Tranexamic Acid In

Gynaecology & Obstetrics

Blood – The essence of Life

LIFE GOES ON

STOP

BLOOD LOSS

STOP

BLOOD LOSS

Women are always at Risk of Losing Blood

FROM MENARCHE TO MENOPAUSE

IN NORMALCY OR PREGNANCY

IN HEALTH OR DISEASE

DUB

APH

DUB

PPH

CX

DUB

HOW TO STOP IT?

Events in Hemostasis1) Vasoconstriction

2) Platelet plug formation3) Blood clotting

4) Fibrinolysis

Events in HaemostasisCOAGULATION:COAGULATION:

Prothrombin Thrombin

Fibrinogen Fibrin

Clotforms

Events in HaemostasisFIBRINOLYSIS:FIBRINOLYSIS:

Plasminogen Plasmin

dissolves

Clot

Events in Hemostasis

COAGULATION COAGULATION AND FIBRINOLYSISAND FIBRINOLYSIS

Events in Hemostasis

COAGULATION COAGULATION AND FIBRINOLYSISAND FIBRINOLYSIS

Presenting Tranexamic Acid

TRANEXAMIC ACID

Tranexamic Tranexamic AcidAcid

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.

Tranexamic Acid

• 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

Mechanism of Action

Tranexamic Acid

• 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.

Pharmacokinetics

Tranexamic Acid

• 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.

Pharmacokinetics

Tranexamic Acid

• 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.

Clinical Pharmacology

Tranexamic Acid

• 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 – Colour vison disorders

Clinical Pharmacology

Tranexamic Acid

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

Pregnancy And Lactation

Ref: Collin Dollery. Tranexamic Acid. In 'Therapeutic Drugs. 2nd edition. 1999.pgT150-T153

Tranexamic Acid

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 SurgeryAvailable in both Oral and Inj. (IV) forms

Uses in OBGYN

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) LeukaemiaLiver disease

Tranexamic Acid• 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.

E B ME B M

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).– Abruptio Placentae.– Persistent Post Partum Hemorrhage

Tranexamic Acid Dosage

1-1.5 gm or 15-25mg /kg 2-4 times daily

Adjust dose in renal impairment

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.

TRANEXAMIC ACID INTERACTIONS

Fibrinolytics such as streptokinase

Hormone replacement therapy (HRT)

Medicines containing oestrogen (such as the oral contraceptive pill)

Benzylpenicillin

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.

Any other use????...

Blood – The essence of Life

STOP BLOOD LOSS WITH

TRANEXAMIC ACID