fibrin and Multiple-Organ-Failure

A well-established development of increasing disease severity leads from sepsis through systemic inflammatory response syndrome, septic shock, multiple organ dysfunction syndrome, and cellular and organismal death. Less commonly discussed are the equally well-established coagulopathies that accompany this. We argue that a lipopolysaccharide-initiated (often disseminated intravascular) coagulation is accompanied by a proteolysis of fibrinogen such that formed fibrin is both inflammatory and resistant to fibrinolysis. In particular, we argue that the form of fibrin generated is amyloid in nature because much of its normal α-helical content is transformed to β-sheets, as occurs with other proteins in established amyloidogenic and prion diseases. We hypothesize that these processes of amyloidogenic clotting and the attendant coagulopathies play a role in the passage along the aforementioned pathways to organismal death, and that their inhibition would be of significant therapeutic value, a claim for which there is considerable emerging evidence.

Topics: Fibrin; Humans; Multiple Organ Failure; Prions; Shock, Septic

Topics: Acute Disease; Aged; Chlamydophila Infections; Chlamydophila pneumoniae; Cryptogenic Organizing Pneumonia; Fatal Outcome; Female; Fibrin; Humans; Multiple Organ Failure; Pneumonia, Bacterial; Pulmonary Alveoli; Respiratory Insufficiency

To review the dual characteristics of disseminated intravascular coagulation (DIC), as both a contributor to multiple organ failure as well as a symptom of severe underlying disease associated with systemic vascular changes.. Published literature data and unpublished results from the authors.. Clinical and experimental studies strongly suggest that DIC contributes to multiple organ failure and death in patients with severe systemic disorders such as sepsis. DIC is evoked by systemic cytokine activity, and the inflammatory response aggravates vascular permeability, inflammation, and cell damage in tissues. In addition to intravascular fibrin formation, thrombin and fibrin generation in tissues is also an important aspect of DIC. An example of DIC at the organ level is adult respiratory distress syndrome, where fibrin in the lung is a characteristic feature. Intravascular fibrin formation and occlusion may elicit a hypoxic response with induction of hypoxia related transcription factors. The resulting ischemic preconditioning may offer protective effects to the involved organ(s).. Overall, the beneficial or harmful effects of activated coagulation and fibrin formation for organ pathology and recovery from DIC remain to be explored. This may be a critical element in the assessment of ischemia-reperfusion effects of specific anticoagulant therapy.

Topics: Anticoagulants; Capillary Permeability; Cytokines; Disseminated Intravascular Coagulation; Endothelium, Vascular; Fibrin; Humans; Inflammation; Microcirculation; Multiple Organ Failure; Respiratory Distress Syndrome; Sepsis; Thrombin

Topics: Animals; Disease Models, Animal; Disease Progression; Drug Evaluation, Preclinical; Fibrin; Fibrinolysis; Humans; Lipoproteins; Multiple Organ Failure; Protein C; Respiratory Distress Syndrome; Sepsis; Treatment Outcome

Topics: Blood Platelets; Complement Activation; Endothelium; Fibrin; Humans; Lung; Multiple Organ Failure; Neutrophils; Respiratory Distress Syndrome; Sepsis; Shock, Traumatic

The histological findings in the heart in cases of fatal sepsis can show myocytolysis, interstitial fibrosis, necrotic contraction band, mononuclear infiltrates, and interstitial edema, which can be used in post mortem diagnosis of sepsis. Septic myocardial calcification is a very rare condition, and only a few cases have been reported in the literature. In general, the pathogenesis of the myocardial calcification has not been well clarified, but two pathogenic mechanisms have been universally recognized: metastatic or dystrophic. We present a rare case of sepsis-related myocardial calcification. Here we report a case involving a 72-year-old white male who was admitted to a hospital for a polytrauma caused by a motorbike accident. On the 110th day of hospitalization, the patient was diagnosed with a septic process and a subsequent transesophageal echocardiogram revealed the presence of a calcification on the right atrial wall. According to the medical history of the patient there were no systemic factors predisposing to calcium crystals deposition in tissues. Patient died due to multi-organ failure in the course of multimicrobial septic shock during the 149th day. The autopsy revealed both the presence of a greenish-brown formation and a greater consistency of the right atrial wall. The histological investigation of the right atrium wall showed a wide calcification area localized at subendocardial level, which contained fibrin deposition and was surrounded by fibrotic tissue.

