akinohanayuki ブログ

学位を持っても、センスのない、感染制御専門薬剤師のブログ.  I have Ph.D. but less sense ID pharmacist.






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Neutropenia is defined as an absolute neutrophil count (ANC) <1500 cells/microL .Certain ethnic populations (eg, African Americans, Yemenites, Ethiopians, some Arabs) have a slightly lower ANC, referred to as benign ethnic neutropenia (BEN).

The most common causes of mild chronic neutropenia in adults are constitutional neutropenia (eg, benign ethnic neutropenia) and dose-related drug-induced neutropenia. Additional causes include nutritional deficiencies, collagen/vascular disorders, infections, and hematologic conditions (eg, myelodysplasia).

Severe acute neutropenia in the adult in the absence of concomitant thrombocytopenia and anemia is almost uniformly due to drug-induced or toxin-induced agranulocytosis. 

Severe chronic idiopathic neutropenia is a rare disorder. In some patients, it is an incidental finding and is well-tolerated without symptoms; such patients need antibiotic coverage with infections, but do not need chronic therapy. Other patients have severe symptoms, including aphthous ulcers and/or frequent infections. These patients require cytokine support (eg, G-CSF). 

The initial evaluation of a patient with neutropenia should determine the cause of the neutropenia and whether there is an active infection. These two factors drive the tempo of further evaluation. We perform a detailed history and physical examination to identify possible underlying causes of the neutropenia. A review of previous complete blood counts (CBCs) with differential, if available, can clarify the duration of the neutropenia. Further laboratory testing is directed based upon suspected causes (eg, for nutritional deficiencies and collagen/vascular disorders).

In some cases, isolated neutropenia may evolve to a more serious condition, while in many others the patient may never become ill. Thus, it is important to balance appropriate periodic reevaluation with avoidance of unnecessary worry in an otherwise healthy individual. Individuals with a stable ANC who are not thought to be at high risk of infection can have their CBC with differential monitored on a periodic basis as an outpatient, at gradually increasing intervals.

Not all patients with neutropenia require a hematologist referral or bone marrow evaluation. We perform bone marrow aspiration and biopsy for patients with unexplained moderate to severe neutropenia, or in whom we suspect diminished bone marrow function and/or a hematologic malignancy. 



The diagnosis of drug-induced neutropenia or agranulocytosis is suspected in a patient with a sudden and/or unexpected onset of neutropenia in whom a drug is suspected as the cause. 

The diagnosis should be suspected if a patient develops fever, mouth sores, or gingival disease inflammation. In particular, the presence of fever and mouth sores may indicate bone marrow suppression.

The diagnosis is confirmed when all of the following are present:

●Low to absent absolute neutrophil count
●Absence of anemia and thrombocytopenia
●A hypocellular bone marrow that shows normal erythropoiesis and megakaryocytopoiesis, but few if any granulocytic precursors.
●Return of the neutrophil count to normal when the offending agent is stopped, with or without the concomitant use of a granulocyte colony-stimulating factor

The differential diagnosis for neutropenia/agranulocytosis unassociated with drugs is extensive and includes both inherited and acquired forms. The most common conditions to be considered in a patient on chronic medications would be concomitant viral infection or possible nutritional deficiency (eg, copper or vitamin B12 deficiency).

The treatment for drug-induced neutropenia or agranulocytosis is immediate cessation of the offending agent. It is important to determine if the neutropenia could be related to an intercurrent infection or other cause before deciding for that the medication is causing the neutropenia. Patients with a secondary infection should be treated with appropriate antibiotics. 

Although randomized controlled studies are not available, we recommend the use of a colony-stimulating factor (granulocyte colony-stimulating factor, G-CSF) if the patient is ill from infection and bone marrow suppression is suspected (Grade 1C). 

In one study of 63 episodes in 61 patients, for example, the mean time to recovery was 12 days with a range of 3 to 56 days

In another series of 10 patients with thionamide-induced agranulocytosis, the median recovery time was 15 days with a range of 5 to 31 days

Older age, sepsis, shock, and renal failure are poor prognostic factors