Heparin-induced thrombocytopenia: An international assessment of the quality of laboratory testing

J Thromb Haemost. 2019 Dec;17(12):2123-2130. doi: 10.1111/jth.14611. Epub 2019 Sep 25.

Abstract

Background: Accurate diagnosis of heparin-induced thrombocytopenia (HIT) is essential to ensure timely treatment and prevent complications. Current diagnostic assays include enzyme-linked immunosorbent assays (ELISAs) and rapid immunoassays (RIs). RIs offer fast turnaround times but were not significantly represented in previous external proficiency testing challenges.

Objectives: To use external proficiency testing to assess qualitative concordance for heparin/PF4 antibody detection.

Methods: From 2013 to 2017, the External Quality Control for Assays and Tests (ECAT) Foundation distributed 10 samples internationally.

Results: In total, 437 laboratories submitted 3149 results. ELISAs accounted for 1484 (47%) responses with RIs accounting for 1665 (53%) responses. RI use increased over the 5-year period. ELISAs classified 96% of both consensus positive and consensus negative samples concordantly. The coefficient of variation (CV) for positive sample optical densities (ODs) ranged from 35% to 50% when combining ELISA assay methods together. Quantitative RIs classified 97% of consensus-positive and 98% of consensus-negative samples concordantly. Qualitative RIs had a higher proportion of discordant responses and classified 88% of consensus-positive samples and 73% of consensus-negative samples concordantly. Of RIs only latex immunoassays and IgG specific chemiluminescent assays identified > 95% of samples concordantly with consensus.

Conclusion: Quantitative RIs and ELISAs classify > 95% of samples concordantly. The ODs from different ELISA methods vary considerably and are not interchangeable. Qualitative RI use is increasing despite a greater proportion of discordant classifications. This includes a higher than expected number of negative classifications for consensus-positive samples among many RIs, challenging their use as "rule out" tests.

Keywords: diagnosis; heparin; immunologic tests; thrombocytopenia; thrombosis.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / blood*
  • Anticoagulants / adverse effects*
  • Anticoagulants / immunology
  • Australia
  • Biomarkers / blood
  • Enzyme-Linked Immunosorbent Assay / standards*
  • Europe
  • Heparin / adverse effects*
  • Heparin / immunology
  • Humans
  • Israel
  • Laboratory Proficiency Testing*
  • North America
  • Observer Variation
  • Platelet Factor 4 / immunology*
  • Predictive Value of Tests
  • Radioimmunoassay / standards*
  • Reproducibility of Results
  • Serologic Tests / standards*
  • Thrombocytopenia / blood
  • Thrombocytopenia / chemically induced
  • Thrombocytopenia / diagnosis*
  • Thrombocytopenia / immunology

Substances

  • Antibodies
  • Anticoagulants
  • Biomarkers
  • PF4 protein, human
  • Platelet Factor 4
  • Heparin