Dental Research Journal / July 2014 / Vol 11 / Issue 4 423 Review Article A review on common chemical hemostatic agents in restorative dentistry Pardis Tarighi1, Maryam Khoroushi2 1Torabinejad Dental Research Center and Department of Operative Dentistry, 2Dental Materials Research Center and Department of Operative Case report A 72-year-old patient visited the Dental School of the University of Bonn to obtain a dental consultation The ADP binds to its own purinergic receptors, most notably P2Y1 and P2Y12. Two other important activities of platelets warrant mention. The interaction of these complexes in toto accelerates the conversion of prothrombin to thrombin by a factor of 2.4 × 106. Two main receptors are involved in adhesion: the glycoprotein (GP) Ia/IIa heterodimer, which binds to collagen directly but weakly, and the GP Ib/IX/V heterotrimer, which binds with high shear strength to connective tissue vWF associated with the collagen surface (Figure 31-1).1 The GP Ib/IX/V–vWF linkage is more of a “tethering” of the platelet to the substrate; later, the adhesion is firmed up by GP IIb/IIIa activation. Later, a fifth step becomes necessary: the controlled breakdown of the clot so that repair and remodeling can occur. Platelet activation is triggered, which leads to initial aggregation by the GP IIb/IIIa receptors binding the GP Ib/IX/V complex. Fibrinogen consists of a mirror image dimer in which each monomer is composed of three intertwined and disulfide bond–linked polypeptide chains. Microvascular video imaging studies show that thrombus formation initially is inefficient. Large or intermediate arteries and veins are generally not severed intentionally without prior ligation, but it is common during the extraction of teeth and other oral surgical procedures to sever small arteriolar, venous, and capillary vessels. Another protein, ATIII, is a serine protease inhibitor (“serpin”) found in the plasma. Fibrin sealant is commercially available in the United States. Extraction was a last and painful resort. An elegant mechanism exists that, instead of destroying thrombin, uses thrombin to catalyze an important set of anticoagulant proteins, the protein C/protein S system. This factor cross-links proteins between the γ-carbon of glutamine in one fibrin strand and the ε-amino group of lysine in the other. Perhaps the most remarkable effect of platelet activation is the procoagulant activity the platelets impart. He is the founder and director of Practical Clinical Courses, an international continuing-education organization initiated in 1981 for dental professionals. It is also an expensive medication; 1 mL of the material costs several hundred dollars. Patients with a platelet count of less than 50,000/mm3 are at risk for surgical or other trauma, but generally do not exhibit spontaneous hemorrhage until the count becomes less than 20,000/mm3. Activated factors VII, IX, and X have specific cofactors associated with them—tissue factor (TF) with VIIa (, The final phase of blood clotting consists of the thrombin-mediated proteolytic cleavage of fibrinogen to fibrin. Collagen accelerates the aggregation of platelets and may have limited effectiveness in patients with platelet disorders or hemophilia. When activating ligands bind to the platelet, the resultant increase in intracellular Ca, As the thrombin is generated, it activates other platelets by stimulating G protein–linked receptors. This reductase is the target of the warfarin-like anticoagulants and is discussed in greater detail later. Platelets have a high density of surface receptors that respond to these proteins, and they undergo an extremely rapid localization to the site of injury, beginning the formation of a thrombus. Both these materials cause delayed healing, particularly oxidized cellulose, which notably interferes with bone regeneration and epithelialization. Fibrin sealant is commercially available in the United States. The oral cavity poses many challenges for operative dentistry from the constraining effect of tongue and cheeks to other obstacles of visualization and isolation, such as sulcular fluid, saliva and gingival bleeding while preparing teeth for restorative procedures. Patients with acquired or genetic bleeding disorders usually have deficiencies in platelet number, platelet function, or faulty or missing clotting factors. The amino terminus Gla domain is crucial for the lipid binding of these proteases to their substrate membranes. If this treatment is inadequate, the clinician must localize the source of bleeding as originating either within the soft tissues or within the bony structures. Activated factors VII, IX, and X have specific cofactors associated with them—tissue factor (TF) with VIIa (a for activated), VIIIa with IXa, and Va with Xa. Microvascular video imaging studies show that thrombus formation initially is inefficient. Thrombocytopenia is frequently drug-induced or associated with other myelogenous diseases; hemophilia disorders are generally inherited. Other applications, such as controlling bleeding after surgery, are not looked on as favorably as in the past, when 20% ferric subsulfate (Monsel’s solution) and 8% zinc chloride were among the most popular agents used. Platelets bind quickly, but a significant percentage of them break free and float away. General and Dental Pharmacology and Therapeutics: General Pharmacology, Anti-septic’s, astringents, obtundents, mummifying agents, bleaching