores da Migração de Macrófagos/sangue , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Biomarcadores/sangue , Coagulação Sanguínea , Feminino , Fibrinólise , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/imunologia , Prognóstico , Sepse/sangue , Sepse/imunologia , Fator de Necrose Tumoral alfa/sangue
15.
Thromb Res ; 121(1): 67-73, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17397908

RESUMO

INTRODUCTION: We conducted a prospective study to test the hypothesis that the activation of neutrophil elastase-mediated fibrinolysis is insufficient to overcome the fibrinolytic shutdown of disseminated intravascular coagulation (DIC) in patients associated with systemic inflammation. MATERIALS AND METHODS: We investigated 45 consecutive patients with systemic inflammatory response syndrome (SIRS) and sepsis, classified as 11 DIC and 34 non-DIC. Fibrin degradation products by neutrophil elastase (Elastase-XDP) and by plasmin (FDP), cross-linked fibrin degradation products (D-dimer), soluble fibrin, antithrombin, protein C, plasminogen activator inhibitor-1 (PAI-1), and urinary trypsin inhibitor (UTI) were measured within 24 h after the patients met either the SIRS or sepsis criteria (day 0), as well as on days 2 and 4. RESULTS: In DIC patients, higher levels of soluble fibrin, PAI-1, and FDP and markedly lower levels of antithrombin and protein C were observed in comparison to those in non-DIC patients. DIC patients showed a significantly higher level of peak Elastase-XDP than non-DIC patients (25.7+/-5.9 vs. 16.3+/-2.6 microg/mL, respectively; p=0.0333). However, we could not find any substantial difference in the levels of Elastase-XDP, UTI, and D-dimer on each day during the study period between the two groups. Good correlations were observed between the levels of D-dimer and Elastase-XDP in both patients with and without DIC (r(s)=0.699 and r(s)=0.817, respectively), but the coefficients of determination in both groups showed low values and the slopes of the regression lines were less than 1.0. A multivariate logistic regression analysis showed the elevated peak Elastase-XDP levels to inversely correlate with death. On the other hand, the DIC patients showed a higher number of organ dysfunctions and a poorer prognosis than did the non-DIC patients. CONCLUSIONS: The activation of the neutrophil elastase-mediated fibrinolytic pathway may be insufficient to overcome the fibrinolytic shutdown by PAI-1 and may in part explain the poor prognosis of DIC patients associated with systemic inflammation.


Assuntos
Coagulação Intravascular Disseminada/sangue , Fibrinólise , Elastase de Leucócito/metabolismo , Síndrome de Resposta Inflamatória Sistêmica/sangue , Adulto , Coagulação Intravascular Disseminada/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/fisiologia , Estudos Prospectivos , Sepse/sangue , Sepse/patologia
16.
Thromb Res ; 120(1): 87-93, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17023030

RESUMO

INTRODUCTION: We conducted this prospective study in order to investigate the hypotheses that an alternative pathway for fibrinolysis is activated in patients who have undergone cardiopulmonary bypass (CPB) surgery and major abdominal surgery and that the levels of fibrin degradation products digested by polymorphonuclear neutrophil elastase (elastase-XDP) and the D-dimer increase in the patients' plasma. MATERIALS AND METHODS: We studied a total of 77 patients who were scheduled to undergo either CPB surgery (36 patients) or major abdominal surgery (41 patients) and then measured the elastase-XDP and D-dimer levels at several time points both during and after the surgeries. The CPB surgery was divided into surgery for aortic dissection (AD) and cardiac surgery. The major abdominal surgery consists of hepatic resection and esophagectomy. RESULTS: The elastase-XDP and D-dimer levels significantly increased in the patients who underwent both CPB surgery and major abdominal surgery. The elastase-XDP levels in AD surgery showed highest values at the end of the CPB, while the levels in the other surgeries reached their peak on the day after the surgery. Statistical difference was seen in the levels of elastase-XDP among the three subgroups undergoing a hepatic resection. While we found significant correlations between the levels of elastase-XDP and D-dimer in patients undergoing CPB surgery and a subsegmentectomy of a cirrhotic liver, the correlation coefficients were markedly low in comparison to those of the other surgeries. CONCLUSIONS: Our findings demonstrated that the elastase-mediated pathway of fibrinolysis is activated to varying degrees depending on the surgery performed. Variations in the correlation coefficients between the levels of elastase-XDP and D-dimer may suggest that elastase-mediated fibrinolysis play a different role from the physiological fibrinolysis mediated by plasmin.


