Tranexamic Acid In Gynaecology & Obstetrics

1. Tranexamic Acid In Gynaecology & Obstetrics

2. Blood – The essence of Life STOP BLOOD LOSS STOP BLOOD LOSS LIFE GOES ON

3. Women are always at Risk of Losing Blood FROM MENARCHE TO MENOPAUSE PPH DUB IN NORMALCY OR PREGNANCY CX DUB DUB APH IN HEALTH OR DISEASE HOW TO STOP IT?

4. Events in Hemostasis 1) Vasoconstriction 3) Blood clotting 2) Platelet plug formation 4) Fibrinolysis

5. Events in Haemostasis COAGULATION: Prothrombin Thrombin Fibrinogen Fibrin forms Clot

6. Events in Haemostasis FIBRINOLYSIS: Plasminogen Plasmin dissolves Clot

7. Events in Hemostasis COAGULATION AND FIBRINOLYSIS

8. Events in Hemostasis Presenting Tranexamic Acid COAGULATION AND FIBRINOLYSIS Tranexamic Acid TRANEXAMIC ACID

9. Tranexamic Acid • Synthetic amino acid, first introduced in Sweden in1969. • Chemically it is Tranexamic-stereo isomer of 1, 4, -aminomethylcyclohexane carboxylic acid. • Formula – C8H15NO2. • Molecular Wt.-157. • Prevents fibrinolysis and breakdown of clot. • It is a competitive inhibitor of plasminogen activation. • At very high concentration, it is also a non competitive inhibitor of Plasmin. • It is also a very weak inhibitor of thrombin.

10. Tranexamic Acid Mechanism of Action • Tranexamic acid inhibits conversion of plasminogen to plasmin, hence prevents breakdown of clot. • Increases collagen synthesis which preserves the fibrin matrix and increases the tensile strength of the clot • These actions of Tranexamic acid help in stabilizing the clot

11. Tranexamic Acid Pharmacokinetics • Absorption after oral administration is 30-50% • Food has no influence on absorption • Peak plasma concentration after 3 hours • Presystemic metabolism ~ nil. Bioavailability 30 – 50% • Plasma half-life ~ 1.4h • Is able to cross the blood-aqueous barrier in the eyes. • Can also cross the damaged blood-brain barrier • Rapidly diffuses into joint fluid and the synovial membrane. • Crosses placenta and also into breast milk. • Excretion unchanged 2 hours.

12. Tranexamic Acid Pharmacokinetics • Plasma protein binding is negligible • Undergoes negligible metabolism in the body. • Mainly eliminated unchanged in the urine. • Excretion occurs by glomerular filtration via the kidneys. • Passes through the placenta and its concentration in the cord blood may reach that of maternal blood.

13. Tranexamic Acid Clinical Pharmacology • The antifibrinolytic effect of Tranexamic acid is related mainly to a reversible complex formation with plasminogen, which prevents its activation to plasmin. • Tranexamic acid is 7 to 10 times more potent than Epsilon-aminocaproic acid [EACA]. • Tranexamic acid produces a considerably higher and more sustained antifbrinolytic activity in tissues than does EACA.

14. Tranexamic Acid Clinical Pharmacology • Adverse effects- are rare and mainly limited to • Nausea, Vomiting & Diarrhea, Allergy and occasionally an Orthostatic reaction. • There is a theoretical risk of an increased thrombotic tendency, like deep vein thrombosis, during prolonged treatment as with any fibrinolysis inhibitors. • Contraindications: - • Severe renal insufficiency • Active intravascular clotting • Thrombo embolic disease • Colourvison disorders

15. Tranexamic Acid Pregnancy And Lactation Pregnancy:Tranexamic acid crosses over to the foetus. It is not known whether a reduction of the normally high fibrinolytic activity in the foetus and neonate is harmful.  Lactation:Tranexamic acid is secreted in the mother's milk. This concentration is only a hundredth of the corresponding serum levels and the drug may be given during lactation without risk to the child.   CATEGORY B Ref: Collin Dollery. Tranexamic Acid. In 'Therapeutic Drugs.2nd edition.1999.pgT150-T153

