Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect on abnormal coagulation tests of infusions of fresh-frozen plasma (F.F.P), prothrombin complex concentrates, and a combination of these treatments was compared in 30 patients with chronic liver disease undergoing needle biopsy. A single dose of F.F.P. (12 ml/kg body-weight) was found to be the least effective therapeutic regimen. The concentrate containing factors II, IX, and X was also not adequate, but the additional administration of factor-VII concentrate corrected the prothrombin-time (P.T.) and "Normotest" (N.T.) in most patients. However, this regimen did not correct the prolonged kaolin activated partial thromboplastin-time (K.P.T.T.). The results of tests for exploring both the extrinsic (P.T. and N.T.) and intrinsic (K.P.T.T.) coagulation systems only became normal after the combined administration of a lower dose of F.F.P. (8 ml/kg body-weight) and of both concentrates (12 units/ml). There was no clinical or laboratory evidence of thrombotic complications. No patient developed acute hepatitis or hepatitis-B surface antigen in the twelve months after biopsy. These results indicate that prothrombin-complex concentrates in combination with F.F.P. may therefore be used to allow liver biopsy to be performed safely in patients presenting with severe coagulation defects.
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PMID:Correction of abnormal coagulation in chronic liver disease by combined use of fresh-frozen plasma and prothrombin complex concentrates. 6 Jun 23

Factor VII levels have been measured in 100 patients with liver disease following parenteral vitamin K1 therapy. There was good agreement between specific factor VII measurements and the one-stage prothrombin time apart from six patients with compensated cirrhosis in whom the prothrombin time was prolonged despite the presence of normal factor VII levels. A mean activity of 58% was found in patients with cirrhosis. Cirrhotic patients with features of hepatic decompensation had a significantly lower mean level of activity (40%) than the "contrast" patients with surgical obstruction of the major bile ducts (93%). Patients with chronic active liver disease had moderate depression of factor VII levels and those with non-cirrhotic liver damage had mean activities similar to the contrast group. Factor VII levels could not be correlated with BSP retention but there was a correlation with serum albumin concentration. It is concluded that the prothrombin time using Quick test with a standardized thromboplastin showing good sensitivity to factor VII, eg, the Manchester reagent (BCT), provides a reliable index of coagulability in chronic liver disease, and specific factor VII assays are not indicated.
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PMID:Factor VII as a marker of hepatocellular synthetic function in liver disease. 100 40

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

Coagulation studies were carried out on 30 patients with chronic liver disease. The clotting defect was complex and involved factors V, VII, IX (Christmas factor), and prothrombin. Some patients showed a significant depression of factor IX in the presence of a normal one-stage prothrombin time. Thrombotest was found to be a good indicator of factor IX deficiency in this group of patients and may be of use as an additional liver function test. The screening of patients with liver disease for surgery or liver biopsy should assess the coagulation factors involved in both intrinsic and extrinsic thromboplastin generation.
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PMID:Coagulation factors in chronic liver disease. 577 51

To assess the nature of the hemostatic abnormalities associated with chronic liver disease, we have simultaneously evaluated the kinetic of radiolabeled platelets, fibrinogen, and plasminogen, together wit tests of platelet and fibrinogen function, and coagulation factors in 60 patients with documented, severe but stable cirrhosis of the liver. The mean platelet survival was substantially reduced (5.8 +/- 1.7 days compared with 9.5 +/- 0.6 days in normals, p less than 0.0001) and splenic sequestration of platelets was increased (mean recovery was 47% +/- 18 vs. 65% +/- 5 in normals, p less than 0.0001). Nevertheless the mean platelet count was nearly normal because platelet production was increased nearly twice normal values (mean turnover was 64,000 +/- 33,000 platelets/microliter/day; p less than 0.0001). The mean rate of fibrinogen removal was shortened (p less than 0.0001) and fibrinogen turnover increased about 20% (p = 0.008) while the mean fibrinogen concentration was not different from the results in normal control subjects (p = 0.212). Autologous and homologous fibrinogen disappeared from the circulation at equivalent rates (r = 0.751; p = 0.008), indicating that fibrinogen from cirrhotic patients was not kinetically different from normal fibrinogen. The mean plasminogen survival was significantly shortened (p less than 0.0001), but the mean plasminogen turnover was not increased (p = 0.388). Thus the plasminogen concentration was reduced (p less than 0.0001). For platelets, fibrinogen, and plasminogen, the production rate was the most important determinant of the concentration in the circulation. The administration of heparin to cirrhotic patients improved the survival of fibrinogen but not of platelets. LeVeen valve implantation generally resulted in parallel shortening of both the platelet and fibrinogen survivals and concentrations. Platelet function as assessed by template bleeding time, platelet retention by glass bead columns, and aggregation induced by ADP, epinephrine, and collagen was normal. Fibrinogen determinations by the Clauss and Jacobsson techniques were equivalent, indicating that the ability to polymerize fibrin monomer was not detectably altered. Sixty percent of patients had an abnormal prothrombin time and half that number had a prolonged partial thromboplastin time. Although most patients had a modest decrease in the prothrombin complex coagulation factors, fibrin degradation products were, in general, not elevated in the circulation. The wide range of values observed suggests that a number of different and complex processes may be ongoing in different patients. Overall, the kinetic data suggest that platelets are initially consumed, perhaps on incompletely endothelialized endovascular surfaces in the liver, and that fibrin subsequently forms secondary to local stasis. The absence of increased production of fibrinogen and plasminogen despite shortened survival times reflects the reduced capability of the cirrhotic liver to increase protein synthesis.
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PMID:Kinetic and functional studies of platelets, fibrinogen, and plasminogen in patients with hepatic cirrhosis. 706 18

