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Neutropenia Contents - 1 Diagnosis - 2 Differential diagnosis - 3 Prevention - 4 Treatment - 5 References Neutropenia is "a decrease in the number of neutrophilic leukocytes in the blood."[1] It is a subset of leukopenia and its subset granulocytopenia. The Absolute Neutrophil Count (ANC) is used to define levels of neutropenia; it can be calculated from components of the complete blood count or directly measured by some blood analyzers. The half-life of a neutrophil is less than one-half of a day. Diagnosis Rather by definition, the diagnosis is a laboratory determination, although history and physical may help establish the cause. Since the routine complete blood count allows computation or measurement of neutrophils, neutropenia may come up on routine screening. Guidelines There are three general guidelines[3] used to classify the severity of neutropenia based on the absolute neutrophil count (ANC) measured in cells per microliter of blood, and reported as a count: - 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. In infants aged 2 weeks to 1 year, the lower limit of normal ANC is 1000/µL. There is variation for ethnicity. [4] When they are available, it is desirable to state predictors and ranges in terms of genetic markers rather than the more imprecise race. Subsequent work indicates that the race-related generic abnormality is the "Duffy antigen receptor for chemokine (DARC), which is associated with the ethnic group to which individuals belong. The single-nucleotide polymorphism strongly associated with race is DARC rs2814778."[5] Neutropenia is more commonly found in women and the elderly. Benign ethnic neutropenia has been observed in Africans, African-Caribbean persons, West Indians Ethiopians, Yemenite Jews and certain Arabs.[6] Grading A more formal grading system is:[7] Differential diagnosis There are many causes of neutropenia. Some causes are caused by infections while others are not. Some causes of neutropenia may include Acquired Immune Deficiency Syndrome (AIDS), influenza, typhus, malaria, tuberculosis, dengue, Rickettsial infections, systemic lupus erythematosus, Sjogren’s syndrome, Felty’s syndrome, Kostmann syndrome, enlargement of the spleen, folate deficiencies and sepsis. Idiopathic and secondary neutropenias Idiopathic neutropenia Idiopathic neutropenia includes many types of neutropenia and can happen at any point in life for unknown reasons. It can occur in both adults and children and the effects are variable based on disease severity. As with any classification of "idiopathic" disease, there is an implication that common causes have been ruled out. Autoimmune neutropenia Autoimmune neutropenia is found in children between six months and four-years-old that have not been diagnosed with congenital neutropenia. This is the most common cause of neutropenia for children in this age group. Severe bacterial infections are rare. Autoimmune neutropenia may also be found in adults, who are usually between the ages of 20 to 40, and most commonly women. This condition is usually associated with other medical conditions. Drug-induced neutropenia Other medical conditions or medicines may cause neutropenia. Cancer patients undergoing chemotherapy could develop neutropenia. Febrile neutropenia Clinical practice guidelines define febrile neutropenia as "a single oral temperature of >=38.3°C (101°F) or a temperature of >=38.0°C (100.4°F) for >= 1 h. Neutropenia is defined as a neutrophil count of <500 cells/mm3, or a count of <1000 cells/mm3 with a predicted decrease to <500 cells/mm3"[9] A clinical prediction rule can estimate the risk of morbidity in the febrile patient with neutropenia.[10] A score of >=21 indicates low risk. Congenital neutropenia with associated immune defects - Neutropenia with abnormal immunoglobulins: This disorder is observed in individuals with X-linked agammaglobulinemia, isolated immunoglobulin A (IgA) deficiency, X-linked hyperimmunoglobulin M (XHIGM) syndrome, and dysgammaglobulinemia type I. In XHIGM, which is due to mutations in the CD40 ligand, patients can actually have normal or elevated levels of IgM but markedly decreased serum IgG levels. - Reticular dysgenesis: Patients demonstrate severe neutropenia, no cell-mediated immunity.[5] agammaglobulinemia, and lymphopenia. Life-threatening infections occur that are refractory to granulocyte colony-stimulating factor (G-CSF).10,11,2 Bone marrow transplantation is the treatment of choice. Primary inherited neutropenias Kostmann syndrome, cyclic neutropenia and autoimmune neutropenia are considered rare medical disorders of the blood. Patients may register with the Severe Chronic Neutropenia Registry (SCNIR) founded in 1994 to monitor the clinical course, treatment and disease outcomes of registered patients. Kostmann syndrome Kostmann syndrome, also known as congenital neutropenia, is present at birth. It was first described in 1956,[11] in the Swedish Kostmann family. Before the availability of granulocyte colony-stimulating factor, it was largely lethal although some family members survived with antibiotic therapy.