Antithrombin III metabolism in patients with liver disease.

Knot, E.A.R.; Cate, J. W. Ten; Drijfhout, H R; Kahlé, L.H.; Tytgat, G. N. J.

doi:10.1136/jcp.37.5.523

Cited by 44 publications

(30 citation statements)

References 32 publications

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“…Depletion of AT III levels during sepsis may partly be the result of a decreased synthe sis [27], increased catabolism due to intravas cular coagulation [28,29] or to an alternate distribution [30]. Albumin is synthesized in the liver and the molecular weight of AT III and albumin is similar.…”

Section: Discussionmentioning

confidence: 99%

Coagulopathy in Disseminated Intravascular Coagulation due to Abdominal Sepsis: Determination of Prothrombin Fragment 1+2 and Other Markers

Okamoto¹,

Takaki²,

Takeda³

et al. 1992

Pathophysiol Haemos Thromb

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To estimate the degree of coagulopathy in abdominal sepsis, we measured the plasma levels of prothrombin fragment 1+2 (F1+2), thrombin-antithrombin III complex (TAT) and plasmin-Α₂-plasmin inhibitor complex (PIC) by the enzyme-linked immunosorbent assay in 38 patients with disseminated intravascular coagulation (DIC). In 20 patients with DIC due to abdominal sepsis, plasma levels of F1+2, TAT and PIC were 2.6 nmol/l, 27.9 µg/l and 1.5 µg/ml, respectively, with a mean antithrombin III (AT III) activity of 41.7%. F1+2, TAT, PIC and AT III levels were 4.7 nmol/l, 75.8 µg/l, 8.8 µg/ml and 70.9% in 18 patients with DIC as the result of malignancy. Though AT III levels in DIC due to sepsis were lower than those in DIC due to malignancy, the levels of F1+2, TAT and PIC in the former were not significantly more increased than those in the latter. The plasma levels of F1+2 were positively correlated with TAT and PIC in DIC patients with malignancy; however, there was no correlation between F1+2 and TAT or PIC in DIC patients with sepsis. In addition, the levels of serum albumin in the two groups were similar. These results suggest that activation of coagulation and fibrinolytic systems may not be so prominent in cases of DIC due to abdominal sepsis, compared to related events in DIC due to malignancy. It is also suggested that the depletion of AT III in cases of sepsis is not only caused by a consumption related to intravascular coagulation or to an alternate distribution of protein. It may relate to nonspecific proteolytic degradation by granulocytic proteinases. F1+2 may be more suitable than TAT for the evaluation of the coagulopathy in DIC patients with sepsis.

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Section: Discussionmentioning

confidence: 99%

Coagulopathy in Disseminated Intravascular Coagulation due to Abdominal Sepsis: Determination of Prothrombin Fragment 1+2 and Other Markers

Okamoto¹,

Takaki²,

Takeda³

et al. 1992

Pathophysiol Haemos Thromb

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“…The GSA-Rmax in hepatocytes was shown to strongly Receptor-binding radiopharmaceuticals provide an opporcorrelate with conventional liver function tests, especially tunity to conduct analytic measurements of a specific interacwith validated indicators of hepatic functional capacity such tion within a normal physiological environment. 15,16 Radiolaas antithrombin III, 25 fibrinogen, 26 and ICGR15. The GSAbeled ASGP was originally developed by Vera et al 17 Tc-GSA Rmax represented both the initial and recycled number of is a similar compound but was developed independently for receptors since the first 30-min period was selected as the use in clinical use.…”

Section: Discussionmentioning

confidence: 99%

Preoperative determination of the surgical procedure for hepatectomy using technetium-99m-galactosyl human serum albumin (99mTc-GSA) liver scintigraphy

