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The Relation of Conjunctival Pallor to the Presence of Anemia Tarang N

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The Relation of Conjunctival Pallor to the Presence of Anemia Tarang N The Relation of Conjunctival Pallor to the Presence of Anemia Tarang N. Sheth, BArtsSc, Niteesh K. Choudhry, MD, Matt Bowes, BSc, Allan S. Detsky, MD, PhD OBJECTIVE: To determine the value of conjunctival pallor in Conversely, if such a finding were absent, the clinician ruling in or ruling out the presence of severe anemia (hemo- may be able to conclude, on the basis of physical exami- globin # 90 g/L) and to determine the interobserver agree- nation alone, that severe anemia need not be considered ment in assessing this sign. further. DESIGN: Patients were prospectively assessed for pallor by at The precise level of hemoglobin that would be consid- least one of three observers. All observations were made ered severe or would warrant more urgent investigation without information of the patient’s hemoglobin value or of depends on a number of factors including the chronicity another observer’s assessment. of the anemia and the presence of comorbid conditions SETTING: Tertiary–care, university-affiliated teaching hospital. such as coronary artery disease. A hemoglobin level of 90 g/L or below might warrant such attention. PATIENTS: Three hundred and two medical and surgical inpa- Signs traditionally used in the physical diagnosis of tients. anemia are pallor of the conjunctivae, nail beds, face, MEASUREMENTS AND MAIN RESULTS: Likelihood ratios (LRs) palms, and palmar creases.1 Of these, only pallor of the calculated for conjunctival pallor present, borderline, and ab- conjunctivae, nail beds, and palms can be used in pa- sent were as follows: pallor present, LR 4.49 (95% confidence tients of any race. Current evidence suggests that con- interval [CI] 1.80, 10.99); pallor borderline, LR 1.80 (95% CI junctival pallor may be a more accurate indicator of the 1.18, 2.62); pallor absent, LR 0.61 (95% CI 0.44, 0.80). Kappa scores of interobserver agreement between paired observers presence or absence of anemia than pallor of the palms or 2 were 0.75 and 0.54. nail beds. In addition, conjunctival pallor has been docu- mented to appear more frequently in patients with severe CONCLUSIONS: The presence of conjunctival pallor, without anemia, and hence may be more sensitive than other other information suggesting anemia, is reason enough to signs.3 perform a hemoglobin determination. The absence of con- junctival pallor is not likely to be of use in ruling out severe Previous studies, however, are limited by small sam- anemia. With well-defined criteria, interobserver agreement ple sizes, examining only white males, reporting results is good to very good. without confidence intervals (CIs), and preselecting patients to ensure that there were equal numbers with and with- KEY WORDS: conjunctival pallor; anemia; physical diagnosis; out anemia.2,3 In a previous prospective study with a likelihood ratios. J GEN INTERN MED 1997;12:102–106. larger sample size, the various signs in the clinical di- agnosis of anemia were considered as an aggregate and results were not reported for individual signs.4 Further- more, conjunctival pallor has been considered as a dichot- omous variable—that is, either present or absent—when hen an internist evaluates a patient in an ambula- in fact there may be cases in which pallor is neither Wtory setting, anemia may be considered in a variety clearly present nor absent. of clinical scenarios. In this context, a physical finding Therefore, there were two principal objectives of this that would alert the physician that the patient is very study. First, we sought to determine the value of the pres- likely to have severe anemia would be valuable. If such a ence of conjunctival pallor in ruling in, and the value of finding were present, the clinician would most certainly the absence of conjunctival pallor in ruling out, the pres- obtain a laboratory determination of the hemoglobin level. ence of severe anemia defined as a hemoglobin concentra- tion of 90 g/L or less. Second, we sought to determine the interobserver agreement in assessing this sign. Also, we Received from the Faculty of Medicine (TNS, NKC), the Depart- were interested in exploring how the operating character- ments of Health Administration and Medicine, and the Pro- istics of conjunctival pallor varied for different hemoglobin gramme in Clinical Epidemiology, and Health Care Research level cutoffs. (The Toronto Hospital Unit) (ASD), University of Toronto, On- tario, Canada, and the Faculty of Medicine, Queen’s University (MB). METHODS Dr. Detsky is supported in part by a National Health Re- search Scholar Award from Health and Welfare Canada. We prospectively assessed 302 medical and surgical Address correspondence and reprint requests to Dr. Detsky: inpatients at The Toronto Hospital, a tertiary-care teach- Eaton North, Ground Floor, Room 246, The Toronto Hospital— ing hospital, for