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)

F VIII activity, F VIII-related antigen and von Willebrand factor were measured in 46 patients with hepatic cirrhosis and in 30 normal individuals. These parameters were significantly higher in hepatic cirrhosis than in the controls. Linear relationships between F VIII activity and F VIII-related antigen and between F VIII-related antigen and von Willebrand factor were found in patients with hepatic cirrhosis as well as in normal individuals. However, in both groups no relationship between F VIII activity and von Willebrand factor was present. The existence of a low-grade intravascular coagulation in hepatic cirrhosis may be postulated but more information about the metabolism of F VIII protein is needed before such a statement can be proven.
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PMID:Antihaemophilic factor A activity, F VIII-related antigen and von Wilebrand factor in hepatic cirrhosis. 40 32

Hemostasis is intimately related to liver function, because most coagulation factors are synthesized by liver parenchymal cells and the liver's reticuloendothelial system serves an important role in the clearance of activation products. The extent of coagulation abnormalities depends upon the degree of disturbed liver function. Acute or chronic hepatocellular diseases may display decreases in the vitamin K-dependent factors (prothrombin; factors VII, IX, and X; proteins C and S), whereas other parameters remain normal. Patients with hepatic failure may present with the entire spectrum of factor deficiencies and may even develop disseminated intravascular coagulation (DIC). Patients with liver cirrhosis have a wide spectrum of abnormalities. Except for factor VIII:C and von Willebrand factor, all procoagulant and inhibitory factors are decreased, which is a reflection of impaired protein synthesis. Abnormal fibrinogen and prothrombin molecules can be identified. Platelets are quantitatively and qualitatively altered, and most patients develop DIC. Vitamin K deficiency leads to the production of abnormal vitamin K-dependent factors. The factors lack gamma-carboxy glutamic acid residues in the NH2-terminal part of their molecules. Surgery associated with the liver leads to major hemostasis alterations. The LeVeen shunt is invariably related to DIC. Bleeding with partial liver resection is mostly mechanically induced, but chronic DIC may be present. Orthotoptic liver transplantation is associated with severe hemorrhages. These are partly due to the pre-existing hemostasis defects and partly due to DIC with a marked fibrinolytic response. This is especially noted during the anhepatic phase and when the donor liver is perfused by the recipient's blood. Postoperative recovery is quick, provided the graft is not rejected. Postoperatively, there may be an initial hypercoagulable state, which could be related to the thrombosis occasionally encountered.
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PMID:Coagulation abnormalities in liver disease. 133 67

Two murine monoclonal antibodies, raised against von Willebrand factor (vWF), were used to construct an enzyme-linked immunosorbent assay (ELISA), for quantitation of vWF antigen (vWFAg) in human plasma and platelets. This assay had a lower limit of sensitivity of 0.0001 IU/ml in buffer, and thus is one to two orders of magnitude more sensitive than other ELISA assays which have been reported. The intraassay, interassay and interdilution coefficients of variation were 4.1, 10.4 and 9.9%, respectively. In normal plasma (n = 20), the vWFAg level was 0.83 (range: 0.42-1.25) IU/ml. In normal washed platelets (n = 10), 0.35 (0.25-0.49) IU/10(9) platelets was found. In plasma obtained from various patient groups the following vWFAg levels (geometric mean and range) were observed: von Willebrand's disease (n = 19): 0.18 (0.02-0.77) IU/ml; patients with liver cirrhosis (n = 20): 3.73 (1.68-9.20) IU/ml; patients with pregnancy-induced hypertension (n = 20): 4.14 (2.28-7.44) IU/ml and patients with malignant disease (n = 10), 2.54 (1.51-5.60) IU/ml. A linear correlation was found between vWFAg levels measured with a polyclonal antibody based Laurell electroimmunoassay (r = 0.92, n = 58) or with a polyclonal antibody based ELISA (r = 0.94, n = 64). The present assay is based on stable and reproducible reagents and allows the specific measurement of vWFAg in plasma and in platelets. This assay may constitute a useful tool for the further investigation of clinical conditions associated with changes in vWFAg levels. In addition, its high sensitivity may facilitate a more detailed study of platelet vWFAg in normal and in pathological conditions.
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PMID:Measurement of von Willebrand factor antigen in plasma and platelets with an enzyme-linked immunosorbent assay based on two murine monoclonal antibodies. 177 82

