Neutrophil count

Male mice exposed to 7.3 mg/kg/day for 13 weeks had significantly decreased spleen weights and decreased neutrophil counts (Hoechst 1984b), indicating that immune activity in mice may also be affected. An intermediate-duration oral MRL of 0.005 mg/kg/day was derived based on the NOAEL of 0.45 mg/kg/day for immunotoxicity identified in the Banerjee and Hussain (1986) study. In support of these positive findings, Khurana et al. (1998) observed decreased macrophage functionality, in the absence of any other apparent toxicological effects, in 1-day-old broiler chicks fed 30 ppm endosulfan in the diet for 4 or 8 weeks. 

Neutropenia associated with interferon or pegylated interferon therapy is defined as an absolute neutrophil count (ANC) of less than 1000 cells/mm3 in rare cases, an ANC less than 500 cells/mm3 maybe observed. The neutropenia is more common and in some cases more severe with pegylated interferon than with unmodified interferon. Neutropenia usually occurs within the first 2 weeks after initiating either formulation of interferon, with the WBC count stabilizing by week four or six. The neutropenia is reversible upon discontinuing therapy. Granulocyte colony-stimulating factor has been used as an adjunctive therapy for interferon-induced neutropenia in hepatitis patients.44... 

Absolute neutrophil count less than 1.5 x 103/mm3 (less than 1.5 x 103/pL or less than 1.5x109/L)... 

TABLE 34-11. Monitoring of White Blood Cell Count and Absolute Neutrophil Count during Clozapine Treatment... 

ANC, absolute neutrophil count WBC, white blood cell. 

One month later, GD is back for a follow-up visit. She notes that her thyrotoxic symptoms are gone, and overall, she feels great. She is receiving propylthiouracil 100 mg three times daily. Her most recentTSH was 0.9 milliunit/L (normal 0.5-2.5 milliunits/L), and her free T4 was 1.6 ng/dL (20.6 pmol/L normal 0.7-1.9 ng/dL, or 9.0-24.5 pmol/L). However, over the past few days she has developed a sore throat and feels achy. She wonders if she has the flu. Her vital signs show a pulse of 92 beats/minute and a temperature of 38.3°C (101 °F). A complete blood count reveals a total white blood cell count of 1 00/mm3 or 0.1 x 1 09/L (normal 4000-10,000/mm3 or 4-10 x 1 09/L) with 15 neutrophils (absolute neutrophil count 150). 

Closely monitor patients for efficacy and toxicity while they are receiving hydroxyurea. Monitor mean corpuscular volume (MCV) because it increases as the level of HbF increases. If the MCV does not increase with hydroxyurea use, the marrow may be unable to respond, the dose may not be adequate, or the patient may be noncompliant.27 HbF levels also can be monitored to assess response. Assess blood counts every 2 weeks during dose titration and then every 4 to 6 weeks once the dose is stabilized. Temporary discontinuation of therapy is warranted if the hemoglobin level is less than 5 g/dL (50 g/L or 3.1 mmol/L), the absolute neutrophil count is less than 2000/mm3 (2 x 109/L), platelets are less than 80,000/mm3 (80 x 109/L), or reticulocytes are less than 80,000/mm3 (80 x 109/L) if the hemoglobin is less than 9 g/dL (90 g/L or 5.6 mmol/L). Monitor for increases in serum creatinine and transaminases. Once the patient has recovered, hydroxyurea may be restarted with a dose that is 2.5 to 5 mg/kg less than the dose associated with the patient s toxicity. Doses then may be increased by 2.5 to 5 mg/kg daily after 12 weeks with no toxicity. 

Vinorelbine 25-30 mg/m2 per week IV Repeat cycles every 7 days (adjust dose based on absolute neutrophil count see product information)"... 

Laboratory monitoring is performed before initiating therapy and before each cycle of chemotherapy. A complete blood count should be obtained prior to each course of chemotherapy to ensure that hematologic values are adequate. In particular, white blood cell counts and absolute neutrophil counts can be decreased in patients receiving chemotherapy such as irinote-can and 5-FU and increase the risk of infection. Baseline liver function tests and an assessment of renal function should be done prior to and periodically during therapy. Other selected laboratory tests include checking for the presence of protein in the urine in patients receiving oxaliplatin and bevacizumab. 

Engraftment is the reestablishment of functional hematopoiesis. It is commonly defined as the point at which a patient can maintain a sustained absolute neutrophil count (ANC) of greater than 500 cells/mm3 (0.5 x 109/L) and a sustained platelet count of greater 20,000/mm3 (20 x 109/L) lasting for 3 or more consecutive days without transfusions. 

The success of the treatment of febrile neutropenia hinges on the adequate recovery of the absolute neutrophil count and either optimal antimicrobial coverage of identified organisms or empirical coverage of unidentified organisms. 

Neutropenia is defined as an absolute neutrophil count (ANC) of less than 0.5 x 10 3/ J.L (0.5 x 109/L) cells or an ANC of less than 1.0 x 103/ J.L (1.0 x 109/L) cells with a predicted decrease to less than 0.5 x 103/ J.L (0.5 x 109/L) cells. The ANC is calculated by multiplying the total white blood cell (WBC) count by the percentage of neutrophils (segmented neutrophils plus bands). Fever is defined as a single oral temperature of 38.3°C (101°F) or greater or a temperature of 38.0°C (100.4°F) or greater for at least 1 hour. The combination of these two factors defines febrile neutropenia.5 The risk of infection during the period of neutropenia depends primarily on two factors ... 

