fibrinopeptide-a and Sepsis

To test the hypothesis that the coagulation system and platelets are activated in sepsis, the uncomplicated and usually earliest stage of the septic process, and to compare the findings detected in sepsis with those found in severe sepsis and septic shock.. Prospective study comparing patients with sepsis, severe sepsis, and septic shock, and healthy volunteers.. General intensive care unit in a tertiary university hospital.. Seventy-four consecutive septic patients (45 with sepsis, 15 with severe sepsis, and 14 with septic shock). Fourteen healthy volunteers served as control subjects.. None.. After blood sampling, molecular activation markers of coagulation (prothrombin fragments 1 and 2, fibrinopeptide A, thrombin-antithrombin complexes, and monomers of fibrin) and of platelets (beta-thromboglobulin and platelet factor 4), several coagulation factors, global tests of coagulation (prothrombin time and activated partial thromboplastin time), and platelet count (PTL) were measured. In sepsis, prothrombin fragments 1 and 2, fibrinopeptide A, thrombin-antithrombin complexes, and monomers of fibrin were increased to 2.52+/-0.21 nmol/L, 20.88+/-2.52 ng/mL, 33.8+/-2.9 microg/L, and 69% positive, respectively, compared with control subjects (0.86+/-063 nmol/L, 1.14+/-0.15 ng/mL, 16.07+/-1.01 microg/L, and 0%, respectively). Beta-Thromboglobulin and the beta-thromboglobulin-to-platelet factor 4 ratio were also increased to 107.87+/-11.87 IU/mL and 8.86+/-1.06, compared with controls (18.36 +/-2.99 IU/mL and 2.67+/-0.52, respectively). With the exception of a decrease in factor XII and an increase in fibrinogen, coagulation factors, global coagulation tests, and PTL were not changed in sepsis. In severe sepsis and mainly in septic shock, coagulation factors were markedly decreased, global coagulation tests were prolonged, and PTL was reduced. All changes were independent of the causative infectious pathogen.. Coagulation system and platelets are strongly activated in sepsis. In this stage, only factor XII is decreased. In contrast, in severe sepsis and mainly in septic shock, most of the coagulation factors are depleted, PTL is decreased, and global coagulation tests are prolonged, indicating exhaustion of hemostasis. Finally, Gram-positive, Gram-negative, and other microorganisms produce identical impairment of coagulation.

Topics: Adolescent; Adult; Aged; Antithrombin III; Biomarkers; Blood Coagulation Disorders; Blood Coagulation Tests; Case-Control Studies; Female; Fibrinopeptide A; Humans; Male; Middle Aged; Peptide Fragments; Peptide Hydrolases; Platelet Activation; Platelet Count; Prospective Studies; Protein Precursors; Prothrombin; Sepsis; Severity of Illness Index; Shock, Septic

To determine the role of plasma tissue factor on disseminated intravascular coagulation (DIC) in trauma and septic patients, and also to investigate the relationships between tissue factor and various thrombin markers, we made a prospective cohort study. Forty trauma patients and 20 patients with sepsis were classified into subgroups according to the complication of DIC. Plasma tissue factor antigen concentration (tissue factor), prothrombin fragment F1+2 (PF1+2), thrombin antithrombin complex (TAT), fibrinopeptide A (FPA), and D-dimer were measured on the day of admission (day 0), and on days 1, 2, 3, and 4 after admission. The levels of plasma tissue factor in the DIC group were more elevated than those of the non-DIC group in both the trauma and the septic patients. In patients with sepsis, tissue factor levels on days 0 through 4 in the non-DIC group showed markedly higher values than those in the control patients (135 +/- 8 pg/ml). Significant correlations between tissue factor and PF1+2, TAT, FPA, and D-dimer were observed in the DIC patients, however, no such correlations were found in the non-DIC patients. These results suggest that elevated plasma tissue factor in patients with trauma and sepsis gives rise to thrombin generation, followed by intravascular coagulation.

