Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

To maintain a closed system during the preparation of blood components, including the removal of buffy coat, many centers use a quadruple blood bag additive solution system which in this study has been reduced to a cheaper triple bag system. The buffy coat and plasma were after centrifugation transferred to the first satellite bag and, after a second spin, the plasma separated from the buffy coat was transferred to the second satellite bag and stored for a fortnight at 4 degrees C. This resulted in a statistically significant increase in platelet factor 4 and elastase activity levels. No significant changes were found in the levels of C1-esterase inhibitor and kallikrein inhibiting activity, thrombin-antithrombin complexes, soluble fibrin, fibrinopeptide A and spontaneous proteolytic activity. The changes observed must be regarded as clinically insignificant. The platelet count is low enough to meet the requirements for platelet poor plasma. Using this blood component separation technique, one can reduce the CPD/additive solution 4-pack blood bag system to a less expensive 3-pack blood bag system.
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PMID:Blood component processing technique and plasma quality. 149 50

Thrombin activity during separation and cryoprecipitation of CPD-blood was monitored by fibrinopeptide A (FPA) determinations. After pooling and lyophilization of cryoprecipitate, the total amount of contaminating fibrin was estimated by N-terminal amino acid analyses. In addition, retention of fibrin in standard transfusion filters (170 micron) was examined by gamma counting of 125I des-AA fibrin monomer enriched cryoprecipitate prior and subsequent to filtration. Prior to pooling of cryoprecipitate, thrombin activity, as estimated by FPA levels, was most pronounced during collection of blood from the blood donors and during cryoprecipitation and thawing of the plasma bags. Comparison of these FPA concentrations to the total amount of fibrin in pooled, freeze dried cryoprecipitate, as estimated by N-terminal analyses, revealed a considerable generation of fibrin during the process of lyophilization. In freeze dried cryoprecipitate, 5.3 per cent (range 3.0-7.5 per cent) of the fibrinogen had been converted to fibrin, implying a fibrin content of 20.3-60.3 mg per bottle of 500 U factor VIII. The amount of fibrin in two bottles of a commercially available factor VIII concentrate, also containing 500 U of factor VIII, was 14.1 and 19.8 mg, respectively. Sham transfusions of 125I des-AA fibrin monomer enriched cryoprecipitate revealed that only 1.0 per cent (range 0-2.5 per cent) of the fibrin was retained in the standard transfusion filters. Thus, substantial amounts of fibrin may be transfused to patients upon treatment with freeze dried cryoprecipitate.
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PMID:Fibrin generation during production of freeze dried antihaemophilic cryoprecipitate. 308 72

In order to estimate the solubility of contaminating fibrin in CPD-blood, thrombin induced fibrin polymerzation in CPD-plasma was examined by light scattering and fibrinopeptide A (FPA) determinations. In addition, I125 fibrin monomer enriched CPD-blood was used to investigate fibrin monomer retention in blood bags and transfusion filters (170 microns) and fibrin distribution in blood components derived from CPD-blood. Initial fibrin polymerization in CPD-blood occurred after conversion of 15 per cent of the fibrinogen to fibrin, implying that substantial amounts of fibrin may be kept solubilized in CPD-blood bags. Only minor amounts of I125 fibrin monomers were retained in blood bags (2.4 per cent) and in transfusion filters (2.9 per cent) after sham transfusions. After separating I125-fibrin monomer enriched CPD-blood into its constituent components, the major part of fibrin (75.0 per cent) could be traced in the cryoprecipitate.
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PMID:Contaminating fibrin in CPD-blood: solubility in plasma and distribution in blood components following separation. 396 24

