Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemical modification of gamma-carboxyglutamic acid (Gla) residues in human prothrombin to gamma-methyleneglutamic acid (gamma-MGlu) residues elicited a conformation similar, if not identical, to that of des-gamma-carboxy prothrombin or PIVKA-II, i.e., prothrombin molecules induced by vitamin K antagonists or vitamin K deficiency states. The reaction seems to proceed sequentially by preferentially modifying a Gla at residue 32 that is located innermost among 10 Gla residues of human prothrombin. The initial modification resulted in nearly 50% losses of barium salt adsorption, the procoagulant activity and thrombin generation by the prothrombinase complex. The subsequent modification of two Gla residues at positions 6 and 16 gave rise to the immunoreactivity to an established monoclonal antibody that specifically recognizes the des-gamma-carboxy prothrombin. Further modification of Gla residues increased the reactivity to the antibody, indicating that the conformation recognized by the antibody was stabilized so as to more readily fit the recognition site of the antibody. The appearance of the immunoreactivity was obviously related to the modification of Gla residues in prothrombin, since all other similarly treated derivatives of prothrombin lacking the Gla-domain failed to react with the antibody. Such chemically modified prothrombins may serve as models for studying abnormal des-gamma-carboxy prothrombin produced in vitamin K deficiency states.
 ...
PMID:Chemical modification of gamma-carboxyglutamic acid residues in prothrombin elicits a conformation similar to that of abnormal (des-gamma-carboxy)prothrombin. 227 30

An estrogen-responsive procoagulant activity is present in the plasma membrane fraction of immature rat uterus. This procoagulant has many of the properties of tissue factor, a widely occurring, integral membrane protein which initiates the intrinsic pathway of coagulation. Procoagulant activity was demonstrated to activate prothrombin in rat uterus, to activate human coagulation factor X, and to cause clot formation by human plasma. Procoagulant activity could be solubilized from the plasma membrane by the detergent octyl glucoside and had an apparent mol wt of 20,000-40,000 by gel filtration. Procoagulant activity was increased 4-fold within 3 h after immature rats were injected with estradiol. The increase was tissue- and hormone specific and was not affected by a warfarin-induced vitamin K deficiency. Coagulation factor VII was required for clot formation by the procoagulant. These properties are consistent with identification of the procoagulant as tissue factor. mRNA for tissue factor was increased in the uterus 3 h after estrogen stimulation. In the preceding paper we showed that prothrombin is increased in the immature uterus within 3 h of estrogen stimulation. The presence of increased amounts of a tissue factor-like procoagulant in the same time period suggests a functional relationship between these two proteins and a possible role for both in uterine development. Thrombin is a growth factor in fibroblasts and endothelial cells. We propose that after estrogen stimulation, prothrombin enters the uterus with the influx of plasma proteins and is activated by the procoagulant to thrombin. We suggest that thrombin might act as a paracrine factor early in the estrogen-stimulated development of the uterus.
 ...
PMID:Estrogen regulation of a tissue factor-like procoagulant in the immature rat uterus. 229 81

A new clotting method is described to assay des-gamma-carboxyprothrombin (DCP), using staphylocoagulase and adsorbed undiluted citrated plasma. The thrombin-coagulase formed was tested with a chromogenic substrate. The results were expressed in milliunits (m.u.). All 96 normal plasmas had less than 15 m.u. (mean 3.58 m.u.). Out of 56 non-hepatectomized cellular hepatocarcinomas, 40 had DCP levels between 20 and 420 m.u. (average between 40 and 60 m.u.); 71.4% of cellular hepatocarcinoma had an increased DCP and 90% were positive either in alpha-foetoprotein or in DCP. Ten cases of non-cellular hepatocarcinomas had normal DCP levels. We found no cases of cirrhosis or chronic hepatitis, whether active or persistent, with abnormal level of DCP. Out of 127 patients tested, no case was found with a high DCP and a low level of "total factor II", which could be interpreted as a vitamin K deficiency. Only one case of hepatocarcinoma had 25 m.u. of DCP and a low total factor II (20%) and 2 had less than 10% total factor II with no detectable DCP.
 ...
PMID:Assay of des-gamma-carboxyprothrombin using staphylocoagulase. Application to the diagnosis of cellular hepatocarcinoma. 242 13

