今日の臨床サポート

その他の白血球分画異常(単球、好塩基球、リンパ球異常)

著者: 樋口敬和 獨協医科大学埼玉医療センター 輸血部

監修: 神田善伸 自治医科大学附属病院 血液科

著者校正/監修レビュー済:2021/03/24
参考ガイドライン:
  1. Lynch DT, Hall J, Foucar K: How I investigate monocytosis? Int J Lab Hem 2018;40:107-1148
  1. Freriel J, Depasse F, Geneviève F: How I investigate basophilia in daily practice. Int J Lab Hem 2020;42:237-245
  1. Chabot-Richards DS, George TI: Leukocytosis. Int J Lab Hem 36: 279-288, 2014
患者向け説明資料

概要・推奨   

  1. 末梢血の単球単球数>800/μl(時に>1,000/μlの場合を単球増多、単球数<200/μlの場合を単球減少とする。
  1. クローン性の単球増多は、単球以外の血球の異常、単球の形態異常などの血液所見から疑うことができることが多い。
  1. 反応性の単球増多自体は非特異的所見であり、単球増多をきたす基礎疾患(原因)を検討する。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
樋口敬和 : 特に申告事項無し[2021年]
監修:神田善伸 : 未申告[2021年]

改訂のポイント:
  1. 内容について定期レビューを行った。

まとめ

疫学情報・病態・注意事項  
  1. 末梢血中の白血球には、好中球、リンパ球、単球、好酸球、好塩基球の5種類がある。ここでは、単球、好塩基球、リンパ球の数的異常を取り上げる。
 
単球:
  1. 成人では末梢血の単球は白血球の1~9%で、単球数>800/μl(時に>1,000/μl)の場合を単球増多、単球数<200/μlの場合を単球減少とする。
  1. 単球の数的異常が単独で生ずることはまれで、通常は他の血球の異常を伴う。
  1. 単球増多の多くは反応性の増加であり、単球数の異常を来す基礎疾患の検討が重要である。
 
好塩基球:
  1. 好塩基球数>150/μlを好塩基球増多、好塩基球数<20/μlを好塩基球減少とする。
  1. クローン性(腫瘍性、一次性)の増多と反応性(二次性)の増多があるが、反応性好塩基球増多を来すことはまれである。
  1. 骨髄増殖性腫瘍、骨髄異形成症候群や一部の白血病で増加することがあり、特に慢性骨髄性白血病で増加する。
  1. IgEが関与する即時型アレルギーの際に増加することがある。
  1. 潰瘍性大腸炎、若年性関節リウマチなどの炎症性疾患、甲状腺機能低下症などの内分泌疾患でも増加することがある。
  1. ときに水痘などの感染症で増加する。
  1. 好塩基球減少を診断することはしばしば困難であるが、好塩基球減少を来す病態が知られている(<図表>)。これらの病態について検討する。
 
リンパ球:
  1. リンパ球は通常末梢血白血球の20~40%であり、一般にリンパ球絶対数>4,000/μlをリンパ球増多、<1,000/μlをリンパ球減少とする。
  1. 腫瘍性(クローン性、一次性)と反応性(二次性)に増加するが、リンパ球増多の多くは反応性のものであり、感染症に伴うものが多く、ウイルス感染症によるものが大部分である。
  1. リンパ系悪性腫瘍を見逃さないことが重要である。
  1. リンパ球減少は、①産生の低下、②破壊の亢進、③再分布、④喪失などの機序により生ずる。
問診・診察のポイント  
問診:
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文献 

