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Treatment of episodes of hereditary angioedema with C1 inhibitor: serial assessment of observed abnormalities of the plasma bradykinin-forming pathway and fibrinolysis.
Ann Allergy Asthma Immunol 2010; 104(1):50-4AA

Abstract

BACKGROUND

Hereditary angioedema (HAE) is typically the result of a deficiency of C1 inhibitor (C1-INH) with gene defects that lead to diminished plasma levels or the production of a dysfunctional protein. Replacement therapy with C1-INH has been shown to be effective in ameliorating episodes of swelling. We have reported elevated baseline levels of bradykinin, C4a, and plasmin-alpha2-antiplasmin complexes in the plasma of patients with HAE compared with the plasma of healthy controls. The production of factor XII fragment on in vitro activation of plasma with HAE has also been observed.

OBJECTIVE

To perform serial assessment of abnormalities of the bradykinin-forming pathway and fibrinolysis in patients with HAE after treatment of episodes of swelling with intravenous C1-INH.

METHODS

We obtained samples of plasma from 9 patients with HAE at a quiescent period (baseline), during an attack of swelling, and at 1, 4, and 12 hours after termination of an infusion of C1-INH. Factor XIIa, kallikrein, and plasmin were each measured by cleavage of synthetic substrates specific for each item.

RESULTS

Each enzyme was strikingly elevated at baseline compared with the levels in pooled healthy plasma, and there was a progressive decline of activity to normal for factor XIIa and plasmin. Kallikrein decreased in 7 of the 9 patients at 1 hour and then decreased in all patients. Bradykinin levels were elevated at the outset in all patients, increased prominently during an attack of swelling, decreased to baseline after 1 hour, and then decreased toward normal by 4 and 12 hours.

CONCLUSION

The plasma levels of factor XIIa, kallikrein, and bradykinin decreased when measured serially subsequent to the infusion of nanofiltered C1-INH.

Authors+Show Affiliations

Division of Rheumatology and Clinical Immunology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA. josephkusum@gmail.comNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20143645

Citation

Joseph, Kusumam, et al. "Treatment of Episodes of Hereditary Angioedema With C1 Inhibitor: Serial Assessment of Observed Abnormalities of the Plasma Bradykinin-forming Pathway and Fibrinolysis." Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology, vol. 104, no. 1, 2010, pp. 50-4.
Joseph K, Tholanikunnel TE, Kaplan AP. Treatment of episodes of hereditary angioedema with C1 inhibitor: serial assessment of observed abnormalities of the plasma bradykinin-forming pathway and fibrinolysis. Ann Allergy Asthma Immunol. 2010;104(1):50-4.
Joseph, K., Tholanikunnel, T. E., & Kaplan, A. P. (2010). Treatment of episodes of hereditary angioedema with C1 inhibitor: serial assessment of observed abnormalities of the plasma bradykinin-forming pathway and fibrinolysis. Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology, 104(1), pp. 50-4. doi:10.1016/j.anai.2009.11.014.
Joseph K, Tholanikunnel TE, Kaplan AP. Treatment of Episodes of Hereditary Angioedema With C1 Inhibitor: Serial Assessment of Observed Abnormalities of the Plasma Bradykinin-forming Pathway and Fibrinolysis. Ann Allergy Asthma Immunol. 2010;104(1):50-4. PubMed PMID: 20143645.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Treatment of episodes of hereditary angioedema with C1 inhibitor: serial assessment of observed abnormalities of the plasma bradykinin-forming pathway and fibrinolysis. AU - Joseph,Kusumam, AU - Tholanikunnel,Tracy E, AU - Kaplan,Allen P, PY - 2010/2/11/entrez PY - 2010/2/11/pubmed PY - 2010/4/8/medline SP - 50 EP - 4 JF - Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology JO - Ann. Allergy Asthma Immunol. VL - 104 IS - 1 N2 - BACKGROUND: Hereditary angioedema (HAE) is typically the result of a deficiency of C1 inhibitor (C1-INH) with gene defects that lead to diminished plasma levels or the production of a dysfunctional protein. Replacement therapy with C1-INH has been shown to be effective in ameliorating episodes of swelling. We have reported elevated baseline levels of bradykinin, C4a, and plasmin-alpha2-antiplasmin complexes in the plasma of patients with HAE compared with the plasma of healthy controls. The production of factor XII fragment on in vitro activation of plasma with HAE has also been observed. OBJECTIVE: To perform serial assessment of abnormalities of the bradykinin-forming pathway and fibrinolysis in patients with HAE after treatment of episodes of swelling with intravenous C1-INH. METHODS: We obtained samples of plasma from 9 patients with HAE at a quiescent period (baseline), during an attack of swelling, and at 1, 4, and 12 hours after termination of an infusion of C1-INH. Factor XIIa, kallikrein, and plasmin were each measured by cleavage of synthetic substrates specific for each item. RESULTS: Each enzyme was strikingly elevated at baseline compared with the levels in pooled healthy plasma, and there was a progressive decline of activity to normal for factor XIIa and plasmin. Kallikrein decreased in 7 of the 9 patients at 1 hour and then decreased in all patients. Bradykinin levels were elevated at the outset in all patients, increased prominently during an attack of swelling, decreased to baseline after 1 hour, and then decreased toward normal by 4 and 12 hours. CONCLUSION: The plasma levels of factor XIIa, kallikrein, and bradykinin decreased when measured serially subsequent to the infusion of nanofiltered C1-INH. SN - 1081-1206 UR - https://www.unboundmedicine.com/medline/citation/20143645/Treatment_of_episodes_of_hereditary_angioedema_with_C1_inhibitor:_serial_assessment_of_observed_abnormalities_of_the_plasma_bradykinin_forming_pathway_and_fibrinolysis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1081-1206(09)00015-5 DB - PRIME DP - Unbound Medicine ER -