[12] The general incidence is 1-2 per million, and mortality in the first year of life remains at 70% without G-CSF, bone marrow transplantation, or peripheral blood stem cell transplantation.[13] It has been believed inherited disease and therefore, more than one family member can be affected, but sporadic occurrence with only one patient in a family may occur. Genetic counseling can be offered to persons with a family history, [14] although the genetics are not completely clear.[12] The disease is usually detected after an infant presents with a severe infection, with severe neutropenia and: - Temperature instability in newborn period - Fever - Irritability - Localized site(s) of infection Neutrophils typically are in an arrested state of development or maturation arrest in the bone marrow. The neutrophils rarely mature to full stage development leaving the patient incapable of fighting off infection. Diagnosis is usually made during infancy. Cyclic neutropenia Cyclic neutropenia also is believed to be inherited. Neutrophil activity runs in cycles, typically 21 days, and range from normal blood counts to low blood counts. It is common for the ANC to drop to less than 200 cells/µl) (0.2 x 109/l). Common symptoms during the low period of the cycle may include mouth ulcers and inflammation. Infections such as otitis media, pneumonia and bacteremia are less likely to be seen. Prevention Hematopoietic colony-stimulating factors for primary prevention of febrile neutropenia may not decrease mortality but do decrease infections in patients undergoing cancer chemotherapy or stem cell transplantation according to a systematic review.[15] Treatment If neutropenia is secondary to another disease or external chemical, that disorder must be treated. When there is both neutropenia and immunoglobulin deficiency, the infection risk is high, and the treatment is intravenous immunoglobulin (IVIG). Using G-CSF Granulocyte colony-stimulating factor can be a potent treatment for severe neutropenia, but it is expensive and not without risk.[16] Granulocyte colony-stimulating factor is indicated in selected settings[17][18] if the projected chance of febrile neutropenia is at least 20%.[19] References - ↑ Anonymous (2015), Neutropenia (English). Medical Subject Headings. U.S. National Library of Medicine. - ↑ Carneiro, José; Junqueira, Luiz Carlos Uchôa (2005). Basic histology: text & atlas. New York: McGraw-Hill, Medical Pub. Division. - ↑ John E Godwin and Christopher D Braden (4 October 2009), "Neutropenia: Introduction", eMedicine - ↑ Dale E. Hammerschmidt (1 January 1999), "It's as simple as black and white!: Race and ethnicity as categorical variables", J Lab Clin Med 133 (1): 10-12, DOI:10.1053/lc.1999.v133.a94932 - ↑ 5.0 5.1 Guido D'Angelo (September 2009), "(Abstract) Ethnic and Genetic Causes of Neutropenia: Clinical and Therapeutic Implications", Laboratory Hematology 15 (3): 25 - 29 - ↑ "(Abstract) Prevalence of neutropenia in the U.S. population: age, sex, smoking status, and ethnic differences.", Ann Intern Med. - ↑ Anonymous (1999). Common Toxicity Criteria (CTC). Cancer Therapy Evaluation Program. Retrieved on 2008-01-06. - ↑ Kush Sachdeva (9 April 2009), "Granulocytopenia: Differential Diagnosis & Workup", eMedicine - ↑ Hughes WT, Armstrong D, Bodey GP, et al (2002). "2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer". Clin. Infect. Dis. Research Blogging. - ↑ Klastersky J, Paesmans M, Rubenstein EB, et al (2000). "The Multinational Association for Supportive Care in Cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients". Clin. Oncol. [e] (See Table 4 for the prediction rule) - ↑ Kostmann R. Infantile genetic agranulocytosis. A new recessive lethal disease in man (1956), at 1-78. - ↑ 12.0 12.1 Carlsson G et al. , "Neutrophil elastase and granulocyte colony-stimulating factor receptor mutation analyses and leukemia evolution in severe congenital neutropenia patients belonging to the original Kostmann family in northern Sweden", Haematologica 91 (5): 589 - ↑ Michael S Tankersley (11 November 2008), "Kostmann Disease: overview", eMedicine: Pediatrics: General Medicine > Allergy & Immunology - ↑ Michael S Tankersley (11 November 2008), "Kostmann Disease: followup", eMedicine: Pediatrics: General Medicine > Allergy & Immunology - ↑ Sung L, Nathan PC, Alibhai SM, Tomlinson GA, Beyene J (September 2007). "Meta-analysis: effect of prophylactic hematopoietic colony-stimulating factors on mortality and outcomes of infection". Ann. Intern. Med. - ↑ Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L, Bennett