Tranexamic Acid for the Prevention of Obstetrical Hemorrhage After Cesarean

Obstetrical hemorrhage is a common cause of maternal morbidity and mortality worldwide. The
frequency and severity of hemorrhage is significantly higher after cesarean delivery than
vaginal delivery. Recent evidence has emerged about the importance of the fibrinolytic
pathway in the pathophysiology of hemorrhage in different clinical scenarios including
trauma-associated bleeding, cardiovascular surgery, and obstetrical hemorrhage. Tranexamic
acid (TXA) inhibits fibrinolysis and is used routinely to prevent hemorrhage in trauma cases
and high risk surgeries. Randomized trials of TXA as a prophylaxis to prevent hemorrhage in
cesarean delivery have been small and of mixed quality; however meta-analysis suggests that
it is effective.

This study is a randomized placebo-controlled trial of 11,000 women to assess whether
tranexamic acid as prophylaxis lowers the risk of postpartum hemorrhage in women undergoing a
cesarean delivery.

Inclusion Criteria:

1. Scheduled or unscheduled cesarean delivery

2. Singleton or twin gestation

Exclusion Criteria:

1. Age less than 18 years

2. Transfusion or planned transfusion of any blood products during the current admission
because the primary outcome is already pre-determined and the need for transfusion
will be unrelated to perioperative hemorrhage

3. Recent diagnosis or history of venous thromboembolism or arterial thrombosis because
TXA is a risk factor for thromboembolism, and its use is contraindicated

4. Known congenital or acquired thrombophilias, including antiphospholipid antibody
syndrome, because of the increased risk of thrombosis

5. Seizure disorder (including eclampsia) because TXA is a GABA receptor antagonist, and
its use has been associated with postoperative seizures

6. Serum creatinine 1.2 or higher or on dialysis, with renal disease, or a history of
renal insufficiency, because TXA is substantially excreted by the kidney, and impaired
renal function may increase the risk of toxic reactions.

7. Sickle cell disease, because of substantial use of perioperative transfusion unrelated
to hemorrhage. Sickle cell trait is not an exclusion per se.

8. Autoimmune diseases such as lupus, rheumatoid arthritis, Sjogren's disease, and
inflammatory bowel disease because of hypercoagulability and the increased risk of
thrombosis or thromboembolism

9. Need for therapeutic dose of anticoagulation before delivery, because the risk of
thrombosis may be increased with TXA

10. Treatment with clotting factor concentrates, because the risk of thrombosis may be
increased with TXA

11. Presence of frank hematuria, because the risk of ureteral obstruction in those with
upper urinary tract bleeding may be increased with TXA

12. Patient refusal of blood products because the primary outcome is then pre-determined

13. Pre-operative receipt of TXA

14. Active cancer, because of risk of thromboembolism

15. Congestive heart failure requiring treatment, because of risk of thrombosis

16. History of retinal disease, because the risk of central retinal artery or vein
obstruction may be increased with TXA

17. Acquired defective color vision or subarachnoid hemorrhage, since TXA is
contraindicated

18. Hypersensitivity to TXA or any of the ingredients

19. No hemoglobin and hematocrit result available from the last 4 weeks, since it is
necessary to measure the post-operative change in hemoglobin and hematocrit

20. Scheduled cesarean delivery and quota for scheduled deliveries already met. Quotas on
the number of scheduled and unscheduled deliveries will be placed to ensure
approximately equal distribution of scheduled and unscheduled cesarean deliveries.

21. Participation in this trial in a previous pregnancy. Patients who were screened in a
previous pregnancy, but not randomized, may be included.