Topics: Aged; Calcinosis; Fatal Outcome; Fibrin; Fibrosis; Heart Atria; Humans; Male; Multiple Organ Failure; Sepsis; Shock, Septic

We prospectively studied (1) the relationships between angiogenic factors, their soluble receptors and organ dysfunction and (2) the effects of disseminated intravascular coagulation (DIC)-induced platelet consumption, thrombin generation, and tissue hypoxia on the expression of the factors and receptors. Fifty patients with sepsis were classified into two subgroups: 37 patients with DIC and 13 patients without DIC. DIC patients showed higher Sequential Organ Failure Assessment (SOFA) scores, the prevalence of multiple organ dysfunction syndrome (MODS) and more increased soluble fibrin and lactate levels. We observed lower levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor 2 (sVEGFR2), angiopoietin 1 (Ang1) and Ang1/Ang2, and higher sVEGFR1 and Ang2 levels in DIC patients, but not significant differences in soluble Tie2 expression during the study period. The levels of VEGF, sVEGFR1, and Ang2 in DIC patients correlated with the SOFA scores. Clear differences were observed in the levels of Ang2 in the DIC patients between survivors and nonsurvivors and between those with and without MODS. The area under receiver operating characteristic curves for predicting death and MODS by Ang2 were 0.710 and 0.784, respectively. The VEGF levels showed a marked correlation with the platelet counts. Soluble fibrin and lactate levels independently predicted increases in the levels of VEGF, sVEGFR1, and Ang2 in DIC patients. In conclusion, VEGF, sVEGFR1, Ang2, and Ang1/Ang2, especially Ang2, may have roles in the development of MODS in sepsis associated with DIC, and VEGF, sVEGFR1, and Ang2 serum levels correlated with the extent of DIC-induced platelet consumption, thrombin generation, and blood lactate levels.

Topics: Angiogenesis Inducing Agents; Angiopoietin-1; Angiopoietin-2; Blood Platelets; Cell Hypoxia; Disseminated Intravascular Coagulation; Female; Fibrin; Humans; Lactic Acid; Male; Middle Aged; Multiple Organ Failure; Neovascularization, Physiologic; Platelet Count; Prospective Studies; ROC Curve; Sepsis; Thrombin; Treatment Outcome; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelial Growth Factors

Coagulopathy and thrombocytopenia often occur in critically ill patients, and disseminated intravascular coagulation (DIC) can lead to multiple organ dysfunction and a poor outcome. However, the relation between coagulopathy and systemic inflammatory response has not been thoroughly clarified. Thus, we evaluated coagulative activity, organ dysfunction, and systemic inflammatory response syndrome (SIRS) in critically ill patients with thrombocytopenia and examined the balance between coagulopathy and systemic inflammation.. Two hundred seventy-three patients, who were admitted to 13 critical care centers in Japan and fulfilled the criteria of platelet count of less than 150*10(9)/L, were included. Coagulative variables (platelet count, fibrin/fibrinogen degradation products, and DIC scores), organ dysfunction index (Sequential Organ Failure Assessment [SOFA] score), and SIRS score in each patient were evaluated for 4 consecutive days after fulfilling the above entry criteria. The effect of SIRS on coagulopathy and organ dysfunction was evaluated in these patients.. Both the maximum SIRS score and entry SIRS score had significant relation to the maximum SOFA score during the observation period. Coagulation disorders indicated by the minimum platelet count, maximum DIC scores, and positivity for DIC worsened gradually with increases in SIRS scores. Both the minimum platelet count and maximum DIC scores were significantly correlated with the maximum SOFA score, indicating that a relation exists between coagulopathy and organ dysfunction.. In critically ill patients with thrombocytopenia, coagulopathy and organ dysfunction progress with significant mutual correlation, depending on the increase in SIRS scores. The SIRS-associated coagulopathy may play a critical role in inducing organ dysfunction after severe insult.