Loss of Factor VIII procoagulant activity (VIII:C) following blood collection is a major problem in providing sufficient amounts for therapeutic use and biochemical analyses. We have examined the effects of inhibition of plasma proteases and maintenance of physiological calcium ion on plasma VIII:C stability. The addition of protease inhibitors such as benzamidine, phenylmethylsulfonyl fluoride (PMSF), aprotinin, or soybean trypsin inhibitor (SBTI) to CPD plasma provided no significant protection against decay of VIII:C activity. Neither the rate of decay in the first 24 hours nor the final VIII:C activity observed after storage for 48-72 hours were significantly altered. On the other hand, addition of DFP or heparin to CPD plasma resulted in a marked improvement in VIII:C stability over 24 hours. This demonstrated that these two inhibitors are effective in preventing VIII:C degradation during storage. In addition to protease inhibition, the importance of maintaining physiological calcium ion was demonstrated by 100% stabilization of VIII:C in heparin plasma. Plasma obtained from CPD plus heparin blood could also be stabilized provided free calcium ion levels were restored to physiological concentrations. The inactivation of VIII:C in CPD plus heparin plasma was completely reversible up to 4 hours after collection. Studies on the recovery of activity after recalcification of CPD plus heparin plasma provided kinetic data which support a renaturation process of VIII:C rather than one due to enzymatic activation. The use of a thrombin-specific chromogenic substrate revealed that after recalcification and during the recovery of VIII:C activity, there was no significant thrombin activity. Although the data suggest that proteolytic degradation plays some part in VIII:C decay, only the maintenance of physiologic calcium ion levels under cover of an effective non-chelating anticoagulant and protease inhibitor allows preservation of VIII:C activity.
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PMID:Stability of VIII:C in plasma: the dependence on protease activity and calcium. 640 38

Blood collected into different anticoagulants was stored in small tubes at +4 degrees C for up to 26 h. Seven blood coagulation analyses were performed under standardized conditions. High yield and stability of factor VIII:C were found for ACD and CPD-adenine. No changes could be found in the other six parameters tested. Whole blood in blood bags could be stored for 2-4 h at +4 degrees C with maximal yield of F VIII:C, with blood stored overnight the recovery was 65%. In plasma F VIII:C was stable for at least 2 h at room temperature. F VIIIR:Ag and F VIIIR:RCoF were stable in both whole blood and plasma. No activation by plasmin as measured by B beta 15-42 could be demonstrated. The initial FPA levels, reflecting thrombin activation, in the donated blood differed individually and in some blood bags very high concentrations were found. The levels of FPA were not correlated to the time for collection of a bag of blood.
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PMID:Improvement of plasma quality as raw material for factor VIII:C concentrates. Storage of whole blood and plasma and interindividual plasma levels of fibrinopeptide A. 641 86

Macromolecular activators of phagocytosis from platelets (MAPP) were not released from platelets prepared from platelet concentrates (PC) obtained after anticoagulation with CPD solution and stored for more than 48 h. The MAPP activity which had escaped into the plasma disappeared after 72 h of storage. After incubation in dialyzed and Ca(2+)-supplemented plasma prepared from the same PC or from fresh peripheral blood, the platelets obtained after storage for 72 h released both MAPP (l-MAPP and s-MAPP) upon thrombin stimulation. Gel filtration studies of the plasma revealed that l-MAPP and s-MAPP were produced from the platelets incubated in plasma fractions corresponding to l-MAPP and s-MAPP, respectively. These observations suggest that platelets accumulate precursors of MAPP, pre-MAPP comprising pre-l-MAPP and pre-s-MAPP, in the presence of Ca2+, and produce and release MAPP when stimulated with thrombin.
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PMID:Recovery of macromolecular activators of phagocytosis from platelets (MAPP) producing and releasing function in stored human platelets. 886 24

A new platelet preservative, ViaCyte trade mark (balanced salt solution, physiological buffer, D-ribose, bovine serum albumin, D-glucose, sterile water) was tested against the presently used storage solution (citrate-phosphate-dextrose; CPD) and results revealed that ViaCyte demonstrated added protection for platelets during storage-induced activation. Following five days of storage at room temperature, only 12.2% of platelets stored in ViaCyte exhibited P-selectin expression at rest and, upon thrombin challenge, 64.2% were activated, an increase of 42%. In control platelets (platelets stored in CDP), 44.4% were activated due to storage-induced lesions, and thrombin stimulation resulted in 47.9% P-selectin expression, an increase of only 2.5%. ViaCyte storage maintained the resting state and preserved platelet function, making more platelets available for activation upon agonist challenge. This preliminary study demonstrated that the presently used standard preservative does not offer protection from storage-induced lesions. Partially dysfunctional platelets do not contribute significantly to hemostasis in vivo and play little role, if any, in clot retraction and wound healing processes.
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PMID:A new platelet preservative. 1248 93

