A 32-year-old woman, gravida 2 para 1, has a spontaneous vaginal delivery. Immediately after delivery of the placenta, the patient has a large amount of vaginal bleeding with passage of fist-sized clots, findings consistent with postpartum hemorrhage. A dose of tranexamic acid is administered. Which of the following is the most likely mechanism of action of this drug?
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This patient has postpartum hemorrhage (PPH). Following placental delivery, maternal hemostasis is typically achieved by uterine contraction, which constrict bleeding placental bed vessels, and activation of coagulation pathways and clot formation at the former placental attachment site. When either mechanism fails, patients may have PPH and life-threatening blood loss. Therefore, medications used to treat PPH commonly increase either uterine contractions or clot formation.
After placental delivery, prothrombotic substances in the decidua (eg, tissue factor) activate the extrinsic coagulation cascade, generating thrombin that converts fibrinogen into fibrin, forming a fibrin clot. At the same time, the fibrinolytic pathway is also activated: tissue plasminogen activator (t-PA) is released by damaged endothelium and cleaves plasminogen to form plasmin, which promotes bleeding by breaking down fibrin clots into fibrin degradation products.
Tranexamic acid (TXA) stabilizes thrombi/clots by inhibiting plasmin formation; therefore, TXA is an antifibrinolytic medication that provides more time for the uterine myometrium to contract and constrict the placental bed blood vessels. The use of TXA for PPH significantly decreases bleeding and is associated with improved maternal morbidity and mortality.
(Choice A) Increasing vitamin K–dependent coagulation factor levels is the mechanism of action for prothrombin complex concentrate (PCC), which contains factors II, IX, and X and variable amounts of factor VII. PCC is commonly used to reverse warfarin-induced anticoagulation or to treat bleeding due to congenital vitamin K–dependent coagulation factor deficiencies.
(Choices B and E) Agents that cause uterine myometrial contractions are known as uterotonic medications. Misoprostol, a synthetic prostaglandin analogue, induces prostaglandin-mediated smooth muscle contraction but has a slow onset of action. In contrast, oxytocin rapidly increases intracellular calcium levels in the uterine myometrium; because of its rapid onset, is the most common uterotonic administered for PPH.
(Choice D) Promotion of the endothelial release of von Willebrand factor is the mechanism of action for desmopressin, which also increases plasma levels of factor VIII. Desmopressin is used in patients with bleeding due to von Willebrand disease or mild hemophilia A.
Educational objective:
Tranexamic acid (TXA) is an antifibrinolytic medication that stabilizes blood clots in hemorrhaging patients. It inhibits plasmin formation, thereby preventing fibrin degradation and clot dissolution. TXA used for the treatment of postpartum hemorrhage improves maternal morbidity and mortality.