scholarly journals Activation of the contact system in insect-sting anaphylaxis: association with the development of angioedema and shock

Blood ◽  
1993 ◽  
Vol 82 (6) ◽  
pp. 1732-1739 ◽  
Author(s):  
PW van der Linden ◽  
CE Hack ◽  
AJ Eerenberg ◽  
A Struyvenberg ◽  
JK van der Zwan
Keyword(s):  
Contact System ◽  
Factor Xii ◽  
C1 Inhibitor ◽  
System Parameters ◽  
Insect Sting ◽  
Activation Products ◽  
History Of ◽  
Sting Challenge ◽  
Insect Stings

Abstract A postulated role of the contact system in anaphylactic reactions to insect stings was investigated. During prospective, in-hospital sting challenge, we collected serial blood samples from five normal volunteers and 16 patients with a history of insect-sting anaphylaxis. Activation of the contact system was assessed by measuring plasma levels of factor XIIa-C1-inhibitor and kallikrein-C1-inhibitor complexes as well as those of cleaved high molecular weight kininogen (HK). In addition, antigenic levels of (pre)kallikrein, factor XII, and HK were measured. No significant changes in contact system parameters were observed in any of the five volunteers or the four patients who did not develop an anaphylactic reaction after sting challenge. In contrast, significant changes in contact system parameters occurred in 7 of the 12 patients with anaphylactic symptoms after challenge. Peak levels of either C1-inhibitor complex were found 5 minutes after the onset of anaphylactic symptoms. The increase in C1-inhibitor was most pronounced in the 4 patients with angioedema, 2 of which also developed shock. However, activation of HK was observed in all four patients with angioedema, the two patients with shock but no angioedema, as well as in 1 of the remaining 6 patients with anaphylactic symptoms other than angioedema or shock. Thus, activation products of the contact system may be involved in the pathogenesis of angioedema and shock in insect- sting anaphylaxis.

scholarly journals Activation of the contact system in insect-sting anaphylaxis: association with the development of angioedema and shock

Blood ◽  
1993 ◽  
Vol 82 (6) ◽  
pp. 1732-1739 ◽  
Author(s):  
PW van der Linden ◽  
CE Hack ◽  
AJ Eerenberg ◽  
A Struyvenberg ◽  
JK van der Zwan
Keyword(s):  
Contact System ◽  
Factor Xii ◽  
C1 Inhibitor ◽  
System Parameters ◽  
Insect Sting ◽  
Activation Products ◽  
History Of ◽  
Sting Challenge ◽  
Insect Stings

A postulated role of the contact system in anaphylactic reactions to insect stings was investigated. During prospective, in-hospital sting challenge, we collected serial blood samples from five normal volunteers and 16 patients with a history of insect-sting anaphylaxis. Activation of the contact system was assessed by measuring plasma levels of factor XIIa-C1-inhibitor and kallikrein-C1-inhibitor complexes as well as those of cleaved high molecular weight kininogen (HK). In addition, antigenic levels of (pre)kallikrein, factor XII, and HK were measured. No significant changes in contact system parameters were observed in any of the five volunteers or the four patients who did not develop an anaphylactic reaction after sting challenge. In contrast, significant changes in contact system parameters occurred in 7 of the 12 patients with anaphylactic symptoms after challenge. Peak levels of either C1-inhibitor complex were found 5 minutes after the onset of anaphylactic symptoms. The increase in C1-inhibitor was most pronounced in the 4 patients with angioedema, 2 of which also developed shock. However, activation of HK was observed in all four patients with angioedema, the two patients with shock but no angioedema, as well as in 1 of the remaining 6 patients with anaphylactic symptoms other than angioedema or shock. Thus, activation products of the contact system may be involved in the pathogenesis of angioedema and shock in insect- sting anaphylaxis.

