C1-inhibitor (C1-INH) deficiency leads to recurrent attacks of mucocutaneous edema. The deficiency may be:
- inherited (hereditary angioedema [HAE]
- acquired (acquired angioedema [AAE]
Both condition have the same clinical picture presenting with angioedema involving:
- gastrointestinal tract
Skin swelling is evident but abdominal angioedema may be a diagnostic challenge. In fact, attacks of abdominal angioedema may mimic surgical emergencies and lead to unnecessary surgeries.
C1 protein, showing subunits C1r, C1s, and the C1q tails. Image source: Wikipedia. Patients with acquired angioedema have low C1q levels AND low C4/C2 levels. In contrast, in hereditary angioedema (HAE) the C1q level is normal.
Classical and alternative complement pathways. Image source: Wikipedia.
Currently, there no laboratory marker to diagnose angioedema attacks.
Coagulation and fibrinolysis are activated during angioedema attacks. This Italian study measured:
- plasma prothrombin fragment F1 + 2 (marker of thrombin generation)
- D-dimer (marker of fibrin degradation)
Prothrombin is produced in the liver. Thrombin is produced by the enzymatic cleavage of two sites on prothrombin.
The coagulation cascade. Image source: Wikipedia, GNU Free Documentation License.
Plasma F1 + 2 level was higher in patients with C1-INH deficiency during remission and further increased during attacks.
Patients without C1-INH deficiency had a normal F1 + 2 level during abdominal colics.
Plasma D-dimer level was also higher in patients with C1-INH deficiency during remission and increased during angioedema attacks.
The authors concluded that patients with C1-INH deficiency have high prothrombin fragment F1 + 2 and D-dimer levels both at baseline and during attacks. Plasma F1 + 2 was more specific than D-dimer since F1 + 2 level was normal in controls without C1-inhibitor (C1-INH) deficiency.
Measurement of F1 + 2 and D-dimer levels may help diagnose acute abdominal attacks in angioedema due to C1-inhibitor deficiency and avoid unnecessary surgery.
Plasma biomarkers of acute attacks in patients with angioedema due to C1-inhibitor deficiency. Cugno M, Zanichelli A, Bellatorre AG, Griffini S, Cicardi M. Allergy. 2009 Feb;64(2):254-7. Epub 2008 Dec 4.
Angioedema: A Short Review