Plasma biomarkers of acute attacks in patients with angioedema due to C1‐inhibitor deficiency

Abstract

Cl-inhibitor (C1-INH) deficiency leads to recurrent attacks of mucocutaneous edema and may be inherited (hereditary angioedema [HAE]) or acquired (acquired angioedema [AAE]), which have the same clinical picture characterized by angioedema involving the skin, gastrointestinal tract, and larynx. Although cutaneous swelling is evident, abdominal angioedema is still a diagnostic challenge and attacks can mimic surgical emergencies. There is currently no laboratory marker for identifying angioedema attacks. As coagulation and fibrinolysis are activated during angioedema attacks, we assessed if plasma measurements of prothrombin fragment F1 + 2 (marker of thrombin generation) and D-dimer (marker of fibrin degradation) can be useful for the diagnosis of angioedema because of C1-INH deficiency, especially in case of hidden locations as abdominal attacks. In addition to complement, we measured plasma levels of F1 + 2 and D-dimer in 28 patients with C1-INH deficiency during acute attacks and remission, 35 patients without C1-INH deficiency during abdominal colics, and 20 healthy subjects. Plasma F1 + 2 levels were higher in patients with C1-INH deficiency during remission than in healthy controls (P = 0.001), and further increased during cutaneous and abdominal attacks (P = 0.0001); patients without C1-INH deficiency had normal F1 + 2 levels during abdominal colics. Plasma D-dimer levels were higher in patients with C1-INH deficiency during remission than in controls (P = 0.012) and increased during angioedema attacks, reaching higher levels than in patients without C1-INH deficiency during colics (P = 0.002). During acute angioedema attacks, patients with C1-INH deficiency have high prothrombin fragment F1 + 2 and D-dimer levels, the measurement of which may have an important diagnostic value.