The intravenous infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) shortens the prolonged bleeding time in patients with congenital or acquired bleeding disorders, including patients with uremia or liver cirrhosis. We carried out a double-blind, placebo-controlled crossover study in ten patients with liver cirrhosis to evaluate whether or not their prolonged bleeding times could be shortened by subcutaneous injections of DDAVP (0.3 microgram/kg), a more practical route of administration than intravenous infusions. One hour after DDAVP injection the bleeding time was significantly shortened (p less than 0.05). After 4 h, however, the bleeding time shortening was no longer statistically significant. There was no bleeding time change after placebo. Plasma levels of von Willebrand factor antigen (vWF:Ag) did not significantly increase after DDAVP or placebo. The study shows that subcutaneous DDAVP is an alternative method for short-term shortening of the bleeding time in liver cirrhosis.
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PMID:Subcutaneous desmopressin (DDAVP) shortens the prolonged bleeding time in patients with liver cirrhosis. 209 87

We tested an in vitro system simulating bleeding time reported by Kratzer et al. Primary hemostasis was studied perfusing an artificial vessel with citrated blood under a constant pressure of 40 mmHg, measuring the blood volume perfused (bleeding volume) and the time until blood flow stopped (bleeding time). The artificial vessel consists of a glass capillary simulating arteriole and a filter covered with collagen type I to provide a surface for the adhesion of platelets. The bleeding volume (mean +/- SD microliters) was 317.7 +/- 93.8 in controls (n = 19), 487.3 +/- 242.1 in idiopathic thrombocytopenic purpura (n = 9), 666.8 +/- 224.1 in aplastic anemia and paroxysmal nocturnal hemoglobinuria (n = 4), greater than 820 in von Willebrand's disease (n = 3), 231.0 +/- 74.5 in hemophilia A (n = 3), 499.0 +/- 269.4 in liver cirrhosis (n = 6), and 457.7 +/- 229.0 in myeloproliferative disorders (n = 11). When citrated blood was applied to this system after incubation with monoclonal antibodies (MoAb) to von Willebrand factor or platelet membrane glycoprotein Ib (GPIb), bleeding volume was significantly increased while no effects were observed after incubation with MoAb to GPIIb/IIIa, factor VIII: CAg and factor XIIIa. These data suggest that in vitro model of primary hemostasis could be used for not only diagnosing bleeding disorders although 'time' is not reliable, but also investigating the mechanisms of hemostasis.
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PMID:[Bleeding time and volume in vitro by THROMBOSTAT]. 231 3

Desmopressin (1-deamino-8-D-arginine vasopressin, abbreviated DDAVP) is a synthetic analogue of the antidiuretic hormone L-arginine vasopressin. Because it can raise circulating levels of factor VIII coagulant activity (FVIII) and von Willebrand factor and shorten the prolonged bleeding time, DDAVP is established as a nontransfusional form of treatment for mild and moderate hemophilia and von Willebrand disease. Recently, DDAVP has also been purported to be useful for shortening the prolonged skin bleeding times that occur with uremia, cirrhosis, and platelet dysfunctions of various etiologies. Finally, there is evidence from controlled clinical trials that DDAVP can reduce blood loss and transfusion requirements for hemostatically normal individuals undergoing spinal fusion surgery and for patients undergoing cardiopulmonary bypass surgery. The purpose of this report is to review the therapeutic applications of DDAVP in congenital and acquired bleeding disorders and to discuss areas in which further basic and clinical research is needed.
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PMID:Desmopressin: a nontransfusional form of treatment for congenital and acquired bleeding disorders. 250 5