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

An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of anti-HCV antibody. We assayed for antibodies against either oligopeptide (S29-1) deduced from the nucleocapsid gene or the product of nonstructural region (NS3) synthesized in a recombinant Escherichia coli (S4). To reduce false-positive results induced by non-specific binding of antibodies with a carrier protein and to increase the sensitivity of an immunoassay, non-fused S4 peptide was prepared by the recombinant DNA technique and site-specific proteolysis (by factor Xa). In 71 non-A, non-B hepatitis patients with chronic liver disease, 70 (98.5%) were positive by S29-1/S4 ELISA as well as by a second-generation test (Abbott II). On the other hand, of 40 serum samples from blood donors, in which anti-N14 (core) and C100-3 antibodies were not detected but hepatitis C virus (HCV) RNA was detectable by polymerase chain reaction (PCR), 24 (60%) were positive by S29-1/S4 ELISA, whereas only 18 (45%) were diagnosed by Abbott II. In addition, based on results in a small group of 92 blood donors, detection of anti-S29-1/S4 antibody correlated well with HCV viremia as confirmed by PCR. These results indicated that the preparation of nonfused protein (S4) by recombinant DNA technique and a combination of S29-1 and S4 as immobilized antigens in an ELISA provide a sensitive and specific diagnosis for HCV infection with good correlation with the presence of viral RNA as confirmed by PCR.
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PMID:A sensitive serodiagnosis of hepatitis C virus (HCV) infection with two non-fused peptides: comparison of antibody responses detected with a newly developed assay and a commercial second-generation test. 768 47

A simple chromogenic substrate assay for the quantitation of tissue factor pathway inhibitor (TFPI) activity in plasma or serum samples was developed. After immobilization on microtiter plates for 20 hours at 4 degrees C, a commercial thromboplastin was incubated for 1 hour at room temperature with 1 U/mL of a prothrombin complex concentrate (Protromplex). After washing, solid-phase Factor Xa activity was measured by a chromogenic substrate (S-2222). Factor Xa generation was progressively inhibited when increasing amounts (1-12 microL) of heated serum or plasma, and recombinant TFPI (1-5 ng/mL), were coincubated with Protromplex. Inhibition by serum or plasma was abolished by anti-TFPI polyclonal antibodies. Plasma levels of TFPI in 25 healthy volunteers were found to be 0.98 +/- 0.19 U/mL (range 0.71-1.52), with an intra- and inter-assay coefficient of variation of 10.7 and 11.1%, respectively. The use of a recombinant human thromboplastin improved the sensitivity and reproducibility of the assay. Plasma levels of TFPI were found to be normal in 10 women at the end of their pregnancies, in 10 patients receiving oral anticoagulant therapy, and in 10 diabetic patients. Significantly higher levels were detected in 10 patients with chronic liver disease and in 10 patients with unexplained juvenile thrombosis. In patients with cardiovascular disease, a 7-day treatment with subcutaneous standard heparin increased TFPI activity. The availability of a simple and rapid assay to measure TFPI that does not require purified coagulation proteins may facilitate studies of the pathophysiologic relevance of this inhibitor.
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PMID:A simple chromogenic substrate assay of tissue factor pathway inhibitor activity in plasma and serum. 772 32

To evaluate the hemostatic effects of desmopressin (DDAVP) in dogs with aspirin-induced platelet dysfunction and hemostatic impairment in chronic liver diseases, 3 microg/kg DDAVP was administrated subcutaneously. In aspirin-induced platelet dysfunction dogs (n=5), prolonged BMBT (buccal mucosal bleeding time) was shortened significantly after DDAVP injection (2.2 +/- 1.2 min, P<0.05). In dogs with chronic liver diseases (n=4), activated partial thromboplastin time (APTT) tended to shorten by 0.9 to 3.0 sec, and prolonged BMBT was shortened in two cases for 4.2 and 1.7 min after DDAVP injection. Therefore, the present results indicated that DDAVP shortened the prolonged BMBT in dogs with aspirin-induced platelet dysfunction and chronic liver disease. DDAVP might be helpful in hemostasis under invasive procedures such as biopsy or surgery for dogs with hemostatic impairment.
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PMID:Effects of DDAVP administrated subcutaneously in dogs with aspirin-induced platelet dysfunction and hemostatic impairment due to chronic liver diseases. 1257 9

Normal coagulation has classically been conceptualized as a Y-shaped pathway, with distinct "intrinsic" and "extrinsic" components initiated by factor XII or factor VIIa/tissue factor, respectively, and converging in a "common" pathway at the level of the FXa/FVa (prothrombinase) complex. Until recently, the lack of an established alternative concept of hemostasis has meant that most physicians view the "cascade" as a model of physiology. This view has been reinforced by the fact that screening coagulation tests (APTT, prothrombin time--INR) are often used as though they are generally predictive of clinical bleeding. The shortcomings of this older model of normal coagulation are nowhere more apparent than in its clinical application to the complex coagulation disorders of acute and chronic liver disease. In this condition, the clotting cascade is heavily influenced by numerous currents and counter-currents resulting in a mixture of pro- and anticoagulant forces that are themselves further subject to change with altered physiological stress such as super-imposed infection or renal failure. This report represents a summary of a recent multidisciplinary symposium held in Charlottesville, VA. We present an overview of the coagulation system in liver disease with emphasis on the limitations of the current clinical paradigm and the need for a critical re-evaluation of the current tenets governing clinical practice. With the realization that there is often limited or conflicting data, we have attempted to represent diverse opinion and experience from the perspectives of both hepatology and hematology beginning with a brief update on the physiology of normal coagulation.
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PMID:Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management. 1700 40


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