Tranexamic acid is an antifibrinolytic drug that inhibits fibrinolysis by reversibly binding to plasminogen. It is effective at reducing surgical bleeding across many procedures like cardiac, orthopedic, and cranial surgery. It also reduces bleeding in gynecological conditions like heavy menstrual bleeding and postpartum hemorrhage. Tranexamic acid is generally well tolerated with side effects including headache, nausea, and diarrhea. It is given orally, intravenously, or topically depending on the condition being treated.

1. Tranexamic Acid
Dr. Rupendra K Bharti
MBBS MD

2. • trans-4-(aminomethyl)cyclohexanecarboxylic
acid

3. Introduction
• It is an antifibrinolytic agent.
• Haemostasis necessitates balance b/w
coagulation cascade that produces a fibrin clot
& fibrinolytic system that dissolves a fibrin
clot.
• Two commercially available antifibrinolytic
agents are Tranexamic acid & Epsilon-
Aminocaproic acid.

4. • It is an synthetic derivative of amino acid
lysine & acts by blocking the action of
plasmin.
• Aprotinin another antifibrinolytic agent acts
by blocking serine proteases has been
withdrawn because of higher mortality. BART
study

5. Pharmacodynamic properties
• It binds reversibly to plasminogen & prevents
its interaction with fibrin.
• Thereby inhibiting the dissolution of fibrin
clots.
• Plasminogen normally binds to lysine residue
on fibrin & is converted to plasmin in the
presence of tissue plasminogen activator
(t-PA).

6. • Plasmin then digests fibrin.
• Tranexamic acid reversibly binds to
plasminogen at the lysine binding site.
• Preventing the binding of plasmin(ogen) to
fibrin & the subsequent degradation of fibrin.
• Binding potency of it to plasminogen is 6 to 10
fold higher as compared to other
antifibrinolytic drugs.

7. • At blood concen. <10mg/mL it has no effect
on other blood parameters except thrombin
time, even at 1 to 10mg/mL concentration, It
prolongs the thrombin time.
• Topical adminstration of it in CNS has caused
seizures in rats.

8. Pharmacokinetic properties
• It is given parenterally (iv mostly), orally &
topically.
• Effective therapeutic plasma concen. is 5 to
10mg/mL or 10 to 15mg/mL for inhibiting
fibrinolysis.
• After i.m. & oral route max. Plasma concen. is
obtained after 0.5 & 2-3hrs hrs respectively.

9. • Bioavailability is 33% of oral drug.
• Not related with meals.
• 3% of the drug is bound to plasma proteins.
• Volume of distribution is 0.39L/kg & renal
clearance is 8.2 L/hr.
• It is metabolized to small extent.
• It crosses placenta, B-B barrier & eye.
• It is excreted in urine.

10. Potential drug Interactions
• Thrombotic risk is increased when given along
with hormonal contraceptives, factor IX, anti-
inhibitor coagulant, thrombin &
haemocoagulase.
• It may exacerbate the procoagulant effects of
tretinoin in pts with ac.PML.
• Along with tissue plasminogen activators it
may reduce efficacy of both drugs.

11. Therapeutic efficacy
• 1: Surgical procedures;
• A:Cardiac surgery; Cardio-Pulmonary Bypass
(CPB) pts.
• Use of the drug significantly reduces post
operative blood loss, reoperations for
bleeding & transfusion requirements.

12. • B: Orthopaedic surgery;
• It is more efficacious in significantly reducing
blood loss & transfusion requirements in total
knee & hip arthroplasty.
• C: Spinal or Cranial surgery;
• It significantly reduced transfusion
requirements & perioperative blood loss.
• It is also efficacious in hepatic, nasal &
prostatic surgery.

13. • 2: Gynaecology;
• A; Heavy menstrual bleeding;
• The drug given in a dose of 3.9-4.5gm/day for
upto 5 days per cycle was shown to reduce
menstrual blood loss from baseline levels.
• Only intrauterine delivery of levonorgesterol
reduced blood loss significantly more.

14. • B:Post Partum haemorrhage;
• High doseage of the drug infused over 7hrs
significantly reduced blood loss in PPH
following vaginal delivery.
• WOMAN study is currently underway to assess
the efficacy of drug compared with placebo in
15000 pts of PPH.
• Primary outcome will be incidence of death or
hysterectomy need.

