Quantification of Functional and Inactivated α2-Macroglobulin in Sepsis

J J Abbink; J H Nuijens; A J M Eerenberg; C C M Huijbregts; R J M Strack van Schijndel; L G Thijs; C E Hack

doi:10.1055/s-0038-1647450

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1991; 65(01): 032-039
DOI: 10.1055/s-0038-1647450

Original Article

Schattauer GmbH Stuttgart

Quantification of Functional and Inactivated α₂-Macroglobulin in Sepsis

Authors

J J Abbink

The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical lmmunology, University of Amsterdam, The Netherlands
J H Nuijens

The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical lmmunology, University of Amsterdam, The Netherlands
A J M Eerenberg

The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical lmmunology, University of Amsterdam, The Netherlands
C C M Huijbregts

The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical lmmunology, University of Amsterdam, The Netherlands
R J M Strack van Schijndel

¹The Medical Intensive Care Unit, Free University of Amsterdam, Amsterdam, The Netherlands
L G Thijs

¹The Medical Intensive Care Unit, Free University of Amsterdam, Amsterdam, The Netherlands
C E Hack

The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical lmmunology, University of Amsterdam, The Netherlands

Abstract

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Summary

Alpha₂-macroglobulin (α₂M) in vitro inhibits numerous proteinases that are generated during inflarnmatory reactions and therefore, probably plays an important role in diseases such as sepsis. To monitor the state of α₂M in sepsis, we developed novel assays for functional and inactive α₂M. Functional α₂M in palsama trypsin. Inactive α₂M (iα₂M) was assessed with a monoclonal antibody, mcAb M1, that specifically reacts with a neodeterminant exposed on iα₂M. This mcAb in combination with chromogenic substrates was used to detect α₂M-proteinase complexes.

Functional α₂M was reduced in plasma from 48 patients with clinical sepsis compared to healthy controls (p <0.0001). Levels of functional α₂M on admission and the lowest levels encountered in 23 patients with shock were lower than in 25 normotensive patienis (p = 0.023 and p = 0.009, respectively). Increased levels of iα₂M (>30 nM) at least on one occasion were found in only 4 of the 48 patients, being not different in hypotensive compared With normotensive patients, and not in patients who died compared with those who survived. Levels of functional α₂M correlated significantly with levels of factor XII and prekallikrein suggesting that decreases in α₂M at least in part were due to contact activation. Indeed, in two patients with increased iα₂M, complexes between α₂M and kallikrein were demonstrated in addition to plasmin- and thrombin-α₂M complexes.

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References

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