Most causes of abnormal bleeding can be determined from a complete blood count including platelet count and bleeding, prothrombin, activated partial thromboplastin, and thrombin times. Occasionally, further evaluation is necessary, such as tests of factor XIII function, fibrinolysis, and vascular integrity. Possible diagnoses include disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, vitamin K deficiency, von Willebrand's disease, heparin-induced thrombocytopenia, acquired inhibitors of factor VIII, lupus anticoagulants, and coagulation disorders related to the acquired immunodeficiency syndrome.
 ...
PMID:Laboratory evaluation of a bleeding patient. 266 Apr 7

Clinical and laboratory evaluation of severe bleeding can detect the presence of an intrinsic or acquired coagulation disorder. The three most common inherited coagulation disorders are factor VIII deficiency (hemophilia A), factor IX deficiency (hemophilia B), and von Willebrand's disease. Vitamin K deficiency, liver disease, and disseminated intravascular coagulation are the most common acquired disorders. A thorough clinical history is crucial to diagnosis. Screening tests that measure prothrombin time, partial thromboplastin time, thrombin time, and platelet count permit initial classification and guide selection of more specific tests. Results can then be used to determine appropriate therapy.
 ...
PMID:Potentially catastrophic bleeding disorders. Approach to diagnosis and management. 267 67

A new method for assaying the activity of des-gamma-carboxyprothrombin (DCP), using staphylocoagulase on undiluted adsorbed plasma, is described. The thrombin-coagulase formed is measured on a chromogenic substrate, and the results are expressed in milliunits per milliliter of increment of the optical density following the release of p-nitroaniline. Levels of DCP in 96 normal subjects were under 10 mU/ml (mean, 3.58 mU/ml). Of 70 nonhepatectomized patients with hepatocellular carcinomas, 74% had increased DCP levels of between 20 and 420 mU/ml (most of the values were between 20 and 100 mU/ml). Des-carboxyprothrombin and alpha-fetoprotein measurements gave complementary information, one marker or the other being positive in 87% of hepatocellular carcinoma. Fourteen of 15 patients with metastatic carcinoma of the liver had normal DCP levels, as did 95 patients with liver cirrhosis and 13 patients with chronic hepatitis. When the level of "total factor II" is below 40%, it is recommended that a second determination of DCP be performed 5 days after the injection of vitamin K, to exclude any vitamin K deficiency (in the case of hepatocellular carcinoma the DCP level will remain elevated). The DCP assay appears more sensitive and more specific than the alpha-fetoprotein assay for the diagnosis of hepatocellular carcinoma; furthermore, both tests are complementary.
 ...
PMID:A new method to assay des-gamma-carboxyprothrombin. Results obtained in 75 cases of hepatocellular carcinoma. 301 18

Detailed coagulation studies were done prospectively on 43 patients with biliary atresia who had undergone Kasai operation (hepatic portoenterostomy). Patients were divided into three groups based on levels of factor V, factor II, and Echis II and/or response to vitamin K: no coagulopathy (46.5% of patients); coagulopathy of liver disease (30.2% of patients); and coagulopathy of vitamin K deficiency (23.3% of patients). Patients with the coagulopathy of liver disease had significantly lower levels of factors XII, V, and antithrombin III as well as longer thrombin times than patients with no coagulopathy or vitamin K deficiency. Factor V levels were decreased only in patients with more advanced liver disease; normal levels of factor V were not usually helpful in differentiating liver disease and vitamin K deficiency. The prothrombin time, factor VII-X levels, and factor II levels were significantly different for all three groups; the most abnormal values occurred in the vitamin K-deficient group. Comparison of the Echis II level to factor II coagulant activity was helpful in deciding whether a coagulopathy was due to liver disease, vitamin K deficiency, or both. Factor VIII levels were elevated in all groups. Factor VIII coagulant activity was significantly higher by the two-stage (TGT) method than by the one-stage (PTT) method. Hypersplenism causing neutropenia and thrombocytopenia was commonly seen after the age of 5 years. Vitamin E deficiency was more common than vitamin K deficiency; however, all vitamin K-deficient patients were vitamin E deficient. Coagulation status correlated well with hepatobiliary scan data, but not serum bilirubin levels. Recommendations for treatment of patients with vitamin K deficiency and/or liver disease are discussed.
 ...
PMID:The multiple coagulopathies of biliary atresia. 669 16

