Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0012739 (disseminated intravascular coagulation)
8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hemostatic system is a dynamic evolving process that is age-dependent. Components of the hemostatic system are synthesized in early fetal life and do not cross the placenta from mother to fetus. However, plasma concentrations of proteins involved in hemostasis significantly differ from adults. Physiological reference ranges are available for premature infants, full-term infants and children from ages 1 to 16 years. In the coagulation system, plasma concentrations of the vitamin K-dependent and contact factors are decreased at birth, whereas other factors such as fibrinogen, FV, FVIII, and FXIII are similar or increased compared with adults at birth. In the fibrinolytic system, plasma concentrations of plasminogen are decreased at birth, whereas tissue plasminogen activator and plasminogen activator inhibitor are increased. Clinically, the hemostatic system of the young is effective and healthy infants do not suffer from spontaneous hemorrhagic complications. However, infants are more vulnerable, compared with older patients, for bleeding in the presence of either congenital or acquired haemostatic defects. Severe congenital bleeding disorders, although rare, frequently present in the newborn period. The most common acquired causes of bleeding newborns include disseminated intravascular coagulation, vitamin K deficiency, and liver disease. A description of these disorders and treatment guidelines are provided.
...
PMID:The relevance of developmental hemostasis to hemorrhagic disorders of newborns. 919 36

The lower temperatures utilized during profound hypothermic circulatory arrest (PHCA) surgery may exacerbate the hypothermia associated platelet and clotting factor dysfunction observed in conventional cardiopulmonary bypass (CPB) procedures. Hypothermia has been shown to impair the activity of the enzymes involved in the platelet activation pathways and to reduce the enzymatic activity of clotting factors upon coagulation activation. The resulting retardation of the generation of fibrin/platelet clot compounded by the presence of heparin may contribute significantly to a bleeding tendency. Excessive fibrinolytic activity may disrupt surgical wound thrombi and exacerbate haemorrhage. There is good evidence that the fibrinolytic activity, mediated predominantly by tissue plasminogen activator (tPA), is a secondary response to thrombin generated by coagulation activation, which is ongoing during CPB despite full heparinization. The effects of hypothermia on the fibrinolytic response remain to be clarified and the extent to which the lower temperatures and blood stasis associated with PHCA moderate this response is unknown. Despite impairment of coagulation activation by hypothermia there appears to be a shift in the hemostatic balance towards thrombosis presumably as a consequence of endothelial cell injury by both hypothermia and stasis induced ischemia. There is evidence that widespread microvascular thrombus deposition may occur as a consequence of stasis in patients undergoing PHCA and that this might result in vascular occlusion and end organ damage. Although it is not uncommon to find laboratory evidence of disseminated intravascular coagulation (DIC) in patients presenting with aortic aneurysm rupture or dissection, the incidence of clinically overt DIC resulting in bleeding is low. The underlying hemostatic disturbance however may contribute to the surgery-associated bleeding diathesis.
...
PMID:Hematological consequences of profound hypothermic circulatory arrest and aortic dissection. 927 46

