The Use of Tranexamic Acid for Hemorrhage Control - Essay Example

?The Use of Tranxamic Acid for Hemorrhage Control in a Pre-hospital Environment ID Number Word Count Module Leaning outcome 1 Normal Clotting Factors in the Blood and Normal Fibrinolysis Coagulation cascade or clotting factor is a series of enzymes-catalyzed reactions that transform soluble fibrinogen into an insoluble fibrin clot. It is triggered in vivo by a binding factor, VII, which is found in the plasma, to tissue factors, which is released from the endothelial cells in case of an injury. This enzyme speeds up the activation of factor IX, which team up with factor VIII, to catalyze the activation of factor X. Dawkins and Deakin (2004 P.93) note that Kallikrein catalyzes activation rate of factor XII, which in turn activates factor XI, then factor IX. They also reveal that factor X speeds up the activation of prothrombin (Factor II) to thrombin. The thrombin form plays two major roles: it breaks the arginine-glycine bonds found in fibrinogen (factor I) to form fragment that polymerizes to form fibrin. It also activates factor XIII whose role is to strengthen the fibrin to form a stable fibrin. Dawkins and Deakin (2004 P.93) note that it is this fibrin that forms the rigid layer of the clot. Physiology of Fibrinolysis Fibrinolysis refers to the process of breaking down of fibrin clot. It is generally catalyzed by serine protease plasmin found in the blood as the inactive proenzyme plasminogen. Dawkins and Deakin (2004 P.94) argue that plasminogen is activated by a plasminogen activator. Since the plasminogen activator also contains fibrin binding site, it also aids in the activation of plasminogen in the presence of fibrin. Tissue plasminogen activator (tPA) is the major plasminogen activator found in vivo, which is released from vascular endothelial cells when stimulated by urokinase and thrombin. The complex plasmin-activator binds to plasmin through lysine binding sites and breaks down fibrin to fibrin degradation products according to Dawkins and Deakin (2004 p.93). Learning outcome 2 How hyperfibrinolysis occurs in massive hemorrhage Blood clots are removed through a process known as fibrinolysis. Enhanced fibrinolytic activity in the blood is referred to as hyperfibrinolysis. Hyperfibrinolysis leads to increased bleeding, which can lead to trauma and death in patients. Lack of alfa-2-antiplasmin in the body is the main cause of hyperfibrinolysis. In addition, hyperfibrinolysis can also be a result of lack of plasminogen activator inhibitor type 1. Severe trauma cases have witnessed the ineffective outcome of hyperfibrinolysis (Akahashi, Tanaka, Minowa, 1996: 61). In trauma patients, bleeding is as a result of the production of fibrinogen degradation products. These fibrinogen degradation products normally affect the regular fibrin polymerization and interfere with the production of platelets. Hyperfibrinolysis leads to the production of plasmin. Plasmin has the ability to proteolytically activate or deactivate several plasmatic and cellular proteins which are important in the process of homeostasis. The degradation of fibrinogen is the main cause of excessive bleeding in trauma patients and other injury victims (Akahashi, Tanaka, Minowa, 1996: 61). Tranexamic acid is the best treatment for hyperfibrinolysis. Several deaths of both citizens and military officers take place in the pre-hospital setting. Tourniquet placement was the treatment method used in the pre-hospital setting before the introduction of Tranexamic acid (Sauaia, Moore, Moore, Moser, Brennan, Read, Pons, 1995: 188). Tourniquet placement has proved to be ineffective due to the number of soldiers and other individual who succumb to survivable injuries. The use of Tourniquet has not been able to control injuries leading to torso exsanguinations. In addition, Tourniquet placement has not also been able to control deaths that result from functional haemorrhage (Spahn & Rossaint, 2005: 130). Intravenous Tranexamic acid has been proved to lower the mortality rate in the pre-hospital setting. The findings of the effectiveness were published in the CRASH-2 study. Tranexamic acid is capable of helping patients overcome the bleeding problems without increasing the risk of thromboembolic complications. CRASH-2 study further found out that the administration of Tranexamic acid was successful when it was administered to patients immediately after injury. Several deaths were able to be avoided after Tranexamic acid was administered within 1 hour of injury. However, when tranexamic acid is administered after 3 hours of injury, the patient is likely to succumb to the injury (CRASH-2 Trial Collaborators, 2010: 25). Effects of hyperfibrinolysis to haemorrhaging patient