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

The current management of thrombotic and vascular disorders has been strongly influenced by the introduction of several new drugs. 1. One of the major impact in the management of venous thromboembolic disorders has been the LMWHs. The newest, third generation heparin, the pentasaccharide inhibits specifically FXa. The elimination half-life of pentasaccharide is about 17 h, which allows a convenient once-daily dosing regime. The effects of pentasaccharide needs antithrombin. 2. Melagatran dipeptid is a specific, reversible direct thrombin inhibitor. It inhibits free and clot bound thrombin. Ximelagatran is a prodrug of melagatran. It is the first clinically used orally acting direct thrombin inhibitor. 3. Recombinant human activated protein C (rh-APC) has some advantages in patients with septic DIC. Qualities of the three new anticoagulants and clinical experiences with them have been summarized.
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PMID:[New anticoagulants in clinical practice]. 1563 34

The anti-thrombic properties of the Korean herbal medicine, Dae-Jo-Hwan (DJW), which is consisted of 11 herbs (indicated as concentrations) of Rehmanniae radix 24%, Hominis placenta 5%, Testudinis carapax 9%, Eucommiae cortex 9%, Asparagi radix 9%, Phellodendri cortex 9%, Achyranthis radix 7%, Liriopis tuber 7%, Angelicae sinensis radix 7%, Ginseng radix 6%, and Schizandrae fructus 3%, were investigated. The extracts of DJW and its 11 herbs, except G. radix, A. sinensis radix and S. Fructus, inhibited the endotoxin-induced hepatic venous thrombosis in high cholesterol diet-treated rats. Also the extract inhibited the endotoxin-induced decrease in blood platelets and fibrinogen, and endotoxin-induced increase in fibrin degradation products (FDP) on disseminated intravascular coagulation in normal rats. In in vitro experiments, the extract was shown to have inhibitory effect on collagen- and ADP-induced blood platelet aggregation, on thrombin-induced conversion of fibrinogen to fibrin and on the activity of plasminogen or plasmin. In conclusion, the protection of extracts of Korean herbs on the ischemic infarction induced artificially might be related to their inhibitory effects on DIC, platelet coagulation and thrombic action.
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PMID:Anti-thrombic activity of Korean herbal medicine, Dae-Jo-Whan and its herbs. 1622 22

During the last decades in Georgia was observed significant increase of cases of visceral leishmaniasis and fight against this disease became important problem as far as the management of this disease is rather problematic. According to references and our clinical experience patients with visceral leishmaniasis are predisposed to bleeding. The objective of our study was the assessment of functional status of hemostasis related to the degree of clinical severity. We have studied platelet count, activated partial thromboplastin time (APTT), prothrombin time, thrombin time, plasma concentration of fibrinogen, the soluble fibrin-monomeric complexes (SFMC), fibrinogen/fibrin degradation products (D-dimer) and anticoagulant protein C. Haemostatic functional tests were studied in 45 patients with visceral leishmaniasis before and after treatment (with 20-25 day intervals). Before treatment the reduction of platelet count was observed in 95%. Prolonged APTT and prothrombin time was found in severe forms of the disease. Thrombin time prolonged in 45.7%, SFMC level was increased in 80% (p=0.003) and D-dimer level in 95.6% (p=0.023). Protein C was in normal value in 73%. The results indicate that leishmania infection affects primary haemostasis, coagulation and fibrinolysis and these alterations are related to the severity of clinical symptoms. Investigation of SFMC and D-dimer showed that in case of visceral leishmaniasis activation of intravascular coagulation takes place, particularly during the severe forms of the disease, study of these markers is of the diagnostic and prognostic importance and the treatment at an early stage of infection may potentially avoid the possibility of developing an uncompensated DIC.
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PMID:[Functional status of haemostasis system in patients with visceral leishmaniasis]. 1636 67

