The Institute for Safe Medication Practices (ISMP) recently warned about the dangers of accidentally giving topical thrombin intravascularly. Thrombin applied topically can help stop oozing blood and minor bleeding from capillaries and small veins. Some thrombin products are produced as a frozen solution. Others come as a powder to be reconstituted, sometimes packaged with a parenteral syringe to help prepare and withdraw the product. Because of its clotting action, topical thrombin should only be applied to the surface of bleeding tissue. It should never be injected systemically, because that can lead to extensive intravascular clotting and death. ISMP points out that topical thrombin has been mistaken for parenteral medication and administered intravascularly, despite labeling on the thrombin vials that warns against injecting the product. The confusion may arise because the vial-and-syringe packaging of some topical thrombin products makes them look like parenterals. ISMP describes several events where this kind of dangerous mix-up occurred. In one case, during cardiac surgery, a labeled syringe containing topical thrombin was placed in the warming pitcher along with heparinized saline syringes of similar volume. The topical thrombin was accidentally given intravenously instead of the heparin. The patient survived but required additional monitoring and an extended hospital stay. And in another example, a hospitalized patient was accidentally given topical thrombin 5,000 units intravenously. Soon afterward, the patient developed cardiopulmonary arrest and could not be resuscitated. ISMP lists a number of ways to reduce the risk of these kinds of accidents. Here are some of them: • Have the pharmacy prepare, label, and dispense the drug whenever possible, including doses used in the OR. • Never leave a topical thrombin vial or syringe at the patient's bedside because it may be confused as a parenteral product. • Add auxiliary warning labels to syringes containing topical thrombin. ISMP recommends repeating the warning that appears on the cartons and vials: "For topical use only - do not inject". • If appropriate for the type of surgery, consider using solutions of topical thrombin that can be used with an absorbable gelatin sponge. It may also be helpful to apply a dry form of topical thrombin on oozing surfaces. • Consider using spray kits, which are available for some topical thrombin products. The spray mechanism can help differentiate the topical thrombin from parenteral products. But never leave reconstituted topical thrombin in an unlabeled syringe before you attach the spray mechanism. FDA Patient Safety News: August 2008 For more information, please see our website: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/psn/transcript.cfm?show=78#4

Koagelet hældes i gazepose og lægges i kapsel. Kapslen lægges i spand med formalin.

Der tilsættes 3 dråber plasma og 2 dråber plasmin til bundfaldet

Blodigt plasma thrombin koagel

The Institute for Safe Medication Practices (ISMP) recently warned about the dangers of accidentally giving topical thrombin intravascularly. Thrombin applied topically can help stop oozing blood and minor bleeding from capillaries and small veins. Some thrombin products are produced as a frozen solution. Others come as a powder to be reconstituted, sometimes packaged with a parenteral syringe to help prepare and withdraw the product. Because of its clotting action, topical thrombin should only be applied to the surface of bleeding tissue. It should never be injected systemically, because that can lead to extensive intravascular clotting and death. ISMP points out that topical thrombin has been mistaken for parenteral medication and administered intravascularly, despite labeling on the thrombin vials that warns against injecting the product. The confusion may arise because the vial-and-syringe packaging of some topical thrombin products makes them look like parenterals. ISMP describes several events where this kind of dangerous mix-up occurred. In one case, during cardiac surgery, a labeled syringe containing topical thrombin was placed in the warming pitcher along with heparinized saline syringes of similar volume. The topical thrombin was accidentally given intravenously instead of the heparin. The patient survived but required additional monitoring and an extended hospital stay. And in another example, a hospitalized patient was accidentally given topical thrombin 5,000 units intravenously. Soon afterward, the patient developed cardiopulmonary arrest and could not be resuscitated. ISMP lists a number of ways to reduce the risk of these kinds of accidents. Here are some of them: • Have the pharmacy prepare, label, and dispense the drug whenever possible, including doses used in the OR. • Never leave a topical thrombin vial or syringe at the patient's bedside because it may be confused as a parenteral product. • Add auxiliary warning labels to syringes containing topical thrombin. ISMP recommends repeating the warning that appears on the cartons and vials: "For topical use only - do not inject". • If appropriate for the type of surgery, consider using solutions of topical thrombin that can be used with an absorbable gelatin sponge. It may also be helpful to apply a dry form of topical thrombin on oozing surfaces. • Consider using spray kits, which are available for some topical thrombin products. The spray mechanism can help differentiate the topical thrombin from parenteral products. But never leave reconstituted topical thrombin in an unlabeled syringe before you attach the spray mechanism.

