Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the behaviour of total protein S, free protein S, protein C and C4b-binding protein fifteen neonates with severe infections, eight with septic shock and in a group of ten healthy newborns. Protein C was decreased in shock and septic patients, but only the shock group showed significant differences compared to normal neonates. Total protein S was normal in both groups of patients, although free protein S had significantly lower values in shock and nonshock infants. C4b-binding protein was higher than normal in septic and shock patients compared to the control group. Decreased values of protein C and free protein S can be explained by the activation of coagulation and their subsequent consumption. On the other hand, the increased levels of C4b-binding protein can affect the distribution of protein S in plasma, producing a shift in protein S to the complexed inactive form. These findings can contribute to an increased risk of microthrombosis during neonatal sepsis.
 ...
PMID:Protein C, protein S and C4b-binding protein in neonatal severe infection and septic shock. 138 81

Protein C, a potent vitamin K-dependent protein activated by an endothelial cell cofactor, thrombomodulin, has anticoagulant and profibrinolytic activity. Free protein S, a cofactor for protein C, potentiates protein C activity at the endothelial cell surface. Pulmonary thromboemboli are a consistent finding in adult respiratory distress syndrome (ARDS). To determine if protein S or protein C were affected by widespread endothelial cell damage in ARDS, we measured bound and free protein S levels and protein C antigenic and functional levels in 18 patients with acute lung injury, 6 critically ill patients without lung history, and 22 normal subjects. Free (PS:F) and bound (PS:Ag) protein S and protein C antigen (PC:Ag) levels were measured using an enzyme-linked immunoassay and protein C function (PC:Fn) by measuring its anticoagulant activity. We found a significant decrease in bound and free protein S levels of both patient groups in comparison to normal and a shift toward the inactive, bound protein S form. In addition, a significant decrease in free protein S compared to bound protein S in both patient groups was observed. While both PC:Ag and PC:Fn were significantly reduced compared to normal, the PC:Fn was significantly and severely decreased out of proportion to the PC:Ag in both patient groups. There was no difference between those with and without lung injury for both protein S and protein C. Analyzed according to etiology of lung injury, there was no difference in the bound and free protein S, nor in PC:Ag and PC:Fn levels between patients with sepsis and trauma. However, there were significant decreases in both protein S and protein C levels compared with normal subjects. Levels of both PS and PC levels in patients who survived did not differ from those who died. In summary, our data show that both protein S and C are markedly deranged in acutely ill patients who suffered from either sepsis or trauma, and these changes are independent of lung injury. The marked reductions in functional activity of PS and PC may be contributing factors to the thromboembolic complications often observed in these patients.
 ...
PMID:Protein S and C alterations in acutely ill patients. 182 9

The neonatal period is probably the only time when a higher incidence of spontaneous thromboembolic complications may occur in the otherwise normal healthy individual, and this may be related to the activation of the coagulation system at the time of parturition. This study was performed to look at the newborn coagulation and anticoagulation systems and compare these with the changes in the maternal circulation in normal cases. Paired umbilical cord venous and maternal venous blood samples were obtained and plasma levels of protein C, protein S, antithrombin III, fibrinopeptide A, fibrinogen, plasminogen, and fibrinolytic inhibitory activity were measured. The maternal plasma level was significantly higher in all cases except for fibrinopeptide A which was similar, and for fibrinolytic inhibitory activity which was lower (p less than 0.05). A significant correlation exists between maternal and newborn protein C levels (p less than 0.02) and fibrinolytic inhibitory activity (p less than 0.05). The findings indicate that parturition leads to a similar degree of activation of the newborn coagulation system as shown by the fibrinopeptide A level. As their anticoagulants and fibrinolytic activity levels are lower and the fibrinolytic inhibitory activity is higher, the newborns are thus predisposed to thrombosis even in the absence of complications such as sepsis.
 ...
PMID:Coagulation and anticoagulation systems in newborns--correlation with their mothers at delivery. Lower levels of anticoagulants and fibrinolytic activity in the newborn. 214 83

