Congenital alpha2-antiplasmin deficiency

Congenital alpha2-antiplasmin deficiency, also known as congenital plasmin inhibitor deficiency or alpha-2-plasmin inhibitor deficiency, is a rare inherited bleeding disorder caused by mutations in the SERPINF2 gene (previously known as PLI or AAP). Alpha2-antiplasmin (also called plasmin inhibitor) is the primary physiological inhibitor of plasmin, the enzyme responsible for breaking down fibrin clots. When this protein is deficient or dysfunctional, plasmin activity is unchecked, leading to premature dissolution of blood clots (hyperfibrinolysis) and a resulting hemorrhagic tendency. The condition primarily affects the hemostatic (blood clotting) system. Individuals with the homozygous or compound heterozygous form (complete deficiency) typically present with a severe bleeding diathesis that may begin in early childhood. Key clinical features include delayed bleeding after trauma or surgery, spontaneous bruising, epistaxis (nosebleeds), gingival bleeding, menorrhagia in women, hemarthrosis (joint bleeding), muscle hematomas, and umbilical cord bleeding in neonates. Heterozygous carriers (partial deficiency) may experience mild bleeding symptoms or remain asymptomatic. Standard coagulation tests such as prothrombin time (PT) and activated partial thromboplastin time (aPTT) are typically normal, which can make diagnosis challenging. Diagnosis is confirmed by measuring alpha2-antiplasmin activity levels in plasma. Treatment is primarily aimed at controlling bleeding episodes and preventing excessive fibrinolysis. Antifibrinolytic agents such as tranexamic acid and epsilon-aminocaproic acid are the mainstay of therapy and are effective in both treating acute bleeding and providing prophylaxis before surgical procedures. Fresh frozen plasma may also be used to replace the deficient protein during severe bleeding episodes. There is no specific alpha2-antiplasmin concentrate currently available.

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