TRANEXEMIC ACID. .pptx

TRANEXEMIC ACID

1. TRANEXAMIC ACID NAVEEN REDDY A JR-TM

2. CONTENTS INTRODUCTION HISTORY MECHANISM OF ACTION PHARMACOLOGICAL PROPERTIES INDICATIONS ADVERSE REACTIONS REFERENCES

3. CLOTTING CASCADE

4. FIBRINOLYSIS The Fibrin clot thus formed gets resorbed and degrades by the process of Fibrinolysis This involves PLASMINOGEN – its activators and inhibitors

5. ANTI-FIBRINOLYTICS Synthetic Lysine analogs that competitively block the lysine binding sites of Plasminogen. Leading to inhibition of activation of plasminogen to plasmin. These include : Ɛ -aminocaproic acid (EACA) Tranexamic Acid (TXA)

6. TRANEXAMIC ACID Synthetic antifibrinolytic 1-( aminomethyl )-cyclohexane-4-carboxylic acid [AMCA] Chemically related to EACA 7 to 10 times more potent than EACA

7. HISTORY OF TRANEXAMIC ACID In 2011, TXA was added to the WHO list of Essential Medicines

8. MECHANISM OF ACTION

9. Available in Intravenous, Oral and Topical formulations Half-life is about 2 hours Oral and IV bioavailability is around 33 to 34% TXA gets distributed well throughout the body It crosses BBB, synovial fluid, semen, Cord blood but not into saliva. Excreted unchanged by the Kidneys.

10. INDICATIONS TXA is indicated in various conditions: Obstetric and Gynaecological Acute Trauma Surgical Hemoptysis Epistaxis Disorders of Primary and Secondary Hemostasis Other Disorders

11. OBSTETRIC AND GYNAECOLOGICAL Abnormal uterine bleeding (AUB) Trials show that TXA use reduces menstrual blood loss by 54% A dose of 1300mg PO 3 times daily for 5 days of menstruation is FDA approved for HMB

12. HMB TRIAL

13. POST PARTUM HEMORRHAGE OBSTETRIC EMERGENCY Defined as blood loss of 500 to 1000ml within the first 24 hours following delivery. The WOMAN (World Maternal Antifibrinolytic Trial) was conducted between 2014 and 2017 among 20,000 woman with PPH. TXA regimen : 1g IV over 10min , if bleeding continues after 30 mins or recurs within 24h a 2 nd dose of 1g IV can be given

14. WOMAN TRIAL (2014 – 2017)

15. ACUTE TRAUMA Acute trauma is a common cause of mortality worldwide across all age groups. Prevention of active hemorrhage is major aim in trauma management TXA usage reduces perioperative bleeding and need for Blood transfusions (CRASH-2 Trial). TXA regimen :- 1g IV over 10min followed by 1g over next 8hours as continuous infusion.

16. CRASH 2 TRIAL 2010

17. The MATTERs Study Military Application of Tranexamic Acid in Trauma Emergency Resuscitation Retrospective Observational Study in the British army facility in Afghanistan, comparing TXA administration with no TXA in patients receiving at least 1 unit of Packed Cells. Results showed that TXA group had lower mortality rates than the No TXA group. It was concluded that the use of TXA with blood component-based resuscitation following combat injury results in improved measures of coagulopathy and survival.

18. CRASH 3 TRIAL (2019)

19. CARDIOTHORACIC SURGERIES (2017)

20. ORTHOPEDIC SURGERIES Regimen: 10mg/Kg IV loading dose before incision followed by 1mg/kg/hour maintenance infusion. Perioperative TXA in patients undergoing Total Hip Arthroplasty showed 30% reduction in Transfusion requirement Patients undergoing Total Knee Replacement showed decreased total blood loss

21. Orthopedic Surgeries An RCT conducted in patients who underwent Spinal Operations found a 49% reduction in blood loss with TXA and an 80% reduction in the need for Blood transfusion. There were no Thrombotic complications like Symptomatic DVT or Pulmonary Embolism found.

22. DENTAL PROCEDURES Excessive bleeding associated with Dental extraction is common in patients with bleeding disorders such as Hemophilias etc., A double-blind trial showed a significantly reduced blood loss and transfusion requirement, in patients with Hemophilia A or B undergoing dental extraction, when TXA was given as 1g oral TDS for five days.

23. HEMOPTYSIS TXA Regimen :- 500 – 1000mg nebulized in 5 to 10ml 0.9%NS Studies found that the use of Antifibrinolytics was safe and associated with a 50% reduction in hospitalization for Hemoptysis .

