Neutropenia

Neutropenia is an abnormally low concentration of

Signs and symptoms of neutropenia include

The causes of neutropenia can be divided between problems that are transient and those that are chronic. Causes can be divided into these groups:^{[1][2][11][12]}

Severe bacterial infections, especially in people with underlying hematological diseases or

Other causes of congenital neutropenia are Shwachman–Diamond syndrome, Cyclic neutropenia, bone marrow failure syndromes, cartilage–hair hypoplasia, reticular dysgenesis, and Barth syndrome. Viruses that infect neutrophil progenitors can also be the cause of neutropenia. Viruses identified that have an effect on neutrophils are rubella and cytomegalovirus.^[1] Though the body can manufacture a normal level of neutrophils, in some cases the destruction of excessive numbers of neutrophils can lead to neutropenia. These are:^[1]

Pathophysiology

The

Neutropenia can be the result of a variety of consequences, including taking certain types of drugs, exposure to environmental toxins, vitamin deficiencies, metabolic abnormalities, as well as cancer, viral or bacterial infections. Neutropenia itself is a rare entity, but can be clinically common in oncology^[35] and immunocompromised individuals as a result of chemotherapy (drug-induced neutropenia). Additionally, acute neutropenia can be commonly seen from people recovering from a viral infection or in a post-viral state. Meanwhile, several subtypes of neutropenia exist which are rarer and chronic, including acquired (idiopathic) neutropenia, cyclic neutropenia, autoimmune neutropenia, and congenital neutropenia.^[36][37]

Neutropenia that is developed in response to chemotherapy typically becomes evident in seven to fourteen days after treatment, this period is known as the Nadir or 'low point'.^[38][39] Conditions that indicate the presence of neutropenic fever are implanted devices; leukemia induction; the compromise of mucosal, mucociliary and cutaneous barriers; a rapid decline in absolute neutrophil count, duration of neutropenia >7–10 days, and other illnesses that exist in the patient.^[31]

Signs of infection can be subtle. Fevers are a common and early observation. Sometimes overlooked is the presence of hypothermia, which can be present in sepsis. Physical examination and accessing the history and physical examination is focused on sites of infection. Indwelling line sites, areas of skin breakdown, sinuses, nasopharynx, bronchi and lungs, alimentary tract, and skin are assessed.^[31]

The diagnosis of neutropenia is done via the low neutrophil count detection on a

Generally accepted reference range for absolute neutrophil count (ANC) in adults is 1500 to 8000 cells per microliter (µl) of blood. Three general guidelines are used to classify the severity of neutropenia based on the ANC (expressed below in cells/µl):^[42]

• Mild neutropenia (1000 <= ANC < 1500): minimal risk of infection
• Moderate neutropenia (500 <= ANC < 1000): moderate risk of infection
• Severe neutropenia (ANC < 500): severe risk of infection.

Each of these are either derived from laboratory tests or via the formula below:

ANC = ${\displaystyle (\%neutrophils+\%bands)\times (WBC) \over (100)}$^[1][42][43]

Treatment

A fever, when combined with profound neutropenia (febrile neutropenia), is considered a medical emergency and requires broad spectrum antibiotics. An absolute neutrophil count less than 200 is also considered a medical emergency and almost always requires hospital admission and initiation of broad spectrum antibiotics with selection of specific antibiotics based on local resistance patterns.^[2]Precautions to avoid opportunistic infections in those with chronic neutropenia include maintaining proper soap and water hand hygiene, good dental hygiene and avoiding highly contaminated sources that may contain a large fungal reservoirs such as mulch, construction sites and bird or other animal waste.^[2]

Neutropenia can be treated with the hematopoietic growth factor

Most cases of neonatal neutropenia are temporary. Antibiotic prophylaxis is not recommended because of the possibility of encouraging the development of multidrug-resistant bacterial strains.[1]

These are cytokines that are present naturally in the body. The factors promote neutrophil recovery following anticancer therapy.^[1]

The administration of intravenous immunoglobulins (IVIGs) has had some success in treating neutropenias of alloimmune and autoimmune origins with a response rate of about 50%. Blood transfusions have not been effective.^[1]

Patients with neutropenia caused by cancer treatment can be given antifungal drugs. A Cochrane review ^[48] found that lipid formulations of amphotericin B had fewer side effects than conventional amphotericin B, though it is not clear whether there are particular advantages over conventional amphotericin B if given under optimal circumstances. Another Cochrane review ^[49] was not able to detect a difference in effect between amphotericin B and fluconazole because available trial data analysed results in a way that disfavoured amphotericin B.

Trilaciclib, a CDK4/6 inhibitor, administered approximately thirty minutes before chemotherapy, has been shown in three clinical trials to significantly reduce the occurrence of chemotherapy-induced neutropenia and the associated need for interventions such as the administration of G-CSF's.^[50] The drug was approved in February 2021 by the FDA for use in patients with extensive-stage small cell lung cancer.^[50]

In November 2023, FDA approved efbemalenograstim alfa.^[51]

Prognosis

If left untreated, people with fever and absolute neutrophil count <500 have a mortality of up to 70% within 24 hours.

• Pancytopenia
• Thrombocytopenia

References