Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Determination of the complement titer in the serum and plasm of 120 patients with chronic liver diseases showed that in eight (7%) patients with cirrhosis of the liver, chronic active or chronic inactive hepatitis complement in the serum was less than half in the plasma. The dissociation of complement serum and plasma was due to cold activation of the classical pathway of complement in vitro since serum drawn from these patients at 37 degrees C lost hemolytic activity in 4 hours when transferred to a cold environment. Neither HB antigen nor cryoglobulin participated in this phenomenon. The activation of complement in the cold could be prevented by increasing the ionic strength, or by adding vitamin E or, to a lesser extent its vehicle HCO-60, while heparin, Trasylol, soybean trypsin inhibitor, or hirudin had no effect. Trans-AMCHA prevented activation in one case. It is speculated that a factor appearing as a result of blood clotting is able to activate the classical pathway of complement in the cold; it is probably not related to Hageman factor (factor XII), factor VII, thrombin, kallikrein.
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PMID:Cold activation of complement i. presence of coagulation-related activator. 5 81

Abnormalities of Hageman factor dependent pathways have been described in a wide variety of human disease states. Congenital deficiencies of factor XII (Hageman trait) prekallikrein (Fletcher trait) and high molecular weight kininogen (Williams, Fitzgerald and Flaujeac traits) although resulting in profound in vitro changes, do not cause in vivo difficulties. In contrast, deficiency of C1 esterase inhibitor (hereditary angioedema) results in significant morbidity and mortality. Acquired diseases may exhibit decreased synthesis of these three proteins in cirrhosis and dengue fever. In vivo activation of factor XII initiated pathways occur in septic shock, disseminated or localized intravascular coagulation, typhoid fever, polycythemia vera, hyperbetalipoproteinemia, coronary artery disease, nephrotic syndrome, transfusion reactions, hemodialysis and extracorporeal bypass. Activation of both the intrinsic system and tissue mediators contribute to the vasomotor phenomena in carcinoid syndrome and postgastrectomy dumping. Roles for factor XII, prekallikrein and kininogen have been suggested in gouty arthritis, allergic disorders and cystic fibrosis but the evidence is not yet convincing in these disorders.
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PMID:Participation of Hageman factor dependent pathways in human disease states. 34 10

The behaviour of prekallikrein (PKK), factor XII, high molecular weight kininogen (HMWK) and kallikrein-inhibitor (KK-I) in 367 patients with various diseases is described. Malignancies lead to elevation of factor XII and KK-I, and reduction of PKK. The effect is more pronounced in patients with metastases. In renal diseases also one or more of the above mentioned parameters are abnormal. Defects requiring dialysis treatment significantly impair the contact factors. In this group low levels of PKK, Factor XII and HMWK and increased KK-I are common. In chronic renal disease patients, only F XII and KK-I are elevated, whereas PKK and HMWK are normal. Kidney transplantation leads to a rise in KK-I and reduction of PKK and HMWK. The values almost normalize few days after the operation. Factor XII, slightly increased immediately after transplantation, remains high in long term transplant recipients, whereas HMWK falls below normal. In liver disease patients, acute and chronic hepatitis, cirrhosis of the liver and coma, PKK is reduced. In cases with acute hepatitis PKK raises with recovery. Cirrhosis and coma lead to low HMWK and factor XII concentrations. KK-I is mostly affected during acute hepatitis, and is then highly increased. Our results clearly demonstrate that the biologic activity of one or more of contact factors is affected in many diseases.
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PMID:Prekallikrein, HMW-kininogen and factor XII in various disease states. 635 59

In liver disease low prekallikrein levels may be found which has been suggested to be due to diminished synthesis. However, it may also be due to endotoxemia accompanying liver disease. To study the last possiblity prekallikrein, endotoxins and Normotest were determined in 18 cirrhosis patients. The relation between the prekallikrein concentration (after 15 min activation) and the Normotest was significant (r = + 0.72, P less than 0.001). Endotoxemia was only found in the more severe forms of liver disease (Normotest below 60%). During endotoxemia the prekallikrein levels were significantly lower than when no endotoxins were present in the blood of the same patients. The Normotest did not differ significantly in these patients in relation to the presence or absence of endotoxins. The activation of prekallikrein was slower in the more severe forms of liver disease. This might be due to reduced levels of factor XII and high molecular weight kininogen. In conclusion the reduced prekallikrein level in liver cirrhosis may be due to both diminished synthesis and endotoxemia. In the more severe forms of liver disease the time necessary to activate prekallikrein is increased.
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PMID:Plasma prekallikrein and endotoxemia in liver cirrhosis. 701 4