24. EPISTAXIS TXA REGIMEN :- TOPICAL: Cotton gauze soaked with injectable form of TXA (500mg in 5ml).

25. COAGULOPATHY AND THROMBOCYTOPENIA SECONDARY TO HEMATOLOGICAL MALIGNANCY Prophylaxis In AML-related bleeding:- 1g IV q6h when platelet count <20K or falling trend <50k, until platelets >20k on two counts. Prophylaxis in APML-re lated bleeding:- 2g IV q8h for 6 days.

26. Von Willebrand Disease TXA REGIMEN:- ORAL – 20mg/kg PO TDS Mouthwash – 5% 10ml QID prn – Swish and Spit TXA, in conjunction with hormonal contraceptives, have shown efficacy in reducing menstrual blood loss in women with vWD

27. OTHER DISORDERS HEREDITARY ANGIOEDEMA An inherited condition due to decreased C1 Inhibitor, presents with swelling of the skin and mucosal tissues of upper respiratory and GI tracts and may result in airway compromise. TXA has been proposed as a means of long-term reduction in the frequency and severity of HAE flares. TXA REGIMEN:- Long-Term prophylaxis – 0.5 to 1g PO TID. Short-Term Prophylaxis – 1g PO QID 48h before and after procedure.

28. MELASMA An acquired skin condition, where Hyperpigmentation is driven by sun exposure, usually occurring in women with exposure to high amounts of UV radiation. TXA Regimen:- 250mg PO BD or 4mg/ml injected intradermal to melasma lesions.

29. ADVERSE EFFECTS Headache (50%) Respiratory (25%): Nasal symptoms GI (20%): Nausea, vomiting, diarrhoea, abdominal pain Neuromuscular(10%): Musculoskeletal pain, arthralgia Fatigue (5%) Visual (<1%)– blurring of vision, impairment of color vision Seizures Hypersensitivity Reactions THROMBOSIS

30. TXA ASSOCIATED SEIZURE

31. TXA AND THROMBOSIS

32. TXA AND THROMBOSIS

33. SUMMARY Lysine Analogue Antifibrinolytic Agent Reduce Fibrinolysis by decreasing the binding of plasminogen and plasmin to fibrin. Well absorbed Orally and also available as IV, topical formulations. Half life is 1 to 2 hours Typical total daily dosage is 3 – 4 g, as 1g q6-8h. Dose should be reduced in Renal failure.

34. SUMMARY

35. SUMMARY

36. REFERENCES Bavli N, Sarode R, Coagulation factor concentrates and pharmacologic therapies for acquired bleeding disorders, Simon TL, Gehrie EA, McCullough J, Roback JD, Snyder EL, Rossi’s Principle of Transfusion Medicine, 6 th edition, UK, John wiley & sons,Ltd ., 2022, 447-448. Hess JR, Huebner BR, Mandell SP, Bulger EM, Transfusion therapy in the care of trauma and burn patients , Simon TL, Gehrie EA, McCullough J, Roback JD, Snyder EL, Rossi’s Principle of Transfusion Medicine, 6 th edition, UK, John wiley & sons,Ltd ., 2022, 479-480. Klein HG, Anstee DJ, Alternatives to allogeneic transfusion, Mollison’s Blood Transfusion in Clinical Medicine, 12 th edition, UK, John Wiley & sons, Ltd., 2014, 817-818.

37. REFERENCES Drugs Affecting Coagulation, Bleeding and Thrombosis, Tripathi KD, Essentials of Medical Pharmacology, 8 th edition, New Delhi, Jaypee Brothers Medical Publishers, 2019, 676. Weitz JI, Blood Coagulation and Anticoagulant, Fibrinolytic, and Antiplatelet Drugs, Brunton LL, Knollmann BC, Goodman & Gillman’s The pharmacological basis of therapeutics, 14 th edition, US, McGraw Hill LLC, 2023, 720-721.

38. REFERENCES Cai J, Ribkoff J, Olson S, Raghunathan V, Al‐ Samkari H, DeLoughery TG, Shatzel JJ. The many roles of tranexamic acid: an overview of the clinical indications for TXA in medical and surgical patients. European journal of haematology. 2020 Feb;104(2):79-87. Relke N, Chornenki NL, Sholzberg M. Tranexamic acid evidence and controversies: an illustrated review. Research and Practice in Thrombosis and Haemostasis . 2021 Jul;5(5):e12546. Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military application of tranexamic acid in trauma emergency resuscitation (MATTERs) study. Archives of surgery. 2012 Feb 20;147(2):113-9.