Four coagulation factors (II, VII, IX, X) are synthesized in the liver as precursor forms. Vitamin K is necessary for their conversion to functional factors. Factor II precursor is antigenically similar to factor II and can be activated to form thrombin by Echis carinatus venom. Forty-one patients with liver disease and 30 patients with vitamin K deficiency (Warfarin treated), were compared with 51 normal patients. Rats with CCl4-induced hepatic necrosis and animals given Warfarin were also studied. The following measurements were made: standard prothrombin time; Echis clotting time; factor II coagulant assay with thromboplastin; factor II assay with Echis venom; and factor II antigen (human) by electroimmunoassay. In animals and humans with liver disease, factor II was reduced, as measured by all techniques. With vitamin K deficiency functional factor II was reduced, but factor II antigen and Echis factor II activity were normal. THe data suggest that the prothrombin time and Echis coagulation methods can be used to differentiate whether the coagulopathy in liver disease is due to reduced precursor levels of factor II, vitamin K deficiency (ie, impaired formation of functional from precursor factor II), or both.
 ...
PMID:Factor II antigen in liver disease and warfarin-induced vitamin K deficiency: correlation with coagulant activity using Echis venom. 677 11

The multiphase process of blood coagulation occurs owing to the interaction of three links of hemostasis--thrombocyte apparatus, plasma factors, and vascular wall components--and is regulated by the neuro-reflectory mechanisms of the coagulating and anticoagulating systems. At the early stage of hemostasis, a set of reactions begins in the thrombocyte apparatus leading to cell aggregation, secretion of the content of granules, synthesis of prostaglandines and eventually to the formation of thrombocyte thrombus. Disorders in ultrastructures and membranes of thrombocytes, particularly in receptor glycoproteins lead to the development of molecular disease of thrombocyte and to the disturbance of hemostasis. Plasma factors are activated by some proteolysis reactions in the realization of which a great role is played by phospholipids; Ca ions and regulatory proteins. The key reaction of hemostasis is activation of prothrombin into thrombin. Hemostasis disorders at this stage are of congenital (factor deficiency) or acquired (vitamin K deficiency) nature and occur at the molecular level. Hemostasis is terminated by a step-wise formation of fibrin. Disorders of one of the stages of this process due to congenital abnormality of fibrinogen results in coagulation defect due to the molecular disease of fibrinogen. The problem of hemostasis is inseparable from that of the mechanism causing the living host resistance to thrombus formation. The regulation of the liquid state of the blood and its coagulated is performed by the combined functioning of the coagulating and anticoagulating systems.
 ...
PMID:[Structural and functional bases of hemostasis and its pathology]. 700 46

Disturbed liver parenchymal cell function adversely impacts on the hemostasis system, the extent of which correlates with the degree of liver disease. Because liver parenchymal cells synthesize most factors of the clotting and the fibrinolytic systems, levels of these procoagulant and anticoagulant as well as profibrinolytic and antifibrinolytic factors will decrease in plasma. These changes may be minor in patients with mild liver disease but are severe in patients with cirrhosis. Thrombocytopenia and thrombocytopathy usually complicate the clinical presentation, and systemic activation of the fibrinolytic system is always seen in cirrhotic individuals. Whether this fibrinolytic activation is primary or secondary in response to DIC is controversial. Some of the laboratory findings in DIC may be a reflection of decreased hepatic clearance of activation products by the reticuloendothelial system of the diseased liver. In patients with vitamin K deficiency or in those receiving oral anticoagulants, only the vitamin K-dependent procoagulants and anticoagulants are altered; all other parameters remain in the normal range. Laboratory changes associated with various surgical interventions involving the liver depend on the underlying pathology. Severe hemorrhages are encountered during orthotopic liver transplantation. During the anhepatic phase and during the reperfusion phase, there is a major activation of the fibrinolytic system. It is unclear whether this fibrinolytic response is primary or secondary. The use of antifibrinolytic agents has markedly reduced the clinical bleeding and, thus, the requirement for blood and blood products. Bleeding associated with partial liver resection is usually mechanical in nature, but peritoneovenous shunt operations can result in DIC. Ascites fluid is the trigger. The injection of thrombin containing sclerosants can also activate the hemostasis system in vivo, although, generally, no clinically detectable adverse reactions are noted.
 ...
PMID:Coagulopathies of liver disease. 787 70


1 2 Next >>