16. Tranexamic Acid Uses in OBGYN To Prevent / reduce blood loss in: - • Dysfunctional Uterine Bleeding • IUD Menorrhagia. • Conization / Amputation of Cervix. • Post Partum Hemorrhage. • Ante Partum Hemorrhage. • During/After Abdominal/Vaginal Surgery Available in both Oral and Inj. (IV) forms

17. TRANEXAMIC ACID OTHER USES After surgery of the prostate (prostatectomy) After bladder surgery Heavy and prolonged menstrual periods (menorrhagia) Nose bleeds (epistaxis) Surgery of the cervix (conisation of the cervix) Bleeding of the cervix Bleeding caused by inflammation of the colon and bowel Bleeding inside the eye (traumatic hyphaema) Surgery or tooth removal (dental extraction) in patients who bleed more easily than normal (haemophiliacs) Angioneurotic oedema (an inherited disease involving swelling of the skin tissue) Leukaemia Liver disease

18. Tranexamic Acid E B M • Tranexamic acid is an effective treatment for reducing heavy menstrual blood loss (A) [RCOG, 1998]. • It reduces menstrual blood loss by 40-50% [Lethaby et al. 2001b]. • Being a plasminogen activator inhibitor, its use is rational as an increase in the level of plasminogen activators is found in the endometrium of women with heavy menstrual bleeding compared to those with normal menstrual loss.

19. Tranexamic Acid in APH & PPH • Bleeding from placental sites usually result from the structural weakness & defects in the placental blood vessels. • Tranexamic acid in doses of 1G (IV/Oral) TDS, by promoting stable coagulation at the site of bleeding, can be of help in- • Placenta Previa (2nd half of pregnancy). • AbruptioPlacentae. • Persistent Post Partum Hemorrhage

20. Tranexamic Acid Dosage 1-1.5 gm or 15-25mg /kg  2-4 times daily Adjust dose in renal impairment

21. TRANEXAMIC ACID WARNINGS Tranexamic acid should be used with caution in: the elderly, children aged under 15 years with heavy or prolonged menstrual periods (menorrhagia), kidney disease, patients with blood in their urine, history of uncontrollable bleeding, pregnancy and breastfeeding, patients with the blood clotting disorder disseminated intravascular coagulation (DIC) which is ongoing, increased fibrinolysis (clot breakdown) caused by DIC, long term treatment of the hereditary condition angioneurotic oedema, women with irregular menstrual periods. It should not be used in: patients with an allergy to tranexamic acid or to any other ingredients in the medicine or patients with an allergy to other anti-fibrinolytics, severe kidney problems (kidney failure), patients who have or have had a blood clot in their blood vessels (thrombosis) particularly in the leg or lung, patients in whom a blood clot has caused a stroke, severe bruising, patients with family members who have had a blood clot in their blood vessels, irregular periods for which the reason is unknown.

22. TRANEXAMIC ACID INTERACTIONS • Fibrinolytics such as streptokinase • Hormone replacement therapy (HRT) • Medicines containing oestrogen (such as the oral contraceptive pill) • Benzylpenicillin

23. Any other use????... Tranexamic Acid was originally used to prevent excessive bleeding in menstrual bleeding , haemophilia and surgery. Later on, by accident the skin whitening qualities of Tranexamic Acid were discovered. TA is also very stable to light, temperature, pH, and oxygen, and no special protections are needed to keep its whitening effect unlike many other agents. It is quickly becoming the skin lightener of choice for men and women who suffer from hyper pigmentation and skin discolorations from conditions like Melasma.

24. Blood – The essence of Life STOP BLOOD LOSS WITH TRANEXAMIC ACID