Validation of whole blood impedance aggregometry as a new diagnostic tool for HIT

Marie-Christine Morel-Kopp; Chee Wee Tan; Timothy A Brighton; Simon McRae; Ross Baker; Huyen Tran; Peter Mollee; Geoffrey Kershaw; Joanne Joseph; Christopher Ward; the ASTH Clinical Trials Group; on behalf of

doi:10.1160/TH11-09-0631

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2012; 107(03): 575-583
DOI: 10.1160/TH11-09-0631

New Technologies, Diagnostic Tools and Drugs

Schattauer GmbH

Validation of whole blood impedance aggregometry as a new diagnostic tool for HIT

Results of a large Australian study

Marie-Christine Morel-Kopp

¹Northern Blood Research Centre, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia

²Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, Sydney, Australia

,

Chee Wee Tan

¹Northern Blood Research Centre, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia

²Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, Sydney, Australia

,

Timothy A Brighton

³SEALS, Prince of Wales Hospital, Sydney, Australia

,

Simon McRae

⁴Department of Haematology SA Pathology, Adelaide, Australia

,

Ross Baker

⁵Department of Haematology, Royal Perth Hospital, Perth, Australia

,

Huyen Tran

⁶Monash Medical Centre, Melbourne, Australia

,

Peter Mollee

⁷Department of Haematology, Princess Alexandra Hospital, Brisbane, Australia

,

Geoffrey Kershaw

⁸Royal Prince Alfred Hospital, Sydney, Australia

,

Joanne Joseph

⁹Haematology Department, St Vincent Hospital, Sydney, Australia

,

Christopher Ward

¹Northern Blood Research Centre, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia

²Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, Sydney, Australia

,

the ASTH Clinical Trials Group

› Author Affiliations

Abstract

Summary

Heparin-induced thrombocytopenia (HIT) remains a challenge, with diagnosis confirmed only by functional assays. The gold standard ¹⁴C-se-rotonin release assay (SRA) is highly sensitive but technically challenging and unsuitable for routine use. We conducted a large study to validate whole blood impedance aggregometry (WBIA) as a suitable diagnostic tool for HIT. WBIA and SRA were used to test 181 samples positive for H-PF4 antibodies by PaGIA or ELISA. Using the same high responder donor, 77 samples were positive by WBIA (aggregation with low-dose but not high-dose heparin). Using the strict definition for SRA positivity, 72 samples were true HIT. In nine samples, serotonin release with high-dose heparin dropped by > 50% but was still >20%; these were retested after a one-half dilution and 8/9 became positive. Ten other samples were discrepant between the two assays: one strongly positive (89% release) and six weakly positive samples by SRA (average release 56%) were WBIA negative. When these samples were retested using a random donor, only two remained SRA positive. Three samples were strongly WBIA positive but SRA negative; two were retested by SRA with 0.5IU/ml heparin and one became positive. Under controlled conditions, using the same selected high-responder donor, WBIA and SRA performed similarly with slightly increased sensitivity of the WBIA when using the strict definition of SRA positivity. WBIA is easy to perform with rapid turn-around time and warrants a multi-laboratory trial to complete its validation as a confirmatory assay for platelet-activating HIT antibodies.

Keywords

Heparin - heparin-induced thrombocytopenia - 4T′s score - serotonin release assay - whole blood impedance aggregometry

Full Text

References

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