Hyperfibrinolysis leads to blood loss and excessive bleeding in haemorrhaging patients. Survival of trauma patients is limited due to effects of hyperfibrinolysis because of coagulopathy that is as a result of excessive bleeding is shown to be the main risk factor in the death of patients. Trauma patients undergo complex coagulopathy such as the activation of tissue factor, and the use of coagulation factors and platelets. Furthermore, trauma patients suffer from haemodilution, hypothermia and metabolic acidosis. Physicians should be able to detect and administer the treatment of coagulopathy since it prevents excessive bleeding in trauma patients (Goerlinger, 2006: 65). How clotting on a positive feedback system can be detrimental to clots Positive feedback system refers to the process whereby once a blood clot begins to form, more clotting are necessitated. This is because plates are never complete cells, they promote more clotting. Thrombin also has direct influence on the clotting process because it leads to the formation of prothrombin that leads to the production of more thrombin (Goerlinger, 2006: 64). Learning outcome 3 Ethical issues are based on the consent provided by victims. Consent refers to the ability of the patient to decide where and who to administer the treatment. Issues of bleeding require immediate actions. The consent of the patient may be unnecessary since the physicians are more concerned with preventing the eminent loss of life due to excessive bleeding. Delayed consent in victims suffering from trauma related bleeding can lead to increased rate of deaths in pre-hospital care (Roberts, Prieto-Merino , Shakur , Chalmers , Nicholl , 2011: 1072). Patients should understand that Tranexamic acid should be administered within 1 hour of injury. Delayed consent is similar to a situation whereby the tranexamic acid is administered within 2 hours of injury. Consent delay only increases the probability of the patient dying from excessive bleeding. On the part of the physicians, it is unethical not to administer tranexamic acid at the recommended time of 1 hour of injury. Delay in the administering of the treatment that can lead to loss of life is unethical and leads to serious legal issues. Ethical issues on the administration of Tranexamic acid relies on the consent procedures (Roberts, Prieto-Merino , Shakur , Chalmers , Nicholl , 2011: 1071). Patients are an important part of the medical team during the treatment process. They have the responsibility to follow instructions that may be given by the physician. Patients are also required to follow the instructions of the physician by cooperating as much as possible with the medical team. In addition, patients should also avail all necessary information to the physician so as to be properly diagnosed. There are serious implications when patients decide to give misleading information concerning their health status. The physician may administer an incorrect diagnosis; in such a situation, the physician is not liable to any consequences. Further, the patient has the responsibility to follow the physician’s orders for the treatment and to pay fees that are reasonable to the type of service provided. Professionalism on the part of physicians dictates that the welfare of the patient is more important than any other factor. Consent of the patient is secondary when the physician has discovered that the life of the patient is at danger. Learning outcome 4 How TXA Can Assist In Stopping Hyperfibrinolysis a) Pharmacokinetics and Pharmacodynamics of TXA. Cap et al. . (2011) define Tranexamic acid (TXA) as an antifibrinolytic acid that inhibits both plasmin activity and plasminogen activation thereby preventing clot breakdown instead of promoting new clot formation. They note that TXA has been in use around the world since the 1960’s to control bleeding. For instance, a recent randomized trial of on more that 20,000 trauma patients confirms how effective TXA is, with regard to the promotion of hemostasis (Cap et al. (2011). TXA (trans-4-(aminomethy) cyclohexanecarboxylic acid) is a small molecule (MW, 157.2), an inhibitor of plasmin activity and plasmonogen activation. It inhabits the lysine-binding sites within plasminogen thereby preventing its binding to lysine remains on fibrin (Cap et al. . 