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)

A two-year mechanistic bioassay in male Crl:CD BR rats was initiated with 50 ppm Wyeth-14,643 (WY) to investigate the relationship between peroxisome proliferating compounds and Leydig cell adenoma formation. After 154 days, the survival rate in the WY group decreased below control levels. After 300 days, the dose was lowered to 25 ppm for the remainder of the study. Gross examination of WY-treated rats either found dead or euthanized in extremis revealed hemorrhages at several sites. To investigate this observation, blood was then collected on test day 281 from 10 randomly selected control and WY-treated rats and a clinical pathological examination was performed. The WY-treated rats had significantly decreased red blood cell count, hemoglobin, and hematocrit, and elevated platelet counts. In the WY-treated rats, prothrombin times in undiluted plasma were similar to the controls, but were markedly prolonged in 2 of 10 rats when the plasma samples were diluted to 25%. Subsequently, blood was collected prior to sacrificing WY-treated rats which were exhibiting clinical signs of anemia. These rats had prolonged prothrombin times, activated partial thromboplastin time, and thrombin clot time when compared to laboratory historical control data (116.7 vs 13.3, 116.4 vs 13.7, and 42.4 vs 25.7 seconds, respectively). In a subsequent, ongoing study, Vitamin K was added to control and WY-treated diets (100 ppm). No survival differences between control and WY-treated rats occurred through 260 days in this second study. These new data suggest that deaths in the WY-treated group in our initial study were due to a vitamin K deficiency. The role of increased serum estradiol, its effects on blood coagulation, and enhanced hepatic cell proliferation in the vitamin K-dependent coagulation processes warrant further investigation.
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PMID:Induction of coagulation effects by Wyeth-14,643 in Crl:CD BR rats. 918 58

Twenty-two cats with liver disease were evaluated for coagulation abnormalities including alterations in prothrombin time, activated partial thromboplastin time, thrombin time, factor VII activity, and platelet count. The purpose of the study was to determine the prevalence of coagulation abnormalities in this population of cats, classify abnormalities according to underlying pathogenesis, and determine if serum biochemical parameters typically used as indicators of liver disease showed any correlation with the coagulation abnormalities present. Study results indicated that at least 1 coagulation abnormality was present in 82% of the cats. Prolongation of prothrombin time was most common (16/22 cats) and factor VII activity was below reference range (< 60%) in 15 cats. When classified according to underlying pathogenesis, vitamin K deficiency was the most common abnormality found (11/22). Other abnormalities were less common and included hepatic synthetic failure (3/22), indeterminate (3/22), and disseminated intravascular coagulation (1/22). Increase in alkaline phosphatase (ALP) activity was the only biochemical abnormality that showed statistically significant correlation with coagulation abnormalities (P = .023). Cats with marked increases in ALP activity were more likely to have coagulation abnormalities than those with only mild increases in ALP activity.
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PMID:Coagulation abnormalities in 22 cats with naturally occurring liver disease. 956 Jul 61

The administration of menaquinone-4 (MK-4), one of subclasses of vitamin K2, significantly reduces bone loss in postmenopausal osteoporotic women. However, concerns have been raised about whether vitamin K administration alters the hemostatic balance by inducing a thrombotic tendency. We investigated were whether the administration of vitamin K in the form of MK-4 induced a thrombotic tendency in 29 elderly patients with osteoporosis (5 men, 24 women; age range 78.7+/-5.1 years). Patients were administered 45 mg/day (three times a day, 30 min after each meal) of MK-4 for 12 weeks. Blood samples were obtained from the patients at 0, 4 and 12 weeks after the start of MK-4 administration. A number of hemostatic parameters remained stable under the markedly increased plasma levels of MK-4. However, in patients with suspected vitamin K deficiency, whose plasma levels of vitamin K or factor VII were low, vitamin-K-dependent clotting factors such as factor VII and prothrombin were gradually increased after administration of MK-4. No changes in the sensitive molecular markers such as TAT and F1+2, which reflect the amount of thrombin generated in the blood stream, were observed, even in those patients with suspected vitamin K deficiency. These results indicate that MK-4 can be administered safely, with regard to maintaining the hemostatic balance, to osteoporotic patients receiving no anticoagulant therapy.
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PMID:Vitamin K administration to elderly patients with osteoporosis induces no hemostatic activation, even in those with suspected vitamin K deficiency. 1184 34

