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Topical perioperative haemostatic agents
- John W Watt, Peter Walsh, Community Dentist (19 April 2005)
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New Concept in Coagulation Theory.
- Wilson Thomas (2 March 2005)
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John W Watt, Anaesthetist , Peter Walsh, Community Dentist
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For the sake of completeness, we would like to add to Madhy and Webster’s helpful review of haemostatic agents [1] by drawing readers’ attention to the efficacy of tranexamic acid as applied topically in cardiac surgery [2], in orthopaedics surgery [3] , and as a mouth wash for up to 5 days following dental extractions for patients on warfarin [4] or for haemophiliacs [5] . The topical use itself brings to mind our experience of the impressive and instantaneous effect of topical ethamsylate when applied to bleeding gingiva of special needs patients with periodontal inflammation undergoing restorative treatment at the gingival margin under general anaesthesia. This proved to be more effective than systemic administration, which was previously used by one of the authors when anaesthetising for a former ophthalmic surgeon undertaking trabeculectomy faced with congested sclerae. Some years ago, systemic ethamsylate was reported to reduce bleeding after transurethral resection of prostate [6], and after tonsillectomy [7], and it has also been used to prevent periventricular haemorrhage in low birthweight infants [8] . The mode of action has until recently been thought to reside in a reduction of prostacyclin synthetase activity [8,9] , but recent work also suggests that ethamsylate works at the very first step of haemostasis by enhancing membrane expression of the platelet and leukoctye adhesion molecule, P-selectin, particularily in the presence of damaged vessel [10]. P-selectin activates tissue factor (TF) [11] which converts Factor VII toVIIa, the initiation phase in coagulation. It would be a pity to loose sight of the therapeutic potential of ethamsylate as our understanding grows of the interwoven coagulation/ inflammation/fibrinolytic pathways. J.W.H.Watt P. M. Walsh Southport,England 1 Mahdy AM, Webster NR Perioperative systemic haemostatic agents. Brit J Anaesth 2004; 93: 842-858 2 De Bonis M, Cavalieri F, Allessandrini F et al. Topical use of tranexamic acid in coronary bypass operations: a double-blind, prospective, randomized, placebo-controlled study. J Thorac Cardiovasc Surg 2000; 119: 575-80 3 Krohn CD, Sorensen R, Lange JE, Riise R, Björnsen S, Brosstad F. Tranexamicacid given into the wound reduced postoperative blood loss by half in major orthopaedic surgery. Eur J Surg Suppl 2003; 588: 57-61 4 Carter G, Goss A Tranexamic acid mouthwash – a prospective randomized study of a 2-day regimen vs 5-day regimen to prevent postoperative bleeding in anticoagulated patients requiring dental extractions. Int J Oral Maxillofac Surg 2003; 32: 504-7 5 Waly NG Local antifibrinolytic treatment with tranexamic acid in haemophilic children undergoing dental extractions. Egypt Dent J 1995; 41: 961-8 6 Symes DM, Offen DN, Lyttle JA, Blandy JP. The effect of dicynene on blood loss during and after transurethral resection of the prostate. Brit J Urol 1975; 47: 203-7. 7 Arora YR, Manford ML Operative blood loss and the frequency of haemorrhage associated with adenotonsillectomy in children: a double-blind trial of ethamsylate Brit J Anaesth 1979; 51: 557-61 8 Benson JW, Drayton MR, Hayward C et al. Multicentre trial of ethamsylate for prevention of periventricular haemorrhage in very low birthweight infants. Lancet 1986; 2: 1297-300 9 Hernandez MR, Alvarez-Guerra M, Escolar G, Chiavaroli C, Hannaert P, Garay RP. The hemostatic agent ethamsylate promotes platetet/leukocyte aggregate formation in a model of vascular injury. Fundam Clin Pharmacol 2004; 18: 423-30 10 Shebuski RJ, Kilgore KS Role of inflammatory mediators in thrombogenesis. J Pharmcol Exp Ther 2002; 300: 729-35 11 Shebuski RJ Kilgore KS Role of inflammatory mediators in thrombogenesis. J Pharmacol Exp Ther 2002 300: 729-35 Conflict of Interest:None declared |
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Wilson Thomas, SpR Anaesthetics UHB, Queen Elizabeth hospital, Birmingham
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Dear Editor, Congratulations to Mahdy and Webster (1) on their thorough and informative review on coagulation and haemostatic agents. However, I would to draw your attention to ‘cell based coagulation’, a recent advance in the physiology of haemostasis. As the older classic coagulation cascade is a good model for explaining the prothrombin time(PT) and activated partial thromboplastin time (APTT), but is clearly inadequate to explain haemostasis in vivo and is inconsistent with clinical observations. Although there are two pathways the intrinsic and extrinsic pathways, deficiency in the intrinsic pathway is not compensated by the extrinsic pathway to activate Factor X in a person with haemophilia. The function of the intrinsic pathway in vitro is still unclear. Cell based coagulation is an updated model that incorporates the key role of cells (2). In this model, haemostasis takes place on two cell surfaces, the TF-bearing cell and the activated platelet. This model is organized into three distinct overlapping steps i.e. Initiation, amplification and propagation phases with the formation of a haemostatic plug (3,4). The major initiating event at the site of injury is the tissue factor of TF- bearing cell that activates FVII to FVIIa. Plasma inhibitors of each step of the coagulation are recognised to have a critical role in controlling and localizing the coagulation reaction. Wilson Thomas. Birmingham, UK Email: ptwilson29@hotmail.com References 1. Mahdy AM, Webster NR. Perioperative systemic haemostatic agents. Br J Anaesth 2004; 93: 842 – 58 2. Robert HR, et al. Molecular biology and biochemistry of the coagulation factors and pathways of hemostasis. In: Beutler E, et al., eds. Williams Hematology. 6th ed., NY: McGraw-Hill; 2001: 1409-34 3. Hoffman M, Monroe DM 3rd. A cell based model of Hemostasis. Thromb Haemost.2001 Jun;85: 958-65 4. Hoffman M. A cell-based model of coagulation and the role of factor VIIa. Blood Rev.2003 Sept;17 Suppl 1:S1-5. Conflict of Interest:None declared |
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