Topics: Adult; Aged; Aged, 80 and over; Antithrombin III; APACHE; Biomarkers; Disseminated Intravascular Coagulation; Endothelium, Vascular; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Humans; Male; Middle Aged; Monocytes; Peptide Fragments; Peptide Hydrolases; Prospective Studies; Prothrombin; Sepsis; Thrombin; Thromboplastin; Wounds and Injuries

To obtain systematic information on the extrinsic coagulation pathway, as well as to investigate the time course of the coagulation abnormalities in sepsis.. Prospective observational study.. General intensive care unit.. Nineteen patients with the diagnosis of severe sepsis or septic shock and nine control patients.. None.. Tissue factor antigen concentration (tissue factor antigen), prothrombin fragment F1+2, thrombin antithrombin III complex, fibrinopeptide A, D-dimer, and antithrombin III concentrations were measured on the day of diagnosis of severe sepsis and septic shock, and on days 1, 2, 3, and 4 after diagnosis. The concentrations of tissue factor antigen, prothrombin fragment F1+2, fibrinopeptide A, and D-dimer were significantly increased in patients with severe sepsis and septic shock compared with control subjects. However, the concentrations of thrombin antithrombin III complex showed no statistical differences between the septic patients and the control subjects. Significantly, low antithrombin III concentrations were observed in the septic patient groups compared with control subjects. With the exception of D-dimer, the concentrations of the hemostatic markers were similar between severe sepsis and septic shock patients. Significant correlations were noted between tissue factor antigen and the disseminated intravascular coagulation score (r2=.236, p< .0001) and the number of dysfunctioning organs (r2=.229, p=.035).. We systematically elucidated coagulation disorders in newly defined sepsis. The extrinsic coagulation pathway is activated in patients with severe sepsis and septic shock. In these patients, enhanced thrombin generation and activation, and fibrin formation were demonstrated when compared with the control subjects. Furthermore, the thrombin generated appears not to be fully neutralized by antithrombin III.

Topics: Adult; Aged; Antithrombin III; Biomarkers; Blood Coagulation; Blood Coagulation Disorders; Case-Control Studies; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Humans; Male; Middle Aged; Peptide Fragments; Peptide Hydrolases; Prospective Studies; Protein Precursors; Prothrombin; Sepsis; Shock, Septic; Thromboplastin

Tissue trauma leads to a severity-dependent activation of plasma and cellular systems. This response can be recorded by determining parameters which represent the activation state of these systems. In severely injured patients with multiple trauma three out of 14 parameters measured at the time of admission proved to be indicators of subsequent septic complications with a high degree of accuracy: Fibrinopeptide A (FPA--the first split product of fibrinogen), the C3 split product C3a, and the elastase-alpha 1 proteinase inhibitor-complex (E alpha 1 PI). In a second series of multiple-injured patients with femoral fractures who did not develop clinical sepsis (N = 25) these parameters were measured continuously to evaluate the influence of injury severity and of therapeutic strategy on the further course. We found a strong correlation between injury severity (ISS) and the degree of activation. The signs of activation decreased rapidly following immediate operative fixation, and remained elevated or even increased after primary femoral traction and secondary stabilization. The operative procedure did not cause any additional activation. Complications such as infection or the formation of haematomas were reflected by raised parameter levels.

Topics: Adolescent; Adult; alpha 1-Antitrypsin; Complement C3a; Female; Femoral Fractures; Fibrinopeptide A; Fracture Fixation; Humans; Injury Severity Score; Male; Middle Aged; Monitoring, Physiologic; Multienzyme Complexes; Multiple Trauma; Pancreatic Elastase; Sepsis; Time Factors

We have evaluated the quantitative relationship between lipopolysaccharide (LPS, endotoxin), fibrinopeptide A (FPA), antithrombin (AT), protein C (PC) and extrinsic pathway inhibitor (EPI) in plasma from 39 consecutively admitted patients with systemic meningococcal disease (SMD). The most severely ill patients with fulminant meningococcal septicemia (n = 13, 6 dead) had significantly (p less than 0.01) higher plasma levels of LPS and FPA and lower levels of PC and AT on admission as compared with the less severe clinical presentations (n = 26, 1 dead). The levels of EPI on admission were significantly (p less than 0.05) higher in nonsurvivors vs survivors with fulminant septicemia. As the disease progressed, the levels of LPS, FPA, AT and PC declined, while the levels of EPI increased. Three of six nonsurviving septicemic patients had levels of EPI greater than 200% within 16 hours of admission vs two of 30 survivors (p = 0.02). The results suggest that increasing levels of LPS in SMD elicit increasing consumption coagulopathy, contributing to the organ pathophysiology. The kinetics of EPI, inhibiting the thromboplastin-FVIIa-FXa complex, differs markedly from the kinetics of AT and PC i.e. increases as opposed to decreases.