Assuntos
Ponte Cardiopulmonar , Procedimentos Cirúrgicos do Sistema Digestório , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinólise , Elastase de Leucócito/metabolismo , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Elastase de Leucócito/análise , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
17.
Am J Hematol ; 81(12): 907-14, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16924643

RESUMO

To evaluate the changes in the antithrombin III (antithrombin) values after initial supplementation to predict outcome in critically ill patients, we conducted a retrospective study. All consecutive patients admitted to the intensive care unit (ICU) and treated with antithrombin were enrolled in the study. Initial doses of 1,500 IU or 30 IU/kg antithrombin concentrates were administered over an hour. The clinical backgrounds of the patients were collected from computer-based records. Serial data of antithrombin were collected from the first day of administration (Day 0) to days 1-4. The patients were subdivided into two groups based on whether they demonstrated an increased antithrombin activity of more than 60% on the first day after the initial supplementation (responders) or not (nonresponders). Four hundred thirty-five patients were enrolled in the present study. Two hundred eighty-eight patients could achieve an antithrombin activity of more than 60%. The outcome was significantly different between the two groups. A logistic regression analysis revealed the day 1 antithrombin level and an initial increase of less than 60% after supplementation to be independently associated with ICU mortality. We also found a significant increase in the platelet counts and fibrinogen levels, and a decrease in the disseminated intravascular coagulation (DIC) scores for the responders. In conclusion, our findings demonstrated the first-day dynamic change in antithrombin activity, and not the basal level, to be able to predict critically ill patient death. This dynamic change was associated with an improvement in the platelet counts, fibrinogen levels, and the DIC score.


Assuntos
Anticoagulantes/administração & dosagem , Anticoagulantes/sangue , Antitrombina III/administração & dosagem , Antitrombina III/análise , Coagulação Intravascular Disseminada/sangue , Unidades de Terapia Intensiva , Adulto , Idoso , Estado Terminal , Coagulação Intravascular Disseminada/mortalidade , Coagulação Intravascular Disseminada/prevenção & controle , Feminino , Fibrinogênio/análise , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas/métodos , Valor Preditivo dos Testes , Análise de Regressão , Estudos Retrospectivos , Fatores de Tempo
18.
Masui ; 54(10): 1149-52, 2005 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-16231772

RESUMO

A 61-year-old woman was transfered to our emergency center because of epidural abcess with neurological deficits. Magnetic resonance imaging (MRI) revealed high intensity (T 2 WI) abscess in the epidural space from 5 th cervical to 3 rd thoracic spine level. Surgical drainage was interfered with her poor general conditions. Instead of surgical approach, we inserted a 4 Fr pig-tail catheter into the epidural space with a loss of resistance method, then made a continuous drainage of the abscess. Her neurological state improved after the procedure. Diminished epidural abscess was found on the MRI after the drainage. We demonstrated successfully treated epidural abscess by percutaneous drainage with a 4 Fr short sheath and pig-tail catheter.


Assuntos
Cateterismo , Drenagem/instrumentação , Drenagem/métodos , Abscesso Epidural/terapia , Feminino , Humanos , Pessoa de Meia-Idade
19.
Masui ; 52(2): 177-9, 2003 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-12649878

RESUMO

Mitral stenosis is one of the complicating cardiac diseases during pregnancy. We experienced cesarean section in a patient with mitral stenosis and severe pulmonary hypertension (94/41 mmHg). During surgery, complete analgesia below T 4 level was obtained by epidural anesthesia with two catheters inserted at L 3-4 and T 11-12 interspaces. By epidural anesthesia, pulmonary arterial pressure decreased to 60/30 mmHg and other hemodynamic variables were stable. A baby (BW:1880 g) was intubated because of tachypnea although Apgar scores were 6-8-8. The anesthetic course of the patient was uneventful.


Assuntos
Anestesia Epidural , Anestesia Obstétrica/métodos , Cesárea , Hipertensão Pulmonar/complicações , Estenose da Valva Mitral/complicações , Complicações Cardiovasculares na Gravidez , Adulto , Feminino , Humanos , Gravidez
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