**1. Introduction**

White blood cells, as granulocytes or leukocytes, are an important component of the host defense system, responsible for protection against bacteria, viruses, fungi, and invading parasites [1]. The white blood cells constitute only 1% of the total blood volume. The term neutropenia describes an absolute decrease in neutrophil numbers [1].

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Neutropenia is defined by a neutrophil count <1.5 × 10<sup>9</sup> /L (<1.2 × 109 /L in black people). The degree of neutropenia predicts the risk of serious bacterial infections. Severe neutropenia is characterized by a profound decrease of circulating neutrophils in case of an absolute lack of circulating neutrophils, classically resulting in a neutrophil count of <0.5 × 109 /L [1, 2].

hypersplenism [2]. Other rarer differential diagnoses include neutropenia secondary to alcoholism, nutritional deficiencies (folic acid, vitamin B12, cooper, etc.), Felty's syndrome, systemic lupus erythematosus or Sjögren's syndrome, and lastly aplastic anemia or parox-

In the literature, acute and severe neutropenia has been shown to be attributable to drugs in 70–90% of cases [2]. Thus, in practice, idiosyncratic drug-induced neutropenia or agranulocytosis should be discussed routinely (considered in first) even if there is a context moving

To date, drug-induced, or drug associated, severe neutropenia, or agranulocytosis is defined

[3]. The presence of fever and sepsis signs is usual, even required, for some authors. In the

All drugs may be the causative agents, particularly: chemotherapy, immune modulator agents or biotherapies. Other daily drugs may also be more rarely incriminated. Such event is called "idiosyncratic" drug-induced neutropenia and agranulocytosis [2, 3]. Either the drug

Currently, the recommended criteria for diagnosing blood cytopenias and for implicating a drug as a causative agent in neutropenia are derived from an international consensus meeting [2, 4]. These criteria are outlined in **Table 1**. As idiosyncratic severe neutropenia and agranulocytosis are life-threatening conditions, no patient was re-challenged with the incriminated

more than 1.5 × 109

disease

administration of the drug)

/L, which occurs as a result of exposure to drugs

/L.

Idiosyncratic Drug-Induced Severe Neutropenia and Agranulocytosis: State of the Art

http://dx.doi.org/10.5772/intechopen.78769

189

Onset of agranulocytosis during treatment or within 7 days of exposure to the drug, with a complete recovery in neutrophil count of

Recurrence of agranulocytosis upon re-exposure to the drug (this is rarely observed, as the high risk of mortality contra-indicates new

Exclusion criteria: history of congenital neutropenia or immune mediated neutropenia, recent infectious disease (particularly recent viral infection), recent chemotherapy and/or radiotherapy and/ or immunotherapy\* and existence of an underlying hematological

/L within one month of discontinuing the drug

ysmal nocturnal hemoglobinuria [2].

at least by a neutrophil count of <0.5 × 109

drug ("theoretical method of reference").

Neutrophil count <0.5 × 109

fever and/or any signs of infection

majority of patients, the neutrophil count is under 0.1 × 109

itself or one of its metabolites may be the causative agent.

**Definition of agranulocytosis Criteria of drug imputability**

/L ± existence of a

\*Immunoglobulins, interferon, anti-TNF antibodies, anti-CD20 (rituximab).

**Table 1.** Criteria for idiosyncratic drug-induced agranulocytosis.

toward another condition.

**4. Definition**

Schultz first introduced the term "agranulocytosis" in 1922, for cases of acute and severe pharyngeal infections, associated with a lack of granulocytes in the blood in relation to drug intake [2]. Such unpredictable event, named "idiosyncratic," is typically serious, with around 50% of cases exhibiting severe sepsis, and a mortality rate of 10–20% [2, 3].

In this chapter, we report and discuss the diagnosis and management of idiosyncratic druginduced, or drug-associated, severe neutropenia, and agranulocytosis.