agents, styptics, disclosing agents, dentifrices, mouth washes, caries and fluorides, Pharmacotherapy of common oral conditions in dentistry. Aspirants are you searching for GPSC Dental Surgeon Exam Date and Exam Centre will be announced soon at online. They typically resorb in 4 to 6 weeks. Dental treatment such as extractions and tinctures were offered by barbers, barber-surgeons, the marketplace charlatan, the toothdrawer, and later the operator for the teeth. A short summary of this paper. https://medical-dictionary.thefreedictionary.com/styptics. The strongest agonist for platelet activation is binding of vWF to the GP Ib/IX/V heterotrimeric receptors.14 When one of these receptors is bound by its specific agonist, an intraplatelet protein cascade begins that ultimately causes activation of Ca++ transporters and movement of Ca++ from stores in the platelet’s dense tubular system to the general intracellular matrix.26 The intracellular increase in Ca++ causes several other changes. Major proteins released include fibrinogen, coagulation factors, vWF, fibronectin, high-molecular-weight kininogen, plasminogen, plasminogen activator inhibitor-1 (PAI-1), platelet-derived growth factor, additional GP IIb/IIIa, and thrombospondin.18. The prime requisite in managing an emergency is maintenance of proper Position (P), Airway (A), Breathing (B), Circulation (C), and Definitive treatment (D). For every glutamate residue carboxylated, one molecule of reduced vitamin K is converted to its epoxide form. 2. styptics, disclosing agents, dentifrices, mouth washes, caries and fluorides, Pharmacotherapy of common oral conditions in dentistry. Thrombin, a serine protease, accelerates the entire cascade by catalyzing cleavage of factor XI to factor XIa, stimulating platelets to activate by the transmembrane protease-activated receptor (PAR), and stimulates conversion of factor XIII to factor XIIIa (not shown). The rate of fibrin clot formation depends on the concentration of the thrombin; 4 IU/mL produces a clot in approximately 1 minute, whereas 500 IU/mL requires only a few seconds. Platelets bind quickly, but a significant percentage of them break free and float away. This reaction is normally slow but is accelerated 1000-fold in the presence of heparan sulfate, a proteoglycan synthesized on the surfaces by endothelial cells. Astringents are usually classified into three groups according to their mode of action: (1) those that decrease the blood supply by narrowing the small blood vessels (e.g., Antibodies may also be generated to the bovine thrombin or bovine factor V; the latter can cross-react with human factor V and lead to an acquired inhibition and bleeding. A Compend of Dental Pathology and Dental Medicine: Containing the Most by George Washington Warren (1903) "styptics are agents which arrest hemorrhage by local Another 20,000 to 40,000 units are stored in the α granules and are released onto the surface or within the local plasma milieu during degranulation. The formation of a patent clot requires four distinct yet interdependent steps: (1) vessel constriction; (2) platelet adhesion, activation, and aggregation; (3) cross-linking of fibrin by the coagulation cascade; and (4) limitation of the blood clot to the area of damage only. Initiation of coagulation after injury is a complex process involving an initial pathway of thrombin generation, which autocatalyzes a subsequent burst of additional thrombin generation sufficient to convert fibrinogen to fibrin (see, The amino terminus Gla domain is crucial for the lipid binding of these proteases to their substrate membranes. The terms astringents and styptics are interchangeable, referring to different concentrations of the same drugs. They may range in severity from mild to moderate to severe; this designation greatly affects what dental interventions can occur. The suitable preparations are primarily salts of several metals, particularly zinc, silver, iron, and aluminum. The true significance of platelets in hemostasis is most evident in the management of patients with thrombocytopenia. FIGURE 31-3 Blood coagulation cascade. Antithrombin III (ATIII) undergoes conformational change in the presence of heparin/heparan, which allows it to bind and sequester factors IIa (thrombin), IXa, Xa, and XIIa. In the case of aspirin or a thienopyridine such as clopidrogel prescribed deliberately to alter platelet function, the relative risks of hemorrhage versus thromboembolism must be considered in relation to the planned procedure. Dental pharmacology is the study of drugs, typically used in the dental field. Temporary hemostasis may be obtained with adrenergic vasoconstrictor agents, generally epinephrine. The cofactors bind the protease and its substrate in approximation to each other and modify the enzyme factor allosterically to have greater activity in the presence of substrate. Each of the clotting factors mentioned is a protease with activity directed at substrate arginyl residues. A chemical styptic works by causing formation of a blood clot by chemical action. Two main receptors are involved in adhesion: the glycoprotein (GP) Ia/IIa heterodimer, which binds to collagen directly but weakly, and the GP Ib/IX/V heterotrimer, which binds with high shear strength to connective tissue vWF associated with the collagen surface (, Platelet adhesion and aggregation. If used in an area where the clot is likely to break down too soon, or in patients with compromised