Topics: Adult; Aged; Analysis of Variance; Blood Coagulation Disorders; Critical Illness; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Multiple Organ Failure; Platelet Count; Sepsis; Systemic Inflammatory Response Syndrome; Thrombocytopenia

Topics: Biomarkers; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Humans; Intensive Care Units; Multiple Organ Failure; Platelet Count; Prothrombin Time; Sepsis; Severity of Illness Index

We investigated the correlation between disseminated intravascular coagulation (DIC) score and hemostatic parameters and sepsis-related organ failure assessment (SOFA) score with clinical outcome of patients with DIC in an intensive care unit (ICU). The SOFA score was markedly elevated in patients with DIC relative to patients without DIC and significantly higher in non-survivors than in survivors. Abnormalities in almost all hemostatic parameters were significant in patients with DIC, but there was no significant difference in almost all hemostatic parameters between survivors and non-survivors. However, plasma antithrombin (AT) levels were significantly lower in non-survivors than in survivors. Soluble fibrin (SF) and tissue type plasminogen activator (tPA)-plasminogen activator inhibitor-I (PAI-I) complex correlated significantly with the SOFA score, whereas AT levels correlated significantly and negatively with the SOFA score. We conclude that the SOFA score is useful for predicting outcome in DIC patients in the ICU, and that hemostatic parameters, especially plasma AT levels, are also useful markers for organ failure and clinical outcome.

Topics: Antithrombins; Biomarkers; Disseminated Intravascular Coagulation; Fibrin; Hemostasis; Humans; Intensive Care Units; Multiple Organ Failure; Plasminogen Activator Inhibitor 1; Sepsis; Severity of Illness Index; Tissue Plasminogen Activator

The effect of higenamine, a benzyl-tetrahydroisoquinoline alkaloid of the roots of Aconitum spp. (Ranunculaceae), on disseminated intravascular coagulation (DIC), was investigated using an experimental DIC rat model. The oral administration of higenamine (10 mg/kg or 50 mg/kg), significantly ameliorated the decrease of fibrinogen level in plasma, the increase of fibrinogen/fibrin degradation product (FDP) level, and the prolongation of prothrombin time (PT) induced by the i. v. infusion of lipopolysaccharide (LPS). The prolongation of activated partial thrombin time (aPTT) and the decrease of platelet count were suppressed. The increase in serum aspartate aminotransferase (AST) and blood urea nitrogen (BUN) were also significantly prevented with higenamine. The above results are suggestive that higenamine has therapeutic potential for DIC and/or accompanying multiple organ failure (MOF).

Topics: Alkaloids; Animals; Aspartate Aminotransferases; Blood Urea Nitrogen; Disease Models, Animal; Disseminated Intravascular Coagulation; Dose-Response Relationship, Drug; Fibrin; Fibrinogen; Injections, Intravenous; Lipopolysaccharides; Male; Multiple Organ Failure; Partial Thromboplastin Time; Plant Roots; Platelet Count; Prothrombin Time; Ranunculaceae; Rats; Tetrahydroisoquinolines

Topics: Adult; Blood Platelets; Fatal Outcome; Female; Fibrin; Humans; Kidney; Multiple Organ Failure; Purpura, Thrombotic Thrombocytopenic; von Willebrand Factor