Structure, Kinetics, and Function of Human and Rhesus Plasma Prekallikreins Are Similar

1992 ◽  
Vol 68 (05) ◽  
pp. 526-533 ◽  
Author(s):  
Dulce Veloso ◽  
Joseph I Smith ◽  
Stephen Denny ◽  
Thomas M Cosgriff
Keyword(s):  
Human Plasma ◽  
Plasma Concentrations ◽  
Contact System ◽  
Factor Xii ◽  
Α2 Macroglobulin ◽  
Activation Products ◽  
Molecular Masses ◽  
And Function ◽  
Human Infections

SummaryTo determine if rhesus monkeys (Macaca mulatta) could serve as a model for studying the role of the contact system in the pathophysiology of human infections, we compared structural, kinetic, and functional characteristics of plasma prekallikrein and its activation products in rhesus and humans. Three prekallikrein variants (85-, 89- and 93-kDa) were revealed in rhesus plasma as compared with the two variants (85- and 88-kDa) in human plasma by immunoblotting with the monoclonal antibody MAb 13G11. The prekallikrein concentration in rhesus plasma was 1.5-fold that in human plasma as determined by computerized immunoblot analyses (CIBA) and amidolytic activity. The electrophoretic mobility of prekallikrein from plasma of both species increased after deglycosylation. Inhibition of prekallikrein activation by MAb 13G11 was 55% (rhesus plasma) and 76% (human plasma), with similar inhibition curves. Immunoblots of activated rhesus plasma showed prekallikrein, complexes of kallikrein with C1 inhibitor, α2-macroglobulin and ~60-kDa inhibitor(s) (viz. antithrombin III), and 45-kDa fragments, like those in activated human plasma. Concentrations and molecular masses of factor XII and high molecular weight kininogen were similar in rhesus and human plasma. The activated partial thromboplastin time (APTT) and prothrombin time were 20.1 ± 1.6 and 9.7 ± 0.3 s for rhesus and 32.0 ±5.6 and 12 ± 0.5 s for human plasma. Human and rhesus APTTs were similar when prekallikrein concentrations in human and rhesus plasma became alike by adding human purified prekallikrein. We conclude that the contact systems of rhesus and humans are similar in many respects and that rhesus should be a useful model to study the role of the contact system in the pathophysiology of human infectious diseases.

The Role of Factor XII in Contact System Activation

Blood ◽  
1998 ◽  
Vol 92 (2) ◽  
pp. 703-704 ◽  
Author(s):  
C. Erik Hack
Keyword(s):  
Contact System ◽  
Factor Xii ◽  
System Activation

DEMONSTRATION OF Cl-INHIBITOR COMPLEXES IN PLASMA BY HIGHLY SENSITIVE RADIOIMMUNOASSAYS USING A MONOCLONAL ANTIBODY AGAINST A NEODETERMINANT ON COMPLEXED Cl-INHIBITOR

1987 ◽  
Author(s):  
J H Nuijens ◽  
C C M Huijbregets ◽  
L G Thijs ◽  
C E Hack
Keyword(s):  
Monoclonal Antibody ◽  
Contact System ◽  
Factor Xii ◽  
Optimal Conditions ◽  
Spleen Cells ◽  
Highly Sensitive ◽  
Factor Xiia

Levels of factor XIIa- and kallikrein-Cl inhibitor (Cl-Inh) complexes in plasma reflect activation of the contact system in vivo. Here, we report the development of radioimmunoassays (RIAs) for these complexes using a monoclonal antibody (mAb K0K12) that reacts with a neodeterminant exposed on Cl-Inh after interaction with proteases. mAb K0K12 was obtained by a fusion experiment with spleen cells of a mouse hyperimmunized with Cl-Inh complexes.Experiments with purified Cl-Inh incubated with either Cls or elastase revealed that the determinant for mAb KOK12 is exposed on complexed as well as proteolytically inactivated (modified) Cl-Inh.Radioimmunoassays (RIAs) for the detection of factor Xlla-Cl-Inh and kallikrein-Cl-Inh complexes were performed as follows: mAb K0K12 was coupled to Sepharose and incubated with the sample to be tested. Binding of Cl-Inh complexes was detected by a subsequent incubation with 125I-antibodies against factor XII or (pre)kallikrein.With these RIAs, activation of 0.1% of factor XII or prekal-likrein in plasma is easily detected.Optimal conditions for blood sampling and processing were established, i.e. conditions that prevented any in vitro activation of factor XII and prekallikrein. Levels of factor XIIa-Cl-Inh and kallikrein-Cl-Inh complexes in plasma samples from normal donors were less than 0.1 U/ml (100 U/ml is the maximal amount of Cl-Inh complexes generated in pooled plasma by DXS). Considerably higher, and fluctuating levels were observed in patients with diseases such as septicaemia. These highly sensitive RIAs will facilitate studies concerning the role of the contact system in human pathophysiology.

