A proactive large platelet-driven screening strategy for the early recognition of MYH9-related disease: a Chinese...

Accurate diagnosis of MYH9-related disease (MYH9-RD) is frequently impeded by a reactive process. Clinical suspicion typically arises only following immune thrombocytopenia (ITP) treatment failure, family history identification, or emergence of extra-hematological manifestations. However, de novo variants or delayed syndromic onset may obscure these indicators, leading to misdiagnosis as ITP and unnecessary immunosuppression.

This study prospectively evaluated a multiparameter platelet size trigger as an accessible screening entry point for early MYH9-RD recognition, independent of a family history, treatment refractoriness, or syndromic features.

Consecutive patients with persistent, unexplained thrombocytopenia were screened using predefined thresholds for mean platelet volume (≥ 14.55 fL), platelet-large cell ratio (≥ 58%), or manual identification of giant platelets when automated values were unobtainable. Individuals meeting any criterion underwent targeted high-throughput sequencing for inherited thrombocytopenia genes (including MYH9), with subsequent confirmation by immunofluorescence.

Among 42 screened patients, 7 (16.7%) were diagnosed with MYH9-RD, including 2 with novel MYH9 variants in the coiled-coil domain, supported by blood smear findings (including giant platelets and neutrophil inclusions), bioinformatics assessment, and structural-modeling data. All 7 patients were diagnosed within 1 month following the screening, avoiding unnecessary ITP-directed therapy. The composite trigger (mean platelet volume, platelet-large cell ratio, and smear-based morphology) provided higher diagnostic yield than any single parameter alone.

This streamlined 3-step strategy provides a practical, potentially resource-conscious pathway for early MYH9-RD diagnosis, 1 better aligned with current clinical practice in China than the existing diagnostic paradigms.