Unmasking Heritable Thrombocytopenia: Insights from R90 Gene Panel Analysis

Background

Thrombocytopenia is a common reason for Haematology referral, with varied causes requiring tailored management. Identifying heritable thrombocytopenia avoids unnecessary monitoring, inappropriate treatment and highlights patients at increased risk of leukaemic potential.

Aims

To evaluate the diagnostic yield of the R90 gene panel in adults with chronic thrombocytopenia and inform a testing pathway.

Methods

A retrospective single-centre review was conducted on patients referred to the Adult Benign Haematology service at University Hospitals Bristol and Weston NHS Foundation Trust. Samples submitted for R90 panel testing for thrombocytopenia between October 2021 and July 2025 were included. Paediatric cases, discarded samples, tests for other indications, duplicates, and missing reports were excluded. Data collected included demographics, family history, mean platelet volume (MPV), blood film findings, platelet counts and genetic results.

Results

Of 642 samples, 57 patients met inclusion criteria; 19 (33.3%) had a genetic variant identified. Median MPV was identical in both groups (11.9 fL) with overlapping ranges (10.6-15.0 vs 9.6-14.8) and no significant difference (p = 0.57). Platelet count nadir was slightly higher in the variant group (median 74 vs 63.5 x 109/L) but not significant (p = 0.20). One patient with a variant and three without had a single previous normal platelet count. Positive family history was significantly more frequent in the variant group (13/19 vs 9/38; OR = 6.98, p = 0.002).

Conclusions

Family history was the only factor significantly associated with a genetic variant, though 31.6% of variant cases reported none. MPV, duration of thrombocytopenia, and platelet nadir were not useful discriminators. We feel R90 testing should be considered for all patients with chronic thrombocytopenia and no prior normal platelet count, even without macrothrombocytopenia or family history, provided they meet National Genomic Test Directory eligibility criteria.