2011). This helps reduce plasminogen activation to plasmin. On the same note, the obstruction of lysine-binding sites on circulating plasmin prevents binding to fibrin and in the process preventing blood clot. Cap et al. . (2011) reveals that TXA is 10 times more effective in vitro than, an older drug of the same category, aminocaproic acid. During therapies, TXA is said not to affect platelet aggregation or count or coagulation parameters. TXA, also known as cyklokapron, is provided in ampoules of 1,000 (mg) in 10 mL water for injection. Typically, the dosage is 10 mg/kg body weight intravenously 3 to 3 times on a daily basis 2 to 8 days. Cap et al. . (2011) notes that TXA is infused at a maximum rate of 1mL per minute. TXA is also available in the form of tablets known as Lysteda. The dosage is given orally as two 650 mg tablets three times daily for a total daily dose of 3,900 mg for a duration not exceeding 5 days. The drug should to be stored at room temperature. b) Biological Rationale for Using TXA in Stopping Hyperfibrinolysis Culligan and Tien (2011 p. 501) note that hemorrhage and coagulopathy remain the major causes of early in-hospital deaths among trauma patients. In respect of stem bleeding, the body reacts by activating its clotting cascade (platelets) to form fibrin clot at the point of vascular injury. Fibrinolysis immediately occurs as a normal response to keep vascular potency, as bleeding gets controlled. Fibrinolysis is interceded by plasmin, a serine protease that dissolves fibrin blood clots. Culligan and Tien (2011 p.501) argue that, under normal circumstances, fibrinolysis may be blown up leading to more bleeding. Drugs such as tranexamic acid are capable of preventing excessive clot breakdown thereby reducing blood loss post injury. c) Why TXA Can Be Detrimental If Administered beyond 3hours Post Injury. Research indicates that TXA should be administered as early as possible to bleeding trauma patients according to Doctor’s Guide (2011). The Guide reveals that a CRASH-2 Trial published by The Lancet in June 2010 found that the administration of TXA to bleeding adult trauma patients reduced mortality rate by close to 10%. Because of this trial, TXA has been used in the treatment of trauma around the world. The study further established that early treatment, especially within one hour, of injury reduced the risk of mortality caused by bleeding by more than 30 percent as compared to placebo. The relative risk (RR) reduction was found to be so significant with regard to penetrating trauma and revealed a trend toward the reduction in blunt trauma (RR, 0.89; 95% confidence interval, 0.77-1.04). Moreover, TXA treatments were found to be more effective when administered in a span of between 1 and 3 hours, in which case it reduced the risk of bleeding to death by more than 20 percent compared to placebo. The research also revealed that there was neither benefit nor possible harm where treatments were delayed for more than 3 and 4 hours (Doctor’s Guide 2011). This reveals how time is an important factor in administering TXA to patients. In patients suffering from severe bleeding be it from accidents or violence, faster treatment with TXA is critical. Dr. Robert asserts that since the discovery of the drug, militaries such as the British military use the therapy in the first hour to treat their wounded defense forces in Afghanistan and to make sure that civilian trauma patients reap positive benefits from the vital early treatment. The same therapy is also being used by US military soldiers in operation in Iraq and Afghanistan (Tan 2012). d) How Toxic TXA Can Be When Incorrectly Administered Research shows that improper and too much use of TXA is very risky to patients who use drugs. Cap et al. (2011 P.s12) notes that the use of TXA in conjunction with procoagulant drugs, which are occasionally administered to trauma patients, such as the activated prothrombin complex concentrate or the recombinant factor VIIa (Novoseven), could cause thrombotic complications. A study reveals that only 17 patients enrolled in the hemorrhage trial received Novoseven (4 in the placebo group and 3 in the TXA group. Cap et al. (2011 p.S13) also argue that there is a possibility that a subgroup of patients who are not recognized in CRASH-2 trial, among them being those with TBI, may also be at high risk of thrombotic or other forms of complications if treated with TXA drug. It is for this reason that the proponents of CRASH-2 are planning a specific analysis of the outcomes in patients suffering from TBI that may help in addressing these concerns according to Gruen and Mitra (2011 p.1-2). Cap et al. (2011 p.s13) reveal that there is the possibility that patients treated with TXA may not obtain any benefit and that health care system may likely be overburdened by the unnecessary costs. They note that the results were a bit promising as there was no increase in occlusive events during the study, despite notable increase in baseline risks associated with such complications within the entire population. Research, for example, reveals that non-bleeding critically ill trauma patients are mostly hypercoagulable and are at high risk of suffering from venous thromboembolism (Cap et al. . 