The status of vitamin K in pregnant women was investigated using the highly sensitive method for des-gamma-carboxyprothrombin (protein induced by vitamin K absence [PIVKA-II]), electrochemiluminescence immunoassay. A gradual elevation of PIVKA-II related to gestational weeks was observed in healthy pregnant women, suggesting that a modest vitamin K deficiency takes place in gestation. Furthermore, throughout gestation the majority of pregnant women exceeded the healthy adult levels in PIVKA-II. Among complicated gestations of preeclampsia, a remarkable elevation of PIVKA-II was observed in severe preeclampsia, in which a high correlation between PIVKA-II level and coagulation parameters, including thrombin-antithrombin (TAT) complexes, was revealed. These data were suggestive that the vitamin K status readily decreased into a deficient status in hypercoagulative conditions. Among other complicated gestations, a moderate elevation of PIVKA-II was demonstrated in hyperemetic conditions, and, if at all, only a slight elevation of PIVKA-II was observed in other maternal diseases. The present study is the first report regarding the changes of PIVKA-II in pregnant women.
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PMID:Des-gamma-carboxyprothrombin (PIVKA-II) levels in maternal serum throughout gestation. 1605 8

Effects of dose and duration of phenobarbital (PB) administration and those of co-administration of PB and vitamin K on blood coagulation-related parameters were examined in specific pathogen-free (SPF) rats of Sprague-Dawley strain kept on an ordinary diet. In Experiment 1, oral administration of PB (0, 25, 50, 100 or 150 mg/kg/day) for 2 weeks induced increases in hepatic cytochrome P450 content and CYP2B expression, prolongation of coagulation time (activated partial thromboplastin time (APTT) and Thrombotest (TBT)) and an increase in anti-thrombin III (AT III) concentration in a dose-dependent manner. In Experiment 2, PB administration (100 mg/kg/day) for up to 14 days produced time-dependent increases in hepatic cytochrome P450 content and CYP2B (CYP2B1 and CYP2B2) expression. APTT was prolonged from day 1 and AT III concentration was increased from day 2, whereas the coagulation time (TBT) was prolonged from day 7. In Experiment 3, APTT prolonged by PB (100 mg/kg/day) was shortened after vitamin K(2) (30 mg/kg/day) co-administration, although AT III concentration was still increased. This suggests that not AT III but PB-induced vitamin K deficiency may play an important role in PB-induced prolongation of coagulation time in SPF rats kept on an ordinary diet.
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PMID:Blood coagulation-related parameter changes in Sprague-Dawley (SD) rats treated with phenobarbital (PB) and PB plus vitamin K. 1867 Jan 62

The modern thrombin generation tests describe different phases of generation of thrombin that is initiation, amplification and inhibition of thrombin generation as well as the integral amount of generated thrombin. We investigated 55 patients with congenital deficiencies of different coagulation factors and analysed the relationship between the nature and the concentration of clotting factors, with different parameters of thrombin generation curve that is lag time, peak, time to peak and the area under curve or endogenous thrombin potential. The endogenous thrombin potential was unaffected by severe deficiency of factors XI and XII, and reduced in factor IX, VII and factor V and VIII deficiencies. The lag time was significantly prolonged in cases of severe factor VII, X and V deficiencies, and was almost normal in cases of factors VIII, IX, combined factors V and VIII, factor XI, XII and XIII deficiencies. The peak height was severely affected in cases of severe factor X, V, VIII and IX deficiency and combined deficiency of multiple vitamin K dependant coagulation factors, and significantly reduced in factor VIII, V, X, XIII and combined vitamin K deficiency.In all the patients with less than 40% thrombin generation, the clinical symptoms were severe. Bleeding symptoms were restricted to epistaxis and ecchymosis when thrombin generation was more than 90% of the normal. In the cases of combined deficiency of factors V and VIII all the values were intermediate as they exhibit mild deficiencies of both factors V and VIII and correlated well with the clinical symptoms. Endogenous thrombin potential of inherited isolated deficiencies of coagulation factors may thus provide an interesting insight about involvement of the deficient factor(s) at different phases of thrombin generation.
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PMID:Spectrum of changes in endogenous thrombin potential due to heritable disorders of coagulation. 1868 41

