Association between megakaryocyte abnormalities on bone marrow smear and response to thrombopoietin receptor agonists in adult patients with primary immune thrombocytopenia.

Impaired platelet production is a mechanism of immune thrombocytopenia (ITP). Morphological abnormalities of megakaryocytes (MKs) are sometimes observed in this disease. Two studies have suggested an association between MK abnormalities and response to corticosteroids in primary ITP, but none have investigated this association for thrombopoietin-receptor agonists (TPO-RAs). This was the aim of this study. The source of population was the French CARMEN registry with prospective follow-up of adult patients with incident ITP. We included patients with primary ITP, treated by TPO-RA and with a bone marrow smear before initiating TPO-RA. MK abnormalities were categorized by the presence of dysplasia and by the stage of maturation. Among 451 patients screened, 38 were included in the analysis. There was no difference in the median percentage of dysplastic MKs between responders to TPO-RA (4.0%, 95% confidence interval - CI: 2.3-6.4) and non-responders (4.5%, 95% CI: 0.7-7.1). There was a slightly higher proportion of granular MKs (4.5%, 95% CI: 3-6) and basophilic MKs (30.1%, 95% CI: 21.9-39.1) in non-responders compared to responders (granular: 2.0%, 95% CI: 0-4.1; basophilic: 21.3%, 95% CI: 11.4-40.7). In conclusion, MK abnormalities were not associated with response achievement in ITP patients treated with TPO-RA in this series of 38 patients.

Analytical sensitivity of four HIV combined antigen/antibody assays using the p24 WHO standard.

BACKGROUND: The Common Technical Specifications for HIV-1 p24 assays published in 2009 fixed the lower limit of detection for obtaining C.E. approval at 2 IU/ml against the WHO standard (first international reference, code NIBSC 90/636); it was previously 50 pg/ml. Some recent fourth generation HIV assays that simultaneously detect antigen and antibody are equivalent to p24 assays, but they were mainly evaluated using p24 antigen standards in pg/ml and little is known of their performance with the IU/ml standard. OBJECTIVES: To evaluate four of the combined serological assays most commonly used for HIV diagnosis in France against the WHO standard in IU/ml. STUDY DESIGN: The analytical sensitivity of four combined p24 antigen and antibody assays (ARCHITECT HIV Ag/Ab Combo, AxSYM HIV Ag/Ab Combo, VIDAS HIV DUO Quick and VIDAS HIV DUO Ultra) and of one p24 assay (VIDAS HIV p24 II) were determined using dilutions of the WHO standard. RESULTS: Four of the five assays had a lower limit of detection below 2 IU/ml: 1.24 for ARCHITECT Combo, 0.66 for VIDAS DUO Ultra, 0.43 for VIDAS DUO Quick and 0.73 to 1.15 for VIDAS p24, while that of AxSYM was close to 2 (1.94-2.25). CONCLUSIONS: We have provided the first data on the lower limit of detection of HIV combined assays using the IU/ml WHO standard and demonstrated the need for a single international standard for comparing assays. We recommend the use of this approach in medical laboratory to validate on site their methods.