International Council for Standardization in Haematology (ICSH) recommendations for laboratory measurement of ADAMTS13.

Ian Mackie,Ilaria Mancini,Johanna Kremer Hovinga,Sam Machin,Joshua Muia,Ross Baker,Sukesh Nair

doi:10.1111/ijlh.13295

Abstract

This guidance document was prepared on behalf of the International Council for Standardization in Haematology (ICSH), by the ADAMTS13 Assay Working Group, which comprises an international group of both clinical and laboratory experts. The document provides recommendations on best practice for the performance of ADAMTS13 assays in clinical laboratories. ADAMTS13 assays support the differential diagnosis of thrombotic microangiopathies and have utility in the management of thrombotic thrombocytopenic purpura (TTP). There are three types of assay: activity, antigen and autoantibody/inhibitor assays. Methods for activity assays differ in terms of sensitivity, specificity, precision and turnaround time. The most widely used assays involve VWF peptide substrates and either chromogenic ELISA or FRET techniques, although chemiluminescence assays and rapid screening tests have recently become available. Tests for autoantibodies and inhibitors allow confirmation of acquired, immune-mediated TTP, while antigen assays may be useful in congenital TTP and as prognostic markers. In this document, we have attempted to describe ADAMTS13 assays and the conditions that affect them, as well as: blood collection, sample processing, quality control, standardization and clinical utility; recognizing that laboratories in different parts of the world have varying levels of sophistication. The recommendations are based on expert opinion, published literature and good clinical laboratory practice.

Highlights

ADAMTS13 (A disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13) is a plasma metalloprotease which is critically involved in the control of von Willebrand Factor (VWF), its major substrate.[1]
The high shear stress found in small arterioles unravels the globular form of ULVWF so that the metalloprotease domain of ADAMTS13 can come into close proximity with the cleavage site in the VWF A2 domain, allowing cleavage
In thrombotic thrombocytopenic purpura (TTP), there is a loss of ADAMTS13 function resulting in the prolonged circulation of ULVWF, which has an increased platelet binding capacity and may participate in platelet aggregate formation in the microcirculation with sequestration and consequent thrombocytopenia

Summary

Introduction

ADAMTS13 (A disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13) is a plasma metalloprotease which is critically involved in the control of von Willebrand Factor (VWF), its major substrate.[1]. May affect ADAMTS13 interaction sites present on VWF (causing reduced activity), but not smaller peptide substrates (which may give higher values) and handling differences may contribute to these changes as well as a variety of in vivo and in vitro factors (Table 2).

Results

Conclusion