Severely burned patients often present a hypercoagulability situation. However, its magnitude, time course, and relationship with organ failure and outcome remains to be established. Forty-three patients were studied on the first and seventh day after burn for hypercoagulability and fibrinolysis parameters. A hypercoagulability and hyperfibrinolysis state was found the first day after burn demonstrated by high levels of activated factor VII (VIIa, p<0.01), thrombin-antithrombin III complex (TAT, p<0.01), tissue plasminogen activator (t-PA, p<0.001) and D dimer (DD, p<0.01) and low levels of antithrombin III (ATIII, p<0.01), protein C (PC, p<0.01), plasminogen (PG, p<0.001) and alpha2 antiplasmin (AP, p<0.001). A paradoxical coexisting hypofibrinolysis was found as suggested by a low global fibrinolytic activity in the euglobulin plasma fraction fibrin plate assay (FA, p<0.01) and high levels of tissue plasminogen activator inhibitor type 1 (PAI-1, p<0.01). On day 7, a less marked hypercoagulability situation was found, with low ATIII (p<0.01) and PC (p<0.01), persisting the hypofibrinolytic situation observed on the first day. Non-survivors (NS) showed higher levels of VIIa (p<0.01), TAT (p<0.05) and t-PA (p<0.05), and lower levels of ATIII (p<0.05), PC (p<0.05) and AP (p<0.001) than survivors (S) on the first day. Also, there was a positive correlation of Marshall organ failure score with ATIII, (r2=0.49, p<0.001), PC, (r2=0.14, p<0.045) and PG levels, (r2=0.41, p<0.0003). Severely burned patients show a state of transient disseminated intravascular coagulation, related to the development of organ failure and outcome.
...
PMID:Degree of hypercoagulability and hyperfibrinolysis is related to organ failure and prognosis after burn trauma. 963 Mar 8

Previous studies suggest that there is a systemic activation of clotting and fibrinolysis in preterm infants with advanced respiratory distress syndrome (RDS). However, there are no data on the hemostatic status in the early stages of the disease; therefore, we studied some of the hemostatic parameters in these patients and made several studies at different times in preterm infants who did or did not develop RDS, using similar protocols. We found normal plasma fibrinogen, protein C, protein S, C4b-binding protein, thrombomodulin, antithrombin III, thrombin-antithrombin III complex, prothrombin fragment 1.2, plasminogen, tissue plasminogen activator, alpha-1 antitrypsin, alpha-2-macroglobulin and protein Z. However, lower D-dimer and higher plasminogen activator inhibitor and von Willebrand factor antigen levels were found within six hours of life in infants who later developed RDS compared to the control group. These findings suggest that disseminated intravascular coagulation is not prominent in the early stages of RDS. Moreover, reduced D-dimer and increased plasminogen activator inhibitor and von Willebrand factor antigen levels are probably related to the abnormalities in the fibrinolytic mechanism due to lung damage in RDS, but further studies are needed to show their pathogenic significance in RDS.
...
PMID:Hemostatic system in early respiratory distress syndrome: reduced fibrinolytic state? 1077 Jan 17

Patients in intensive care may be at high risk of in vivo platelet activation because comorbid conditions, such as infections, septicemia, shock, disseminated intravascular coagulation, and cancer represent procoagulant states. Hyperreactivity of platelets with or without a decline of cell count may result in thromboembolic complications potentially associated with the phenomenon of heparin-induced thrombocytopenia. We analyzed the data of 10 patients highly suspected of having heparin-induced thrombocytopenia during their intensive care treatment of 29 plus or minus 22 days. In seven patients, thrombocytopenia coincided with thromboembolic complications. Six patients had additionally undergone fibrinolytic therapy before starting activated partial thromboplastin time-adapted alternative anticoagulation with r-hirudin. In three patients, the platelet count decreased without a clinical manifestation, of heparin-induced thrombocytopenia. R-Hirudin treatment monitored by activated partial thromboplastin time and prothrombin time (PT) was effective and safe. The target value for activated partial thromboplastin time was a twofold prolongation. In four of five patients with deep venous thrombosis, a partial recanalization of the lower extremity could be achieved. Three patients with pulmonary embolism associated with deep venous thrombosis in two cases and in one additional case with an acute myocardial infarction did clinically profit from fibrinolysis with recombinant tissue plasminogen activator (rtPA) and r-hirudin treatment. Two lethal events probably caused by the underlying multimorbidity could not be prevented. No recurrence of thrombosis occurred, and there were no severe bleeding complications attributed to r-hirudin treatment. Platelet counts were significantly reduced on day 9.4 plus or minus 6.4 of heparin administration in all cases (>50% decrease related to the initial values) from 224,000 plus or minus 126,000/microL to 96,000 plus or minus 61,000/microL, and increased during rhirudin treatment to mean values of 224,000 plus or minus 126,000/microL. The heparin-induced platelet activation assay (HIPAA) assay was positive in 8/10 cases, whereas the PF4 enzyme-linked immunosorbent assay showed a positive result in four of eight analyzed cases. In four cases, the assays were concordantly positive. The PF4 enzyme-linked immunosorbent assay was not performed in two cases.
...
PMID:Heparin-induced thrombocytopenia: a critical risk/benefit analysis of patients in intensive care treated with R-hirudin. 1089 75