Neutropenia is a condition characterized by a decrease in blood neutrophil count below 1.5 X 109 cells per litre a normal blood count is (2.0-7.5) X 109 cells per litre. Its clinical symptoms include the occurrence of frequent and usually serious infections, often requiring hospitalization. Neutropenia may be caused by a number of factors (Table 10.6), at least some of which are responsive to CSF treatment. Particularly noteworthy is neutropenia triggered by administration of chemotherapeutic drugs to cancer patients. Chemotherapeutic agents (e.g. cyclophosphamide, doxorubicin and methotrexate), when administered at therapeutically effective doses, often induce the destruction of stem cells and/or compromise stem cell differentiation. 

Bacterial infections are associated with elevated granulocyte counts (neutrophils, basophils), often with increased numbers of immature forms (band neutrophils) seen in peripheral blood smears (left-shift). With infection, peripheral leukocyte counts may be very high, but are rarely higher than 30,000 to 40,000/mm3. Low neutrophil counts (neutropenia) after the onset of infection indicate an abnormal response and are generally associated with a poor prognosis for bacterial infection. 

If the white blood cell (WBC) count is less than 3,000/mm3 or the absolute neutrophil count (ANC) is less than 1,000/mm3, the antipsychotic should be discontinued, and the WBC count monitored closely until it returns to normal. 

GM-CSF was approved in 1991 by the United States Food and Drag Administration (FDA) to support transplant associated neutropenia and mobilize stem cells. In Europe, it is also approved for prophylactic treatment following dose intensive chemotherapy. However, the rate of absolute neutrophil count (ANC) recovery in response to treatment with GM-CSF in patients receiving myelosuppressive chemotherapy or in the... 

G-CSF increases the number of progenitor cells in the bloodstream tenfold. It has been used in the treatment of patients with myelodysplastic syndromes (MDS 8.8) where it can increase neutrophil counts and sometimes improve neutrophil function in these patients. Because some leukaemic cells are able to proliferate rather than differentiate in response to G-CSF, this CSF may potentially induce a leukaemic transformation in these patients however, its combined use with cytotoxic agents such as cytosine arabinoside appears to decrease this possibility. No doubt clinical trials already underway will establish the optimal treatment regimen for G-CSF, so that the beneficial effects of this cytokine for the treatment and management of haematological disorders can be realised. 

There has been a great deal of interest in the use of colony-stimulating factors to treat MDS. GM-CSF and G-CSF, which have been used in clinical trials, offer a potential dual benefit. Firstly, they can affect neutrophil development in the bone marrow, and so can improve the neutropenia that is associated with these disorders. Secondly, they have the potential to increase or repair the function of circulating neutrophils. Indeed, there are some reports to indicate that these CSFs can result in enhanced function of peripheral blood neutrophils in these patients. Most patients show improvements in neutrophil counts after GM-CSF or G-CSF administration. In some cases, this has been associated with a decrease in the number of infective episodes. 

Ticlopidine can cause life-threatening hematological adverse reactions, including neutropenia/agranulocytosis and thrombotic thrombocytopenic purpura (TTP). Neutropenia/agranulocytosis Neutropenia defined as an absolute neutrophil count (ANC) less than 1,200 neutrophils/mm occurred in 50 of 2048 (2.4%) stroke patients who received ticlopidine in clinical trials. Neutropenia is calculated as follows ANC = WBC x % neutrophils. In 17 patients (0.8%) the neutrophil count was less than 450/mm. ... 

Laboratory monitoring includes complete blood count, especially the absolute neutrophil count, platelet count, and the appearance of the peripheral smear. Thrombocytopenia induced by ticlopidine is occasionally unrelated to TTP. Further investigate for a diagnosis of TTP with the occurrence of any acute, unexplained reduction in hemoglobin or platelet count. Discontinue ticlopidine if there are laboratory signs of TTP or the neutrophil count is less than 1200/mm. ... 

Lead exposure Not a substitute for effective abatement of lead exposure. Neutropenia Mild to moderate neutropenia has been observed in some patients receiving succimer. While a causal relationship to succimer has not been definitely established, neutropenia has been reported with other drugs in the same chemical class. Obtain a complete blood count with white blood cell differential and direct platelet counts prior to and weekly during treatment. Withhold or discontinue therapy if the absolute neutrophil count (ANC) is below 1200/mcL and follow the patient closely to document recovery of the ANC to above 1500/mcL or to the patient s baseline neutrophil count. There is limited experience with reexposure in patients who have developed neutropenia. Therefore, rechallenge such patients only if the benefit of succimer therapy clearly outweighs the potential risk of another episode of... 

Lab test abnormalities Discontinue the drug in any patient whose white blood cell count or absolute neutrophil count falls below normal levels. White blood cell and differential counts are recommended for patients who develop fever and sore throat (or other signs of infection) during therapy. 

Monitoring Patients must have a blood sample drawn for a WBC count before initiation of treatment with clozapine and must have subsequent WBC counts done at least weekly for the first 6 months of continuous treatment. If WBC counts remain acceptable (WBC at least 3,000/mm, absolute neutrophil count [ANC] at least 1,500/mm ) during this period, WBC counts may be monitored every other week thereafter. After the discontinuation of clozapine, continue weekly WBC counts for an additional 4 weeks. 

Unlabeled uses Lithium carbonate (300 to 1,000 mg/day) has improved the neutrophil count in patients with cancer chemotherapy-induced neutropenia, in children with chronic neutropenia, and in AIDS patients receiving zidovudine. 

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