conjunctival pallor. Patients were in- General Division, 200 Elizabeth St., Toronto, Ontario, M5G 2C4, cluded in the study if they were over 18 years of age, able Canada. to consent, and willing to participate. Patients were ex- 102 JGIM Volume 12, February 1997 103 cluded if they had not had a laboratory measurement of To analyze the accuracy of conjunctival pallor, we hemoglobin level within 3 days of our clinical assessment used a Bayesian conceptual framework.5 This approach or had a transfusion between their last blood sample and involves the incorporation of new information, “the test our clinical assessment. The study was approved by The result,” into risk information that is known before the test Toronto Hospital Research Ethics Committee, and in- is done, “the pretest probability.” To convey the degree of formed written or verbal consent was obtained from all added information used in revising the pretest probabili- participants. ties when the physical diagnosis results are known, we At the outset, 25 patients were seen by three observ- used the method of likelihood ratios.6 That is, each level ers together to standardize assessments. Pallor was clas- of the sign (pale, borderline, and normal) is associated sified as being present, borderline, or absent. Subsequent with a specific likelihood ratio, which, when applied to the patients were assessed by at least one of three observers, pretest probability, revises it to a posttest probability in without information of the patient’s hemoglobin value or either the upward or downward direction. of another observer’s assessment (in cases in which there Likelihood ratios have two advantages over sensitivity were more than one observer). Observers A and B were and specificity, which are the traditional approaches to medical students at various stages of training, and ob- describing test characteristics. Likelihood ratios do not server C was an experienced general internist. Pale con- require that test results be divided simply into positive junctivae were those with very little or no evidence of red and negative, and one can use a simple nomogram to con- color on the anterior rim, which matched the fleshy color vert pretest probability into posttest probability without of the posterior aspect of the palpebral conjunctiva, as referring to Bayesian formulas.7 For a test with several seen in Figure 1. Conjunctivae that were normal had full types of results (for example, conjunctival pallor absent, or nearly full redness of the anterior rim, as seen in Fig- borderline, and present), one would like to see a progres- ure 2. Borderline conjunctivae were those with neither sion of likelihood ratios that starts very close to 0, virtu- clearly red nor clearly pale anterior rims or those in which ally ruling out disease, and goes above 10, virtually ruling one conjunctiva was pale and the other was normal. in disease. Before examination, the patients’ age, gender, date of In the present study, likelihood ratios with confidence last blood sample, and date of last transfusion (if received) intervals were determined using version 6 of Centor’s re- were obtained. Conjunctivae were examined under as ceiver-operating characteristic (ROC) curve analyzer.8 Re- much natural light as possible. When natural light was liability was measured by a k score of agreement between insufficient, a small pen flashlight was used. For the 150 paired observers.9 cases in which two observers assessed the same patient, observations were made within 30 minutes of each other. RESULTS When the observers disagreed, the patient was reexam- ined and a consensus assessment was obtained. This Of the 338 patients who were approached, 10 refused consensus assessment was used in data analysis. to participate, and 23 were unable to consent due to lan- After examination, patients’ charts were reviewed for guage barriers or limitations imposed on them by their admitting diagnosis and the presence of HIV, malignancy, medical condition. Of the 305 patients remaining, 3 were or sickle cell anemia. Hemoglobin levels were determined excluded because they had not had a blood sample within by an individual other than the observers. 72 hours of clinical assessment. Therefore, 302 patients FIGURE 1. Pale conjunctiva. Note that the color of the pale FIGURE 2. Normal conjunctiva. Note the full reddness of the anterior rim and the posterior part of the conjunctiva are the anterior rim and its dissimilarity to the posterior aspect of the same. conjunctiva. 104 Sheth et al., Conjunctival Pallor and Anemia JGIM Table 1. The Ages of Patients with and Without tients are shown in Table 2. HIV was present in 8%, ma- Severe Anemia lignancy in 19%, and sickle cell anemia in 2% of patients. Likelihood ratios with 95% CIs are presented in Table Hemoglobin Mean 3. For pallor present, the likelihood ratio was 4.49 for a Range (g/L) Number Mean Age Hemoglobin (g/L) hemoglobin less than or equal to 90 g/L. For borderline Hg # 70 4 40 67 cases, the likelihood ratio was 1.80.
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