In this study, we have established a pig model that can combine extensive hemodynamic monitoring with simultaneous repetitive (serial) blood sampling for the study of multiple variables related to the hemostatic system. Sixteen healthy young pigs were studied to evaluate the influence of continuous endotoxin infusion on hemodynamic patterns and activation of coagulation and fibrinolysis. The chief aim of the study was to investigate the applicability of analytical methods primarily developed for use with human plasma samples in quantification of factors and reaction products of the porcine coagulation and fibrinolytic systems, and further, to use these methods to study the longitudinal changes in the plasma levels of these hemostatic variables as a consequence of endotoxin infusion. We found that acute, controlled endotoxemia induced a hemodynamic state of shock and reduced pulmonary gas exchange. Simultaneously, a gradual increase in peripheral blood mononuclear cell tissue factor activity was demonstrated, and increased maximally 5.5-fold 4 hours after onset of endotoxin infusion. Thrombin-antithrombin complexes increased in plasma to maximum levels after 3 hours, accompanied by an ethanol gelation test that was regularly positive after 1 to 2 hours, and fibrin monomer levels that gradually increased maximally 3.8-fold after 6 hours. These changes were followed by gradual decreases of both fibrinogen and factor VII levels, mainly due to consumption. Plasma levels of tissue type plasminogen activator activity peaked at 1.5 hours (11.3-fold increase), whereas the peak of plasminogen activator inhibitor-1 activity (14-fold increase at 4.5 hours) was delayed compared to tissue plasminogen activator and completely extinguished plasma tissue plasminogen activator activity. The sequential activation of coagulation and fibrinolysis established a procoagulant state favoring disseminated intravascular coagulation and microthrombus formation, potentially leading to multiple organ dysfunction.
...
PMID:Hemodynamic changes and systemic activation of coagulation and fibrinolysis during controlled endotoxemia in pigs. 1089 51

In a porcine model of Gram-positive sepsis, 28 juvenile pigs were studied to evaluate the effect of a continuous infusion of live serogroup A streptococci (GAS) on the activation of coagulation and fibrinolysis. Plasma levels of thrombin-antithrombin (TAT) complexes, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) activities were measured using commercially available kits. The continuous infusion of GAS [(3-5) x 10(8) colony-forming units/kg per h] caused early signs of severe septicaemia in the pigs, with pulmonary hypertension, systemic hypotension, reduced cardiac output and liver hypoperfusion, ultimately leading to shock with a high mortality. There was a sequential and ordered activation of the coagulation, fibrinolytic and antifibrinolytic systems. GAS infusion induced a gradual, maximally 2.5-fold increase in plasma TAT levels. Plasma t-PA activity levels peaked at 2 h (nine-fold increase), whereas the peak of PAI-1 activity was delayed (eight-fold increase at 4 h). These findings are similar to changes observed during endotoxin infusion. This procoagulant state favours disseminated intravascular coagulation and microthrombus formation, ultimately threatening tissue viability.
...
PMID:Systemic activation of coagulation and fibrynolysis in a porcine model of serogroup A streptococcal shock. 1093 4

