Transcript Tranexamic Acid in Gynaecology & Obstetrics

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