The accumulation of soluble fibrin (SF) in the blood plasma causes acceleration of the final stage of blood coagulation. It increases functional activity of a hemostasis system platelet link, that is the precondition of thrombotic complication. Accumulation of SF in the blood plasma is accompanied by proportional reduction of coagulation time in ancistron and thrombin time tests, and also the intensification of platelets aggregation process. A conclusion was drawn that for early diagnostics of the DIC-syndrom it is expedient to carry out complex estimation of the hemostasis system with obligatory definition of the blood SF content, performance of ancistron and thrombin time tests, and also study of platelets aggregation.
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PMID:[Effect of soluble fibrin on the blood coagulation process and platelets aggregation]. 1710 Mar 19

Recombinant activated factor VII has been used successfully in many cases of traumatic and surgical bleeding complications that were unresponsive to standard treatment. However, because disseminated intravascular coagulation can develop from a thrombin burst as a side effect of recombinant activated factor VII, it is not yet established for bleeding complications induced by disseminated intravascular coagulation. This article presents 3 patients with severe sepsis and fulminant disseminated intravascular coagulation. Excessive microvascular bleeding persisted despite conventional therapy, and surgical intervention and radiologic embolization did not control bleeding. After administration of recombinant activated factor VII, bleeding ceased in all patients, and no overt thromboembolic events occurred. One patient survived to be discharged from the hospital. The other 2 patients died from refractory multiorgan failure and overall poor prognosis. Recombinant factor VIIa might be an option for the treatment of severe bleeding complications in the case of DIC refractory to the conventional therapy.
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PMID:Administration of recombinant activated factor VII (NovoSeven) in three cases of uncontrolled bleeding caused by disseminated intravascular coagulopathy. 1763 94

The primary focus of the blood coagulation system is the prevention of blood loss. The system is regulated by various inhibitors, and by the fibrinolytic system, which removes the final product of the blood coagulation system, the fibrin clot. The fibrinolytic system is activated in the course of coagulation activation. The thrombin-activated fibrinolysis inhibitor (TAFI) is an important regulator of fibrinolysis. TAFI is activated by thrombin, and activation is enhanced in the presence of thrombomodulin. TAFIa, the product of TAFI activation, removes lysine residues from fibrin, which are essential for the binding of t-PA, plasminogen, and plasmin to fibrin. The fibrin loses its cofactor activity in t-PA-induced plasminogen activation, resulting in less plasmin, and the remaining plasmin finds less binding sites on fibrin, resulting in an increased resistance of the clot towards plasmin proteolysis. High concentrations of thrombin result in high TAFIa-activity and consequently in highly resistant fibrin clots. Patients with hyperprothrombinaemia consequently display elevated TAFIa-levels, which may contribute to the risk for thrombosis. Treatment with recombinant factor VIIa also leads to high concentrations of thrombin, resulting in fibrin clots with enhanced resistance towards fibrinolysis. At low thrombin concentration, as observed in patients with bleeding disorders or patients treated with anticoagulant drugs, less TAFIa is produced in the course of coagulation activation, and the clots are less resistant towards fibrinolysis. TAFIa-inhibitors are currently being developed for the treatment of throboembolic disorders or hypofibrinolytic DIC. Enhancement of TAFIa-activity may be helpful in patients with bleeding.
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PMID:[The TAFI system. The new role of fibrinolysis]. 1793 67