CL, Cantor SB, Crawford J, Cross SJ, Demetri G, Desch CE, Pizzo PA, Schiffer CA, Schwartzberg L, Somerfield MR, Somlo G, Wade JC, Wade JL, Winn RJ, Wozniak AJ, Wolff A (2006 Jul 1), "2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline", J Clin Oncol 24 (19): 3187-205 - ↑ Kuderer NM, Dale DC, Crawford J, Lyman GH (2007). "Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: a systematic review". Clin. Oncol. Research Blogging. ACP JC Review - ↑ Frei, Emil; Kufe, Donald W.; Holland, James F. (2003). Cancer medicine 6: Granulocyte colony-stimulating factor. Hamilton, Ont: BC Decker. Full text - ↑ Smith TJ, Khatcheressian J, Lyman GH, et al (2006). "2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline". Clin. Oncol. Research Blogging.
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Neutropenija – uzroci, simptomi i liječenje Neutropenija je poremećaj granulocita, koji karakterizira neuobičajeno mali broj neutrofila. Neutrofili obično čine 50-70% cirkulirajućih bijelih krvnih stanica, a njihova primarna uloga je obrana protiv infekcija uništavajući bakterije u krvi. Stoga, bolesnici s neutropenijom su više osjetljivi na bakterijske infekcije i bez brzog liječenja mogu razviti za životna opasna stanja (neutropenična sepsa). Neutropenije mogu biti akutne ili kronične, ovisno o trajanju bolesti. Pacijent ima kroničnu neutropeniju ako stanje traje duže od tri mjeseca. Ovaj naziv se ponekad koristi naizmjenično s pojmom leukopenija (smanjen broj bijelih krvnih stanica), s obzirom na to da su neutrofili najrasprostranjeniji leukociti, iako je ispravnije smatrati neutropeniju jednom od varijanti leukopenije. Postoje brojni uzroci neutropenije, a oni se u grubo mogu podijeliti na one kod kojih postoje problemi u proizvodnji stanica od strane koštane srži i one kod kojih je problem u uništavanju stanica negdje drugdje u tijelu. Liječenje ovisi o prirodi uzroka, a naglasak je stavljen na prevenciju i liječenje infekcije. Vrste neutropenije Postoje tri glavne smjernice koje se koriste za klasifikaciju težine neutropenije na temelju apsolutnog broja neutrofila, mjereno stanicama u mikrolitru krvi: - Blaga neutropenija (apsolutni broj neutrofila ≤ 1000 < 1500) – minimalni rizik od infekcije - Umjerena neutropenija (apsolutni broj neutrofila ≤ 500 < 1000) – umjereni rizik od infekcije - Teška neutropenija (apsolutni broj neutrofila <500) – veliki rizik od infekcije Znakovi i simptomi Neutropenija može biti nedijagnosticirana, no općenito se otkrije kada pacijent razvije teške infekcije ili sepsu. Neke uobičajene infekcije mogu imati neočekivane rezultate kod osoba s neutropenijom. Stvaranje gnoja, primjerice, može izostati, s obzirom da to zahtijeva cirkuliranje neutrofilnih granulocita. Neki uobičajeni simptomi neutropenije uključuju temperaturu i česte infekcije. Ove infekcije mogu izazvati neka stanja, kao što su: - Čirevi u ustima - Proljev - Peckanje prilikom mokrenja - Neobično crvenilo - Bol ili otekline oko rane - Upala grla Dijagnoza Smanjeni broj neutrofila može se otkriti potpunom krvnom slikom. Kada je dijagnoza neizvjesna, ili postoji sumnja na ozbiljne uzroke, često je potrebna i biopsija koštane srži. Uzroci neutropenije Uzroci neutropenije mogu se podijeliti u sljedeće skupine: Smanjena proizvodnja u koštanoj srži: - Aplastična anemija - Trovanje arsenom - Maligne bolesti - Neki lijekovi - Nasljedni poremećaji (primjerice, kongenitalna neutropenija, ciklička neutropenija) - Zračenje - Nedostatak vitamina B12, folne kiseline ili bakra - Povećano uništavanje: - Autoimuna neutropenija - Kemoterapijski tretmani, primjerice kod raka i autoimunih bolesti Marginalizacija i vezivanje - Hemodijaliza Lijekovi - flecainide - feniton - indomethacin - propiltiouracila - carbimazole - klorpromazina - trimetoprim/sulfametoksazol - cotrimoxazole Tu je često i blaga neutropenija u virusnim infekcijama, kao i stanje koje se naziva jutarnja pseudoneutropenija, koja bi mogla biti posljedica nekih antipsihotičnih lijekova. Liječenje Ne postoji idealna terapija kod neutropenije, no od pomoći mogu biti faktori rasta, koji potiču proizvodnju bijelih krvnih stanica, naročito faktor koji potiče granulocitnu koloniju (G-CSF) i faktor koji potiče granulocitnu makrofagnu koloniju (GM-CSF). Primjerice, filgrastim može biti djelotvoran kod kemoterapije, osoba s prirođenim oblicima neutropenije, uključujući teške prirođene neutropenije, autoimuni recesivni Kostann cindrom, cikličke neutropenije i myelokathexis. Prehrana kod neutropenije Smjernice za prehranu kod osoba s neutropenijom su sljedeće: Izbjegavajte: - sirovo voće i povrće - brzu prehranu i gazirana pića - sir - obrađeno meso - orašaste plodove, pečene ili svježe mljevene, kao i maslac od orašastih plodova - jogurt Sve namirnice trebale bi biti dobro kuhane, a jaja tvrdo kuhana. Izvor: Wikipedia.org