Desmopressin acetate 0.3 microgram/kg was given intravenously to nine patients with chronic liver disease and to a further six such patients in a double blind controlled study versus placebo. Desmopressin acetate significantly shortened the bleeding time compared with basal values in both groups and compared with placebo. There was also a significant decrease in partial thromboplastin time (but not prothrombin time) and significant increases in factor VIII and its components, von Willebrand factor and ristocetin cofactor activity, but not in factors VII, IX, X, XI, or XII. Increased fibrinolysis could be blocked by concomitant administration of tranexamic acid. No important side effects were seen. The multimer pattern of von Willebrand factor was studied for the first time in chronic liver disease. It was normal, but after administration of desmopressin acetate the percentage of multimers of higher molecular weight increased significantly. This may be an important mechanism in the shortening of the bleeding time in cirrhosis, as has been shown in uraemia and other conditions after administration of desmopressin acetate. Desmopressin acetate may be useful in correcting defects in primary haemostasis in chronic liver disease.
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PMID:Desmopressin and bleeding time in patients with cirrhosis. 393 77

The effects of standardized venous occlusion (VO) on factor VIII-von Willebrand factor (F VIII-VWF) components (F VIII:C, F VIIIR:AG, F VIIIR:RCof) and on fibrinolytic activity were investigated in 45 healthy subjects, in 28 women on oral contraceptives, and in 78 patients with various chronic diseases (28 with peripheral arterial disease, 19 with liver cirrhosis, 13 with rheumatoid arthritis, and 18 with diabetes). All the three F VIII-VWF components showed highly significant increases, although not of the same magnitude, with consequent variations in the ratios between them. A significant activation of fibrinolysis was also demonstrated with both euglobulin lysis time (ELT) and diluted blood clot lysis time (DBCLT). A strong linear correlation between pre- and post-stasis values was recorded for all the F VIII-VWF components and for the two fibrinolysis tests. No significant relationship was, on the contrary, found between F VIII-VWF and fibrinolytic parameters.
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PMID:Correlation between changes induced by venous occlusion on factor VIII-von Willebrand factor components and fibrinolytic activity. 642 15

Numerous abnormalities of plasmatic coagulation and platelet function may contribute to the bleeding in liver cirrhosis with a defective platelet-von Willebrand factor interaction being a potential mechanism. To analyze GPIb and von Willebrand factor in cirrhosis, we quantified the number of GPIb molecules on the platelet surface by flow cytometry, assessed the total (and indirectly the internal) pool of GPIb by ELISA and measured the circulating amount of glycocalicin in plasma as a measure of proteolytic activity and platelet turnover. Von Willebrand factor was characterized by ELISA, by its ristocetin-cofactor activity and by multimer analysis. Botrocetin-induced agglutination was used for functional analysis. The data from 8 well-characterized cirrhosis patients indicate that total GPIb is insignificantly increased to 46,000 +/- 5,000 molecules/P (normal: 39,500 +/- 2,000 [SEM]), surface-GPIb is normal with some variability and that the glycocalicin levels are 2-3 times higher than would be expected from the platelet count (= 100 +/- 5 x 10(9)/l). Von Willebrand factor antigen levels and activity were 400-500% of normal with a 22% reduction of the high molecular weight multimers. A significant hyperagglutination response to botrocetin was observed with platelets from both patients and controls using patient plasma as a source of von Willebrand factor. In conclusion, a hyperresponsiveness rather than a defective platelet-von Willebrand factor interaction can be observed in cirrhosis which may compensate for other hemostatic problems and appears to be mediated primarily by increased levels of von Willebrand factor.
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PMID:Quantitative and qualitative analysis of platelet GPIb and von Willebrand factor in liver cirrhosis. 749 66

A simple and easily reproducible in vitro clot lysis test less frequently indicated increased rate of fibrinolysis in chronic hepatic disease than expected. In hepatic cirrhosis clot lysis slows down as the condition deteriorates or as the plasma concentration of von Willebrand factor increases, thus the test may have certain prognostic value. The present observations suggest that the occasional acceleration of fibrinolysis in cirrhosis may be related to either increased production or decreased clearance of tPA, and is not due to impaired fibrinolysis inhibitor system.
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PMID:[Fibrinolysis in chronic liver diseases studied by in vitro blood coagulation tests]. 783 17


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