The Dynamics of Thrombin and Platelet Activation in Thrombosis and Inflammation Hybrid was selected by The Medicines Company and their agency Lifebrands USA to create a 10-minute animation centered on the role of thrombin in coagulation and intracoronary thrombosis and inflammation. The sequence featured here is from Chapter 1, which examines our current understanding of hemostasis and how it has evolved from the older "coagulation cascade" to a dynamic cell-based model that is more accurate - both physiologically and clinically. The main challenge for this scene was to cleanly and simply depict mature plaque bursting from inside an artery wall, the generation of thrombin at the site of disrupted plaque, platelet aggregation and activation, and the creation of fibrin, which leads to the formation of a clot. The client had very specific ideas for the way they wanted thrombin to be depicted, since its role was key to their story. http://www.hybridmedicalanimation.com

The Institute for Safe Medication Practices (ISMP) recently warned about the dangers of accidentally giving topical thrombin intravascularly. Thrombin applied topically can help stop oozing blood and minor bleeding from capillaries and small veins. Some thrombin products are produced as a frozen solution.

THE BLOOD CLOTTING CASCADE 1. A cut occurs and Hageman Factor sticks to the surface of cells near the wound. Bound Hageman Factor reacts with another enzyme called HMK to produce Activate Hageman. 2. Pre Kallikrein reacts with Activated Hageman to produce Kallikrein. 3. Hageman Factor also reacts with HMK and Kallikrein to form Activated Hageman. 4. PTA reacts with Activated Hageman and HMK to produce Activated PTA. 5. Christmas Factor reacts with Activated PTA and Convertin to produce Activated Christmas Factor. 6. Antihemophilic Factor is activated by Thrombin to produce Activated Antihemophilic Factor. 7. Stuart Factor reacts with Activated Christmas Factor and Activated Antihemophilic Factor to produce Activated Stuart Factor. 8. Proconvertin is activated by Activated Hageman Factor to produce Convertin. 9. When a cut occurs, Tissue Factor (which is only found outside of cells) is brought in near the wound where it reacts with Convertin and Stuart Factor to produce Activated Stuart Factor. (Note that step 9 involves an extrinsic process whereas step 7 is an intrinsic process.) 10. Proaccelerin is activated by Thrombin to produce Accelerin. 11a. GLU-Prothrombin reacts with Prothrombin Enzyme and Vitamin K to produce GLA-Prothrombin. (Note that Prothrombin cannot be activated in the GLU form so it must be formed into the GLA form. In this process ten amino acids must be changed from glutamate to gama carboxy glutamate.) 11b. GLA-Prothrombin is them able to bind to Calcium. This allows GLA-Prothrombin to stick to surfaces of cells. Only intact modified Calcium-Prothrombin Complex can bind to the cell membrane and be cleaved by Activated Stuart and Accelerin to produce Thrombin. 12. Prothrombin-Ca (bound to cell surface) is activated by Activated Stuart to produce Thrombin. 13. Prothrombin also reacts with Activated Stuart and Accelerin to produce Thrombin. (Step 13 is much faster than step 12.) 14. Fibrinogen is activated by Thrombin to produce Fibrin. Threads of Fibrin are the final clot. However, it would be more effective if the Fibrin threads could form more cross links with each other. 15. FSF (Fibrin Stabilizing Factor) is activated by Thrombin to form Activated FSF. 16. When Fibrin reacts with Activated FSF many more cross ties are made with other Fibrin filaments to form a more effective clot. Well now, I am wondering to myself whether you are experiencing frustration or intrigue, weariness or excitement. There are a lot of details but let me ask you a leading question. Is this intricate system something that man developed or is it something that man has discovered? Blood clotting is not an invention of man. It is the invention of either God or "Mother Nature" (i.e., it invented itself). Regardless of how you believe the clotting cascade came to be, (Accident or Design) the fact remains that blood clotting is a clear example of irreducible complexity which clearly indicates design. Let us next consider that this irreducibly complex system of blood clotting must have a way to remove the clot once the wound has healed. How is this done? 17a. A blood protein, Plasminogen is activated by + - Pa to produce Plasmin. This acts like tiny chemical scissors which cuts up the Fibrin filaments of the clot. 17b. The rate at which the clot is broken up is controlled by yet another blood protein named Alpha 2 Antiplasm, which in turn inactivates Plasmin. One of the most important parts of this whole blood cloning machine is the ability it has to keep the clotting localized to the area of the wound and to stop the clotting cascade. What is the biggest killer of human beings? That's right, blood clots. Most heart attacks and strokes are caused by blood clots lodging. I believe the way your body shuts down the clotting cascade is as fascinating as the clotting process itself. 18. An%###!hrombin inactivates Activated Christmas, Activated Stuart and Thrombin. 19. Protein C is activated by Thrombin to produce Activated Protein C. 20. Activated Protein C inactivates Accelerin and Activated Antihemophilic. 21. Finally, Thrombomodulin which lines the inside of your blood vessels prevents Thrombin from activating Fibrinogen.

