scholarly journals Factor VII activating protease (FSAP) is not essential in the pathophysiology of angioedema in patients with C1 inhibitor deficiency

2022 ◽  
Vol 142 ◽  
pp. 95-104
Author(s):  
Olav Rogde Gramstad ◽  
Sai Priya Sarma Kandanur ◽  
Michael Etscheid ◽  
Erik Waage Nielsen ◽  
Sandip Mahadev Kanse
Keyword(s):  
Factor Vii ◽  
C1 Inhibitor ◽  
C1 Inhibitor Deficiency

scholarly journals Activation of the Coagulation Cascade in C1-Inhibitor Deficiencies

Blood ◽  
1997 ◽  
Vol 89 (9) ◽  
pp. 3213-3218 ◽  
Author(s):  
Massimo Cugno ◽  
Marco Cicardi ◽  
Bianca Bottasso ◽  
Raffaella Coppola ◽  
Raffaella Paonessa ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Plasma Levels ◽  
Coagulation Cascade ◽  
Factor Vii ◽  
Enzyme Linked Immunosorbent Assay ◽  
Factor Xii ◽  
C1 Inhibitor ◽  
C1 Inhibitor Deficiency ◽  
Edema Formation ◽  
Acquired Angioedema

AbstractActivation of the contact and complement systems in C1-inhibitor deficiencies is thought to contribute to the pathogenesis of angioedema attacks by releasing kinins. Trigger stimuli of attacks may also activate coagulation. This is particularly important because experimental data suggest that thrombin, the main enzyme of the coagulation cascade, increases vascular permeability and can thus influence edema formation. We have studied 19 patients with hereditary angioedema (HAE) during remission, 5 HAE patients during acute attacks, and 6 patients with acquired angioedema (AAE) during remission and during seven attacks. Thirty normal subjects, matched for sex and age, served as controls. Generation of thrombin was measured by enzyme-linked immunosorbent assay (ELISA) as plasma levels of the prothrombin fragment 1 + 2 (F1 + 2); the initiators of the tissue factor and contact coagulation pathways were investigated by measuring plasma levels of activated factor VII (FVIIa) coagulometrically and activated factor XII (FXIIa) by ELISA. Cleavage of high molecular weight kininogen (HK) was evaluated by immunoblotting analysis. F1 + 2 was slightly increased during remission and further significantly increased during attacks in both HAE (P = .0115) and AAE. FVIIa and FXIIa, normal during remission, increased strikingly during attacks in both HAE (P = .0022 and P = .0044) and AAE. During remission, cleaved HK was normal in HAE and high in AAE; during attacks it increased in HAE (P = .0008) and remained elevated in AAE. Our data indicate that in C1-inhibitor deficient patients there is increased generation of thrombin during attacks, with signs of activation of both the contact and tissue factor coagulation pathways. In conclusion, C1-inhibitor deficiency, whether hereditary or acquired, has demonstrable activation of the coagulation and kinin-forming cascades during attacks and that thrombin should be considered a possible contributing factor in the pathogenesis of edema in HAE and AAE.

scholarly journals The Global Registry for Hereditary Angioedema due to C1-Inhibitor Deficiency

2021 ◽  
Author(s):  
Andrea Zanichelli ◽  
Henriette Farkas ◽  
Laurance Bouillet ◽  
Noemi Bara ◽  
Anastasios E. Germenis ◽  
...  
Keyword(s):  
Hereditary Angioedema ◽  
Rare Condition ◽  
C1 Inhibitor ◽  
C1 Inhibitor Deficiency ◽  
Therapeutic Decisions ◽  
Life Threatening ◽  
Enhance Patient Care ◽  
Electronic Support ◽  
The Impact ◽  
Global Registry

AbstractHereditary angioedema (HAE) is a rare condition, mostly due to genetic deficiency of complement C1 inhibitor (C1-INH). The rarity of HAE impedes extensive data collection and assessment of the impact of certain factors known to affect the course of this disabling and life-threatening disease. Establishing a global registry could assist to overcome such issues and provides valuable patient data from different countries. The HAE Global Registry is a disease-specific registry, with web-based electronic support, where data are provided by physicians and patients through a dedicated application. We collected data between January 1, 2018, and August 31, 2020. Data on 1297 patients from 29 centers in 5 European countries were collected. At least one attack was recorded for 497 patients during the study period. Overall, 1182 patients were diagnosed with HAE type 1 and 115 with type 2. At the time of database lock, 389 patients were taking long-term prophylactic medication, 217 of which were on danazol. Most recorded attacks affected the abdomen, were generally moderate in severity, and occurred in patients who were not on prophylactic treatment (70.6%, 6244/8848). The median duration of attacks was 780 min (IQR 290–1740) in patients on prophylactic medication and 780 min (IQR 300–1920) in patients not on continuous prophylactic medication. In conclusion, the establishment of a registry for C1-INH-HAE allowed collection of a large amount of data that may help to better understand the clinical characteristics of this disease. This information may enhance patient care and guide future therapeutic decisions.

