The Impact Of Intravenous Tranexamic Acid On The Coagulation And Fibrinolysis Indices Of Rats

Objective: Melasma is a kind of acquired increased skin pigmentation, which is very common among people. People of Asian countries are easily to have this disease.A large number of Chinese women were plagued by this disease. Chloasma facial symmetry parts yellow or light brown flaky patches is very common. There are serious or even dark brown or pale black patches, patches of various sizes, varied shapes, edges more clearly or showing diffuse of its clinical features.Chloasma is also known as "hudieban", "liver spots", etc, which is a very common but it has clinically difficult to cure and has a strong characteristic of recurrent. Although there is no subjective symptoms in patients with melasma but a serious impact on the patient’s appearance and increase the psychological burden of the patients. Pathogenesis of melasma is unknown and complicated, now that oral contraceptives, pregnancy, endocrine disorders, gynecological diseases, use of poor quality cosmetics, genetic factors, ultraviolet radiation etc, are thought to be to its pathogenesis.Tranexamic acid is commonly used as a hemostatic clinical, tranexamic acid by partial performance competitively intervention fibrin, fibrin clumps formed by the cleavage of interference so as to achieve the purpose of treating patients with bleeding. Part of the structure of tranexamic acid and tyrosine is similar.The tyrosinase of the body in the process of the metabolism of the drug may be inhibited by tranexamic acid leading to decreased activity.Tyrosine in the body primarily through the final metabolites after numerous reaction is melanin, it can be seen from the above-described process of tranexamic acid to reduce melanin production. Tranexamic acid has been used clinically for nearly 40 years. In the last few years because of its whitening efficacy, it has gain widespread concern, Tranexamic acid in the cosmetic industry has been used more widely, but the secure use of antifibrinolytic drug tranexamic acid in the treatment of melasma and other pigmentation diseases has not been confirmed. Tranexamic acid itself is an anti-fibrinolytic drugs. When patients use anti-fibrinolytic drugs the risk of thrombosis will increase. Such patients′pigmentation disorder on which the use of tranexamic acid drugs′safety needs to be verified. In this study, clinical dose of tranexamic acid in the treatment of melasma converted into the corresponding dose in rats and injected into the tail vein of rats. Rats used tranexamic acid twice a week with this dose for 3 months. After the rats using tranexamic acid three monthes, all Wistar rats′fibrinolysis and coagulation parameters were measured, including: D-Di(D- dimer), APTT(activated partial thromboplastin time), ATⅢ(antithrombin Ⅲ), FIB(fibrinogen), TT(thrombin time) and PT(prothrombin time). Through these indicators to determine whether tranexamic acid can cause coagulation and fibrinolysis parameters in rats′blood system disorder which results in rats hypercoagulable states and thrombosis. So the results of this study can be used to evaluate the the clinical drug safety of tranexamic acid. This experiment for clinical use of tranexamic acid in the treatment of melasma and other diseases can be used to guide clinical practice.Methods: This study used 30 healthy female Wistar rats weighing 250 ± 20 g, which were bought from the Experimental Animal Center of Hebei Medical University. With a standard rat diet one week, rats had free access to water. One week later, the 30 rats were randomly divided into three groups.There were 10 rats every group. Three groups were Tranexamic acid low dose group(79mg / kg), tranexamic acid high dose group(158mg / kg), and the control group. Tranexamic acid concentrations were 2.5%, 5% in low and high dose group and the control group used the same volume of saline. Rats in each group were taken intravenously administered, administered twice a week, and once weekly statistical weight of rats, according to the weight of rats to adjust the dose. After three months of rat tail vein injection of tranexamic acid, gave the rats 10% chloral hydrate by intraperitoneal injection and the rats were anesthetized. The rats were fixed with medical tape in animal experimental stage, routine disinfection of skin preparation, after cutting the abdominal, got 2.7ml inferior vena cava blood into the vacuum blood collection(3.2% sodium citrate 1: 9 anticoagulant), upside down and mixed it. This study used Beckman ACLTOP7000 automatic coagulation analyzer to detect coagulation and fibrinolysis indicators of all rats: ATⅢ, APTT, FIB concentration, TT, D-Di, PT. After obtaining blood samples of rats, cut part of the kidney tissue, and liver tissue, using a 10% neutral buffered formalin fixed specimens. Kidney tissue and liver tissue samples fixed 24 hours after dealling with conventional embedded in paraffin. The study used light microscopy to contrast renal tissue and liver tissue structure of rats after paraffin sections routine HE staining.Results:1 The coagulation and fibrinolysis of the experimental group1.1 tranexamic acid low-dose group compared with the control group: ATⅢ, APTT, FIB, TT, D-Di, PT showed no significant difference(P> 0.05).1.2 tranexamic acid high-dose group compared with the control group: PT prolonged, the difference was significant(P <0.05); ATⅢ, APTT, FIB concentration, TT, D-Di indicators showed no significant difference(P> 0.05).1.3 tranexamic acid low dose group and high-dose tranexamic acid group compared: PT prolonged, the difference was significant(P <0.05); ATⅢ, APTT, FIB concentration, TT, D-Di showed no significant difference(P> 0.05)2 liver and kidney tissue pathology observedThis study used light microscopy to detect liver and kidney tissue of rats: tranexamic acid high and low dose group(158mg/kg、79mg/kg) compared with the control group, liver and kidney tissue(HE × 200) showed no obvious abnormalities. Conclusion: In this study, low-dose group tranexamic acid did not affect the coagulation and fibrinolysis of the healthy female rats and did not cause disturbances of the rats′coagulation and fibrinolysis. The rats did not appear hypercoagulable state. The tranexamic acid dose of high-dose group affected some clotting function of the rats. The study could not observe high and low doses of tranexamic acid causing liver and kidney tissue structure significant pathological changes.