Tranexamic Acid In Gynaecology

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Tranexamic Acid In Gynaecology Obstetrics
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Blood The essence of Life
STOP BLOOD LOSS
STOP BLOOD LOSS
LIFE GOES ON
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Women are always at Risk of Losing Blood
FROM MENARCHE TO MENOPAUSE
DUB
PPH
IN NORMALCY OR PREGNANCY
CX
DUB
DUB
APH
IN HEALTH OR DISEASE
HOW TO STOP IT?
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Events in Hemostasis
1) Vasoconstriction
3) Blood clotting
2) Platelet plug formation
4) Fibrinolysis
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Events in Haemostasis
COAGULATION
Prothrombin
Thrombin
Fibrinogen
Fibrin
forms
Clot
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Events in Haemostasis
FIBRINOLYSIS
Plasminogen
Plasmin
dissolves
Clot
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Events in Hemostasis
COAGULATION AND FIBRINOLYSIS
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Events in Hemostasis
Presenting Tranexamic Acid
COAGULATION AND FIBRINOLYSIS
TRANEXAMIC ACID
Tranexamic Acid
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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.

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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

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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.

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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.

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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.

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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
• Colour vison disorders

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Tranexamic Acid
Pregnancy And Lactation

• PregnancyTranexamic 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. 
• LactationTranexamic 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
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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

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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
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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.

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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

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Tranexamic Acid Dosage
1-1.5 gm or 15-25mg /kg ? 2-4 times daily Adjust
dose in renal impairment
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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.
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TRANEXAMIC ACID INTERACTIONS

• Fibrinolytics such as streptokinase
• Hormone replacement therapy (HRT)
• Medicines containing oestrogen (such as the oral
  contraceptive pill)
• Benzylpenicillin

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