ANAPHYLACTIC SHOCK AFFER INSECT-STING CHALLENGE IN 138 PERSONS WITH A PREVIOUS INSECT-STING REACTION

PEDIATRICS ◽  
1994 ◽  
Vol 94 (2) ◽  
pp. 249-250
Author(s):  
Peter Cvietusa ◽  
Joseph Spahn ◽  
Allen ADinoff
Keyword(s):  
Blood Pressure ◽  
Anaphylactic Reaction ◽  
Anaphylactic Shock ◽  
Severe Reaction ◽  
Angiotensin I ◽  
Significant Information ◽  
Arterial Blood ◽  
Insect Sting ◽  
History Of ◽  
Sting Challenge

Purpose of the Study. The goal of the study was to establish the frequency with which anaphylactic reactions reoccur after sting challenge in persons with previous insect-sting anaphylactic reactions, as well as the relation between the severity of anaphylaxis and levels of catecholamines and angiotensins. Methods. One hundred thirty-eight patients with a history of an anaphylactic reaction and eight normals (including five patients who had been previously stung) were subjected to provocation test with the relevant insect. Blood samples were collected and assayed for epinephrine, norepinephrine, dopamine, and angiotensin I and II levels. Findings. "Only" 39 of 138 (28%) patients with a previous insect sting anaphylactic reaction developed anaphylactic symptoms after sting challenge. Only those with a history of a severe reaction developed anaphylactic shock. No change in cardiovascular mediators or blood pressure was seen in patients with no or mild reactions, while those patients with anaphylactic shock had a mean arterial blood pressure drop of 33%. Significant increases in epinephrine, norepinephrine, and angiotensin II were observed within 5 minutes after the onset of symptoms and were strongly correlated with a drop in blood pressure. Dopamine and angiotensin I levels did not change significantly in any participants. Reviewers' Comments. The repeat rate of systemic reactions of 28% is substantially lower than the previously reported rate of 60% (Hung KJ, et al. NEJM. 1978;299:157). Unfortunately, the present study does not provide significant information regarding the study population, particularly the time lapsed between the original and rechallenge stings. We are all aware of the associated problems of beta-blockers and anaphylaxis.

scholarly journals Recent insights into the role of the contact pathway in thrombo-inflammatory disorders

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 60-65 ◽  
Author(s):  
Maurits L. van Montfoort ◽  
Joost C.M. Meijers
Keyword(s):  
Molecular Weight ◽  
Small Molecules ◽  
Antisense Oligonucleotides ◽  
Contact System ◽  
Factor Xii ◽  
High Molecular Weight Kininogen ◽  
Vascular Beds ◽  
Contact Pathway

Abstract The contact pathway of coagulation consists of the proteins factor XI, factor XII, prekallikrein, and high-molecular-weight kininogen. Activation of the contact system leads to procoagulant and proinflammatory reactions. The contact system is essential for surface-initiated coagulation, as exemplified by aPTT, but there is probably no role for the contact system in initiating physiologic in vivo coagulation. However, over the last few years, there has been renewed interest, especially because of experimental evidence suggesting that the contact system contributes to thrombosis. Knockout mice deficient in one of the contact proteins were protected against artificially induced thrombosis. Furthermore, inhibiting agents such as monoclonal antibodies, antisense oligonucleotides, and small molecules were found to prevent thrombosis in rodents and primates in both venous and arterial vascular beds. Although it remains to be established whether targeting the contact system will be effective in humans and which of the contact factors is the best target for anticoagulation, it would constitute a promising approach for future effective and safe antithrombotic therapy.

