Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency
ABSTRACT Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) is characterized by relapsing skin swellings, abdominal pain attacks, and, less frequently, potentially life-threatening laryngeal attacks.
This study determined the mortality of patients with and without the diagnosis of HAE-C1-INH and analyzed fatal laryngeal attacks.
A cohort of 728 patients from 182 families with HAE-C1-INH was evaluated for death cases by analyzing pedigrees. Detailed information on fatal laryngeal attacks in 36 patients was obtained by questioning relatives and treating physicians.
Of the 214 patients who had died, 70 asphyxiated during a laryngeal attack. Mortality by asphyxiation was higher in patients with undiagnosed HAE-C1-INH (63 cases) than in patients with diagnosed HAE-C1-INH (7 cases). The lifespan of asphyxiated patients with undiagnosed HAE-C1-INH was on average ∼31 years shorter than patients with undiagnosed HAE-C1-INH who died of other causes. Three phases were distinguished in the fatal laryngeal attacks. Phase 1, the predyspnea phase, lasted on average for 3.7 ± 3.2 hours (range, 0-11 hours). Phase 2, the dyspnea phase, lasted on average for 41 ± 49 minutes (range, 2 minutes to 4 hours). Phase 3, the loss of consciousness phase, lasted on average for 8.9 ± 5.1 minutes (range, 2-20 minutes).
The high mortality in patients with undiagnosed HAE-C1-INH underscores the need to identify these patients and diagnose their condition. The analysis of fatal laryngeal attacks gives further insight into their course, thus helping to avoid fatalities in the future.
SourceAvailable from: Christian Drouet
Dataset: 1411Madsen C1InhPolymers PlosOne
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ABSTRACT: Background. Controlling prekallikrein activation by C1-Inhibitor (C1Inh) represents the most essential mechanism for angioedema patient protection. C1Inh function in the plasma is usually measured based on the residual activity of the C1s protease not involved in the pathological process. We have herby proposed an alternative enzymatic measurement of C1Inh function based on contact phase activation and correlation with angioedema diagnostic requirements. Methods. The contact phase was reconstituted using the purified components, with C1Inh standard or plasma sample. The kinetics of the amidase activity were monitored using Pro-Phe-Arg-pNA, independently of alpha2-Macroglobulin (α2M).We prevented any interference from a possible high plasma kininogenase activity by pre-incubating the samples with protease inhibitor. Receiver operating characteristics (ROC) were used to calculate the assay’s diagnostic performance. Results. The calibration curve was built using C1Inh standard (threshold limit 0.10mU, i.e. 0.2pmol) and C1Inh function was quantified in the sample, with a reference interval established based on healthy individuals (n=281; men: 0.61-1.10U/mL, median: 0.85U/mL; women: 0.42-1.08U/mL, median: 0.74U/mL). The median values of female donors were lower than those of the others due to estrogen, yet C1Inh function remained within the reference interval. The ROC curve calculation provided the following optimum diagnostic cut-off values: women 0.36U/mL (area under curve [AUC]: 0.99; sensitivity: 93.48%; specificity: 99.37%); men 0.61U/mL (AUC: 1; sensitivity: 100.0%; specificity: 100.0%). Conclusion: The performance outcome provided features suitable for angioedema diagnostic or follow-up. Established by means of the kinin formation process, this assay should be preferred over the method based on a C1s protease target.Allergy 05/2015; DOI:10.1111/all.12657 · 6.00 Impact Factor
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ABSTRACT: Acute attacks of hereditary angioedema are characterized by recurrent localized edema. These attacks can be life threatening and are associated with substantial morbidity and mortality. To determine factors associated with hospital admission of patients with an acute attack of hereditary angioedema presenting at the emergency department. This was a multicenter prospective observational study of consecutive patients (January 2011 through December 2013) experiencing an acute hereditary angioedema attack and presenting at the emergency department at 1 of 4 French reference centers for bradykinin-mediated angioedema. Attacks requiring hospital admission were compared with those not requiring admission. Of 57 attacks in 29 patients, 17 (30%) led to hospital admission. In multivariate analysis, laryngeal and facial involvements were associated with hospital admission (odds ratio 18.6, 95% confidence interval 3.9-88; odds ratio 7.7, 95% confidence interval 1.4-43.4, respectively). Self-injection of icatibant at home was associated with non-admission (odds ratio 0.06, 95% confidence interval 0.01-0.61). The course was favorable in all 57 cases. No upper airway management was required. Most patients attended the emergency department because they were running out of medication and did not know that emergency treatment could be self-administered. Risk factors associated with hospital admission were laryngeal and facial involvement, whereas self-injection of icatibant was associated with a return home. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 04/2015; DOI:10.1016/j.anai.2015.04.005 · 2.75 Impact Factor