Abstract
BackgroundThe activation of plasma enzyme systems contributes to hereditary angioedema attacks. We aimed to study the activation markers of the fibrinolytic, coagulation, and contact systems in a larger number of paired samples obtained from the same C1-INH-HAE patients in symptom-free periods and during attacks.MethodsEleven parameters (Factors XI, XII, and C1-inhibitor activity; the concentrations of the D-dimer, prothrombin fragments 1 + 2, plasminogen, plasminogen activator inhibitor-1 [PAI-1], thrombin-anti-thrombin III [TAT] complex, fibrinogen) were measured along with prothrombin time and activated partial thromboplastin time (aPTT), using commercial kits. We compared these markers in samples obtained from the same 39 patients during attack-free periods and during 62 edematous episodes. Forty healthy subjects of matching sex and age served as controls.ResultsCompared with the healthy controls, significantly higher FXI and FXII activity (p = 0.0007, p = 0.005), as well as D-dimer (p < 0.0001), prothrombin fragments 1 + 2 (p < 0.0001), and TAT (p = 0.0303) levels were ascertained in the patients during symptom-free periods. The evaluation of samples from symptom-free periods or obtained during attacks revealed the increase of FXII activity, as well as of the concentration of D-dimer, prothrombin fragments 1 + 2, and TAT during edematous episodes. PAI-1 level, prothrombin time, and aPTT decreased significantly during attacks, compared with symptom-free periods. D-dimer level was significantly higher during multiple- vs. single-site attacks.ConclusionsComparing a large number of paired samples from symptom-free periods or from edematous episodes allowed accurate appraisal of the changes occurring during attacks. Moreover, our study pointed out that individual episodes may be characterized by different marker patterns.
Highlights
The activation of plasma enzyme systems contributes to hereditary angioedema attacks
Evaluation of coagulation parameters in symptom-free periods and during attacks, in the same C1-INH-HAE patients In order to analyze the activation of the coagulation cascade during edematous attacks – as it had been suggested previously – we determined the plasma coagulation parameters in samples collected from the same C1-INHHAE patients in symptom-free periods and during attacks
The activity of factor XII was enhanced in the symptom-free period, compared with that observed in the healthy subjects (p = 0.0050), and increased further significantly during attacks in the same C1-INH-HAE patients (Fig. 1a)
Summary
The activation of plasma enzyme systems contributes to hereditary angioedema attacks. C1-inhibitor (C1-INH) – the deficiency of which causes hereditary angioedema (C1-INH-HAE) types I and II – is a regulator of the complement, contact, coagulation, and fibrinolytic systems, as it inhibits rapidly activated factor XII (FXIIa), activated factor XI (FXIa), and kallikrein [1,2,3,4,5]. HAE) [12] can activate the contact system via the stressinduced release of HSP-90, or the direct endothelial cell activation of circulating factor XII, during which large areas of endothelium are exposed [13]. These stimuli are important activators of the coagulation cascade through the expression of tissue factor and the activation of factor VII [14]. Binding induces intercellular gap formation [15], which leads to edema [14, 16, 17]
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