著者: S R Meisel, H Pauzner, M Shechter, Z Zeidan, D David
雑誌名: Cardiology. 1998 Jul;90(1):52-7.
Abstract/Text Infiltration by mononuclear cells, mostly monocytes, into necrotic myocardial tissue can be detected beyond the 3rd day after the onset of infarction. These monocytes, mobilized by an unknown mechanism, initiate phagocytosis of necrotic tissue. We observed in patients having sustained an acute myocardial infarction (AMI) a significant increase in monocyte count 2-3 days following presentation, possibly representing peripheral recruitment of monocytes to the injured myocardium. To establish this observation, we prospectively documented monocyte and neutrophil counts throughout hospitalization in 186 consecutive patients (118 patients having sustained an AMI, 34 patients with angina, and 34 patients admitted for nonischemic reasons). Average monocyte count, which rose on the 2nd day and reached a peak on day 3, was significantly elevated in these patients compared with control subjects (p < 0.001). Neutrophil count exhibited a similar phase-shifted response. Peak monocyte count exceeded 800/mm3 (upper limit of normal range) in 69 (58%) of AMI patients but in only 3 of the 68 (4%) non-AMI patients, yielding a sensitivity and specificity of 58 and 95%, respectively, for the diagnosis of AMI by this criterion. A significant correlation between maximal creatine kinase (CK) representing the extent of myocardial necrosis and peak monocyte count was shown (r = 0.51, p < 0.0001). A correlation between CK and monocyte count sum of days 1-3 (r = 0.51, p < 0.001) was found in a substudy of 25 patients with AMI. Similarly, a correlation was shown with cardiac function score as evaluated by 2-dimensional echocardiography (p < 0.001 and p < 0. 008 for difference between CK sum and monocyte count sum of high and low echo score groups, respectively). Hence, the peak monocyte count recorded during the immediate postinfarction period provides a bedside marker of the extent of myocardial damage that is the preponderant prognostic determinant. If validated in future studies this phenomenon may have diagnostic and prognostic implications.

PMID 9693172  Cardiology. 1998 Jul;90(1):52-7.
著者: Mathias Hensel, Lena Grädel, Alexander Kutz, Sebastian Haubitz, Andreas Huber, Beat Mueller, Philipp Schuetz, Thomas Hügle
雑誌名: Medicine (Baltimore). 2017 Jul;96(28):e7404. doi: 10.1097/MD.0000000000007404.
Abstract/Text Monocytosis is associated with chronic infections such as tuberculosis or endocarditis as well as rheumatic and myeloproliferative disorders. Monocytes are also involved in the pathogenesis of atherosclerosis, coronary artery disease, and stroke. The value of monocytosis as a prognostic marker in different diagnostic groups in the emergency setting, however, has not been investigated so far.The aim of the article is to study monocytosis as an outcome factor in the emergency setting.In a Swiss register study, we analyzed monocyte counts in 4238 patients aged >18 years who were admitted to the emergency department of a regional tertiary care hospital. Monocytosis was defined as 0.8×10 cells/L. Diagnoses were grouped into infection, cardiovascular, neurological, metabolic, gastrointestinal, pulmonary, or other. Thirty-day mortality was defined as the primary endpointA total of 1217 patients with monocytosis were identified. Patients with monocytosis at admission suffered more frequently from respiratory symptoms (17.7% vs 8.9%, P <.001) and infection as the final diagnosis (20.8% vs 10.3%, P <.001) while neurological diagnoses were significantly lower in the monocytosis group (15.3% vs 30.9%, P <.001). Patients with monocytosis suffered from more comorbidities such as congestive heart failure, chronic obstructive pulmonary disease, tumor, diabetes, or renal failure but not dementia. When adjusted for age, gender, comorbidities, and main diagnosis, the 30-day mortality (P = .002) and length of stay (P = .001) were significantly higher in patients with monocytosis. The 30-day mortality in patients with monocytosis was most notably influenced by a cardiological diagnosis (odds ratio 3.91).An increased monocyte count predicts adverse outcome in patients admitted to the emergency department. Mechanistic studies will be necessary to specify the potentially detrimental role of monocytosis in critical illness.

PMID 28700476  Medicine (Baltimore). 2017 Jul;96(28):e7404. doi: 10.10・・・
著者: Friedrich Wimazal, Ulrich Germing, Michael Kundi, Thomas Noesslinger, Sabine Blum, Philipp Geissler, Christian Baumgartner, Michael Pfeilstoecker, Peter Valent, Wolfgang R Sperr
雑誌名: Cancer. 2010 May 15;116(10):2372-81. doi: 10.1002/cncr.25036.
Abstract/Text BACKGROUND: Lineage involvement and maturation arrest are considered to have prognostic significance in patients with myelodysplastic syndromes (MDS). However, although the prognostic value of neutropenia, thrombocytopenia, and monocytosis have been documented, little is known about the impact of eosinophils and basophils.
METHODS: The authors examined the prognostic significance of eosinophils and basophils in 1008 patients with de novo MDS. Patients were enrolled from 3 centers of the Austrian-German MDS Working Group and were analyzed retrospectively. Blood eosinophils and basophils were quantified by light microscopy, and their impact on survival and leukemia-free survival was calculated by using Cox regression.
RESULTS: Eosinophilia (eosinophils >350/microL) and basophilia (basophils >250/microL) predicted a significantly reduced survival (P < .05) without having a significant impact on leukemia-free survival. In multivariate analysis, eosinophilia and basophilia were identified as lactate dehydrogenase (LDH)-independent prognostic variables with International Prognostic Scoring System (IPSS)-specific impact. Although elevated LDH was identified as a major prognostic determinant in IPSS low-risk, intermediate-1 risk, and high-risk subgroups, the condition "eosinophilia and/or basophilia" was identified as a superior prognostic indicator in the IPSS intermediate-2 risk subgroup.
CONCLUSIONS: The evaluation of eosinophils and basophils in patients with MDS was helpful and may complement the spectrum of variables to optimize prognostication in MDS.

