Applied Evidence

Thrombocytopenia and neutropenia: A structured approach to evaluation

Camp Lejeune Family Medicine Residency, Naval Medical Center Camp Lejeune, NC (Dr. Temple); Naval Hospital Pensacola, Fla (Dr. Burns)
[email protected].

The authors reported no potential conflict of interest relevant to this article.


From The Journal of Family Practice | 2018;67(7):E1-E8.


Is the patient severely ill?

The prognosis of the patient is related both to the etiology of the neutropenia, as well as to the nadir of the neutrophil count. Patients who have an ANC <500 cells/mcL or who have inadequate bone marrow reserves are at highest risk for an overwhelming infection.20,21 The absence of oral ulcers and gingivitis and/or the presence of purulent material at the site of an infection are signs of adequate bone marrow reserves.

Additionally, neutropenia may be the source—or the result—of a serious life-threatening illness. This distinction may not be readily apparent at the time of the patient’s presentation. If signs or symptoms of a severe illness are apparent (fever, hypotension, tachycardia, ANC <500 cells/mcL), admit the patient to the hospital for evaluation and initiation of antibiotics.

Is the neutropenia chronic?

A review of previous CBCs will identify whether this condition is new or chronic. A persistent, mild neutropenia (ANC 1000-1500 cells/mcL) in a healthy individual is consistent with benign familial or ethnic neutropenia (see TABLE 6).20 If prior CBCs are unavailable, then a diagnosis of chronic neutropenia may be established by verifying the persistence of mild neutropenia over time.

Congenital causes of neutropenia

Cyclic neutropenia is a periodic neutropenia (occurring every 2-5 weeks) associated with mild illnesses that are related to the nadir of the neutrophil count. The diagnosis is established by obtaining serial CBCs twice weekly for 4 to 6 weeks, which reflect cycling of the neutrophil count.20,22

Are any medications contributing to the neutropenia?

Medications that suppress bone marrow or that interfere with other immune-mediated processes are the most common cause of acquired neutropenia.23 Drug-induced agranulocytosis is defined as an ANC <500 cells/mcL due to exposure to a drug that results in immunologic or cytotoxic destruction of neutrophils.24

A persistent, mild neutropenia in a healthy individual is consistent with benign familial or ethnic neutropenia.

A systematic review of case reports of drug-induced agranulocytosis (a decrease in peripheral neutrophil count to <500 cells/mcL) revealed that although at least 125 drugs were probably related to agranulocytosis, only 11 drugs were responsible for 50% of cases (carbimazole, clozapine, dapsone, dipyrone, methimazole, penicillin G, procainamide, propylthiouracil, rituximab, sulfasalazine, and ticlopidine), and fatality rates were higher (10% vs 3%) among those patients with a nadir <100 cells/mcL.25 TABLE 725 lists medications that can be associated with agranulocytosis. Depending on prior exposure to a drug, neutropenia/agranulocytosis can occur within hours to months of exposure to the causal drug and can take a few days to 3 weeks to resolve after cessation.25,26

Medications that can be associated with agranulocytosis

Continue to: Has the patient had any recent illnesses?


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