Leukopenia (WBC count of <3.8K/uL) and/or neutropenia (<1.8K/uL, both institutional lab cutoffs), are commonly encountered by physicians on routine blood testing on otherwise healthy patients. This finding, whether incidental or not, often leads to hematology referrals. A broad work up may be pursued in an attempt to find a definitive diagnosis. We conducted this study to assess the utility of testing for anti-nuclear antibody (ANA) as well rheumatoid factor (RF) in patients with leukopenia/neutropenia and whether or not a positive serology led to a rheumatologic diagnosis.
After obtaining institutional review board approval, we searched for outpatient hematology consults with a diagnosis of leukopenia and/or neutropenia using ICD-9 and ICD-10 diagnostic codes between 2005-2015 at Henry Ford Hospital. Data points included demographics and antibody serology. Patients were excluded if they had a known hematologic disorder, known rheumatologic disorder or were on active chemotherapy. A positive ANA or RF were considered if titers were >1:80 or RF >14 IU/mL, respectively as these are institutional cutoffs. Complete blood counts were reviewed for patients who were not excluded based on above criteria. Hematology and rheumatology notes were reviewed looking for symptoms suggestive of autoimmune conditions or if an alternative diagnosis was made.
A total of 561 patients were seen in our outpatient clinic during the 10 year interval with an associated diagnostic code for leukopenia/neutropenia.199 were excluded due to incomplete data or inadequate follow up period, 35 patients for known malignancy, 14 for known rheumatologic disorder, and 122 for being on active chemotherapy. The remaining 191 patients were reviewed for data analysis. Patient demographics are summarized in table 1.
A total of 116 patients (61%) were tested for ANA, of which 27 (23%) were positive. 22 of those 27 (81%) patients were referred to rheumatology, 6 of which were diagnosed with rheumatologic diseases (22%). RF was tested in 110 patients (58%), of which 15 were positive (14%) all were referred to rheumatology, and 5(42%) were diagnosed with rheumatologic diseases. Test results, referral rate and rheumatologic diagnosis are listed in table 2.
The majority of patients who were diagnosed with rheumatologic disorders had associated findings suggestive of underlying disease (3 patients with systemic lupus erythematosus (SLE) had mild thrombocytopenia (100-150K/uL), 1 patient with mixed connective tissue disease had Raynaud's phenomenon, 3 patients with rheumatoid arthritis (RA) had arthralgias and 1 had myalgias, all with correlating physical exam or radiographic findings).
Other alternative diagnoses for leukopenia/neutropenia included drug induced, viral and bacterial infections, hematologic malignancies, ethnic neutropenia, transient leukopenia, and idiopathic.
Ambulatory hematology consults for leukopenia/neutropenia are a common occurrence in practice. Our study showed that 11 patients out of 191 (6%) were found to have an associated rheumatologic disorder, with the majority having other signs/symptoms or associated lab abnormalities suggestive of autoimmune disease. This study shows that testing for ANA and RF in patients with leukopenia/neutropenia are of limited clinical utility in asymptomatic patients with no other lab abnormalities and it should not be part of a routine work up unless directed by symptoms. Primary care providers need to screen for other abnormalities (symptoms/clinical findings) in order to identify patients that would benefit most from subspecialty referral.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.