Detection of Activation of the Contact System of Coagulation In Vitro and In Vivo: Quantitation of Activated Hageman Factor-C1-Inhibitor and Kallikrein-C1-Inhibitor Complexes by Specific Radioimmunoassays

1987 ◽  
Vol 58 (02) ◽  
pp. 778-785 ◽  
Author(s):  
J H Nuijens ◽  
C C M Huijbregts ◽  
M Cohen ◽  
G O Navis ◽  
A de Vries ◽  
...  
Keyword(s):  
Contact System ◽  
Factor Xii ◽  
Plasma Samples ◽  
C1 Inhibitor ◽  
Hageman Factor ◽  
Plasma Factor ◽  
Factor Xiia ◽  
Kallikrein Activity

SummaryRadioimmunoassays (RIAs) for the detection of C1-inhihitor (C1-Inh) complexed to either kallikrein or activated Hageman factor (factor XIIa) are described. Kallikrein-C1-Inh or factor XIIa-C1-Inh complexes were bound to Scpharosc to which monospecific antibodies against (pre)kallikrein or factor XII, respectively, were coupled. Bound complexes were subsequently detected by an incubation with affinity purified 125I-labeled antibodies against Ci-Inh. These RIAs were used to detect activation of the contact system of coagulation in vitro and in vivo. Addition of dextran sulfate (DXS) (20 μg/ml) to fresh plasma resulted at 37° C in the rapid generation of amidolytic kallikrein activity, which was maximal after 1 to 2 min of incubation and subsequently decreased within a few minutes. The generation of kallikrein activity coincided with the appearance of both kallikrein-C1-Inh and factor XIIa-C1-Inh complexes. However, in contrast to kallikrein activity, both types of complexes remained detectable in the incubation mixtures during the incubation period. Experiments with purified kallikrein, C1-Inh and partly purified β-factor XIIa, and activation experiments in plasmas deficient in either factor XII or prekallikrein, demonstrated the specificity of both RIAs. The minimal amount of DXS that resulted in the generation of measurable amounts of both types of complexes in plasma was 2-3 μg per ml. Similar experiments with kaolin showed that with limiting amounts of activator (1-2 mg/ ml), only kallikrein-C1-Inh complexes were detected in plasma. When larger amounts of kaolin were added to plasma, factor XIIa-C1-Inh complexes were additionally detected in plasma. In plasma samples obtained from healthy donors under conditions that prevented activation of the contact system in vitro, very low levels of both factor XIIa-C1-Inh and kallikrein-C1-Inh complexes were measured, representing approximately 0.3% activation of both factor XII and prekallikrein. In serial plasma samples from a patient with adult respiratory distress syndrome, increased levels of both types of complexes were detected. The radioimmunoassays described in this paper provide useful tools to detect activation of the contact system in vitroas well as in vivo.

Activation of the Intrinsic Pathway of Coagulation in Children with Meningococcal Septic Shock

1995 ◽  
Vol 74 (06) ◽  
pp. 1436-1441 ◽  
Author(s):  
Walter A Wuillemin ◽  
Karin Fijnvandraat ◽  
Bert H F Derkx ◽  
Marjolein Peters ◽  
Willem Vreede ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Septic Shock ◽  
Intensive Care ◽  
Contact System ◽  
Morbidity And Mortality ◽  
Factor Xii ◽  
C1 Inhibitor ◽  
Intrinsic Pathway ◽  
Factor Xi ◽  
Meningococcal Septic Shock

SummaryMeningococcal septic shock (MSS) is complicated by activation of coagulation, fibrinolytic, and complement systems. We studied the contact system of the intrinsic pathway of coagulation in thirteen children with MSS. Activation was assessed upon admittance to the intensive care unit and 48 h thereafter, based on the measurement of factor XII- (FXII), prekallikrein- and factor XI (FXI) antigen levels, as well as on the detection of FXIa-FXIa inhibitor, FXIIa-C1-inhibitor, and kallikrein-C1-inhibitor complexes, respectively. Levels of FXII, prekallikrein and FXI were reduced to about 50% in all patients on admission, and were significantly higher 48 h later. FXIIa-C1-inhibitor complexes were elevated in 7 patients, and kallikrein-C1-inhibitor complexes in 2 patients. FXIa-α1-antitrypsin complexes were elevated in all patients, FXIa-C1-inhibitor complexes in nine, and FXIa-anti-thrombin III complexes in one patient. We conclude that patients with MSS have activation of the contact system, which may contribute to activation of coagulation, and thus to morbidity and mortality.

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