Little in vitro research exists discussing platelet gel composition and the resulting strength and degradation characteristics using point-of-care technologies. There must be a quantifiable way of determining the structural integrity of the resulting formed platelet gel thrombus. The Thrombelastograph Hemostasis Analyzer (TEG) and Sonoclot measure the elasticity of a clot as it forms and subsequently degrades naturally. The objective of this study was to determine the application of TEG and Sonoclot technologies as point-of-care devices for technicians using platelet gel therapy. The collected bovine blood was anticoagulated with CPD and processed using a previously published plasma sequestration protocol, using normal saline as a wash solution. The resulting platelet-rich plasma was stored in a sequestration bag in a water bath to maintain the blood temperature at 37 degrees C. Sequestered bovine platelet-rich plasma was made into platelet gel using three different thrombin concentrations. A total of 30 experiments were performed on the platelet gel product using both the TEG and the Sonoclot. We discovered that 6 of the Sonoclot tests and 15 of the TEG tests were valid. None of the TEG clot signatures and nine of the Sonoclot signatures were discovered to be invalid. A chi2 test was performed on the resultant data. The value of the chi2 test was calculated to be 12.86, which translated into a p value of less than 0.001. Despite the vast use and growing popularity of platelet gels, a method in which to quantify platelet gels has yet to be reported. There remains a possibility that gels formed with different concentrations of components may prove useful in different areas of surgery or their uses may expand to a broader spectrum of medicine. However, technology to quantify platelet gels must first be standardized. On the basis of the data collected in this study, it was determined that the TEG and the Sonoclot are not equally capable of analyzing platelet gel clots. The TEG is a valid means for analysis, whereas the Sonoclot provided unreliable analysis based on a Chi-squared test.
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PMID:Quantifying platelet gel coagulation using Sonoclot and Thrombelastograph hemostasis analyzer. 1580 57

We have discovered a novel small-molecule (3-phosphinoylpropionic acid) inhibitor of activated thrombin activatable fibrinolysis inhibitor (TAFIa), BX 528, which had an IC (50) of 2 nM in an enzymatic assay and 50 nM in an in-vitro clot lysis assay, with 3,500- to 35,000-fold selectivity against other carboxypeptidases, such as CPN, CPZ and CPD, and 5- and 12-fold selectivity against CPE (CPH) and CPB, respectively. At 10 micro M, BX 528 had no significant activity (<50% inhibition or antagonism) in a panel of 137 enzymes and receptors. It had no effects on blood coagulation and platelet aggregation up to 300 and 10 micro M, respectively. The plasma half-life following intravenous administration was 0.85 hours in rats and 4.5 hours in dogs. No significant metabolism was detected in human, dog or rabbit hepatic microsomes, and no significant inhibition of cytochrome P450 3A4 and 2D6 up to 30 micro M. No cytotoxic or cell proliferative effects were found in three hepatic and renal cell lines up to 300 micro M and no mutagenic activity was seen in the Ames II screen. There were no significant hemodynamic effects in rats and dogs up to 100 and 30 mg/kg with peak plasma drug concentrations of approximately 1,000 and 300 micro M, respectively. In an in-vivo complement activation model in guinea pigs, BX 528 showed minimal inhibition of plasma CPN activity up to 60 mg/kg with peak plasma concentrations up to 250 micro M. Thus, these data demonstrate that BX 528 is a novel, potent, selective and safe TAFIa inhibitor.
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PMID:A novel inhibitor of activated thrombin-activatable fibrinolysis inhibitor (TAFIa) - part I: pharmacological characterization. 1720 Jul 70

The management of dental patients taking either antiplatelet medication, anticoagulant medication or both has been well established in the previous literature. Recently, new generations of drugs have emerged which are becoming increasingly common, including direct thrombin inhibitors, factor X inhibitors and a new class of oral thienopyridines. The implications of these drugs for the dental surgeon are not yet fully known. Awareness remains low and there is very little information available within the literature on safe use during surgery. This review paper aims to provide some guidance for dental practitioners performing invasive procedures. CPD/CLINICAL RELEVANCE: A new generation of anticoagulant and antiplatelet drugs have serious implications for patients undergoing surgery and their use is increasing.
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PMID:A New Generation of Antiplatelet, and Anticoagulant Medication and the Implications for the Dental Surgeon. 2685 9


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