Hematology Referrals for Leukopenia in the Bronx Rarely Result in Clinically Significant Diagnoses: First Steps Towards and Evidence-Based Referral Guideline

Introduction

Incidentally noted neutropenia in otherwise well individuals is a frequent reason for referral to specialist hematology clinics. In the vast majority of these patients a diagnosis of constitutional or ethnic neutropenia will be made, without clinical significance. However, because of an enduring concern about the possibility of a more sinister underlying incipient process, hematologists may variously order an extensive investigative workup. This concern is magnified by a recent Danish population study that revealed a surprisingly high rate of subsequent diagnoses of hematological malignancy, particularly in individuals with severe neutropenia. There is currently no standard approach to such referrals, with significant heterogeneity among consulting hematologists, in particular with regard to the use of specialized investigations such as bone marrow biopsy.

As a first step in the development of an evidence-based algorithmic approach to the workup of patients referred for incidentally discovered neutropenia, we assembled and analyzed a cohort of patients referred to the Einstein academic hematology practice. This practice consists of 4 clinics, 2 of which are fellows' clinics, and serves a referral area that encompasses most of the Bronx. Being that the referral population is predominantly Hispanic and Black, our hypothesis was that a relatively higher proportion of referred patients would be found to have constitutional neutropenia than that expected in White population studies.

Results

During a 2-year period from July 2013 until July 2015 a total of 318 patients with a diagnostic code for neutropenia or leukopenia were seen as outpatient referrals to hematology. Of these, 33 patients who were found to have known hematological or malignant diagnoses within the preceding 24 months, and a further 58 patients noted to have been seen by hematology under different diagnostic codes on prior occasions, were excluded. The cohort for analysis thus consisted of 228 patients. The demographic characteristics of this cohort can be seen in the table below. Within the cohort 16 (7%) were designated as severe neutropenia having at least one recorded ANC <500/mL.

Outcomes were analyzed for the period of 1 year subsequent to the index encounter.

During this time, 4 patients (1.8%) received clinically significant hematological diagnoses requiring ongoing care; aplastic anemia, chronic lymphocytic leukemia, non-Hodgkins lymphoma (2 patients).

In the same 1 year period hospital admissions for sepsis were documented in 5 patients.

Conclusions.

Outpatient referrals for leukopenia entail a disproportionately high share of hematologists' time, and expense to the system, when considered against the very low probability of a clinically significant outcome. This appears to be particularly true when considered within a population where ethnic neutropenia is prevalent. The finding substantiates the need for development and institution of leukopenia referral recommendations for primary care providers, that will identify patients who may be safely observed, in distinction to those in whom a specialized hematological workup is warranted. Further research in this regard, which is already underway, entails chart review and case analysis, to better determine variables predictive of the above outcomes.

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