scholarly journals Treatment of Hereditary Angioedema

2021 ◽  
Vol 31 (1) ◽  
pp. 1-16
Author(s):  
T Caballero
Keyword(s):  
Hereditary Angioedema ◽  
New Drugs ◽  
Current Therapy ◽  
Factor Xii ◽  
Short Term ◽  
Kinin System ◽  
C1 Esterase Inhibitor ◽  
Kallikrein Kinin System ◽  
Esterase Inhibitor

Hereditary angioedema due to C1-esterase inhibitor deficiency (C1-INH-HAE) is a rare autosomal dominant disease. In the last decade, new drugs and new indications for old drugs have played a role in the management of C1-INH-HAE. This review examines current therapy for C1-INH-HAE and provides a brief summary of drugs that are under development. Increased knowledge of the pathophysiology of C1-INH-HAE has been crucial for advances in the field, with inhibition of the kallikrein-kinin system (plasma kallikrein, activated factor XII) as a key area in the discovery of new drugs, some of which are already marketed for treatment of C1-INH-HAE. Pharmacological treatment is based on 3 pillars: treatment of acute angioedema attacks (on-demand treatment), short-term (preprocedure) prophylaxis, and long-term prophylaxis. The 4 drugs that are currently available for the treatment of acute angioedema attacks (purified plasma-derived human C1 esterase inhibitor concentrate, icatibant acetate, ecallantide, recombinant human C1 esterase inhibitor) are all authorized for self-administration, except ecallantide. Purified plasma-derived human C1 esterase inhibitor concentrate is the treatment of choice for short-term prophylaxis. Tranexamic acid, danazol, intravenous and subcutaneous nanofiltered purified plasma-derived human C1 esterase inhibitor concentrate, and lanadelumab can be used for long-term prophylaxis. New drugs are being investigated, mainly as long-term prophylaxis, and are aimed at blocking the kallikrein-kinin system by means of antiprekallikrein, antikallikrein, and anti–activated FXII action.

Hereditary angioedema: Pathophysiology (HAE type I, HAE type II, and HAE nC1-INH)

2020 ◽  
Vol 41 (6) ◽  
pp. S14-S17 ◽  
Author(s):  
H. James Wedner
Keyword(s):  
Serine Protease ◽  
Hereditary Angioedema ◽  
Normal Activity ◽  
Genetic Alterations ◽  
Type I ◽  
Factor Xii ◽  
Kinin System ◽  
Major Pathway ◽  
Major Mechanism ◽  
Kallikrein Kinin System

The pathophysiology of hereditary angioedema (HAE) in virtually all cases is the result of the uncontrolled production of the vasoactive peptide bradykinin. C1 inhibitor (C1-INH) is a serine protease inhibitor, which, under normal circumstances, is the regulator of critical enzymes that are active in the cascades that result in bradykinin generation. In the classic forms of HAE, C1-INH is not produced in sufficient quantities (<40% of normal) or the function is <40% of normal activity. The major pathway for the production of bradykinin is the “contact system,” also known as the kallikrein-kinin system. This system begins with the activation of factor XII (FXII) to FXIIa, by a variety of physiologic and pathologic stimuli. FXIIa is a serine protease that binds to surfaces and cleaves prekallikrein to the active serine protease kallikrein. Kallikrein then cleaves high-molecular-weight kininogen to release the nonapeptide bradykinin. Bradykinin binds to the bradykinin β2 receptor, which increases vascular permeability and allows the flow of fluids into the extracellular space and results in angioedema. The two major enzymes generated in this cascade FXIIa and kallikrein are inhibited by C1-INH, which is the major regulator of this cascade. Failure to adequately control the production of bradykinin is thus the major mechanism for HAE. Several other types of HAE in which C1-INH is not decreased (HAE nlC1-INH) have been described. The alterations in FXII and plasminogen (also a serine protease inhibited by C1-INH) like with classic HAE are the result of dysregulation of bradykinin generation. Only genetic alterations in angiopoietin-1 may not be related to bradykinin generation, rather related to the control of the effect of bradykinin on the vascular endothelium.

scholarly journals Features of diagnostics and clinical approaches to case management of patients with hereditary angioedema without C1 esterase inhibitor deficiency. Analysis of the clinical case

2020 ◽  
Vol 17 (1) ◽  
pp. 58-65
Author(s):  
Daria S Fomina ◽  
Elena N Bobrikova ◽  
Sofia A Serdotetskova
Keyword(s):  
Case Management ◽  
Hereditary Angioedema ◽  
Clinical Case ◽  
Medical Society ◽  
Differential Diagnostics ◽  
Factor Xii ◽  
C1 Esterase Inhibitor ◽  
Primary Diagnostics ◽  
Genetic Features ◽  
Esterase Inhibitor

This article describes the clinical, biochemical and genetic features of hereditary angioedema (HAE) with normal level and functional activity of C1 esterase inhibitor. The discussion includes pathogenesis, diagnostics and case management of patients with hereditary angioedema without C1 esterase inhibitor deficiency. The materials of few scientific sources about patients with HAE without C1 esterase inhibitor deficiency in stages and our own clinical case (the female patient of fertile age with a confirmed mutation associated with factor XII (Hageman) deficiency) was given. The article describes the current state of the issue of the algorithm of primary diagnostics and differential diagnostics of HAE without C1 esterase inhibitor deficiency based on international and Russian data. It has been suggested that the new understanding of pathogenesis and treatment of patients with HAE without C1 esterase inhibitor deficiency is encouraging and becoming accessible to the medical society.

