Plasmatic Markers of Acute Attack in Patients with Angioedema Due to C1 Inhibitor Deficiency

RATIONALE: C1-INH controls protease activity in complement, contact, coagulation and fibrinolytic systems. Its deficiency causes recurrent angioedema of the skin, bowel mucosa and upper airway. Aim of this study was the identification of plasmatic markers to distinguish angioedema due to C1-INH deficiency. Since activation of fibrinolytic system and generation of thrombin occur during angioedema in C1-INH deficiency, we used commonly available methods to measure prothrombin fragment F1+2 and fibrin fragment D-Dimer as markers of thrombin generation and fibrinolysis. METHODS: 25 patients with C1-INH deficiency in remission and 25 during angioedema were compared with 20 healthy controls. F1+2 was measured by ELISA; D-Dimer was measured by ELISA and a latex method. RESULTS: F1+2 was higher in patients in remission, 331 ± 72 pmol/ml (mean ± SEM), than in controls, 167 ± 22 pmol/ml, p=0.007. F1+2 further increased during angioedema, 1482 ± 222 pmol/ml, p=0.0001. D-Dimer was higher in patients in remission (1521 ± 544 ng/ml with ELISA and 544 ± 168 ng/ml with latex method) than in controls (516 ± 150 ng/ml with ELISA and 111 ± 28 ng/ml with latex method), p=0.007. D-Dimer plasma levels were further increased in 25 patients during angioedema (2932 ± 1074 ng/ml with ELISA and 800 ± 196 ng/ml with latex method), but did not reach statistical significance. CONCLUSIONS: Our data demonstrate that patients with C1-INH deficiency have increased level of F1+2 and D-Dimer. During acute attacks, these values further increase and thus can be proposed as useful tools for recognizing angioedema due to C1-INH deficiency.