Hemophilia

Hemophilia therapy Cyklokapron^® (tranexamic acid), a synthetic derivative of lysine, is an antifibrinolytic drug that prevents fibrin clot disintegration by binding to plasminogen and disrupting the interaction of plasmin(ogen) with fibrin.¹ In both primary and secondary care, tranexamic acid is used to prevent and cure excessive bleeding.² In patients with hemophilia, Cyklokapron injection is used for a brief period of time (2-8 days) to decrease or prevent hemorrhage and lessen the need for replacement therapy during and after tooth extraction. Each mL of sterile intravenous injection solution includes 100 mg of tranexamic acid and water for injection to 1 mL.³ 

Original approval of Cyklokapron for intravenous use was obtained from the US Food and Drug Administration (FDA) on December 30, 1986.⁴ 

Mechanism of Action

Tranexamic acid’s antifibrinolytic properties are achieved by reversible interactions at several plasminogen binding sites. In native human plasminogen, 4 to 5 lysine binding sites have a low affinity for tranexamic acid while 1 has a high affinity. Plasminogen’s high-affinity lysine site is essential for fibrin binding. Plasminogen is displaced from the surface of fibrin when the high-affinity binding site is saturated with tranexamic acid. Although conformational changes in plasminogen can produce plasmin, binding to and breaking down of the fibrin matrix is prevented. In concentrations of 1 mg/mL and 10 mg/mL, tranexamic acid causes prolongation of thrombin time. It has an antifibrinolytic effect that lasts for approximately 17 hours in various tissues and for up to 8 hours in the serum. It is found to have no effect on platelet count, coagulation time, or different coagulation factors in whole blood or citrated blood from healthy individuals at concentrations up to 10 mg/mL blood.⁵ 

Get full prescribing information on Cyklokapron at MPR

Efficacy in Trials and Trial Results

Tranexamic acid is only licensed by the FDA for heavy menstrual bleeding and short-term prevention in patients with hemophilia.⁶ 

Limited data in hemophilia patients undergoing tooth extractions was found in 2 Cochrane reviews by Wardrop et al⁷ and Watterson et al.⁸ There is little evidence for the use of antifibrinolytics in patients with hemophilia. The limited research available suggests that tranexamic acid could be effective as an adjunct to platelet transfusions, reducing platelet consumption and the complications that come with it.⁷ Adjuvant antifibrinolytic medication to minimize perioperative bleeding in individuals with hemophilia undergoing dental extractions is supported by low-quality evidence.⁸ 

Oral tranexamic acid is an efficacious and safe form of medical treatment in women with menorrhagia, according to an open noncomparative study. It also improves their quality of life.⁹

Warnings, Precautions, and Adverse Reactions

In cases of renal failure, epilepsy, benign gynecological operations, and fibrinolysis due to disseminated intravascular coagulation without considerable bleeding, tranexamic acid administration is not advised.¹⁰

Nausea, vomiting, diarrhea, fatigue, seizures, headache, backache, abdominal pain, pulmonary embolism, deep vein thrombosis, anaphylaxis, altered colour vision, and other visual impairments are all possible side effects.⁶

Drug-Drug Interactions

When coupled with combination hormonal contraceptives, factor IX complex concentrates, anti-inhibitor coagulant concentrates, thrombin, batroxobin, or hemocoagulase, the thrombotic risk involved with tranexamic acid may be exacerbated.¹ 

It has the potential to increase tretinoin’s procoagulant actions in patients with acute promyelocytic leukaemia, leading to thrombotic events. When tranexamic acid and tissue plasminogen activators are administered together, the efficacies of both medications may be lowered.¹ 

References

1. McCormack PL. Tranexamic acid: a review of its use in the treatment of hyperfibrinolysis. Drugs. 2012;72(5):585-617. doi:10.2165/11209070-000000000-00000
2. Tengborn L, Blombäck M, Berntorp E. Tranexamic acid–an old drug still going strong and making a revival. Thromb Res. 2015;135(2):231-242. doi:10.1016/j.thromres.2014.11.012
3. Cyklokapron. US Food and Drug Administration. January 2011. Accessed December 15, 2021.
4. [email protected]: FDA-approved drugs. US Food and Drug Administration. Accessed December 15, 2021.
5. Cyklokapron. Package insert. Pfizer; 2021. Accessed December 15, 2021.
6. Chauncey JM, Wieters JS. Tranexamic acid.  In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021.
7. Wardrop D, Estcourt LJ, Brunskill SJ, et al. Antifibrinolytics (lysine analogues) for the prevention of bleeding in patients with haematological disorders. Cochrane Database Syst Rev. 2013;(7):CD009733. doi:10.1002/14651858.CD009733.pub2
8. Watterson C, Beacher N. Preventing perioperative bleeding in patients with inherited bleeding disorders. Evid Based Dent. 2017;18(1):28-29. doi:10.1038/sj.ebd.6401226
9. Srinil S, Jaisamrarn U. Treatment of idiopathic menorrhagia with tranexamic acid. J Med Assoc Thai. 2005;88 Suppl 2:S1-S6.
10. Pabinger I, Fries D, Schöchl H, Streif W, Toller W. Tranexamic acid for treatment and prophylaxis of bleeding and hyperfibrinolysis. Wien Klin Wochenschr. 2017;129(9-10):303-316. doi:10.1007/s00508-017-1194-y

Reviewed by Kyle Habet, MD, on 12/27/2021.

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Harshi Dhingra, MD

Harshi Dhingra is a licensed medical doctor with specialization in Pathology. She is currently employed as faculty in a medical school with a tertiary care hospital and research center in India. Dr. Dhingra has over a decade of experience in diagnostic, clinical, research, and teaching work, and has written several publications and citations in indexed peer reviewed journals. She holds medical degrees for MBBS and an MD in Pathology.