Plasma Kallikrein-Kinin System in Patients with Uncomplicated Sepsis and Septic Shock-Comparison with Cardiogenic Shock

1987 ◽  
Vol 58 (02) ◽  
pp. 709-713 ◽  
Author(s):  
F Martínez-Brotóns ◽  
J R Oncins ◽  
J Mestres ◽  
V Amargós ◽  
C Reynaldo
Keyword(s):  
Septic Shock ◽  
Cardiogenic Shock ◽  
Antithrombin Iii ◽  
Factor Xii ◽  
Kinin System ◽  
Normal Limits ◽  
At Iii ◽  
Sepsis And Septic Shock ◽  
Kallikrein Kinin System ◽  
Esterase Inhibitor

SummaryAlterations of the kallikrein-kinin system consistent with activation and increased consumption have been re2ported in septic patients and it has been suggested that this activation could contribute to the development of septic shock.The aim of this work was to confirm these alterations in septic patients and to investigate the possible existence of similar changes in subjects developing cardiogenic shock secondary to myocardial infarction as a model of non septic shock.Patients with septic shock, especially in fatal cases, showed a highly significant decrease in levels of factor XII, prekallikrein, high molecular weight kininogen (HMW-kininogen), α2-macro-globulin (α2-M) and antithrombin III (AT-III). C1-esterase inhibitor (C1-INH) activity was increased in uncomplicated sepsis but came back to normal or was slightly decreased in septic shock.Components and inhibitors of the kallikrein-kinin system were within normal limits in patients with cardiogenic shock.Our findings support the idea of a contribution of the kallikrein-kinin system to the development of septic shock though this system does not seem to play a significant role in the pathogenesis of cardiogenic shock or seem to be altered as a consequence of it.

Successful Long-Term Prophylactic Treatment With Subcutaneous C1 Esterase Inhibitor in a Patient With Hereditary Angioedema

2019 ◽  
Vol 33 (6) ◽  
pp. 907-911
Author(s):  
Janina Hahn ◽  
Melanie Nordmann-Kleiner ◽  
Susanne Trainotti ◽  
Thomas K. Hoffmann ◽  
Jens Greve
Keyword(s):  
Quality Of Life ◽  
Hereditary Angioedema ◽  
Prophylactic Treatment ◽  
Upper Airway ◽  
Venous Access ◽  
Current Standard ◽  
C1 Esterase Inhibitor ◽  
Esterase Inhibitor

Background: Hereditary angioedema (HAE) patients suffer from recurrent swellings. Current standard therapy consists of C1 esterase inhibitor (C1-INH) and bradykinin receptor B2 antagonists. Severe courses require prophylactic treatment. For such patients, it has been demonstrated that the intravenous (IV) administration of C1-INH [C1-INH(IV)] is safe and effective. A new prophylactic option is subcutaneous (SC) treatment with C1-INH. Methods and Case: We present the case of an HAE patient placed on prophylactic C1-INH(IV) therapy due to frequent attacks when managed with on-demand therapy. An implanted port allowed the periodical and safe application of medication until the device was explanted due to an infection. Due to the poor venous access, repeated IV application failed. Therefore, we began a SC treatment with 1500 IU C1-INH [C1-INH(SC)] as long-term prophylaxis and analyzed the clinical course over 16 months. Results: Under the SC prophylaxis, the number of attacks were reduced to 1/month in comparison to 4.33/month with no prophylactic treatment and 1.83/month with C1-INH(IV). No severe attacks and no attack within the upper airway occurred over the 16 months of C1-INH(SC) treatment. As a result, quality of life improved, as measured by the Angioedema quality of life questionaire (AE-QoL). Conclusion: Self-administered SC prophylactic use of C1-INH over a period of 16 months seems to be a well tolerated and efficient. The patient’s quality of life improved, and by learning self-application, the patient gained independence.

scholarly journals Management of Patients with Hereditary Angioedema During the COVID-19 Pandemic

2021 ◽  
Vol 19 (3) ◽  
pp. 166-173
Author(s):  
Eray YILDIZ ◽  
Şevket ARSLAN ◽  
Fatih ÇÖLKESEN ◽  
Filiz Sadi AYKAN ◽  
Recep EVCEN ◽  
...  
Keyword(s):  
Hereditary Angioedema ◽  
Clinical Symptoms ◽  
Type I ◽  
Type Ii ◽  
Kinin System ◽  
Beneficial Effects ◽  
Phone Calls ◽  
History Of ◽  
Kallikrein Kinin System

