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Combination of thrombin-antithrombin complex, plasminogen activator inhibitor-1, and protein C activity for early identification of severe coagulopathy in initial phase of sepsis: a prospective observational study.

ABSTRACT: INTRODUCTION: Current criteria for early diagnosis of coagulopathy in sepsis are limited. We postulated that coagulopathy is already complicated with sepsis in the initial phase, and severe coagulopathy or disseminated intravascular coagulation (DIC) becomes overt after progressive consumption of platelet and coagulation factors. To determine early diagnostic markers for severe coagulopathy, we evaluated plasma biomarkers for association with subsequent development of overt DIC in patients with sepsis. METHODS: A single-center, prospective observational study was conducted in an adult ICU at a university hospital. Plasma samples were obtained from patients with sepsis at ICU admission. Fourteen biomarkers including global markers (platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen and fibrin degradation product (FDP)); markers of thrombin generation (thrombin-antithrombin complex (TAT) and soluble fibrin); markers of anticoagulants (protein C (PC) and antithrombin); markers of fibrinolysis (plasminogen, ?2-plasmin inhibitor (PI), plasmin-?2-PI complex, and plasminogen activator inhibitor (PAI)-1); and a marker of endothelial activation (soluble E-selectin) were assayed. Patients who had overt DIC at baseline were excluded, and the remaining patients were followed for development of overt DIC in 5 days, and for mortality in 28 days. RESULTS: A total of 77 patients were enrolled, and 37 developed overt DIC within the following 5 days. Most patients demonstrated hemostatic abnormalities at baseline with 98.7% TAT, 97.4% FDP and 88.3% PC. Most hemostatic biomarkers at baseline were significantly associated with subsequent development of overt DIC. Notably, TAT, PAI-1 and PC discriminated well between patients with and without developing overt DIC (area under the receiver operating characteristic curve (AUROC), 0.77 (95% confidence interval, 0.64 to 0.86); 0.87 (0.78 to 0.92); 0.85 (0.76 to 0.91), respectively), and using the three together, significantly improved the AUROC up to 0.95 (vs. TAT, PAI-1, and PC). Among the significant diagnostic markers for overt DIC, TAT and PAI-1 were also good predictors of 28-day mortality (AUROC, 0.77 and 0.81, respectively). CONCLUSIONS: Severe coagulation and fibrinolytic abnormalities on ICU admission were associated with subsequent development of overt DIC. A single measurement of TAT, PAI-1, and PC activity could identify patients with ongoing severe coagulopathy, early in the course of sepsis.

SUBMITTER: Koyama K

PROVIDER: S-EPMC4056264 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Combination of thrombin-antithrombin complex, plasminogen activator inhibitor-1, and protein C activity for early identification of severe coagulopathy in initial phase of sepsis: a prospective observational study.

Koyama Kansuke K Madoiwa Seiji S Nunomiya Shin S Koinuma Toshitaka T Wada Masahiko M Sakata Asuka A Ohmori Tsukasa T Mimuro Jun J Sakata Yoichi Y

Critical care (London, England) 20140113 1

<h4>Introduction</h4>Current criteria for early diagnosis of coagulopathy in sepsis are limited. We postulated that coagulopathy is already complicated with sepsis in the initial phase, and severe coagulopathy or disseminated intravascular coagulation (DIC) becomes overt after progressive consumption of platelet and coagulation factors. To determine early diagnostic markers for severe coagulopathy, we evaluated plasma biomarkers for association with subsequent development of overt DIC in patient ...[more]