15. • C:Uterine bleeding irregularities;
• The pts treated with 250mg qid of drug for 5
days stopped bleeding within 7days in greater
number then with placebos in pts using i.m.
DMPA or levonorgesterel.
• At 4 weeks the mean bleeding-free interval
was longer.

16. • 3: Gastrointestinal bleeding;
• The efficacy of i.v. or oral drug in upper GI
bleed due to erosion or ulcer.
• There was reduction in mortality & was
associated with lower proportions of pts
requiring surgery.

17. • 4: Subarachonoid haemorrhage;
• In pts with SAH rebleeding occurs in 20% of
survivors.
• Pts treated with the drug demonstrated a
significant reduction in incidence of
rebleeding.
• No beneficial effect on cerebral ischemia.

18. • 5: Trauma;
• Haemorrhage is a major cause of in-hospital
mortality in trauma pts. CRASH-2 study
• The drug significantly reduced all causes of
mortality at 4weeks and rate of death due to
bleeding.
• It did not reduce the proportion of pts
requiring blood product transfusion or its
amount.

19. • 6: Hereditary Angioneurotic oedema;
• Reduction in number & severity of attacks of
oedema with drug, although not all pts
responded to treatment.
• The action is thought to involve counteracting
the activation of the fibrinolytic system that is
associated with functional deficiency of C1-
esterase inhibitor.

20. • 8: Military use;
• I.M. Use in the form of autoinjector for non
compressible torso haemorrhage prior to
evacuation may save lives.
• Bleeding extremities that are amenable to pre
hospital treatment with tourniquet constitutes
1/3 of all potential survivable combat injuries.

21. • 7: Pts having haemophilia or on
anticoagulants;
• The drug given was effective in reducing
bleeding after dental extraction or dental
scaling.
• Less effect was seen in ocular surgery, sinus as
well conization of cervix.

22. Pharmacoeconomic Considerations
• Markhov model over a lifetime horizon was
used to estimate the cost effectiveness
(incremental cost per life-year gained) of drug
use in trauma pts with significant
haemorrhage.
• It would be cost effective with 48$ for
Tanzania, 66$ for India, 64$ for UK. 2008-
2009.

23. Tolerability
• Well tolerated drug.
• Adverse Effects are :
• Headache, nausea, vomiting, diarrhoea,
dyspepsia, dysmenorrhoea, dizziness, back
pain, numbness, phosphenes & anaemia.
• Arthralgia, musculoskeletal pain, muscle
cramps, migraine.
• Too rapid i.v. can cause hypotension.

24. • Long term use of the drug also causes above
mentioned side effects & also viral URTI,
diarrhoea & insomnia in heavy menstrual
bleeding.
• No increased risk of DVT, pulmonary
embolism, cerebral thrombosis, CRAO & CRVO
have been reported rarely.
• Not associated with increased incidence of MI,
myocardial ischaemia, stroke, mortality & DVT.

25. • Their have been increased incidence of post
operative convulsive seizures in pts with
cardiac surgery with CPB.
• Not associated with increased incidence of
anaphylaxis or allergy.

26. Dosage & adminstration
• 3-4gm/day in three divided doses for upto 4 or
5 days per cycle in menorrhagia.
• 0.5-1gm i.v. during surgery or 0.5-2.5gm by i.v.
infusion each time as required.
• It is Contraindicated in pts. receiving thrombin
due to increased risk of thrombotic
complications.
• Caution is required in pts. who are bedridden,
renal impairment, elderly.

27. Place Of Tranexamic acid in the
Treatment of Hyperfibrinolysis
• It is an attractive option in the prevention of
excess blood loss since it inhibits fibrinolysis
without apparantly affecting blood
coagulation parameters to any marked extent.
• It is rapidly absorbed and is a reversible
inhibitor with an elimination half life of 2-3 hrs
• It can be given parenterally, orally or topically.

28. • Pharmacoeconomic analysis of the drug use in
surgical pts in African countries suggest that it
would save lives in countries with blood
shortage.
• While in other it would save money by
reducing overall transfusion requirements and
also would cut down the risk of transmission
of blood borne and viral diseases.

29. • It is life saving, cost effective, used in variety
of conditions, well tolerated & associated with
very few severe or serious adverse effects.
• Thus Tranexamic acid is an effective and well
tolerated antifibrinolytic agent.

30. THANK YOU