hemostasis, a protease inhibitor such as aprotinin can be added to delay fibrinolysis. styptic: [ stip´tik ] 1. arresting hemorrhage by means of an astringent quality. A final inhibitor, tissue factor pathway inhibitor (TFPI), is first activated by factor Xa and then binds to the tissue factor (TF)/VIIa complex to interrupt conversion of additional factor X. aPC, Activated protein C. Strict control of the coagulation cascade is mediated by several proteins that act as natural anticoagulants, all of which rely on the first traces of thrombin from the nearby wound site to activate them. Activation of both of these receptors is required for maximal aggregation of the platelets to one another. The diffusing factor IXa binds tightly to the factor VIIIa cofactor, and this IXa/VIIIa complex efficiently activates additional factor X to Xa. Fibrin sealant, also sometimes referred to as fibrin glue, is one of the more promising hemostatic aids to appear in recent years.5 With this agent, the concept of the application of topical thrombin is taken one step further. Assistant professor of periodontia, School of Dentistry, Temple University, Philadelphia. The α granules contain factors V and IX; factor V is apparently complexed with multimerin, a carrier protein (see Box 31-1). As before, factor Xa then binds to adjacent factor Va, and this time a much larger burst of prothrombin conversion to thrombin occurs. Precautions, which may include the administration of clotting factors or hospitalization or both, are prudent in these cases. INTRODUCTION. The use of thrombin is not without problems. Major blood vessels are unlikely to be ... (styptics), tannic acid, tranexamic acid, and fibrin glue.2 Sequential literature reviews in 19983 and 20004 Before the process is described, a brief review of the crucial factors and cofactors and how they function is warranted. Currently available thrombin, especially the bovine products, may be relatively crude preparations that still contain plasmin, a fibrinolytic agent (discussed subsequently). Newly formed factor Xa rapidly binds to circulating factor V and activates it to Va. Cellulosic acid, similar to tannic acid, inactivates thrombin; the use of cellulose sponge in conjunction with this procoagulant is ineffective. IN DENTISTRY DENTAL PHARMACOLOGY DRUGS SPECIFICALLY USED 12/26/2018 PATKI 1 PART2 2. Arachidonic acid is a substrate for cyclooxygenase (COX), yielding the prostaglandin endoperoxides PGH2 and PGG2. Epinephrine solutions and dry cotton pellets impregnated with racemic epinephrine are available for topical application, but other methods to control bleeding are generally preferred. On activation the GP undergoes a conformational change, however, which imparts high affinity for its ligands. As a result, thrombus formation is much slower than would be the case if all the platelets that physically aggregate remained bound.1. Dental surgery, including simple and surgical tooth extractions, is unlike surgery performed on most other parts of the body. AHF, Antihemophilic factor; TF, tissue factor. Structure of matter and Principles of Adhesion, Important Physical properties applicable to Dental materials, Biological consideration in use of Dental materials, Gypsum and Gypsum products, Dental pharmacology 1. The collagen plug, similar to microfibrillar collagen, serves to accelerate the aggregation of platelets and form a physical barrier. The factor Xa/Va complex settles into the adjacent cellular membrane (using the hydrophobic Gla domain), where it acts on circulating prothrombin to generate a very small amount of thrombin. Exposed collagen at the site of injury stimulates initial weak platelet adhesion by the glycoprotein, Activation of platelets is a crucial step in forming a proper thrombus. cuvettes is often not achievable by styptics. The presence of these proteins, particularly vWF, stimulates a “catch and grab” response in the platelets, causing them to leave the laminar flow of the blood and adhere to the injured area. With proper evaluation and supportive therapy (, Procoagulant Preparations Used in the Management of Bleeding Disorders, Patients with a platelet count of less than 50,000/mm, 23: Drugs for Treating Orofacial Pain Syndromes, 55: Prescription Writing and Drug Regulations, 21: Nonopioid Analgesics, Nonsteroidal Anti-inflammatory Drugs, and Antirheumatic and Antigout Drugs, 19: Introduction to Antinociceptive Drugs, Pharmacology and Therapeutics for Dentistry 6e, Hemophilia B (Christmas disease), depressed with vitamin K deficiency, Generally no clinical symptoms but may have thromboses, rare, Fibrin-stabilizing factor, Laki-Lorand factor, fibrinase, Delayed bleeding, defective healing, rare. In conjunction with this procoagulant is ineffective procoagulant and signal transduction functions of small arteries and arterioles has several. With hematopoietic disease, and patients receiving therapies known to affect hemostasis an normal! 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Leonard Rosenthal, D.D.S the constriction wanes, and the layers. Often accompany dental procedures moistened, they become difficult to handle are concentrated forms of hemophilia are genetically disorders!, after it is maintained only for a short period ( 5 to 20 minutes ) • chloride-., resulting in filopod formation luminal patency its ligands Gla domain is crucial for generating a local response.
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