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.
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.
D000368:Aged; D000933:Antifibrinolytic Agents; D000990:Antithrombin III / Q000032:analysis; D002675:Child, Preschool; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000150:complications* / Q000628:therapy; D005260:Female; D005341:Fibrinolysin / Q000032:analysis; D006801:Humans; D008107:Liver Diseases / Q000097:blood / Q000175:diagnosis*; D008297:Male; D010196:Pancreatic Elastase / Q000097:blood; D011480:Protease Inhibitors / Q000097:blood*; D018805:Sepsis / Q000097:blood / Q000175:diagnosis*; D012770:Shock, Cardiogenic / Q000097:blood / Q000175:diagnosis*; D013577:Syndrome; D013917:Thrombin / Q000032:analysis; D000515:alpha 1-Antitrypsin / Q000032:analysis; D000979:alpha-2-Antiplasmin / Q000032:analysis
D000933:Antifibrinolytic Agents; D011480:Protease Inhibitors; D000515:alpha 1-Antitrypsin; D000979:alpha-2-Antiplasmin; C037742:plasmin-plasmin inhibitor complex; D000990:Antithrombin III; D010196:Pancreatic Elastase; D013917:Thrombin; D005341:Fibrinolysin