scholarly journals Pathways of Neutrophil Granulocyte Activation in Hereditary Angioedema with C1 Inhibitor Deficiency

2021 ◽  
Author(s):  
Erika Kajdácsi ◽  
Nóra Veszeli ◽  
Blanka Mező ◽  
Zsófia Jandrasics ◽  
Kinga Viktória Kőhalmi ◽  
...  
Keyword(s):  
Hereditary Angioedema ◽  
Blood Cells ◽  
White Blood Cells ◽  
Neutrophil Granulocytes ◽  
C1 Inhibitor ◽  
C1 Inhibitor Deficiency ◽  
Prodromal Phase ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein

AbstractHereditary angioedema (HAE) with C1-inhibitor deficiency belongs to bradykinin-mediated angioedemas. It is characterized by recurrent subcutaneous and/or submucosal swelling episodes (HAE attacks) and erythema marginatum skin rash as a pre-attack (prodromal) phase. HAE attacks were shown to be accompanied by peripheral blood neutrophilia. We aimed to find molecular mechanisms that may explain the distinct role of neutrophil granulocytes in HAE. Plasma levels of blood cells and factors related to neutrophil activation (cytokines, chemokines, chemotactic factors, enzymes, and neutrophil extracellular trap) were measured in plasma samples obtained from patients during symptom-free periods (n = 77), during prodromal phase (n = 8) and attacks (n = 14), during a spontaneously resolved attack (n = 1), and in healthy controls (n = 79). Higher counts of white blood cells, lymphocytes, and neutrophil granulocytes were found in symptom-free patients compared with controls; these cell counts were elevated further during HAE attacks. The level of chemokine (C–C motif) ligand 5, monocyte chemoattractant protein-1, and myeloperoxidase were also higher in the symptom-free patients than in the controls. Levels of monocyte chemoattractant protein-1, leukotriene B4, neutrophil elastase, and myeloperoxidase were elevated during attacks. During erythema marginatum, white blood cells and monocyte count and levels of interleukin 8 were elevated compared with symptom-free period. Similar changes were detected during the attack follow-up. We conclude that the activation of NGs in symptom-free periods and a further increase observed during attacks suggests that NGs may be involved in the pathomechanism of HAE with C1-INH deficiency.

Cardiopulmonary By-pass in a Patient with Acquired C1 Inhibitor Deficiency

1997 ◽  
Vol 20 (3) ◽  
pp. 175-177 ◽  
Author(s):  
R. Castelli ◽  
M. Cicardi ◽  
M. Gardinali ◽  
L.C. Zingale ◽  
C. Savi ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Contact System ◽  
Bleeding Complications ◽  
C1 Inhibitor ◽  
C1 Inhibitor Deficiency ◽  
Deficient Patient ◽  
Coagulation And Fibrinolysis

C1 inhibitor (C1-INH) regulates, complement, contact system, coagulation and fibrinolysis. Bleeding complications during cardiopulmonary bypass (CPB) have been described in a deficient patient. We report a 72 year old man affected with acquired C1-INH deficiency who successfully underwent CPB.

scholarly journals A case of hereditary angioedema due to C1-inhibitor deficiency with recurrent abdominal pain diagnosed 40 years after the occurrence of the initial symptom

2021 ◽  
Author(s):  
Daisuke Honda ◽  
Isao Ohsawa ◽  
Keiichi Iwanami ◽  
Hisaki Rinno ◽  
Yasuhiko Tomino ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Hereditary Angioedema ◽  
Recurrent Abdominal Pain ◽  
Acute Attack ◽  
Severe Abdominal Pain ◽  
Initial Symptom ◽  
C1 Inhibitor ◽  
Self Administration ◽  
C1 Inhibitor Deficiency ◽  
Appropriate Treatment

AbstractHereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) is a rare disease, which induces an acute attack of angioedema mediated by bradykinin. HAE-C1-INH can cause serious abdominal pain when severe edema develops in the gastrointestinal tract. However, because it takes a long time, 13.8 years on average in Japan, from the occurrence of the initial symptom to the diagnosis due to low awareness of the disease, undiagnosed HAE-C1-INH patients sometimes undergo unnecessary surgical procedures for severe abdominal pain. We herein present a 56-year-old patient with HAE-C1-INH, who underwent numerous abdominal operations. He frequently needed hospitalization with the administration of opioid due to severe abdominal pain. However, after he was accurately diagnosed with HAE-C1-INH at 55 years of age, he could start self-administration for an acute attack with icatibant, a selective bradykinin B2 receptor antagonist. Consequently, he did not need hospitalizing for ten months after the beginning of the treatment. A series of an accurate diagnosis and appropriate treatment for HAE-C1-INH improved his quality of life. Thus, HAE-C1-INH should be considered, when we meet patients with unidentified recurrent abdominal pain. This case highlights significance of an early diagnosis and appropriate treatment for HAE-C1-INH.

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