Utility and Patterns of Vitamin B12 and Folate Testing in Patients with Isolated Thrombocytopenia

Background:Deficiencies of vitamin B12 and folate are commonly considered in the differential diagnoses of thrombocytopenia. However, the utility of measuring vitamin B12 and folate levels during the evaluation of isolated thrombocytopenia is unclear.

Methods:In this retrospective review, we studied the frequency of ordering vitamin B12 and folate levels among patients with isolated thrombocytopenia (platelet count < 150 x 10⁹/L without anemia or neutropenia) evaluated at our institution from 2015-2016. We also collected information on the specialty of the ordering clinician.

Results:During the study period, 129 patients with isolated thrombocytopenia were evaluated by hematology (67.4%), inpatient medicine (inpatient internal medicine and emergency department physicians) (16.3%), outpatient internal medicine (9.3%), and other departments (7.0%). Vitamin B12 levels were tested in 57 (44.2%) patients, and of these a methylmalonic acid (MMA) was ordered for 13 (22.8%), all of which were normal. Three patients (5.3%) had low vitamin B12 levels (179, 148, 143 ng/L; normal 180-914 ng/L), but only one had an MMA performed, which was normal, indicating no vitamin B12 deficiency. The remaining two were ultimately diagnosed with idiopathic thrombocytopenic purpura and hypersplenism, respectively. Mean corpuscular volume (MCV) was tested in 128 of the patients, and of those 24 (18.8%) had macrocytosis. Of those with macrocytosis, 14 (58.3%) had vitamin B12 levels tested, compared with 41.3% of patients with normal MCV, though this was not statistically significant (P= 0.131). Folate levels were tested in 37 (28.7%) patients, and none were low. Of patients with macrocytosis, 37.5% had folate levels tested compared with 26.9% of those with normal MCV (P= 0.303). The ultimate causes of the patients' thrombocytopenia were determined to be: idiopathic thrombocytopenic purpura (37.2%), hypersplenism (14.7%), liver disease (7.0%), medication-induced (5.4%), other causes (18.6%), and unknown (17.1%). In the unknown group, all patients had platelet counts > 100 x 10⁹/L and therefore did not meet diagnostic criteria for idiopathic thrombocytopenic purpura based on the practice guidelines of the American Society of Hematology. Vitamin B12 testing was most frequently ordered by clinicians from internal medicine (75.0%), followed by inpatient medicine (42.9%) and hematology (41.4%). Folate testing was most frequently ordered by clinicians from inpatient medicine (33.3%), hematology (29.9%), and internal medicine (8.3%).

Conclusion:At our institution, testing for vitamin B12 and folate levels is a common practice in the evaluation of isolated thrombocytopenia. However, no patient was diagnosed to have thrombocytopenia associated with vitamin B12 or folate deficiency during the time period examined. Though these tests are neither expensive nor invasive, when repeated needlessly over time additive costs and extraneous data can cause confusion and misdirection in patient care. Therefore, given the extremely low likelihood of vitamin B12 deficiency causing isolated thrombocytopenia, it would seem best to consider testing only if there are other findings suggestive of vitamin B12 or folate deficiency. Though this advice is most relevant to hematology, it is also important for other specialties, particularly general internal medicine, to consider.