THE BLOOD CLOTTING CASCADE 1. A cut occurs and Hageman Factor sticks to the surface of cells near the wound. Bound Hageman Factor reacts with another enzyme called HMK to produce Activate Hageman. 2. Pre Kallikrein reacts with Activated Hageman to produce Kallikrein. 3. Hageman Factor also reacts with HMK and Kallikrein to form Activated Hageman. 4. PTA reacts with Activated Hageman and HMK to produce Activated PTA. 5. Christmas Factor reacts with Activated PTA and Convertin to produce Activated Christmas Factor. 6. Antihemophilic Factor is activated by Thrombin to produce Activated Antihemophilic Factor. 7. Stuart Factor reacts with Activated Christmas Factor and Activated Antihemophilic Factor to produce Activated Stuart Factor. 8. Proconvertin is activated by Activated Hageman Factor to produce Convertin. 9. When a cut occurs, Tissue Factor (which is only found outside of cells) is brought in near the wound where it reacts with Convertin and Stuart Factor to produce Activated Stuart Factor. (Note that step 9 involves an extrinsic process whereas step 7 is an intrinsic process.) 10. Proaccelerin is activated by Thrombin to produce Accelerin. 11a. GLU-Prothrombin reacts with Prothrombin Enzyme and Vitamin K to produce GLA-Prothrombin. (Note that Prothrombin cannot be activated in the GLU form so it must be formed into the GLA form. In this process ten amino acids must be changed from glutamate to gama carboxy glutamate.) 11b. GLA-Prothrombin is them able to bind to Calcium. This allows GLA-Prothrombin to stick to surfaces of cells. Only intact modified Calcium-Prothrombin Complex can bind to the cell membrane and be cleaved by Activated Stuart and Accelerin to produce Thrombin. 12. Prothrombin-Ca (bound to cell surface) is activated by Activated Stuart to produce Thrombin. 13. Prothrombin also reacts with Activated Stuart and Accelerin to produce Thrombin. (Step 13 is much faster than step 12.) 14. Fibrinogen is activated by Thrombin to produce Fibrin. Threads of Fibrin are the final clot. However, it would be more effective if the Fibrin threads could form more cross links with each other. 15. FSF (Fibrin Stabilizing Factor) is activated by Thrombin to form Activated FSF. 16. When Fibrin reacts with Activated FSF many more cross ties are made with other Fibrin filaments to form a more effective clot. Well now, I am wondering to myself whether you are experiencing frustration or intrigue, weariness or excitement. There are a lot of details but let me ask you a leading question. Is this intricate system something that man developed or is it something that man has discovered? Blood clotting is not an invention of man. It is the invention of either God or "Mother Nature" (i.e., it invented itself). Regardless of how you believe the clotting cascade came to be, (Accident or Design) the fact remains that blood clotting is a clear example of irreducible complexity which clearly indicates design. Let us next consider that this irreducibly complex system of blood clotting must have a way to remove the clot once the wound has healed. How is this done? 17a. A blood protein, Plasminogen is activated by + - Pa to produce Plasmin. This acts like tiny chemical scissors which cuts up the Fibrin filaments of the clot. 17b. The rate at which the clot is broken up is controlled by yet another blood protein named Alpha 2 Antiplasm, which in turn inactivates Plasmin. One of the most important parts of this whole blood cloning machine is the ability it has to keep the clotting localized to the area of the wound and to stop the clotting cascade. What is the biggest killer of human beings? That's right, blood clots. Most heart attacks and strokes are caused by blood clots lodging. I believe the way your body shuts down the clotting cascade is as fascinating as the clotting process itself. 18. An%###!hrombin inactivates Activated Christmas, Activated Stuart and Thrombin. 19. Protein C is activated by Thrombin to produce Activated Protein C. 20. Activated Protein C inactivates Accelerin and Activated Antihemophilic. 21. Finally, Thrombomodulin which lines the inside of your blood vessels prevents Thrombin from activating Fibrinogen.

