Delayed Diagnosis of Adult Haemoglobinopathies: An Exploratory Retrospective Study of Diagnostic Trajectories and a...

Delayed diagnosis of haemoglobinopathy in adulthood is a recognised but incompletely characterised clinical problem, particularly in populations with high carrier prevalence. Adults with thalassaemia syndromes and haemoglobin variants are frequently misclassified as having iron deficiency or other common causes of microcytic anaemia, leading to prolonged diagnostic uncertainty, inappropriate iron supplementation and deferred access to genetic counselling and disease-specific management. The present exploratory study aimed to characterise diagnostic trajectories and candidate clinical cues associated with delayed recognition in a small single-centre cohort.

This was a retrospective, descriptive, single-centre pilot study of 19 adults who received a confirmed haemoglobinopathy diagnosis after a prolonged diagnostic delay, defined as a documented interval of ≥ 12 months between the first recorded abnormal haematological finding or symptom onset and the final confirmed diagnosis. We extracted clinical presentation, laboratory parameters, diagnostic pathway and retrospectively identified candidate clinical cues. Data are reported descriptively. As a secondary, hypothesis-generating exercise, we describe the components and cohort-level distribution of a preliminary clinical suspicion framework-the Haemoglobinopathy Suspicion Score (HSS) derived from the recurrent features observed in this dataset. No external comparator group was available; all analyses are descriptive and exploratory only.

Median age at diagnosis was 39.0 years (IQR 31.0-53.5); five patients (26.3%) were diagnosed at age ≥ 54 years. The cohort was predominantly of Greek origin (18/19, 94.7%) with combined α/β phenotypes predominating (12/19, 63.2%). Recurring descriptive features within this small cohort included a combined microcytosis-hemolysis laboratory profile: median MCV was 63.6 fL (IQR 61.8-67.6), ferritin 201 ng/mL (IQR 89.6-283.9) and total bilirubin 1.8 mg/dL (IQR 1.1-2.3). Persistence of microcytic anaemia despite documented iron supplementation was retrospectively identified in 12/19 patients (63.2%; exact 95% CI 38.4%-83.7%). Iron deficiency anaemia was the initial misdiagnosis in 6/19 patients (31.6%). Patients consulted a median of 2.0 specialties (IQR 1.0-2.5) before a correct diagnosis was established. Applying HSS components retrospectively, a score of ≥ 3 was present in 18/19 patients (94.7%); this observation is descriptive only and cannot be interpreted as diagnostic performance in the absence of a comparator population.

This exploratory single-Centre pilot study identifies recurring descriptive features associated with diagnostic delay in a small cohort of adults with haemoglobinopathy. The proposed HSS is a preliminary, hypothesis-generating clinical suspicion framework and has not been validated for clinical use. Larger, prospective, multicentric studies with appropriate comparator populations are required to derive and formally validate any bedside suspicion tool for this setting.