PAI-1 deficiency can be safely and efficiently managed with antifibrinolytic therapy. Both epsilon-amino caproic acid (EACA) and tranexamic acid (TA) have been documented to control and prevent bleeding.20,52,53,57,58,60 Antifibrinolytic agents inhibit plasmin generation and are not derived from blood products. In addition to assisting in bleeding cessation, antifibrinolytic agents can be used prophylactically to prevent bleeding prior to surgery or other invasive procedures.20,49,52
Menorrhagia also can be effectively managed with hormonal suppression therapy or antifibrinolytic agents (EACA or TA) when started a few days before the onset of menses at a low dose with an increase to full dose at the onset of the cycle.20,67,69
Based on the experience at our center (the IHTC) in treating two pregnant women with complete PAI-1 deficiency, we have suggested the use of antifibrinolytic agents – tranexamic acid (TA) or EACA for intermittent bleeding in the first and second trimester, continuous prophylactic use from 26 weeks’ gestation through delivery, and for at least two weeks postpartum. However, we need more data to support the use and safety of these agents in pregnancy and postpartum/lactation period. There are no studies regarding the safety of EACA or TA during breast feeding. EACA has been classified as category C and TA as Category B by United States Food and Drug Administration.69
Intravenous and oral routes have been used for EACA and TA. No specific doses are recommended for PAI-1 deficiency; however, standard doses for these agents have been utilized with success (EACA: 50-100 mg/kg/dose orally every 6 hours with a maximum dose of 3 grams/dose; TA: 25 mg/kg three times a day).
Severe bleeding events, including intracranial hemorrhage with or without hematoma evacuation, have been successfully managed with intravenous fibrinolytic inhibitors. Fresh frozen plasma (dose 10–15 mL/kg) may be utilized to acutely increase PAI-1 activity at initiation of therapy before achievement of steady-state levels of antifibrinolytic agents. The need for ongoing treatment with fresh frozen plasma is dependent on the individual patient’s circumstances and response to therapy. FFP does not appear to be an effective treatment for PAI-1 deficiency, specifically during pregnancy as mentioned in the case above.62 There is no purified or recombinant PAI-1 replacement concentrate currently available.
Prognosis: Although bleeding events associated with injury, surgery or menses can result in life-threatening hemorrhage, many patients with PAI-1 deficiency may do well owing to the efficacy of antifibrinolytic treatment. However, early diagnosis and appropriate therapeutic intervention are necessary for optimal outcomes. The life expectancy of an individual with PAI-deficiency is unknown and may be established going forward as currently identified patients are followed-up long-term.49
Treatment centers: To search for a treatment center near you, visit the World Federation of Hemophilia’s Passport: Global Treatment Centre Directory by visiting https://www.wfh.org/en/page.aspx?pid=1264 .
Rare Coagulation Disorders Resource Room, an extension of the RBDD Registry (eu.rbdd.org), was developed in collaboration with the Indiana Hemophilia & Thrombosis Center (www.innovativehematology.org).
The Resource Room serves as a platform to promote international collaboration to increase knowledge of these very rare disorders and to improve the care of affected individuals. The international RBDD mission, under the leadership of Dr. Peyvandi, will continue to be expanded over time.
The Resource Room thanks all contributing authors of the website articles that have made this valuable information available to the global community of both individuals affected with rare coagulation disorders and their healthcare providers.
