α₂‐Antiplasmin and its deficiency: fibrinolysis out of balance

Abstract

Summary. Fibrinolysis serves an important role in the process of coagulation, ensuring that clots that are formed in response to injury resolve after the injured tissue is repaired. Fibrinolysis occurs because the protein plasminogen is converted to the active serine protease plasmin by its activating molecules (primarily tissue plasminogen activator). One of the inhibitors of fibrinolysis is a 2 -antiplasmin, which acts as the primary inhibitor of plasmin(ogen). Congenital deficiency of a 2 -antiplasmin causes a rare bleeding disorder because of increased fibrinolysis. Despite the rare nature of this disorder, understanding of the actions of a 2 -antiplasmin and the results of its deficiency has provided the opportunity for better understanding of the fibrinolytic system in both how it affects the risk of bleeding and its impact on other bodily systems. Here, we review the history of the discovery of a 2 -antiplasmin, our understanding of its genetics and function, and our current knowledge of its congenital deficiency. We also discuss some of the current avenues of investigation into its impact on other diseases and physiological states.

α2-Antiplasmin is involved in bone loss induced by ovariectomy in mice

“…Discussion α 2 -AP is a serine protease inhibitor that rapidly sequesters plasmin into a stable inactive complex and thereby regulates fibrinolysis [17,18]. However, Kawashita et al reported that α 2 -AP also enhances dendritic growth in hippocampal neurons independently of the fibrinolytic system [24].…”

“…Plasmin inhibition by α 2 -AP is almost instantaneous, and leads to the formation of a stable inactive complex [17]. Significant bleeding tendency is observed in patients with homozygous α 2 -AP deficiency, highlighting its physiological significance [17,18]. Heterozygous patients have mild or no bleeding tendency [17,18].…”

“…Significant bleeding tendency is observed in patients with homozygous α 2 -AP deficiency, highlighting its physiological significance [17,18]. Heterozygous patients have mild or no bleeding tendency [17,18]. The role of α 2 -AP in bone metabolism and in the pathogenesis of osteoporosis remains unknown, although several studies suggest various activities besides inhibition of fibrinolysis [19,20].…”

The Dynamics of the Hemo- static Parameters in Physio- logical Pregnancy and After Delivery

“…At the same time, the results published by Holmes and Wallace [7] evidence the significant dynamic decrease of α 2-AP activity closer to delivery, which is in agreement with our results. It is interesting to note that inherited and acquired α2-AP deficiency is associated with severe bleedings due to uncontrolled hyperfibrinolysis [97].…”

Evaluating for Suspected Child Abuse: Conditions That Predispose to Bleeding

“…Heterozygous patients can have bleeding in response to trauma, surgery, or dental procedures or can be asymptomatic. 93,98 Intramedullary hematomas of long bones, which can occur without a history of trauma, are an unusual feature of homozygous AP deficiency. 99,100 Similar lesions have been seen in patients with afibrinogenemia.…”