Carboxypeptidase R (CPR) exists in precursor form (proCPR) in plasma in contrast to carboxypeptidase N (CPN), which is present in the active state. CPR plays two important roles, one of which appears to be the control of the inflammatory response by inactivation of anaphylatoxins such as complement-derived C3a and C5a. Therefore, an increase in CPR activity may facilitate rapid inactivation of these inflammatory mediators generated at the site of bacterial infection. Upregulation of proCPR expression during the inflammatory response initiated for instance by endotoxin (lipopolysaccharide) should play a role in suppressing hyper-reactivity as seen in septic shock. CPR also functions as an inhibitor of fibrinolysis, where its ability to prevent binding of plasminogen to lysine residues on fibrin clots significantly lengthens tissue plasminogen activator (tPA)-induced fibrinolysis time. Therefore, upregulation of proCPR production during the inflammatory response may exacerbate thrombosis contributing to the development of disseminated intravascular coagulation as well as other conditions involving thrombosis. Co-administration of tPA and a specific inhibitor of CPR, such as potato carboxypeptidase inhibitor, which does not affect CPN, may be useful in thrombolytic therapy.
...
PMID:Carboxypeptidase R is an inactivator of complement-derived inflammatory peptides and an inhibitor of fibrinolysis. 1141 58

Sepsis and trauma are the two most common causes of disseminated intravascular coagulation and multiple organ dysfunction syndrome. Both disseminated intravascular coagulation and the systemic inflammatory response syndrome often lead to multiple organ dysfunction syndrome. The current studies have evaluated the relationship between the anaphylatoxin, C5a, and changes in the coagulation/fibrinolytic systems during the cecal ligation and puncture (CLP) model of sepsis in rats. CLP animals treated with anti-C5a had a much improved number of survivors (63%) compared to rats treated with pre-immune IgG (31%). In CLP rats treated with pre-immune IgG there was clearly increased procoagulant activity with prolongation of the activated partial thromboplastin time and prothrombin time, reduced platelet counts, and increased levels of plasma fibrinogen. Evidence for thrombin formation was indicated by early consumption of factor VII:C, subsequent consumption of factors XI:C and IX:C and anti-thrombin and increased levels of the thrombin-anti-thrombin complex and D-dimer. Limited activation of fibrinolysis was indicated by reduced plasma levels of plasminogen and increased levels of tissue plasminogen activator and plasminogen activator inhibitor. Most of these parameters were reversed in CLP rats that had been treated with anti-C5a. Production of C5a during sepsis may directly or indirectly cause hemostatic defects that can be reduced by blockade of C5a.
...
PMID:Anti-c5a ameliorates coagulation/fibrinolytic protein changes in a rat model of sepsis. 1200 Jul 38

PURPOSE: To discuss the current rationale for the use of specific and nonspecific therapies for thrombotic microangiopathy in thrombocytopenia-associated pediatric multiple organ failure syndromes. Methods: Pertinent PubMed and MEDLINE citations and proceedings of recent critical care meeting presentations were reviewed. RESULTS: Critical care clinicians have reported using antithrombin III concentrate, protein C concentrate, activated protein C, prostacyclin and its analogues, heparin, tissue factor pathway inhibitor concentrate, plasma infusion, plasma exchange, whole blood exchange, pentoxifylline, tissue plasminogen activator, urokinase, and streptokinase with perceived therapeutic benefits in patients with thrombocytopenia-associated multiple organ failure, including those with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, disseminated intravascular coagulation syndrome, and secondary thrombotic microangiopathy syndrome without prolonged prothrombin time/activated partial thromboplastin time. CONCLUSION: Assuming that underlying disease is remediable, a consensus has developed that thrombotic microangiopathy is a therapeutic target in children with thrombocytopenia-associated multiple organ failure syndromes. Studies are warranted to delineate efficacious use of specific and nonspecific therapies to prevent and reverse thrombotic microangiopathy in these patients.
...
PMID:Microvascular thrombosis in pediatric multiple organ failure: Is it a therapeutic target? 1279 40


<< Previous 1 2 3 4 5 6 Next >>

---