Andersohn F, Konzen C, Garbe E.
Systematic review: agranulocytosis induced by nonchemotherapy drugs.
Ann Intern Med. 2007 May 1;146(9):657-65. doi: 10.7326/0003-4819-146-9-200705010-00009.
Abstract/Text
BACKGROUND: Nonchemotherapy drug-induced agranulocytosis is a rare adverse reaction that is characterized by a decrease in peripheral neutrophil count to less than 0.5 x 10(9) cells/L due to immunologic or cytotoxic mechanisms.
PURPOSE: To systematically review case reports of drugs that are definitely or probably related to agranulocytosis.
DATA SOURCES: English-language and German-language reports in MEDLINE (1966 to 2006) or EMBASE (1989 to 2006) and in bibliographies of retrieved articles.
STUDY SELECTION: Published case reports of patients with nonchemotherapy drug-induced agranulocytosis.
DATA EXTRACTION: One reviewer abstracted details about cases and assessed causality between drug intake and agranulocytosis by using World Health Organization assessment criteria.
DATA SYNTHESIS: Causality assessments of 980 reported cases of agranulocytosis were definite in 56 (6%), probable in 436 (44%), possible in 481 (49%), and unlikely in 7 (1%). A total of 125 drugs were definitely or probably related to agranulocytosis. Drugs for which more than 10 reports were available (carbimazole, clozapine, dapsone, dipyrone, methimazole, penicillin G, procainamide, propylthiouracil, rituximab, sulfasalazine, and ticlopidine) accounted for more than 50% of definite or probable reports. Proportions of fatal cases decreased between 1966 and 2006. More patients with a neutrophil count nadir less than 0.1 x 10(9) cells/L had fatal complications than did those with a neutrophil count nadir of 0.1 x 10(9) cells/L or greater (10% vs. 3%; P < 0.001). Patients treated with hematopoietic growth factors had a shorter median duration of neutropenia (8 days vs. 9 days; P = 0.015) and, among asymptomatic patients at diagnosis, had a lower proportion of infectious or fatal complications (14% vs. 29%; P = 0.030) than patients without such treatment.
LIMITATIONS: Case reports cannot provide rates of drug-induced complications, sometimes incompletely assess or describe important details, and sometimes emphasize atypical features and outcomes.
CONCLUSIONS: Many drugs can cause nonchemotherapy drug-induced agranulocytosis. Case fatality may be decreasing over time with the availability of better treatment.
日本臨床腫瘍学会 編集：発熱性好中球減少症（FN）診療ガイドライン改訂第2版 ～がん薬物療法時の感染対策～. 南江堂. 2017.
Fattizzo B, Zaninoni A, Consonni D, Zanella A, Gianelli U, Cortelezzi A, Barcellini W.
Is chronic neutropenia always a benign disease? Evidences from a 5-year prospective study.
Eur J Intern Med. 2015 Oct;26(8):611-5. doi: 10.1016/j.ejim.2015.05.019. Epub 2015 Jun 8.
Abstract/Text
AIM: To evaluate infections and oncohematologic evolution in adult patients with chronic idiopathic and autoimmune neutropenia in a prospective study.
PATIENTS AND METHODS: 76 consecutive patients were enrolled from September 2008 to April 2012. Complete blood counts and clinical evaluation were performed at enrolment, at month 3, 6, and then every 6 months. Anti-neutrophil antibodies were tested by GIFT method.
RESULTS: Patients (49 chronic idiopathic- and 27 autoimmune neutropenia) were followed for a median of 5 years (range 24-84 months). At enrolment, neutropenia was mild in 44 patients (median neutrophils 1.27×10(3)/μL), moderate in 23 (median 0.8×10(3)/μL), and severe in 9 (median 0.4×10(3)/μL). Neutrophil counts showed a great inter-subject but no intra-subject variability, with lower values in autoimmune neutropenia, in males, and in MGUS cases. Over time, no grade >3 infections occurred; 13/49 chronic idiopathic and 6/27 autoimmune neutropenia patients experienced a grade 2 event, irrespective of mean and nadir neutrophil values. Bone marrow evaluation at enrolment showed reduced cellularity in 23% of cases, and dyserythropoietic features in 55%, with no definite hematologic diagnosis. During the follow-up, 5 cases were diagnosed with NK expansion, 4 with hairy cell leukemia, and 3 with myelodysplasia (1 myelomonocytic leukemia, 1 refractory cytopenia with unilineage dysplasia, and 1 multilineage dysplasia), with a median time to evolution of 30 months.
CONCLUSION: Chronic idiopathic and autoimmune neutropenia, although usually benign, deserve hematological follow-up with a bone marrow evaluation at diagnosis and a re-evaluation in the presence of worsening neutropenia, appearance of additional cytopenias, and lymphocytosis.
Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
Newman KA, Akhtari M.
Management of autoimmune neutropenia in Felty's syndrome and systemic lupus erythematosus.
Autoimmun Rev. 2011 May;10(7):432-7. doi: 10.1016/j.autrev.2011.01.006. Epub 2011 Jan 18.