Objective: The aim of this study was to determine the clinical course and treatment outcomes of patients with hereditary angioedema (HAE) after infection with coronavirus disease 2019 (COVID-19). Materials and Methods: Thirty-nine patients with HAE were included in this study. These patients were regularly followed up over phone calls since the first COVID-19 case was seen in our country. Patients were asked to visit the hospital if there was a history of contact with a confirmed COVID-19 patient or if the patient developed clinical symptoms of COVID-19.Results: There were 21 (54%) patients with type I HAE, and 18 (46%) with type II HAE. All patients received treatment for angioedema attacks (C1-inhibitor [C1-INH], icatibant), and seven (20%) received long-term prophylaxis (danazol). Treatment for attacks was continued for all patients during the pandemic. Patients taking danazol were switched to long-term prophylaxis using the C1-INH concentrate. Eleven (28%) patients with HAE developed COVID-19 during this study. Only one patient had severe COVID-19. Six patients (54.5%) were diagnosed with type II HAE, and five (45.5%) were diagnosed with type I HAE. The most common COVID-19 symptoms were fever (7/11; 64%) and myalgia (6/11; 55%). Mild angioedema attacks were experienced by 36% (4/11) of the HAE patients diagnosed with COVID-19. Icatibant was used in all patients.Conclusion: Agents used for HAE block the kallikrein-kinin system and may be useful in the treatment of COVID-19. Considering their beneficial effects on COVID-19, it is recommended that HAE patients should continue the use of agents blocking the kallikrein-kinin system. Keywords: COVID-19, hereditary angioedema, kallikrein-kinin system, bradykinin, C1-INH

scholarly journals Features of diagnostics and clinical approaches to case management of patients with hereditary angioedema without C1 esterase inhibitor deficiency. Analysis of the clinical case

2020 ◽  
Vol 17 (1) ◽  
pp. 58-65
Author(s):  
Daria S Fomina ◽  
Elena N Bobrikova ◽  
Sofia A Serdotetskova
Keyword(s):  
Case Management ◽  
Hereditary Angioedema ◽  
Clinical Case ◽  
Medical Society ◽  
Differential Diagnostics ◽  
Factor Xii ◽  
C1 Esterase Inhibitor ◽  
Primary Diagnostics ◽  
Genetic Features ◽  
Esterase Inhibitor

This article describes the clinical, biochemical and genetic features of hereditary angioedema (HAE) with normal level and functional activity of C1 esterase inhibitor. The discussion includes pathogenesis, diagnostics and case management of patients with hereditary angioedema without C1 esterase inhibitor deficiency. The materials of few scientific sources about patients with HAE without C1 esterase inhibitor deficiency in stages and our own clinical case (the female patient of fertile age with a confirmed mutation associated with factor XII (Hageman) deficiency) was given. The article describes the current state of the issue of the algorithm of primary diagnostics and differential diagnostics of HAE without C1 esterase inhibitor deficiency based on international and Russian data. It has been suggested that the new understanding of pathogenesis and treatment of patients with HAE without C1 esterase inhibitor deficiency is encouraging and becoming accessible to the medical society.

scholarly journals In Vitro Modeling of Bradykinin-Mediated Angioedema States

2020 ◽  
Vol 13 (9) ◽  
pp. 201
Author(s):  
François Marceau ◽  
Hélène Bachelard ◽  
Xavier Charest-Morin ◽  
Jacques Hébert ◽  
Georges E. Rivard
Keyword(s):  
Analytical Techniques ◽  
Ace Inhibition ◽  
Factor Xii ◽  
Kinin System ◽  
Angiotensin I Converting Enzyme ◽  
B1 Receptor ◽  
Kallikrein Kinin System ◽  
Esterase Inhibitor

Kinins (peptides related to bradykinin, BK) are formed from circulating substrates, the kininogens, by the action of two proteases, the kallikreins. The only clinical application of a BK receptor ligand, the B2 receptor antagonist icatibant, is the treatment of the rare hereditary angioedema (HAE) caused by the deficiency of C1-esterase inhibitor (C1-INH). Less common forms of HAE (genetic variants of factor XII, plasminogen, kininogen) are presumably mediated by increased BK formation. Acquired forms of BK-mediated angioedema, such as that associated with angiotensin-I converting enzyme (ACE) inhibition, are also known. Antibody-based analytical techniques are briefly reviewed, and support that kinins are extremely short-lived, prominently cleared by ACE. Despite evidence of continuous activation of the kallikrein–kinin system in HAE, patients are not symptomatic most of the time and their blood or plasma obtained during remission does not generate excessive immunoreactive BK (iBK), suggesting effective homeostatic mechanisms. HAE-C1-INH and HAE-FXII plasmas are both hyperresponsive to fibrinolysis activation. On another hand, we suggested a role for the alternate tissue kallikrein–kinin system in patients with a plasminogen mutation. The role of the BK B1 receptor is still uncertain in angioedema states. iBK profiles under in vitro stimulation provide fresh insight into the physiopathology of angioedema.

Sign in / Sign up

Export Citation Format

Share Document