FDA recently approved a new medical adhesive called Artiss to attach skin grafts onto burn patients. Artiss is made by Baxter Healthcare. Artiss has a lower thrombin concentration than other fibrin sealants, which gives surgeons more time to position the skin graft over a burn before the graft starts to adhere to the skin. In a multicenter clinical trial, Artiss was compared to surgical staples using two different wound sites on the same patient. The results showed that Artiss was comparable to staples in achieving complete wound closure. The most frequent adverse events, which were seen in both treatment groups, included bleeding and fluid collection in the tissues. Both of these events are common during skin grafting.

http://www.proteolysis.org A1AT: Alpha-1-antitrypsin. A1AT is inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Inhibits trypsin, chymotrypsin and plasminogen activator. The aberrant form inhibits insulin-induced NO synthesis in platelets, decreases coagulation time and has proteolytic activity against insulin and plasmin. Proteomics is the large-scale study of proteins, particularly their structures and functions. The term "proteomics" was coined to make an analogy with genomics, the study of the genes. An interesting use of proteomics is using specific protein biomarkers to diagnose disease. A number of techniques allow to test for proteins produced during a particular disease, which helps to diagnose the disease quickly. Techniques include western blot, immunohistochemical staining, enzyme linked immunosorbent assay (ELISA) or mass spectrometry. Proteins of interest to biological researchers are usually part of a very complex mixture of other proteins and molecules that co-exist in the biological medium. This presents two significant problems. First, the two ionization techniques used for large molecules only work well when the mixture contains roughly equal amounts of constituents, while in biological samples, different proteins tend to be present in widely differing amounts. If such a mixture is ionized using electrospray or MALDI, the more abundant species have a tendency to "drown" or suppress signals from less abundant ones. The second problem is that the mass spectrum from a complex mixture is very difficult to interpret because of the overwhelming number of mixture components. This is exacerbated by the fact that enzymatic digestion of a protein gives rise to a large number of peptide products.To contend with this problem, two methods are widely used to fractionate proteins, or their peptide products from an enzymatic digestion. The first method fractionates whole proteins and is called two-dimensional gel electrophoresis. The second method, high performance liquid chromatography is used to fractionate peptides after enzymatic digestion. In some situations, it may be necessary to combine both of these techniques. Design & production: Kosi Gramatikoff, PhD; client: Beckman Coulter/GenWayBio