Purpura fulminans (PF) is a cutaneous manifestation of a dramatic and deadly syndrome of systemic disseminated intravascular coagulation (DIC). It is characterized by microvascular thrombosis in the dermis followed by perivascular haemorrhage. Since two other related syndromes involve the protein C (PC) system, we undertook a serial study to investigate the levels of PC and protein S (PS) in two patients with acquired PF. Laboratory findings were consistent with DIC, and both patients were treated with blood replacement and heparin therapy. The levels of PC activity were very low during the initial 24-36 h after onset and gradually increased until returning to normal levels. The total and 'free' PS were also abnormal during the initial onset of PF. The total and free PS increased to normal after 4-6 d. Although the pathogenesis is not fully understood, the infection and sepsis appears to consume PC and PS selectively during the PF and DIC phase. Acquired PF appears to selectively involve the PC system in a similar fashion to two other syndromes of PF-like lesions.
 ...
PMID:Protein C and protein S levels in two patients with acquired purpura fulminans. 214 90

Tumor necrosis factor/cachectin (TNF) is a mediator of the septic shock state, which can modulate hemostatic properties of the vessel wall. The interaction of TNF with endothelium is not cytotoxic, rather it is receptor mediated and results in a change in receptor expression on the endothelial cell surface, enabling endothelium to actively promote coagulation. Anticoagulant mechanisms, including the protein C/protein S system and fibrinolysis are suppressed, whereas the initiation and propagation of procoagulant activity is enhanced. This unidirectional shift in vessel wall coagulant activity favoring clot formation could contribute to the coagulopathy associated with sepsis and indicates a mechanism through which the coagulation system serves as an integral part of the host response.
 ...
PMID:Tumor necrosis factor/cachectin-induced modulation of endothelial cell hemostatic properties. 282

The baboon model of E. coli sepsis illustrates three concepts with respect to the host response and vascular endothelium. First, the endothelium is the primary target. E. coli sepsis is an acute inflammatory disease of the vascular endothelium. Second, the endothelium is not a passive target. Initially it regulates both the inflammatory and coagulopathic aspects of E. coli sepsis through membrane associated regulatory receptor/plasma protein assemblies including protein C/thrombomodulin, activated protein C/protein S, C4bBP/protein S, tissue factor pathway inhibitor/Xa, antithrombin III/glycosaminoglycans. Third, when overridden by inflammatory events, the endothelium can change its anticoagulant phenotype and mount a massive procoagulant fibrinolytic counter-attack on its luminal side through the expression of tissue factor and release of tissue plasminogen activator. Fourth, again when overridden by inflammatory events, the endothelium can change its antioxidant phenotype and produce a "distal" tissue hypoxia on its abluminal side through induction of free radical generation and peroxidation of mitochondrial lipid membranes of those tissues with high metabolic rates. It has become increasingly clear that the so-called anticoagulant systems which act on the proximal factors of the clotting cascade (protein C, TFPI, AT-III, PGI2) also attenuate the amplification of the inflammatory response. Aspects of the mechanism by which this occurs are coming to light. This includes the attenuation of Il-6 response by TFPI and the attenuation of the complement effects by C4bBP/PS. The specifics of these observations in the E. coli sepsis model will be reviewed.
 ...
PMID:Studies on the inflammatory-coagulant axis in the baboon response to E. coli: regulatory roles of proteins C, S, C4bBP and of inhibitors of tissue factor. 783 58

The proband, a 43-year-old woman, suffered from right transverse sinus thrombosis during oral contraceptive treatment. A month after stopping the drug, her plasma activities of antithrombin III, protein C, protein S, heparin cofactor II, plasminogen and plasminogen activator inhibitor were normal, but her plasma histidine-rich glycoprotein (HRG) level was only 21% of the normal level of 109.5 +/- 51.5% (mean +/- 2 SD). The HRG concentrations in her plasma determined on four different occasions over 6 months were similar. She showed no clinical signs of liver insufficiency or sepsis. Low levels of plasma HRG (20% to 35% of normal) were also found in her aunt, uncle and two daughters. These results suggest that congenital HRG deficiency is inheritary in this family.
 ...
PMID:Congenital histidine-rich glycoprotein deficiency. 823 32

This study evaluates the contact system, coagulation inhibitors and fibrinolysis in 23 full-term newborns with sepsis (8 with septic shock). The results were compared with a group of 20 healthy newborns. Blood samples were obtained at the time of clinical diagnosis and 3 days after the antibiotic therapy was started. The results showed that: severe infection was associated with activation of the contact system, depletion of anticoagulant proteins and elevation of C4b-binding protein levels. There was a shift in protein S to the complexed inactive form, and the thrombin-antithrombin complexes increased. These changes occurred in parallel to both activation and inhibition of fibrinolysis. These changes were more pronounced in the septic shock patients than in nonshock neonates. After therapy, this procoagulant state decreased among survivor patients while in those who died, the abnormalities in coagulation did not improve. Our study suggests that neonatal sepsis induces a hypercoagulable state that persists in nonsurvivor neonates despite a correct treatment.
 ...
PMID:Coagulation, fibrinolytic and kallikrein systems in neonates with uncomplicated sepsis and septic shock. 827 17

