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


Massimo Cugno, MD
Department of Internal Medicine
University of Milan
Via Pace 9
20122 Milano


Background:  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.

Objective:  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.

Methods:  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.

Results:  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 (= 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).

Conclusions:  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.