PMID: 24410881

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Project description:Background Detecting the changes of coagulation function in the early stage of postpartum hemorrhage (PPH), which is the leading cause of maternal death, is the key to treatment this serious disease, however, there is less effective assessment methods. Thrombomodulin (TM), thrombin-antithrombin complex (TAT), plasmin-α2-plasmininhibitor complex (PIC), and tissue plasminogen activator-inhibitor complex (t-PAIC) are the new direct indicators for coagulation and fibrinolysis, and considered sensitive molecular markers of the fibrinolytic system changing. The aim of this study was to investigate the changes of these 4 new indicators in the early stage of PPH. Methods We retrospectively reviewed the new coagulate indicators, TM, TAT, PIC, and t-PAIC, obtained from PPH patients at Guangzhou Women and Children’s Medical Center from January 2021 to July 2021. According to the amount of blood loss, the patients were divided into 3 groups: Mild group (blood loss <1,500 mL, n=17), Severe group (blood loss ≥1,500 mL, n=24); another 12 women who did not experience PPH were selected as the Normal group (n=12). The four indicators were measured at the time of PPH happened, or immediately when baby was born in the Normal group, and evaluated for the prediction of PPH. Results The t-PAIC level of the Severe group was significantly lower than the other 2 groups (Normal group vs. Mild group vs. Severe group: 13.9±2.0 vs. 9.4±1.8 vs. 7.5±0.9, P=0.020), and the PIC level was the highest (Normal group vs. Mild group vs. Severe group: 1.1±0.2 vs. 2.7±0.8 vs. 2.9±0.6, P=0.012). There was no significant difference in TM and TAT among the 3 groups. The odds ratio (OR) value of t-PAIC was 0.822, 95% confidence interval (CI): 0.697–0.970, P=0.020. The area under the curve (AUC) of PIC was 0.5, and t-PAIC was 0.775, the cut-off point was 6.295, the specificity was 75%, and the sensitivity was 75%. Conclusions With the increasing of blood loss, t-PAIC decreased gradually, and is associated with severe PPH. This indicator may be a new predictor of PPH, and should be used in the early period of PPH for treatment.

Project description:BACKGROUND:Pulmonary coagulopathy has become an important therapeutic target in adult respiratory distress syndrome (ARDS). We hypothesized that combining intravenous recombinant human antithrombin (rhAT), nebulized heparin, and nebulized tissue plasminogen activator (TPA) more effectively improves pulmonary gas exchange compared with a single rhAT infusion, while maintaining the anti-inflammatory properties of rhAT in ARDS. Therefore, the present prospective, randomized experiment was conducted using an established ovine model. METHODS:Following burn and smoke inhalation injury (40% of total body surface area, third-degree flame burn, and 4 × 12 breaths of cold cotton smoke), 18 chronically instrumented sheep were randomly assigned to receive intravenous saline plus saline nebulization (control), intravenous rhAT (6 IU/kg/h) started 1 hour after injury plus saline nebulization (AT i.v.) or intravenous rhAT combined with nebulized heparin (10,000 IU every 4 hours, started 2 hours after injury), and nebulized TPA (2 mg every 4 hours, started 4 hours after injury) (triple therapy, n = 6 each). All animals were mechanically ventilated and fluid resuscitated according to standard protocols during the 48-hour study period. RESULTS:Both treatment approaches attenuated ARDS compared with control animals. Notably, triple therapy was associated with an improved PaO2/FiO2 ratio (p = 0.007), attenuated pulmonary obstruction (p = 0.02) and shunting (p = 0.025), as well as reduced ventilatory pressures (p < 0.05 each) versus AT i.v. at 48 hours. However, the anti-inflammatory effects of sole AT i.v., namely, the inhibition of neutrophil activation (neutrophil count in the lymph and pulmonary polymorphonuclear cells, p < 0.05 vs. control each), pulmonary transvascular fluid flux (lymph flow, p = 0.004 vs. control), and systemic vascular leakage (cumulative net fluid balance, p < 0.001 vs. control), were abolished in the triple therapy group. CONCLUSION:Combining intravenous rhAT with nebulized heparin and nebulized TPA more effectively restores pulmonary gas exchange, but the anti-inflammatory effects of sole rhAT are abolished with the triple therapy. Interferences between the different anticoagulants may represent a potential explanation for these findings.

Dataset Information

Combination of thrombin-antithrombin complex, plasminogen activator inhibitor-1, and protein C activity for early identification of severe coagulopathy in initial phase of sepsis: a prospective observational study.

Publications

Combination of thrombin-antithrombin complex, plasminogen activator inhibitor-1, and protein C activity for early identification of severe coagulopathy in initial phase of sepsis: a prospective observational study.

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