Patients with severe haemophilia A and an inhibitor may become refractory to FEIBA and/or recombinant factor VIIa (rFVIIa). Sequential therapy with both products has been reported in such patients. In this pilot study, we examined the safety and efficacy of combined rFVIIa and FEIBA therapy in patients with haemophilia A and inhibitors during bleeding episodes. We also tried to evaluate whether thrombin generation (TG), by various mixtures of these agents, can serve as a guide for tailoring therapy. TG was measured in plasma taken from eight haemophilia A patients. Increasing concentrations of rFVIIa, FEIBA or both were added ex vivo to the plasmas, and TG was induced by recalcification. Since low concentrations of rFVIIa and FEIBA had either an additive or a synergistic effect in all patients, the lowest combination, yielding TG comparable or lower than TG achieved with either FEIBA 100 U kg(-1) or rFVIIa 160 microg kg(-1) alone, was selected for the treatment of bleeding episodes. Five patients with a high titre of an inhibitor (8-1300 BU), including one previously refractory to infusions of rFVIIa at doses up to 400 microg kg(-1) X4 daily, were treated with combinations of 30-70 microg kg(-1) rFVIIa and 20-30 U kg(-1) FEIBA during a total number of 400 bleeding episodes with excellent haemostatic effect. No adverse events and no DIC were observed following these infusions. Concomitant infusion of low-dose rFVIIa and low-dose FEIBA, seems to be safe, efficacious and economical in patients refractory to rFVIIa and probably other haemophilia A patients with an inhibitor.
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PMID:Concomitant infusion of low doses of rFVIIa and FEIBA in haemophilia patients with inhibitors. 1947 16

Clotting disorders are associated with the severe, early and complicated forms of PE. Compensated hypercoagulability states associated with a thrombocytopenia (PLT<150k/mm(3)) affect 25 to 50% of severe PE patients. Laboratory markers of platelet and endothelial activation are the early increase of fibronectin levels, the worsening of the thrombocytopenia and the raised platelet turnover. The excessive thrombin formation is physiologically compensated by a rise in thrombin-antithrombin (TAT) complex levels, which is the most specific marker of a PE pregnancy, and a decrease in anti-thrombin (AT) activity. The placenta induced depression of the fibrinolysis appears to contribute towards the hypercoagulable state. The etiological importance of the erythrocyte and leucocyte activation with regards to the abnormal clotting activation is highlighted in the setting of maternal systematic inflammatory disease. The state of compensated coagulopathy found in the PE patient can suffer a pro-coagulatory imbalance because of a quantitative, or a qualitative failure (i.e. thrombophilia) of the physiological coagulation inhibitors, or a combination of both. This disseminated intravascular coagulation, qualified as chronic, is associated with clinically evident signs of foeto-placental unit impairment (i.e. IUGR, foetal death) with or without systemic repercussions in the mother (i.e. renal failure, HELLP syndrome, eclampsia). This set of haemostatic disturbances found in the PE patient is a dynamic phenomenon, which can evolve by the hour therefore requires frequent laboratory investigations. Delivery remains the only curative treatment for these haemostatic disturbances. A better understanding of the aetiology of DIC in PE, an early detection method and a specific identification of the at-risk patients could allow prophylactic and curative treatment.
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PMID:[Clotting disorders and preeclampsia]. 2047 89

Disseminated Intravascular Coagulation is a clinicopathological syndrome where widespread intravascular coagulation occurs in response to an inciting process. The pathophysiology for this disorder is complex with an important role for thrombin, the central regulator of the coagulation process. Since the clinical spectrum of DIC is variable due to its dynamic nature, the laboratory diagnosis should ideally be not based on a single marker or an isolated set of results. The treatment should primary focus on the management of the underlying triggering condition with blood products used as resuscitative measures. Newer therapeutic modalities have been recently tried with success although the management of DIC still remains a major challenge.
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PMID:Current concepts in the management of disseminated intravascular coagulation. 2268 34

Disseminated intravascular coagulation in obstetrics is commonly seen associated with massive hemorrhage due to different etiological factors. It may also be seen with intrauterine demise, infections, and hepatic conditions. It is associated with very high maternal and perinatal morbidity and mortality. A battery of laboratory tests (prothrombin time, partial thromboplastin time, thrombin time, and plasma fibrinogen) can be used in the diagnosis, but no single test in isolation is sensitive and specific enough for diagnosis. Cornerstone of management is to identify the underlying pathology for disseminated intravascular coagulation. This chapter looks into molecular basis of obstetric DIC and identifies important laboratory tests, along with management. It also identifies topics of future research in the field of obstetric DIC.
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PMID:Disseminated intravascular coagulation. 2391 24


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