Coagulation, Bradykinin, Polyphosphates, and Angioedema

Hereditary angioedema is a rare genetic disorder in which mutations affecting C1 inhibitor or coagulation factor XII lead to uncontrolled activation of the contact pathway, causing episodes of severe, potentially life-threatening tissue swelling driven largely by excess bradykinin signaling through kinin receptors. Research in this area maps how molecular triggers — including polyphosphates released from platelets and the interplay between factor XII, factor XI, and tissue kallikreins — amplify plasma kallikrein activity and bradykinin production in ways that classical complement-focused models did not fully anticipate. Emerging therapies such as bradykinin-receptor antagonists and factor XI antisense oligonucleotides have validated several of these mechanistic nodes as druggable targets, though predicting attack frequency and severity from a patient's specific genotype remains an unsolved problem. An active direction is clarifying exactly how polyphosphates and other surface-bound activators initiate contact activation in vivo, which could reveal why some mutation carriers experience frequent crises while others remain largely asymptomatic.

Works

47,329

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761,335

Keywords

Hereditary AngioedemaKinin Receptor FamilyCoagulation Factor XIIPolyphosphateC1 Inhibitor DeficiencyBradykinin-Receptor Antagonist