**8. Biological data**

a non-specific sore throat, acute tonsillitis or sinusitis. More rarely, patients have first, as a not

It is important to note that without medical intervention, particularly immediate antibiotics administration, natural history of agranulocytosis include severe and potentially life-threatening infections with often signs of general sepsis and septicemia (fever, chills, hypotension, etc.). During the evolution, documented pneumonia as well as anorectal, skin or oropharyngeal infections and septic shock were the most reported infections [2, 3]. To date, classical manifestations as necrotic tonsillitis and perinea gangrene or are

In our experience (203 patients), the clinical manifestations include: isolated fever (unknown origin) (26.3%); septicemia (13.9%); documented pneumonia (13.4%); sore throat and acute tonsillitis (9.3%); and septic shock (6.7%) [5]. While in hospital 19.2% of the patients worsened clinically and exhibited features of severe sepsis, septic shock, or systemic inflammatory

However, besides these "loud" clinical manifestations, clinicians must keep in mind that the signs of these infections may be sometimes crude and atypical because of the neutropenia (**Figure 1**). For practitioners, it is to note that pneumonia is often asymptomatic because of the lack of neutrophil cells. In this situation, thoracic CT-scan may be proposed with much better results than X-ray (**Figure 2**). Similarly, when antibiotics are administered prophylactically, or at the beginning of this adverse event, both the patient's complaints and the physical findings

may be "masked," and fever is often the only clinical sign detected [2].

**Figure 1.** Chest radiography in a patient with absolute neutrophil count <0.1 × 109

/L: "Masked" pneumonia.

expected and brutal event, a severe deep and potentially life-threatening infection [2].

exceptional.

response syndrome (SIRS).

192 Hematology - Latest Research and Clinical Advances

Theoretically, acute neutropenia is classically diagnosed in a blood sample, resulting in a neutrophil count of <0.5 × 109 /L [3, 5]. In this setting, monocyte and basophile counts may be increased. In the majority of patients, the neutrophil count is under 0.1–0.2 × 109 /L.

In this setting, bone marrow examination may not be required in for all patients but is pivotal to exclude an underlying pathology, particularly in the elderly to rule out myelodysplastic disorders and malignant hematological diseases [1, 2]. Bone marrow examination may be particularly required in case of associated anemia, thrombocytopenia or abnormal blood cells. In such patients with idiosyncratic drug-induced agranulocytosis, the bone marrow typically shows a lack of mature myeloid cells, whereas in other cases, immature cells from the myelocyte stage are preserved. This latter appearance is described as "myeloid maturation arrest" [2, 3].

In severe neutropenia, multiple microbiological specimens should be taken, as in the case of post-chemotherapy neutropenia. With such multiple microbial samples, a causative pathogen, typically Gram-negative bacilli or Gram-positive cocci (mainly Staphylococcus spp.), was isolated in 30% of cases [3]. Fungi are also involved as secondary infective agents (>10%), however, in a few percent of cases regarding neutropenia related to chemotherapy. To date, modern molecular techniques have further facilitated identification of microbial pathogens, allowing for aggressive interventions that appear to improve patient outcomes as documented later in the paper.