This review presents the rationale for and main results of coagulation inhibitor substitution during experimental and human sepsis. Activation of the contact system induces activation of the classical complement pathway with generation of anaphylatoxins, of the kinins pathway and of fibrinolysis. Physiologic inhibition depends on the C1-inhibitor (C1-Inh.). Septic patients exhibit a relative deficiency of biologically active C1-Inh. Substitution with concentrations of C1-Inh has been safely performed and preliminary results are consistent with a possible beneficial effect on hypotension and vasopressor requirement in septic shock. The extrinsic pathway is the main initial coagulation process involved in sepsis-induced DIC. Endothelial and monocyte generation of tissue factor (TF) is activated by bacterial products and endotoxin. Activation of TF is counteracted by a specific tissue factor pathway inhibitor (TFPI). The potential for TFPI substitution to inhibit the activation of the coagulation cascade in sepsis requires further study. Thrombin generation is inhibited by antithrombin III (AT III) and the protein C-protein S system. During sepsis, AT III is consumed and degraded by elastase. Animal studies have shown that DIC and death were prevented by high doses of AT III concentrates. Although a significant reduction in the duration of biological symptoms of DIC has been reported in most human studies, the usefulness of AT III substitution in human sepsis is still debated. None of the studies was able to document a statistically significant reduction in mortality. Protein C is activated by thrombomodulin and, with its cofactor protein S, inhibits factors Va and VIIIa. The free level of protein S depends on the level of the C4b binding protein (C4bBP), an acute-phase complement regulatory protein. During sepsis, protein C activity is significantly reduced, either by acute consumption or by thrombomodulin down-regulation, and increased levels of plasma C4bBP inhibit protein S. Infusion of activated protein C and protein S substitution both protect animals from the lethal effects of bacteria. Combining these different coagulation inhibitors should be carefully studied before its use in septic patients is recommended.
 ...
PMID:Coagulation inhibitor substitution during sepsis. 863 34

The endothelium plays an important role in the regulation of haemostasis by producing substances such as thrombomodulin (TM). The influence of long-term volume replacement with different types of fluid on the TM-protein C-protein S system was investigated in a prospective, randomized study. Thirty trauma patients and 30 patients suffering from sepsis after major surgery received either 10% low-molecular weight (LMW) hydroxyethylstarch solution (HES-trauma, n = 15; HES-sepsis, n = 15) or 20% human albumin (HA-trauma, n = 15; HA-sepsis, n = 15) for 5 days to maintain central venous pressure (CVP) between 12 and 16 mm Hg. Plasma concentrations of TM, protein C, (free) protein S and thrombin-antithrombin (TAT) were measured in arterial blood samples obtained on the day of admission to the intensive care unit or on the day of diagnosis of sepsis and over the next 5 days. There were no differences between HA- and HES-treated trauma patients. Protein C and protein S also did not differ between HA- and HES-treatments. At baseline, TM plasma concentrations were increased to > 40 micrograms litre-1 in both sepsis groups only. In the HA-sepsis group, TM increased significantly (from 48.1 (SD 13.9) to 68.4 (13.0) micrograms litre-1), whereas it remained almost unchanged in the HES-sepsis group. In HES-sepsis patients, protein C (from 51.0 (10.1) to 71.9 (8.9)%) and protein S (from 19.0 (6.0) to 40.8 (11.4)%) increased significantly during the study, whereas both remained reduced in HA-patients. TAT (indicating intravascular coagulation) did not differ between the two fluid groups. We conclude that in trauma patients, the type of volume therapy had no influence on the TM-protein C-protein S system. In sepsis patients, volume therapy with HES was beneficial, whereas infusion of HA had no substantial positive effect on endothelial-associated coagulation.
 ...
PMID:Does the type of volume therapy influence endothelial-related coagulation in the critically ill? 3286 9


1 2 3 4 5 6 7 Next >>