Topics: Antithrombin III; Disseminated Intravascular Coagulation; Endotoxins; Factor VII; Fibrinogen; Fibrinopeptide A; Humans; Lipopolysaccharides; Lipoproteins; Meningitis, Meningococcal; Meningococcal Infections; Multiple Organ Failure; Neisseria meningitidis; Protein C; Sepsis; Thromboplastin

Topics: alpha 1-Antitrypsin; Antithrombin III; Blood Proteins; Burns; Cell Division; Complement Activation; Endothelium; Endotoxins; Factor XII; Fibrinopeptide A; Fibronectins; Humans; Inflammation; Peritonitis; Prekallikrein; Sepsis; Wounds and Injuries

Topics: alpha 1-Antitrypsin; Antithrombin III; Blood Transfusion; Fibrinopeptide A; Fibrinopeptide B; Humans; Immunoassay; Kinetics; Leukocyte Elastase; Pancreatic Elastase; Plasma; Platelet Count; Protease Inhibitors; Sepsis; Thrombin

The prompt reduction of elevated fibrinopeptide A (FPA) levels (normal less than 1.3 pmole/ml) by heparin therapy in patients with thromboembolism suggests that measuring the FPA level may provide a good index of disease activity and be a useful method of monitoring therapy. Sepsis or malignancy may elevate FPA levels and coexist with thromboembolism. FPA levels were surveyed in 51 patients with thromboembolism (including 15 with concurrent sepsis or malignancy) during heparin treatment in an attempt to distinguish the effects of coexistent disease and the progression of thromboembolism. The anticoagulant effect of heparin was within the therapeutic range for 81% of the study period. In patients with thromboembolism alone and marked resolution of emboli on repeat lung scan, the mean daily FPA levels were lower than the values in patients with minimal resolution (p less than 0.005). In patients with marked resolution of pulmonary embolism or venous thrombosis and a concurrent disorder, the mean FPA level remained elevated compared to normal values in patients with thromboembolism alone. These results suggest that FPA levels monitored during heparin therapy of thromboembolism may be useful as an index of disease activity except in the presence of coexisting sepsis or malignancy.

Topics: Adenocarcinoma; Adult; Aged; Anticoagulants; Carcinoma, Squamous Cell; Female; Fibrinogen; Fibrinopeptide A; Heart Failure; Heparin; Humans; Leukemia, Lymphoid; Lupus Erythematosus, Systemic; Male; Middle Aged; Polycythemia Vera; Pulmonary Embolism; Sepsis; Thromboembolism

The mechanism of isolated thrombocytopenia in septicemia is unknown, but compensated disseminated intravascular coagulation (DIC) has been suggested as a possible cause. To investigate this possibility, platelet counts and sensitive assays for in vivo thrombin and plasmin generation, including fibrinogen gel chromatography and fibrinopeptide A (FPA) assays, were obtained on 31 septicemic patients. Fifteen of 17 patients with gram-negative septicemia and 8 of 14 patients with gram-positive septicemia had thrombocytopenia. Platelet survival studied demonstrated a decreased platelet survival. In 11 of 12 patients with severe thrombocytopenia (platelet count less than 50,000mul), there was laboratory evidence of intravascular coagulation. In contrast, there was little evidence of intravascular coagulation in 8 of 11 patients with moderate thrombocytopenia (platelet counts 50,000 to less than 150,000/mul) or in 7 of 8 patients with normal platelet counts. This report indicates that while DIC accompanies thrombocytopenia in many patients with severe thrombocytopenia, there is frequently little evidence for intravascular coagulation in patients with moderate thrombocytopenia. It is apparent that factors other than intravascular thrombin must play a role in producing the thrombocytopenia of septicemia.

Topics: Adult; Aged; Blood Platelets; Cell Survival; Disseminated Intravascular Coagulation; Female; Fibrinogen; Fibrinolysin; Fibrinopeptide A; Humans; Male; Middle Aged; Platelet Count; Sepsis; Thrombin; Thrombocytopenia