Kinga Viktória Kőhalmi1, Blanka Mező2, Nóra Veszeli2, Szabolcs Benedek3, Adrienne Fehér4, Ágnes Holdonner5, Milos Jesenak6, Lilian Varga5, Henriette Farkas7. 1. Hungarian Angioedema Reference Center, 3rd Department of Internal Medicine, Semmelweis University, Budapest H-1125, Hungary; Hospital of Hospitaller Brothers of St. John of God, Department of Rheumatology, Budapest H-1023, Hungary. 2. MTA-SE Research Group of Immunology and Hematology, Hungarian Academy of Sciences and Semmelweis University, Budapest H-1125, Hungary. 3. 3rd Department of Internal Medicine, Semmelweis University, Budapest H-1125, Hungary. 4. Department of Laboratory Medicine, Semmelweis University, Budapest H-1085, Hungary. 5. Hungarian Angioedema Reference Center, 3rd Department of Internal Medicine, Semmelweis University, Budapest H-1125, Hungary. 6. Department of Pediatrics, Martin University Hospital, Martin, Slovakia. 7. Hungarian Angioedema Reference Center, 3rd Department of Internal Medicine, Semmelweis University, Budapest H-1125, Hungary. Electronic address: farkas.henriette@med.semmelweis-univ.hu.
Abstract
BACKGROUND: Hereditary angioedema (HAE) with C1-inhibitor deficiency (C1-INH-HAE) is characterized by recurrent episodes of subcutaneous/submucosal edema, which may be preceded by erythema marginatum (EM) as a prodromal symptom. Our aim was to analyze the changes occurring in the parameters of the coagulation system during the development of EM and HAE attacks. MATERIALS AND METHODS: Eight C1-INH-HAE patients (1 male, 7 females, median age: 41.7 years) were studied. Blood samples were obtained from all patients (during symptom-free periods, EM, and HAE attacks), as well as from 20 sex- and age-matched healthy controls. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, Factor V, Factor VII, Factor X, Factor XI, and Factor XII levels were measured. RESULTS: D-dimer levels were significantly lower, whereas aPTT was significantly prolonged in healthy controls vs. the values measured during the symptom-free period (p = 0.0497; p = 0.0043), in the presence of EM (p = 0.002; p = 0.0002), or during HAE attacks (p < 0.0001; p = 0.0002). We observed the following differences between samples taken during HAE attacks vs. in symptom-free periods: D-dimer levels were significantly elevated (p = 0.0391), while aPTT was significantly shorter during HAE attacks (p = 0.0159). D-dimer levels were significantly higher during EM than in symptom-free periods (p = 0.0078). Comparing the samples drawn during EM or during HAE attacks, there were no significant differences in the study parameters. CONCLUSIONS: D-dimer levels were elevated during EM and this suggests that EM may be part of the HAE attack. Nevertheless, further research into the complement and kinin-kallikrein systems is needed in more patients for a better understanding of the pathomechanism of EM.
BACKGROUND:Hereditary angioedema (HAE) with C1-inhibitor deficiency (C1-INH-HAE) is characterized by recurrent episodes of subcutaneous/submucosal edema, which may be preceded by erythema marginatum (EM) as a prodromal symptom. Our aim was to analyze the changes occurring in the parameters of the coagulation system during the development of EM and HAE attacks. MATERIALS AND METHODS: Eight C1-INH-HAEpatients (1 male, 7 females, median age: 41.7 years) were studied. Blood samples were obtained from all patients (during symptom-free periods, EM, and HAE attacks), as well as from 20 sex- and age-matched healthy controls. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, Factor V, Factor VII, Factor X, Factor XI, and Factor XII levels were measured. RESULTS: D-dimer levels were significantly lower, whereas aPTT was significantly prolonged in healthy controls vs. the values measured during the symptom-free period (p = 0.0497; p = 0.0043), in the presence of EM (p = 0.002; p = 0.0002), or during HAE attacks (p < 0.0001; p = 0.0002). We observed the following differences between samples taken during HAE attacks vs. in symptom-free periods: D-dimer levels were significantly elevated (p = 0.0391), while aPTT was significantly shorter during HAE attacks (p = 0.0159). D-dimer levels were significantly higher during EM than in symptom-free periods (p = 0.0078). Comparing the samples drawn during EM or during HAE attacks, there were no significant differences in the study parameters. CONCLUSIONS: D-dimer levels were elevated during EM and this suggests that EM may be part of the HAE attack. Nevertheless, further research into the complement and kinin-kallikrein systems is needed in more patients for a better understanding of the pathomechanism of EM.