The aim of this double-blind, placebo-controlled crossover study was to investigate the effect of 1-deamino-8-D-arginine vasopressin (dDAVP) on hemostasis in patients with chronic liver disease. Nine consecutive patients with biopsy-proven liver cirrhosis and related coagulation abnormalities received in a random order dDAVP, 0.5 microgram/kg, or saline intravenously. Blood samples were taken before dDAVP infusion and 30, 60 and 180 min after its end. dDAVP infusion induced a statistically significant shortening of the bleeding time from 9 min (range 6.5-15.5) to 6 min (range 4.5-9.5) at 1 h after the infusion. The activated partial thromboplastin time was significantly shortened at 30 and 60 min after dDAVP infusion. Plasma levels of factor VIII, XI and XII coagulant activities were significantly increased at all sampling times after dDAVP infusion. The maximum increase over basal values in plasma levels of factor VIII, XI and XII was 63, 22 and 40%, respectively. dDAVP did not induce any significant changes of prothrombin time, thrombin clotting time, fibrinogen, plasma levels of factor II, V, VII, IX, X, factor XII antigen, protein C (activity and antigen), antithrombin III, plasminogen and alpha 2-antiplasmin. Placebo infusion did not produce any significant changes in the evaluated parameters. We conclude that dDAVP can positively influence the hemostatic system in patients with liver cirrhosis. The clinical relevance of this hemostatic improvement deserves further evaluation.
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PMID:Effects of desmopressin on hemostasis in patients with liver cirrhosis. 748 63

We studied extrinsic and intrinsic fibrinolysis in 20 patients with cirrhosis (nine mild/moderate, group 1; 11 severe, group 2) and 19 normal controls to define the role of intrinsic (contact factor medaited) fibrinolysis in cirrhosis. Global plasma fibrinolytic activity (fibrin plate lysis) was similar in all groups. Dextran sulphate activated contact factor mediated fibrinolysis was decreased in group 2 (median 95.2%) compared with group 1 (121.0%) and controls (131.7%). Tissue plasminogen activator antigen (t-PA Ag) levels were increased in group 2 (28.2 ng/ml) compared both with group 1 (8.5 ng/ml) and controls (5.9 ng/ml). Plasma t-PA activity was raised in group 2 (5.50 IU/ml) and group 1 (5.25 IU/ml) versus controls (0.82 IU/ml). Plasminogen activator inhibitor-1 (PAI-1 Ag) levels were raised in group 2 (28.0 IU/ml) versus controls (8.5 IU/ml) but PAI activity was similar in all groups. Factor XII activity was decreased in group 2 (48.76 u/dl), but not group 1, versus controls (89.1 u/dl). Prekallikrein activity was decreased both in group 2 (27.27 u/dl) and group 1 (33.01 u/dl) versus controls (108.59 u/dl) and was lower in group 2 than group 1. C1-esterase inhibitor chromogenic activity was decreased in group 1 (102.30 u/dl) and group 2 (58.76 u/dl) versus controls (116.24 u/dl). The normal global fibrinolytic activity despite increased t-PA activity may be due to a concomitant increase in PAI. The decreased intrinsic fibrinolysis in severe cirrhosis, unaccompanied by a rise in C1-esterase inhibitor, may be explained by the decreased factor XII and prekallikrein activity. These changes are probably due to reduced liver cell mass.
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PMID:Decreased contact factor mediated fibrinolysis in cirrhosis. 813 76

Bradykinin, a nonapeptide with vasodilatory and permeabilizing activity, is generated through the cleavage of high-M(r) ('high-molecular-weight') kininogen by kallikrein, and its generation is facilitated by plasmin. In the ascitic fluid of patients with cirrhosis, there is massive cleavage of high-M(r) kininogen and activation of fibrinolysis, but bradykinin has never been measured directly. In the ascitic fluid of 24 patients with cirrhosis, we measured bradykinin-(1-9)-nonapeptide levels by RIA after liquid-phase and subsequent HPLC extraction, and those of its catabolic product bradykininin-(1-5)-pentapeptide by ELISA after liquid-phase extraction. Cleaved high-M(r) kininogen, activated factor XII and plasmin-antiplasmin complexes were measured in ascitic fluid and plasma. Plasma renin activity (PRA) was also determined. As a control, we also analysed plasma from 24 healthy subjects matched for sex and age with the patients. In the ascitic fluid from patients with cirrhosis, the median bradykinin-(1-9) concentration was 3.3 fmol/ml (range 0.2-29.0 fmol/ml), and the median bradykinin-(1-5) concentration was 210 fmol/ml (range 58-7825 fmol/ml). The levels of bradykinin-(1-5) in ascitic fluid were higher in patients with refractory ascites [median 1091 fmol/ml (range 58-7825 fmol/ml)] than in patients with responsive ascites [134 fmol/ml (72-1084 fmol/ml)] (P=0.010). Ascitic fluid levels of bradykinin-(1-9) were not related to the severity of ascites. PRA was higher in patients with refractory ascites [23.0 ng x h(-1) x ml(-1) (7.9-80.0 ng.h(-1).ml(-1))] than in patients with responsive ascites [6.9 ng x h(-1) x ml(-1) (0.9-29.4 ng x h(-1) x ml(-1))] (P=0.002). In ascitic fluid, 48% (19-68%) of high-M(r) kininogen was cleaved, and plasmin-antiplasmin complexes were more concentrated than in plasma (P=0.0001). In conclusion, in the ascitic fluid of patients with cirrhosis, both bradykinin-(1-9) and bradykinin-(1-5) are present, with cleavage of high-M(r) kininogen and activation of fibrinolysis. The highest levels of the long-lived metabolite bradykinin-(1-5) were found in the ascitic fluid of patients with refractory ascites and high PRA. Activation of the kinin system may therefore be involved in decompensating cirrhosis, but a cause-effect relationship remains to be established.
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PMID:Bradykinin in the ascitic fluid of patients with liver cirrhosis. 1172 53