(c) 2010 American Cancer Society.
PMID 20209617  Cancer. 2010 May 15;116(10):2372-81. doi: 10.1002/cncr.・・・
著者: C E H Grattan, G Dawn, S Gibbs, D M Francis
雑誌名: Clin Exp Allergy. 2003 Mar;33(3):337-41.
Abstract/Text BACKGROUND: The basopenia of chronic urticaria relates to histamine releasing autoantibodies in the serum of patients with autoimmune urticaria. This reduction in circulating basophils may be due to active recruitment into weals. If so, it might be expected that numbers in blood would be reduced when urticaria is active and increased after treatment. The primary aim of this study was to look at diurnal variation of basophil numbers in patients with chronic ordinary urticaria (not physical or vasculitic) in relation to disease activity and the effect of treatment with antihistamines and corticosteroids, and to compare the results with healthy controls. A secondary aim was to compare a standard manual counting method with automated basophil counts and to look at numbers of other circulating leucocytes that might be relevant to urticaria pathogenesis.
METHODS: Manual basophil counts using a toluidine blue stain and automated 5-part differentials (Coulter Gen. S) were performed at 4-hourly intervals from 08.00 to 20.00 in 10 healthy controls (six women, age 24 to 63 years) and seven chronic urticaria patients (five women, 24 to 50 years). All chronic urticaria patients had severe daily or almost daily urticaria. Only one of six chronic urticaria sera showed in vitro basophil histamine releasing activity. Counts were performed without treatment, after a week of taking loratadine 10 mg daily and after 3 days of adding prednisolone at 0.6 mg/kg/day (maximum 40 mg). Daily urticarial activity scores (UAS) were derived from weal numbers and itch, maximum 7.
RESULTS: There was no significant overall diurnal variation of basophil numbers in healthy controls or chronic urticaria patients. Mean (SE) manually counted basophil were higher in healthy controls than chronic urticaria (43.4/ microL (2.1) vs. 4.4 (0.8), P < 0.001). Basophil counts were reduced in healthy controls on steroids (19.2 (1.9), P < 0.001) but increased in chronic urticaria (8.9 (1.9), P < 0.001). Loratadine did not influence them. UAS fell on treatment (3.3 (0.4) baseline, 1.4 (0.5) on loratadine and 0.5 (0.2) on prednisolone with loratadine, P < 0.001). There was a negative linear correlation between basophil numbers and UAS in untreated chronic urticaria patients (P = 0.001, Spearman rank correlation). Manual and automated basophil counts showed poor agreement. Lymphocyte numbers were lower in chronic urticaria than healthy controls. Neutrophils increased whereas lymphocytes and eosinophils decreased in all subjects on prednisolone. They were unaffected by loratadine.
CONCLUSION: The results are consistent with the hypothesis that circulating basophils may be recruited from blood into urticarial weals during disease activity. Automated counts are not suitable for assessing basophil numbers in chronic urticaria. The relevance of reduced lymphocyte numbers in chronic urticaria needs to be explored.

PMID 12614448  Clin Exp Allergy. 2003 Mar;33(3):337-41.
著者: Marcela Chisté, Elena Vrotsos, Carlos Zamora, Antonio Martinez
雑誌名: Ann Diagn Pathol. 2013 Jun;17(3):295-7. doi: 10.1016/j.anndiagpath.2012.05.004. Epub 2012 Jun 7.
Abstract/Text Chronic lymphocytic leukemia/small lymphocytic lymphoma is a neoplasm composed of monomorphic small B lymphocytes in the peripheral blood, bone marrow, spleen, and lymph nodes, forming proliferation centers in tissue infiltrates (Muller-Hermelink HK, Montserrat E, Catovsky D, et al. Chronic lymphocytic leukaemia/small lymphocytic lymphoma, in Swerdlow SH (ed). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France, International Agency for Research on Cancer, 2008, pp. 180-182). We report a case of a 77-year-old man with a medical history of chronic lymphocytic leukemia who presented with worsening chest pain over 8 weeks. Imaging studies revealed severe aortic stenosis and moderate mitral regurgitation. He subsequently underwent minimally invasive aortic valve replacement and mitral repair at our institution. Grossly, the specimen consisted of a trileaflet valve with multiple yellow-white focally hemorrhagic and calcified nodules over its surface. Histologically, a lymphocytic infiltrate composed of monotonous small cells with scant cytoplasm was seen as well as calcification and fibrosis. Immunohistochemical stains were positive for CD20, PAX5, CD5, and CD23. To our knowledge, this is the first reported case of an immunohistochemically documented chronic lymphocytic leukemia/small lymphocytic lymphoma to involve a cardiac valve.

