Evaluation of paroxysmal nocturnal hemoglobinuria screening by flow cytometry through multicentric interlaboratory comparison in four countries

Am J Clin Pathol. 2015 Dec;144(6):858-68. doi: 10.1309/AJCPWMWJ7XDNQ3SN.

Abstract

Objectives: Paroxysmal nocturnal hemoglobinuria (PNH) is currently diagnosed by flow cytometry; although highly sensitive, its interpretation and reporting appear as critical as its technique. Thus, we developed a quality control scheme for the French-speaking region based on the international recommendations for PNH screening.

Methods: After a topical workshop, we proposed a 1-year, two-step survey program to any volunteering French-speaking clinical laboratory. The first survey consisted of sending raw data files to evaluate gating and the interpretation strategy of each center. The second stipulated sending fresh whole-blood samples to evaluate the whole process and its practice.

Results: Forty-nine participants from voluntary centers returned results for each of the two successive surveys. On virtual survey, 27% reported false-positive PNH created by immature granulocytes, whereas the minor PNH clone was not detected by 9%. On fresh survey, 63% of centers used at least the same six-color combination (CD24, CD14, CD33, CD15, CD45, and fluorescent aerolysin), and nearly 70% of participants were able to perform a sensitivity test less than 0.1% on neutrophils. All participants detected the major PNH clone, yet 16% returned false-positive results for the non-PNH clone case.

Conclusions: We succeeded in rallying numerous French-speaking clinical laboratories for both surveys and in harmonizing the technical practice by highlighting common pitfalls.

Keywords: Accreditation; Flow cytometry; Interlaboratory comparison; PNH; Robust statistics.

Publication types

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

MeSH terms

  • False Positive Reactions
  • Flow Cytometry / methods*
  • Flow Cytometry / standards*
  • Hemoglobinuria, Paroxysmal / diagnosis*
  • Humans