Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
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Reference intervals for coagulation parameters have been rarely determined in dogs for the STA Compact automated coagulation analyzer, so it is the aim of the current study to validate assays and establish reference ranges for its use in canine specimens. Coagulation parameters were assessed in 56 healthy dogs with a median age of 2 years and evenly distributed sex. The 95% reference intervals were as follows: 1-stage prothrombin time = 5.7-8.0 sec; activated partial thromboplastin time (APTT) = 10.0-14.3 sec; thrombin time (TT) = 11.9-18.3 sec; fibrinogen = 1.3-3.1 g/l; antithrombin (AT) = 107.9-128.0%; D-dimer = 0.023-0.65 microg/ml; anti-factor Xa = 0.04-0.26 IU/l; and activated protein C (APC) ratio = 2.0-3.0. Protein C and S activity was markedly below (<-20%) and factor VIII was 2- to 11-fold above the human calibration standard, so a standard curve had to be prepared from canine pooled plasma. Reference intervals for protein C, protein S, and factor VIII were 75.5-118.9%, 74.4-160.5%, and 70.9-136.4%, respectively, compared with a canine standard curve. Streptokinase-activated plasminogen assay was not suitable for dogs. There was no significant impact of sex on hemostasis test results. Factor VIII activity, AT, protein C, protein S, and APC ratio were overestimated in hemolytic plasma, whereas fibrinogen, TT, and APTT were underestimated. Lipemia resulted only in false-high D-dimers. This study provided useful reference intervals for dogs, but some human tests (i.e., protein C, protein S, factor VIII, and plasminogen) required modification.
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PMID:Reference intervals and method optimization for variables reflecting hypocoagulatory and hypercoagulatory states in dogs using the STA Compact automated analyzer. 1990 Dec 80

Streptokinase (SK) is a potent clot dissolver but lacks fibrin clot specificity as it activates human plasminogen (HPG) into human plasmin (HPN) throughout the system leading to increased risk of bleeding. Another major drawback associated with all thrombolytics, including tissue plasminogen activator, is the generation of transient thrombin and release of clot-bound thrombin that promotes reformation of clots. In order to obtain anti-thrombotic as well as clot-specificity properties in SK, cDNAs encoding the EGF 4,5,6 domains of human thrombomodulin were fused with that of streptokinase, either at its N- or C-termini, and expressed these in Pichia pastoris followed by purification and structural-functional characterization, including plasminogen activation, thrombin inhibition, and Protein C activation characteristics. Interestingly, the N-terminal EGF fusion construct (EGF-SK) showed plasmin-mediated plasminogen activation, whereas the C-terminal (SK-EGF) fusion construct exhibited 'spontaneous' plasminogen activation which is quite similar to SK i.e. direct activation of systemic HPG in absence of free HPN. Since HPN is normally absent in free circulation due to rapid serpin-based inactivation (such as alpha-2-antiplasmin and alpha-2-Macroglobin), but selectively present in clots, a plasmin-dependent mode of HPG activation is expected to lead to a desirable fibrin clot-specific response by the thrombolytic. Both the N- and C-terminal fusion constructs showed strong thrombin inhibition and Protein C activation properties as well, and significantly prevented re-occlusion in a specially designed assay. The EGF-SK construct exhibited fibrin clot dissolution properties with much-lowered levels of fibrinogenolysis, suggesting unmistakable promise in clot dissolver therapy with reduced hemorrhage and re-occlusion risks.
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PMID:Amino-Terminal Fusion of Epidermal Growth Factor 4,5,6 Domains of Human Thrombomodulin on Streptokinase Confers Anti-Reocclusion Characteristics along with Plasmin-Mediated Clot Specificity. 2697 70