Thrombin time test

Several new compounds have been reported that affect the formation of a fibrin clot. Aromatic diamidines, such as, 21, were reported to inhibit several proteolytic enzymes including thrombin.74 Concanavalin A (a globulin protein from the jack bean) inhibits fibrin formation by inhibiting the lipoprotein cofactor in the production of thrombin and thus decreasing the rate of thrombin production.75 Several antibiotics (penicillins and cephalosporins) have been reported to affect fibrin clot formation as well as platelet function. Cephalothin (22) has been shown to delay fibrin polymerization and thus prolong the activated partial thromboplastin time (APTT) and thrombin time tests.78... 

Accepting the above limitations of our knowledge of the true in vivo reaction sequence, a series of clot-endpoint tests has been used for many years to determine the hemostatic balance in any patient. The first, known as the thrombin time test, can be used to measure the concentration of fibrinogen (B15). The second assay, the activated partial thromboplastin time test (APTT), measures the components of the intrinsic pathway (M4). These include the serine proteases (Factors XII, XI, X, and II), the cofactors (Factors VIII and V) and again, fibrinogen. Most of the hereditary deficiencies... 

The thrombin time was determined similarly by incubation of 2 IU of crude bovine thrombin (10 IU/mL, Miles Laboratories) with the beads for 5 min at room temperature in an albumin-coated glass tube, followed by 0.2 mL of citrated human plasma. The time to clot was noted by tilting the test tube gently every few seconds. PBS, after incubation with heparin-PVA beads for 5-60 min, was analyzed for the presence of heparin using both toluidine blue and the thrombin time test (PBS in place of gel beads). 

Plasma thrombin time test 10 to 15 seconds Greater than 1 5 seconds... 

A number of laboratory tests are available to measure the phases of hemostasis described above. The tests include platelet count, bleeding time, activated partial thromboplastin time (aPTT or PTT), prothrombin time (PT), thrombin time (TT), concentration of fibrinogen, fibrin clot stabifity, and measurement of fibrin degradation products. The platelet count quantitates the number of platelets, and the bleeding time is an overall test of platelet function. aPTT is a measure of the intrinsic pathway and PT of the extrinsic pathway. PT is used to measure the effectiveness of oral anticoagulants such as warfarin, and aPTT is used to monitor heparin therapy. The reader is referred to a textbook of hematology for a discussion of these tests. 

Bivalirudin is a direct thrombin inhibitor that has found utility for reducing the rate of acute reocclusion in patients treated with PCI. It is preferential to heparin in PCI when HIT is present. This drug is a derivative of hirudin, which is a dedicated thrombin inhibitor with no other in vivo activities of significance. The molecule is semisynthetic the C-terminal of hirudin is linked by a polyglycine spacer to the tetrapeptide region of the N-terminal that reacts with the thrombin active site (22). It is monitored by the activated clotting time test. Its pharmacologic properties are shown in Table I. 

Thrombin Time (TT). To 0.1 ml of citrated plasma 0.1 ml of diethylbarbiturate-citrate buffer, pH 7.6 (Behring Werke, Marburg) is added and the mixture is incubated for 1 min at 37 °C. Then 0.1 ml of bovine test-thrombin (30 IU/ml, Behring Werke, Marburg) is added and the coagulometer is started. The time to clot formation is determined. The TT measures effects on fibrin formation. 

Each of these tests is also affected by the final common pathway, the endpoint of which is tested by the thrombin time. This tests the formation of a fibrin clot by the addition of exogenous thrombin and calcium. It is sensitive to the level of endogenous fibrinogen and to the presence of inhibitors of thrombin (heparin, PDFs). 

In human medicine, starches with smaller average molecular weights have less profound effects on hemostasis (Treib et al 1999). This may also be the case in horses, although only one dose has been tested. In healthy horses, a 8ml/kg dose of a 10% pentastarch solution resulted in a slight decrease in the thrombin time 12 h after administration, which returned to normal after 24 h. No effect on prothrombin time or partial thromboplastin time was documented (Meister et al 1992). In healthy horses, the initial phase half-life of pentastarch is 5.6 h and the terminal phase half-life is 122 h. However, the effects on PCV, plasma total solids and plasma viscosity appear to last only 12-24 h (Meister et al 1992). In equine clinical cases, the half-life may be as short as 2h (Hermann et al 1990). Pentastarch, although available in the USA, is only approved for leukapheresis in human medicine. 

Purified thrombin is added to plasma samples and the time for clotting is measured. This test, the thrombin time (TT), primarily reflects the concentration of fibrinogen. However, it also reflects the ability of the fibrinopeptides to be cleaved and the polymerization of fibrinogen. Separation of these three contributions requires a quantitative measurement of the concentration of fibrinogen that is not related to time for clot formation. The thrombin time can be prolonged if heparin is present in the patient s plasma sample because it will promote preferential inactivation of the added thrombin by antithrombin and reduce the amount of thrombin that can act on fibrinogen. 

Liberators of antithrombin and/or heparin cofactor. The latter proteins appear to be secreted by the liver, and result in hypocoagulability in thrombin titration tests and increase the sensitivity of the coagulation time and other tests to heparin. Papain releases antithrombin. ... 

Mechanism and effects Coumarins interfere with the normal posttranslational modification of clotting factors in the liver, a process that depends on vitamin K. The vitamin K-dependent factors include II (thrombin), VII, IX, and X. Because these factors have half-lives of 8-60 hours in the plasma, an anticoagulant effect is observed only after sufficient time has passed for the preformed normal factors to be eliminated. The action of warfarin can be reversed with vitamin K, but recovery requires the synthesis of new normal clotting factors and is therefore slow (6-24 hours). More rapid reversal can be achieved by transfusion with fresh or frozen plasma that contains normal clotting factors. The effect of warfarin is monitored by means of the prothrombin time (PT, or pro time ) test. 

At doses of 2 g daily of the compound lapachol, a prolonged thrombin time was observed, while other tests of clotting gave normal results (Block et al. 1974). 

At doses of 2 g daily of the compound lapachol, thrombin time was prolonged and required correction with vitamin K. Other tests of clotting gave normal results (Block et al. 1974). No toxicity was observed at doses up to 1.5 g daily. At doses over 1.5 g/day, nausea and vomiting were reported as adverse events (Block et al. 1974). 

There are many other coagulation tests described in the literature which investigators have used to evaluate the lipid materials. These include the whole blood clotting time in glass or silicone-treated tubes, the thrombin generation test, and the prothrombin consumption test using clotted blood or platelet-free native plasma. In general they are modifications or variations of the basic principles involved in the assays mentioned above. 

Lab test abnormalities In general, adjust the dosage (infusion rate) according to the aPTT ratio (patient aPTT at a given time over an aPTT reference value, usually the median of the laboratory normal range for aPTT see Administration and Dosage). Other thrombin-dependent coagulation assays are affected by lepirudin. 

Aliquots (0.45 ml) of the euglobulin solution are transferred to test tubes, and 0.05 ml thrombin (Test Thrombin, Behring Werke) (25 U/ml) are added. The tubes are transferred to a water bath at 37 °C. The time interval between the addition of thrombin and the complete lysis of the clots is measured. 

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