2011 P.s13). Research also shows that, despite the likely huge number of such patients in CRASH-2, no difference could be established in the rate of thromboembolism. Culligan and Tien (2011 p.501) note that, a part from the risk of thromboembolic events that TXA has on patients, it is also associated with acute gastrointestinal disturbances leading to frequent vomiting, nausea and even diarrhea. Patients who use this drug for long are also likely to suffer from visual problems (changes in color perception and blurry vision). Cap et al. . (2011) argue that TXA should be used with a lot of caution especially in the setting of urinary track bleeding because ureteral obstruction caused by clot has been reported. Learning outcome 5 Tranexamic acid should be administered to patients at the scene of the disaster and soldiers at the battlefield immediately after the injury. CRASH-2 study shows that Tranexamic acid can be administered through intravenous, oral, and intramuscular administration. Practical pre-hospital application requires the use of intramuscular route of application. This is because peak plasma levels can be realized before the patient is taken to the hospital (CRASH-2 Trial Collaborators, 2010: 25). Intramuscular auto injector should be used to administer Tranexamic acid in the battlefield and at the various scenes of disaster. Pre-hospital medics have found the use of the tranexamic acid auto injector to be important in the care treatment of injury victims. In addition, the auto injector helps the medics to treat no compressible torso haemorrhage, while at the same time looking at the best way to speed the evacuation of the victim to the hospital. A tranexamic acid auto injector is capable of controlling the mortality rate in disasters and at the battle field (Kauvar & Wade, 2005: 5). Ethics of carrying/not carrying Tranexamic acid The life of the patient should be of more value that the price and the efficacy of tranexamic acid. Patients should not be denied treatment because they cannot afford to pay for the services of the physician while administering tranexamic acid. The price of the drug is relatively high, most people may not be able to afford the price but in cases of emergency, the physician has no choice but to help the trauma patient in overcoming the bleeding situation. References Akahashi Y, Tanaka T, Minowa H (1996). Hereditary partial deficiency of plasminogen activator inhibitor 1 associated with a lifelong bleeding tendency. Int J Hematol 1996;64:61-8 Bramsen, T. (1976). Traumatic hyphaema treated with the antifibrionic drug tranexamic acid. Acta Ophthalmol (Copenh). April (2p): 205-256 Cap, A. P., Baer, D. G., Orman, J.A, Aden, J., Ryan, K., and Blackbourne, L. H. (2011). Tranexamic acid for trauma patients: A critical review of the literature: The journal of Trauma, injury, infection, and critical care. Volume 71, Number 1, July supplement. CRASH-2 Trial Collaborators (2010). Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet 2010; 376: 23-32. Culligan, W. B., & Tien, H. C. (2011). Tranexamic acid autoinjection for prehospital care of noncomrehensible hemorrhage: The journal of Trauma, injury, infection, and critical care. Volume 71, Number 1, July supplement 1. Dawkins, S., & Deakin, C. (2004). Anti-fibrinolytic therapy: A forgotten option for minimizing blood loss and transfusion requirements? Scand J Trauma Resusc Emerg Med. Pp.12-92. Doctors Guide (2011). Tranxamic acid should be given as early as possible to bleeding trauma patients. Retrieved from: http://www.pslgroup.com/dg/25e09a.htm Goerlinger K (2006). Coagulation management during liver transplantation. Haemostaseologie 2006;26 (3 Suppl 1):S64-76. Gruen, R. L., & Mitra, B. (2011). Tranexamic acid for trauma. The National Trauma ResearchInstitute. 24 March, Do/:10.1016/S0140-6736(11)60396-6. Pp.1-2. Kauvar DS, Wade CE (2005): The epidemiology and modern management of traumatic hemorrhage: US and international perspectives. Crit Care 2005, 9(Suppl 5):S1-9. Osler, W. (2011). Tranexamic acid (TXA) in tactical combat casualty care guideline revision recommendation committee on tactical casualty care. 11 August. Roberts I, Prieto-Merino D, Shakur H, Chalmers I, Nicholl J (2011). Effect of consent rituals on mortality in emergency care research. Lancet 2011; 377: 1071-1072. Sauaia A, Moore FA, Moore EE, Moser KS, Brennan R, Read RA, Pons PT (1995): Epidemiology of trauma deaths: a reassessment. J Trauma 1995, 38:185-193 Spahn DR, Rossaint R (2005): Coagulopathy and blood component transfusion in trauma. Br J Anaesth 2005, 95:130-139. Tan, D. K. (2012). Pre-hospital trauma and critical care: Bringing research to the field. 18th Annual Trends in Trauma Conference. May 10. Read More