The Accuracy of Physical Examination to Diagnose Anemia Among Patients 5 Years of Age or Older: A Systematic Review of the Literature

BACKGROUND: Anemia remains a significant public health challenge, with a disproportionate impact on lower-income patients residing in areas of lesser healthcare resources. These patients frequently share limited access to routine laboratory testing, and as a result, physical examination still serves as a critical tool for anemia assessments. Significant efforts have been directed toward quantifying the accuracy of physical exam to diagnose anemia among pediatric patients, who may face developmental delays stemming from nutritional deficiencies. Nonetheless, the widespread prevalence of anemia contributes to substantial cardiovascular burden for a large volume of older patients. We sought to evaluate the accuracy of clinical exam techniques to diagnose anemia among patients 5 years of age or older.

METHODS: A systematic review of five databases (MEDLINE via OVID, EMBASE, Scopus, Global Health and Global Health Archives, and WHO Global Index Medicus) was conducted to evaluate studies published before February 2020. Studies that 1) compared non-invasive physical exam techniques with anemia diagnoses using standard laboratory measurements and 2) solely assessed or separately reported the diagnostic accuracy of physical exam techniques for patients 5 years or older were considered for inclusion. Studies that 1) investigated patients with specific hematologic conditions, namely sickle cell anemia, thalassemia, and acute leukemia, and/or 2) evaluated the utility of novel non-invasive devices to measure hemoglobin concentration were excluded. Two authors initially screened titles and abstracts from the search results using the Covidence web-based software platform. The full-text publications of selected abstracts were reviewed thereafter. The diagnostic accuracies of individual and collective physical exam techniques to diagnose anemia were documented. This systematic review was registered with PROSPERO.

RESULTS: The systemic literature search yielded 6,457 unique studies after removal of duplicates. Following screening of titles and abstracts, 97 studies were selected for full-text analysis. Fourteen studies were ultimately selected for inclusion. Evaluation of subjects under the age of 5 years and lack of comparison between physical exam findings and anemia diagnoses were the two most common reasons for exclusion at time of full-text analysis. Of the 14 selected publications, 8 studies solely assessed pregnant females, 3 solely assessed hospitalized patients, and 3 evaluated the general population. Five studies were conducted in South Asia, and 4 were conducted in Africa. The most frequently evaluated physical exam technique was assessment of clinical pallor, and the anatomical sites most often examined were conjunctivae, nail bed, and palms. The diagnostic accuracy ranged widely for pallor assessments of conjunctivae (sensitivity: 19% - 97%, specificity: 65% - 100%), nailbed (sensitivity: 41% - 65%, specificity: 58% - 93%), and palms (sensitivity: 33% - 91%, specificity: 54% - 93%). Similarly, sensitivity and specificity of collectivizing at least two or more physical exam findings to diagnose anemia ranged from 26% to 96% and 13% to 99%, respectively.

CONCLUSIONS: Though frequently implemented in practice, the accuracy of assessing clinical pallor to diagnose anemia is unclear. The wide range in previously reported associations between exam findings and anemia diagnoses is likely due to heterogenous populations being investigated. More robust studies are required to identify the most optimal exam technique or combination of techniques to screen and/or diagnose anemia among patients without concurrent pregnancy or significant co-morbidities.