Hypoxia and ischaemia influence blood coagulation and fibrinolysis. This study has been made to determine whether human cardiopulmonary arrest causes fibrin formation and reduction of fibrinolysis. Serial levels of fibrinopeptide A (FPA), fibrinopeptide B beta 15-42 (FPB beta 15-42), D-dimer, tissue plasminogen activator antigen concentration (t-PA antigen), t-PA activity, plasminogen activator inhibitor-1 antigen concentration (PAI-1 antigen), and PAI-1 activity were determined in 63 patients with out-of-hospital cardiopulmonary arrest. In the resuscitated patients, the markedly elevated FPA (194.8 +/- 54.2 ng/ml) at the beginning of cardiopulmonary resuscitation (CPR) significantly decreased to 32.4 +/- 9.1 ng/ml at 24 h after admission (p < 0.01), however, this was still about 20 times that of the normal controls. FPB beta 15-42 and D-dimer increased from the start of CPR to 60 min (189.3 +/- 97.4 ng/ml; p < 0.01 and 7726 +/- 3556 ng/ml; p < 0.001, respectively), and then decreased at 24 h after arrival at the Emergency Department (40.4 +/- 11.1 ng/ml and 5434 +/- 1049 ng/ml, respectively). At 30 min after arrival, FPA and FPB beta 15-42 significantly differed between the resuscitated patients and the patients who died (p < 0.001 and P < 0.05, respectively). Although t-PA antigen and t-PA activity was elevated at the time of arrival, 24 h thereafter, no-t-PA activity was detected. At 24 h after admission, PAI-1 antigen and PAI-1 activity were significantly increased (472.2 +/- 145.5 ng/ml; p < 0.001 and 103.6 +/- 36.1 IU/ml; p < 0.001, respectively). In conclusion, during and after CPR in patients with out-of-hospital cardiac arrest, massive fibrin generation with consecutive impairment of fibrinolysis were observed. These fibrin-mediated events may have some role in the derangement of vital organ function after cardiac arrest.

Topics: Aged; Biomarkers; Blood Coagulation Factors; Brain Ischemia; Cardiopulmonary Resuscitation; Female; Fibrin; Fibrinolysis; Heart Arrest; Humans; Male; Middle Aged; Multiple Organ Failure; Plasminogen Activator Inhibitor 1; Reperfusion Injury; Tissue Plasminogen Activator

According to our hypothesis ICU patients with signs of early hypercoagulation should develop more organ system failures that result in higher mortality rates and longer treatment periods. Routine coagulation tests are unreliable for measuring early hypercoagulation.. Soluble fibrin (SF), reflecting hypercoagulation, was assessed at an early stage in 101 ICU patients. A spectrophotometric method using chromogenic peptide substrates was employed. The patients were divided into four groups, depending on the patient's highest level of SF within the first week after admission: Group I (21 patients), SF < 15 nmol/L (reference level); Group II (27 patients), SF 15-29 nmol/L; Group III (26 patients), SF 30-50 nmol/L and Group IV (27 patients), SF > 50 nmol/L. The number of secondary failing organ systems and the ventilator time, ICU time and mortality rates were recorded.. There was a significant increase in the number of secondary failing organ systems (P < 0.0001) and a significantly increased mortality for the groups with higher SF (P = 0.01). There was a mean of 0.6, 1.3, 2.4, and 3.4 failing organs and a mortality of 14%, 22%, 30%, and 46% in the respective groups. The ventilator time and the ICU time were longest in Group III, but again shorter for Group IV (with the highest mortality). The mean ventilator times were 2.7, 6.4, 8.4, and 5.9 days and the mean ICU times were 4.1, 8.6, 10.3, and 7.3 days in the respective groups. Thirteen patients with SF > 100 nmol/L had a mean of 4.2 failing organ systems and an 85% mortality.. Soluble fibrin, a marker of hypercoagulation, seems to predict organ system failure and outcome in ICU patients.

Topics: Critical Care; Female; Fibrin; Humans; Male; Middle Aged; Multiple Organ Failure; Prognosis; Respiration, Artificial; Solubility; Survival Analysis; Time Factors

Topics: Adult; Aged; Aged, 80 and over; Animals; Bacterial Infections; Blood Coagulation; Complement System Proteins; Disseminated Intravascular Coagulation; Dogs; Endotoxins; Female; Fibrin; Humans; Male; Microcirculation; Middle Aged; Multiple Organ Failure