Topical hemostats, fibrin sealants, and surgical adhesives are regularly used in a variety of surgical procedures involving multiple disciplines. Generally, these adjuncts to surgical hemostasis are valuable means for improving wound visualization, reducing blood loss or adding tissue adherence; however, some of these agents are responsible for under-recognized adverse reactions and outcomes. Bovine thrombin, for example, is a topical hemostat with a long history of clinical application that is widely used alone or in combination with other hemostatic agents. Hematologists and coagulation experts are aware that these agents can lead to development of an immune-mediated coagulopathy (IMC). A paucity of data on the incidence of IMC contributes to under-recognition and leaves many surgeons unaware that this clinical entity, originating from normal immune responses to foreign antigen exposure, requires enhanced post-operative vigilance and judicious clinical judgment to achieve best outcomes.Postoperative bleeding may result from issues such as loosened ties or clips or the occurrence of a coagulopathy due to hemodilution, vitamin K deficiency, disseminated intravascular coagulation (DIC) or post-transfusion, post-shock coagulopathic states. Other causes, such as liver disease, may be ruled out by a careful patient history and common pre-operative liver function tests. Less common are coagulopathies secondary to pathologic immune responses. Such coagulopathies include those that may result from inherent patient problems such as patients with an immune dysfunction related to systemic lupus erythrematosus (SLE) or lymphoma that can invoke antibodies against native coagulation factors. Medical interventions may also provoke antibody formation in the form of self-directed anti-coagulation factor antibodies, that result in problematic bleeding; it is these iatrogenic post-operative coagulopathies, including those associated with bovine thrombin exposure and its clinical context, that this panel was convened to address.The RETACC panel's goal was to attain a logical consensus by reviewing the scientific evidence surrounding IMC and to make recommendations for the clinical recognition, diagnosis and evaluation, and clinical management of these complications. In light of the under-recognition and under-reporting of IMC, and given the associated morbidity, utilization of health care resources, and potential economic impact to hospitals, the panel engaged in a detailed review of peer-reviewed reports of bovine thrombin associated IMC. From that clinical knowledge base, recommendations were developed to guide clinicians in the recognition, diagnosis, and management of this challenging condition.
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PMID:Building an immune-mediated coagulopathy consensus: early recognition and evaluation to enhance post-surgical patient safety. 1946 80

Use of a coagulation panel [prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT) and fibrinogen], intended for evaluation of bleeding, tripled over 6 years, out of proportion to admissions, surgery, or transfusions. To determine whether the panels were ordered appropriately, we classified 28,737 sets of panel results into groups followed by chart reviews to determine typical patient histories. In 39% of panels, PT/PTT was normal. Prolonged PT occurred in 33% of results, due to liver failure (8%), warfarin (23%), and presumed vitamin K deficiency (69%). Prolonged PTT occurred in 34% of results and was primarily associated with long PT or lupus inhibitors. Prolonged PTT and TT (15% of panels) indicated heparin therapy. Fibrinogen was normal in 98% and low in 1.4%. Critical fibrinogen (below 100 mg/dl, 0.6% of panels) was associated with bleeding in 90% of patients. Only 8% of panel orders were clinically indicated based on patient history. Clinician interviews indicated many were unaware the panel included fibrinogen and TT. Interventions included an education program and an order form change. The education program had no effect on overall order volume or test selection. A later order form change made TT and fibrinogen a separate order. This reduced TT and fibrinogen testing by 90% without complaints or changes in blood transfusion statistics. We conclude that many coagulation test panel orders were not clinically indicated, that PT more often diagnosed vitamin K deficiency than bleeding risk, and that order-based restriction of testing was more effective than educational programs at introducing change in clinical test utilization.
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PMID:Reducing the use of coagulation test panels. 2193 88

Rejection of the sample with repeated blood withdrawal is always an unwanted consequence of sample nonconformity and preanalytical errors, especially in the most vulnerable population - children. Here is presented a case with unexpected abnormal coagulation test results in a 2-year-old child with no previously documented coagulation disorder. Child is planned for tympanostomy tubes removal under the anaesthesia driven procedure, and preoperative coagulation tests revealed prolonged prothrombin time, activated partial thromboplastin time and thrombin time, with fibrinogen and antithrombin within reference intervals. From the anamnestic and clinical data, congenital coagulation disorder was excluded, and with further investigation, sample mismatch, clot presence and accidental ingestion of oral anticoagulant, heparin contamination or vitamin K deficiency were excluded too. Due to suspected EDTA carryover during blood sampling another sample was taken the same day and all tests were performed again. The results for all tests were within reference intervals confirming EDTA effect on falsely prolongation of the coagulation times in the first sample. This case can serve as alert to avoid unnecessary loss in terms of blood withdrawal repetitions and discomfort of the patients and their relatives, tests repeating, prolonging medical procedures, and probably delaying diagnosis or proper medical treatment. It is the responsibility of the laboratory specialists to continuously educate laboratory staff and other phlebotomists on the correct blood collection as well as on its importance for the patient's safety.
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PMID:Unexpected abnormal coagulation test results in a 2-year-old child: A case report. 3183 29


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