Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thrombin (Thr), plasmin (Pl) and elastase (ELP) are serine proteinases which are quickly inactivated by their specific inhibitors (AT III, alpha 2AP, alpha 1AT), if intravascular activation of coagulation and fibrinolytic system or if release from PMN granulocytes by different stimuli (F.I., endotoxin, activated factor XII, a.o.) occurs. The immunological determination of the developing proteinase inhibitor complexes (PIC) AT III-Thr, alpha 2AP-Pl and alpha 1AT-ELP gives information as to whether intravascular coagulation, hyperfibrinolysis or unspecific proteolysis induced by elastase have taken place. Despite the high antiprotease activity in the plasma the a.m. serine proteinases may exert their proteolytic activity towards their specific substrates in vivo. In infectious diseases, fulminant hepatic failure and cardiac shock a complex consumption of coagulation factors and inhibitors may cause severe coagulation defects, microcirculatory disturbances and bleeding tendency. The PICs behaviour was determined in more than 80 patients with infectious diseases, in 5 patients with fulminant hepatic failure (FHF) and 7 patients with cardiac shock. Only in infectious diseases, mainly in septic complications, and septic complications during FHF and cardiac shock, are alpha 1AT-ELP levels found to be highly elevated. After cardiac shock, in FHF and in infectious diseases coagulation and fibrinolysis may additionally be activated. In this case AT III-Thr and alpha 2AP-Pl complexes could be detected in the patients plasma. This indicates that intravascular coagulation and hyperfibrinolysis has additionally taken place. To prevent bleeding complications a replacement therapy with plasma derivatives (AT III, plasminogen concentrate, PPSB and FFP) has been successfully performed in several patients with septic complications and in the 5 patients with FHF and the 7 patients with cardiac shock. No bleeding complication occurred, and the haemostatic balance could be maintained in the treated patients. AT III replacement therapy is necessary to stop DIC, PPSB improves severe coagulation defects, only FFP may additionally provide alpha 1AT, alpha 2AP and factor V. In acute renal failure sometimes plasminogen replacement is necessary to maintain a normal activity of the fibrinolytic system. The complex consumption of coagulation proteins in infectious diseases, FHF and cardiac shock cannot successfully be treated with an anticoagulant such as heparin alone.
 ...
PMID:The proteinase inhibitor complexes (antithrombin III-thrombin, alpha 2antiplasmin-plasmin and alpha 1antitrypsin-elastase) in septicemia, fulminant hepatic failure and cardiac shock: value for diagnosis and therapy control in DIC/F syndrome. 242 25

In inflammation, particularly in septicaemia, complex coagulation disorders may lead to a dangerous haemorrhagic diathesis. The conventional concept for this syndrome called DIC implicates the occurrence of active thrombin in the circulation, which may be followed by hyperfibrinolysis due to plasmin formation. In this study data are presented suggesting an important role for a third proteolytic system, granulocytic elastase. The complexes of plasmin and elastase with their specific inhibitors, alpha 2-antiplasmin-plasmin (alpha 2AP-PI) and alpha 1-antitrypsin-elastase (alpha 1AT-ELP) were determined immunologically. The alpha 1AT-ELP appears mainly in gram-negative septicaemia, particularly in meningococcal disease. The estimation of alpha 2AP-PI and alpha 1AT-ELP, together with a method for the detection of the antithrombin III--thrombin complex which remains to be established, is a suitable tool for for the differential diagnosis of the consumption of coagulation proteins. The assumption that at least three proteolytic systems participate in the development of the haemorrhagic diathesis during inflammation leads to the concept of a broad, comprehensive substitution therapy with e.g. concentrates of AT III, PPSB, or fresh frozen plasma. The aim of this treatment is to replace not only the consumed procoagulatory factors, but also the lacking inhibitors in order to control this "abnormal proteolysis syndrome".
 ...
PMID:The clinical significance of alpha 1-antitrypsin-elastase (alpha 1AT-ELP) and alpha 2-antiplasmin-plasmin (alpha 2AP-PL) complexes for the differentiation of coagulation protein turnover: indications for plasma protein substitution in patients with septicaemia. 293 57

The prognosis of septicaemia depends on the occurrence of complications such as shock and coagulation defects. The damage to haemostasis is usually explained by the action of the main coagulation and fibrinolysis enzymes, thrombin and plasmin. This paper presents data concerning the role of a third protease, granulocytic elastase. 82 patients who had been admitted to our hospital with suspected septicaemia were examined. Septicaemia was proven in 22 patients by the growth of microorganisms in blood cultures, and was clinically diagnosed in 9 patients. The plasma levels of neutrophil elastase-like protease complexed to a1antitrypsin (a1AT-ELP) were measured by zone immunoelectrophoresis assay (ZIA). The a1AT-ELP values were significantly increased in the 31 septic as compared to the 51 non-septic patients. In patients with complicated septicaemia, negative correlations of a1AT-ELP with factor XIII and the coagulation inhibitor antithrombin III were demonstrable. Among the patients with septic complications, the 3 who survived exhibited a dramatic decrease of a1AT-ELP, whereas in the other 16 patients who died the levels remained elevated. It might be of therapeutic significance that in 9 patients receiving fresh plasma and AT III-concentrate substitution for DIC the a1AT-ELP levels dropped, whereas they remained high in the other septicaemia patients. There were no correlations between a1AT-ELP and the a2antiplasmin-plasmin complexes (a2AP-P1), but strong correlations with signs of coagulation. The data suggest an interaction of coagulation and elastase release, probably involving the Hageman factor.
 ...
PMID:Participation and interactions of neutrophil elastase in haemostatic disorders of patients with severe infections. 329 74