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Thursday, 5 December 2013

Neutropenia - Treatments of Types of Neutropenia

Neutropenia is defined as a condition of  abnormally low number of neutrophils, as a  result of granulocyte disorder of that leads to Immunodeficiency with lower than normal  circulating white blood cells. Patients with neutropenia are susceptible to bacterial infections causes of neutropenic sepsis.
Neutropenia is either problems in the production of the cells by the bone marrow and destruction of the cells from somewhere else in the body, if  neutrophil count falls below 1,000 cells per microliter of blood.
Neutropenia can be classified into acute and chronic types, depending to the duration of the illness. Some researchers divided severity of the disease, depending to the absolute neutrophil count (ANC) and is described as follows(a).
1. Mild neutropenia, when the ANC falls below a lower limit of 1500 per mm3 (1.5 x 109 /1), but remains higher than 1000 per mm3 (1.0 x 109 /1).
2. Moderate neutropenia, when the ANC falls between 500 per mm3 and 1000 per mm3 (0.5 x 109 /1 - 1.0 x 109 /1)
3. Severe neutropenia, when the ANC falls below 500 per mm3 (0.5 x 109 /1)
Treatment depending to types of Neutropenia
1. Severe autoimmune neutropenia
According to the study by the,in the study to systematically review the clinical presentations and management of periodontitis patients with neutropenia and present a patient with severe autoimmune neutropenia of twenty-four case reports describing a total of 33 patients, showed that improvements in periodontal condition were observed in 86% of patients who were administered adjuvant systemic antibiotics compared to 47% of patients who were not given supplemental therapy. Granulocyte-colony stimulating factor was administered to 67% of the neutropenic patients, and both improvement and progression of the hematological condition were monitored. Scaling and root planing, in combination with systemic antibiotics to supplement therapy for the underlying disease, have been successful in most cases(61).

2. Febrile neutropenia
Febrile neutropenic patients are at greater risk of getting bacterial and fungal infections. Empirical antifungal therapy is considered if the fever persists despite broad-spectrum antibiotics including vancomycin, According to the study by the Postgraduate Institute of Medical Education and Research,  to determine the response of empirical amphotericin B deoxycholate (dAMB) starting either on day 4 or day 8 in febrile neutropenic patients not responding to broad-spectrum antibiotics and without localisation of fever. Fifty-six patients with persistent neutropenic fever despite 72 h of antibiotic therapy were randomly assigned to receive dAMB either starting on day 4 (group A, n = 27, median age 23 years) or starting on day 8 (group B, n = 29, median age 25 years). Satisfactory response (patient remaining afebrile for 48 h and maintaining absolute neutrophil count >500 μl-1 ) occurred in 85.2% of patients in group A vs. 69.5% in group B (P = 0.209). Patients in group A took significantly fewer days to become afebrile than group B (5.4 ± 3.9 days vs. 11.3 ± 4.0 days, P = 0.0001). The adverse side effects of dAMB (nephrotoxicity, hypokalemia and hypomagnesemia) occurred at similar rates in both groups. Early addition of empirical dAMB in febrile neutropenic patients leads to their early defervescence and decreased dose requirement(62).

2. Treatment of Neutropenia as a result of chemotherapy in cancer patients
Cytotoxic chemotherapy suppresses the hematopoietic system, impairing host protective mechanisms and limiting the doses of chemotherapy that can be tolerated. Neutropenia, the most serious hematologic toxicity, is associated with the risk of life-threatening infections as well as chemotherapy dose reductions and delays that may compromise treatment outcomes.  According to the study by the University of Rochester School of Medicine and Dentistry, Neutropenia represents a major dose-limiting toxicity of chemotherapy and is associated with an increased risk of infection, impaired patient quality of life, and interference with the delivery of full-dose chemotherapy. These complications increase not only morbidity and mortality associated with cancer treatment but also the overall cost of care for cancer patients. Conversely, chemotherapy-induced neutropenia as a surrogate for delivered dose intensity has been associated with improved cancer survival. Administration of myeloid growth factors, such as filgrastim and pegfilgrastim, reduces the risk for neutropenic complications and facilitates the delivery of full-dose chemotherapy. There is an ongoing effort to identify patients at increased risk for developing neutropenic complications who would likely benefit from preemptive myeloid growth factor therapy. Appropriate use of myeloid growth factors is associated with reduced neutropenic complications, improved patient quality of life, and potentially improved disease control and long-term survival(63).

3. Cyclic neutropenia
In the study of six patients with cyclic neutropenia treated with recombinant human granulocyte colony-stimulating factor (G-CSF) for 3 to 15 months, found that uring the first 40 months of treatment, no typical mouth ulcers or bacterial infections occurred; recurrent gingivitis improved. We conclude that G-CSF is effective for the treatment of cyclic neutropenia in humans(64).

4. Congenital neutropenia
In recent years, the converging efforts of hematologists, immunologists and geneticists have led to the discovery of the genetic and biochemical basis of severe congenital neutropenia; cyclic neutropenia; warts, hypogammaglobulinemia, immunodeficiency, myelokathexis or WHIM syndrome and other rarer conditions associated to neutropenia. According to the study by the University of Brescia, although the diagnosis of congenital neutropenia includes many disorders of distinct origin and variable prognosis, their treatment is still based on granulocyte colony stimulating factor administration. Understanding the pathogenesis of these forms of neutropenia and their evolution will focus future studies on the mechanisms of normal and pathological myelopoiesis and on the development of the most appropriate treatment for each type of neutropenia(65). But other researchers indicated that the treatment with G-CSF is not sufficient to correct all of the functional deficiency of neutrophils, and this might account for the consistent risk of infections observed in SCN patients(66).
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Sources
(a) http://www.neutropenia.ca/about/what-is-neutropenia
(61) http://www.ncbi.nlm.nih.gov/pubmed/17379159
(62) http://www.ncbi.nlm.nih.gov/pubmed/23635971
(63) http://www.ncbi.nlm.nih.gov/pubmed/23844563
(64) http://www.ncbi.nlm.nih.gov/pubmed/2469956
(65) http://www.ncbi.nlm.nih.gov/pubmed/15640692
(66) http://www.ncbi.nlm.nih.gov/pubmed/17311988