Abstract/Text
Autoimmune neutropenia, caused by neutrophil-specific autoantibodies is a common phenomenon in autoimmune disorders such as Felty's syndrome and systemic lupus erythematosus. Felty's syndrome is associated with neutropenia and splenomegaly in seropositive rheumatoid arthritis which can be severe and with recurrent bacterial infections. Neutropenia is also common in systemic lupus erythematosus and it is included in the current systemic lupus classification criteria. The pathobiology of the autoimmune neutropenia in Felty's syndrome and systemic lupus erythematosus is complex, and it could be a major cause of morbidity and mortality due to increased risk of sepsis. Treatment should be individualized on the basis of patient's clinical situation, and prevention or treatment of the infection. Recombinant human granulocyte colony-stimulating factor is a safe and effective therapeutic modality in management of autoimmune neutropenia associated with Felty's syndrome and systemic lupus erythematosus, which stimulates neutrophil production. There is a slight increased risk of exacerbation of the underlying autoimmune disorder, and recombinant human granulocyte colony-stimulating factor dose and frequency should be adjusted at the lowest effective dose.
Copyright © 2010 Elsevier B.V. All rights reserved.
DeZern AE, Malcovati L, Ebert BL.
CHIP, CCUS, and Other Acronyms: Definition, Implications, and Impact on Practice.
Am Soc Clin Oncol Educ Book. 2019 Jan;39:400-410. doi: 10.1200/EDBK_239083. Epub 2019 May 17.
Abstract/Text
Unexplained blood cytopenias can be a clinical challenge for patients and clinicians alike. The relationship between these cytopenias and myeloid neoplasms like myelodysplastic syndromes (MDS) is currently an area of active research. There have been marked developments in our understanding of clonal hematopoiesis based on findings of somatic mutations in genes known to be associated with MDS. This has led to newer terms to describe precursor states to MDS, such as clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS). These conditions may allow earlier diagnosis, modify surveillance for MDS, and guide additional therapies. This review summarizes recent updates in the field for affected patients.
Firnhaber C, Smeaton L, Saukila N, Flanigan T, Gangakhedkar R, Kumwenda J, La Rosa A, Kumarasamy N, De Gruttola V, Hakim JG, Campbell TB.
Comparisons of anemia, thrombocytopenia, and neutropenia at initiation of HIV antiretroviral therapy in Africa, Asia, and the Americas.
Int J Infect Dis. 2010 Dec;14(12):e1088-92. doi: 10.1016/j.ijid.2010.08.002. Epub 2010 Oct 18.
Abstract/Text
BACKGROUND: Hematological abnormalities are common manifestations of advanced HIV-1 infection that could affect the outcomes of highly-active antiretroviral therapy (HAART). Although most HIV-1-infected individuals live in resource-constrained countries, there is little information about the frequency of hematological abnormalities such as anemia, neutropenia, and thrombocytopenia among individuals with advanced HIV-1 disease.
METHODS: This study compared the prevalence of pre-antiretroviral therapy hematological abnormalities among 1571 participants in a randomized trial of antiretroviral efficacy in Africa, Asia, South America, the Caribbean, and the USA. Potential covariates for anemia, neutropenia, and thrombocytopenia were identified in univariate analyses and evaluated in separate multivariable models for each hematological condition.
RESULTS: The frequencies of neutropenia (absolute neutrophil count ≤1.3×10⁹/l), anemia (hemoglobin ≤10g/dl), and thrombocytopenia (platelets ≤125×10⁹/l) at initiation of antiretroviral therapy were 14%, 12%, and 7%, respectively, and varied by country (p<0.0001 for each). In multivariable models, anemia was associated with gender, platelet count, and country; neutropenia was associated with CD4+ lymphocyte and platelet counts; and thrombocytopenia was associated with country, gender, and chronic hepatitis B infection.
CONCLUSIONS: Differences in the frequency of pretreatment hematological abnormalities could have important implications for the choice of antiretroviral regimen in resource-constrained settings.
Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Halfdanarson TR, Kumar N, Li CY, Phyliky RL, Hogan WJ.
Hematological manifestations of copper deficiency: a retrospective review.
Eur J Haematol. 2008 Jun;80(6):523-31. doi: 10.1111/j.1600-0609.2008.01050.x. Epub 2008 Feb 12.
Abstract/Text
Copper deficiency is an established cause of hematological abnormalities but is frequently misdiagnosed. Copper deficiency can present as a combination of hematological and neurological abnormalities and it may masquerade as a myelodysplastic syndrome. We reviewed the records of patients with hypocupremia and hematologic abnormalities identified between 1970 and 2005. Patients with hypocupremia unrelated to copper deficiency (e.g. Wilson's disease) were excluded. Forty patients with copper deficiency and hematological abnormalities were identified. Ten patients (25%) had undergone bariatric (weight reduction) surgery and an additional 14 patients (35%) had undergone surgery on the gastrointestinal tract, most commonly gastric resection. In 12 cases, no cause for copper deficiency was identified. Anemia and neutropenia were the most common hematologic abnormalities identified and the majority of the patients also had neurologic findings, most commonly due to myeloneuropathy. Abnormalities observed on bone marrow examination including vacuoles in myeloid precursors, iron-containing plasma cells, a decrease in granulocyte precursors and ring sideroblasts may be valuable clues to the diagnosis. Copper deficiency is an uncommon but very treatable cause of hematologic abnormalities.