Kwon

1997

Hepatology

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differences are thought to depend mainly on the effective Technetium-99m-diethylenetriaminepentaacetic acidhepatic blood flow and the intra-, extrahepatic shunt. galactosyl human serum albumin (Tc-GSA) is a new liverAshwell and Morell demonstrated the existence of a hepatic scintigraphy agent which binds to the asialoglycoprobinding receptor for asialoglycoproteins (ASGP) with the intein receptors. We evaluated the preoperative assessvestigation of ceruloplasmin metabolism. 6 They found that ment for hepatectomy using Tc-GSA liver scintigraphy.ceruloplasmin molecules, which lack a sialic acid residue, Ninety patients with hepatocellular carcinoma were adrapidly disappeared from the circulation and were taken up mitted for elective hepatectomy. Tc-GSA scintigraphy by hepatocytes. 7 This activity was found to be exclusively was conducted after the intravenous injection of Tcassociated with a protein termed ASGP receptors (ASGPR) GSA, and maximal removal rate of Tc-GSA (GSA-Rmax)in the sinusoidal membrane of hepatocytes. 8 Sawamura et was calculated using a radiopharmacokinetic model. al. 9 reported that a decrease in the number of ASGPRs led Measurement of GSA-Rmax, conventional liver function, to the accumulation of ASGP in the sera of galactosamineand 15-minute retention rate of indocyanine green treated rats. In addition, this receptor decreases in patients (ICGR15) was carried out preoperatively. The relationwith chronic liver disease. 10ships between liver functions, histological activity index Technetium-99m-diethylenetriaminepentaacetic acid-ga-(HAI), ICGR15, and GSA-Rmax values were estimated. A lactosyl, human serum albumin (Tc-GSA), is a new liver scinsignificant correlation was obtained between GSA-Rmax tigraphy agent which binds to the ASGPR on hepatocytes. and ICGR15 (r Å .534, P õ .0001). Preoperative discrepanMaximal removal rate of Tc-GSA (GSA-Rmax) using a radiocies between GSA-Rmax and ICGR15 values were seen pharmacokinetic model decreased with the severity of liver in 15 patients. In these cases, the GSA-Rmax values cordisease, and there was also a significant difference in the related well with the total HAI scores (r Å .595, P õ .02), GSA-Rmax between the chronic hepatitis and normal liver but no significant correlation was seen between the groups. 11 The purpose of this study was to evaluate the clini-ICGR15 and HAI scores. Two patients died of postoperacal utility of the GSA-Rmax for the preoperative assessment tive liver failure within 2 months of the operation. These of hepatectomy in patients with hepatocellular carcinoma. 1992 and December 1995. The mean age of all patients was 61 years, with a range of 43 to 77 years. There were 72 (80%) male and 18 (20%) female patients, yielding a male:female ratio of 4:1; 59 patients It is well known that patients with a normal liver tolerate (65.6%) had cirrhosis. Surgical resections were performed according a 70% to 80% hepatectomy and that regeneration of the liver to the liver anatomy of Couinaud.12 Surgical procedures were mainly determined usi...

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“…Liver disease is often associated with hemostatic abnormalities such as decreased plasma levels of coagulation factors and inhibitors [ 1,2], dysfibrinogenemia [3 -61, thrombocytopenia, platelet dysfunction, and disseminated intravascular coagulation (DIC) 17-91. In addition, accelerated fibrinolysis has long been recognized .…”

Section: Introductionmentioning

confidence: 99%

Fibrinolysis and fibrinogenolysis in liver disease

et al. 1990

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Patients with liver disease frequently have hemostatic abnormalities which include accelerated fibrinolysis. In order to assess the fibrinolytic state in liver disease, plasma levels of fibrinogenolysis products (FgDP), fibrinolysis products (FbDP), and fibrinogenolysis plus fibrinolysis products (TDP) were measured with newly developed enzyme-linked immunosorbent assays based on monoclonal antibodies in 36 patients with liver disease (six patients with acute hepatitis, seven with chronic hepatitis, ten with liver cirrhosis, 11 with hepatocellular carcinoma, and two with intrahepatic cholestasis). As compared with healthy subjects, mean plasma levels of FbDP (1,083 +/- SD 1,254 vs. 236 +/- 100 ng/ml, P = 0.005) and TDP (1,773 +/- 1,814 vs. 669 +/- 212 ng/ml, P = 0.001) were significantly elevated in patients with liver disease, whereas FgDP was normal (389 +/- 202 vs. 396 +/- 132 ng/ml, P = 0.87). Plasma FbDP correlated very well with TDP (r = 0.986, P less than 0.00001) in liver disease. In addition, FbDP and TDP but not FgDP correlated with plasma concentrations of thrombin-antithrombin III complex. When plotted by the disease categories, the magnitude of elevations of FbDP and TDP was the most prominent in acute hepatitis followed by hepatocellular carcinoma. These findings indicate that activation of fibrinolysis occurs following thrombin generation, but increased primary fibrinogenolysis is rare in liver disease.

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Antithrombin III metabolism in patients with liver disease.

Cited by 44 publications

References 32 publications

Coagulopathy in Disseminated Intravascular Coagulation due to Abdominal Sepsis: Determination of Prothrombin Fragment 1+2 and Other Markers

Coagulopathy in Disseminated Intravascular Coagulation due to Abdominal Sepsis: Determination of Prothrombin Fragment 1+2 and Other Markers

Preoperative determination of the surgical procedure for hepatectomy using technetium-99m-galactosyl human serum albumin (99mTc-GSA) liver scintigraphy

Fibrinolysis and fibrinogenolysis in liver disease

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