Copyright © 2013 Elsevier Inc. All rights reserved.
PMID 22683202  Ann Diagn Pathol. 2013 Jun;17(3):295-7. doi: 10.1016/j.・・・
著者: Nitin J Karandikar, Erin C Hotchkiss, Robert W Mckenna, Steven H Kroft
雑誌名: Am J Clin Pathol. 2002 May;117(5):819-25. doi: 10.1309/DU0B-EBFL-3EXY-VUFP.
Abstract/Text We prospectively evaluated 52 consecutive cases of newly identified absolute lymphocytosis to determine the hematologic and immunophenotypic features of transient stress lymphocytosis (TSL). The lymphocytosis in all cases was associated with an acute stressful event and ranged from 4,000 to 10,400/microL (4.0-10.4 x 10(9)/L). Compared with healthy individuals, patients with TSL showed an increase in the total WBC, absolute lymphocyte (ALC), absolute neutrophil (ANC), and platelet counts with no difference in hemoglobin levels. Immunophenotypic analyses of 38 cases revealed increases in absolute numbers of T B, and natural killer cells. Both CD4+ and CD8+ T cells were increased, predominantly accountedfor by an increase in memory cell subsets, with no change in gamma/delta T cells. Follow-up studies showed a significant reduction in the ALC with a concurrent increase in the ANC and reduction in hemoglobin values. The reduction in lymphocytes at resolution was accompanied by reduction in all broad Iymphocyte subsets. However, naive and memory subsets showed different patterns of alteration within the CD4+ and CD8+ populations, suggesting that acute stress differentially affects the in vivo distribution of these subsets.

PMID 12090434  Am J Clin Pathol. 2002 May;117(5):819-25. doi: 10.1309/・・・
著者: Andy C Rawstron, Fiona L Bennett, Sheila J M O'Connor, Marwan Kwok, James A L Fenton, Marieth Plummer, Ruth de Tute, Roger G Owen, Stephen J Richards, Andrew S Jack, Peter Hillmen
雑誌名: N Engl J Med. 2008 Aug 7;359(6):575-83. doi: 10.1056/NEJMoa075290.
Abstract/Text BACKGROUND: A diagnosis of chronic lymphocytic leukemia (CLL) requires a count of over 5000 circulating CLL-phenotype cells per cubic millimeter. Asymptomatic persons with fewer CLL-phenotype cells have monoclonal B-cell lymphocytosis (MBL). The goal of this study was to investigate the relation between MBL and CLL.
METHODS: We investigated 1520 subjects who were 62 to 80 years of age with a normal blood count and 2228 subjects with lymphocytosis (>4000 lymphocytes per cubic millimeter) for the presence of MBL, using flow cytometry. Monoclonal B cells were further characterized by means of cytogenetic and molecular analyses. A representative cohort of 185 subjects with CLL-phenotype MBL and lymphocytosis were monitored for a median of 6.7 years (range, 0.2 to 11.8).
RESULTS: Monoclonal CLL-phenotype B cells were detected in 5.1% of subjects (78 of 1520) with a normal blood count and 13.9% (309 of 2228) with lymphocytosis. CLL-phenotype MBL had a frequency of 13q14 deletion and trisomy 12 similar to that of CLL and showed a skewed repertoire of the immunoglobulin heavy variable group (IGHV) genes. Among 185 subjects presenting with lymphocytosis, progressive lymphocytosis occurred in 51 (28%), progressive CLL developed in 28 (15%), and chemotherapy was required in 13 (7%). The absolute B-cell count was the only independent prognostic factor associated with progressive lymphocytosis. During follow-up over a median of 6.7 years, 34% of subjects (62 of 185) died, but only 4 of these deaths were due to CLL. Age above 68 years and hemoglobin level below 12.5 g per deciliter were the only independent prognostic factors for death.
CONCLUSIONS: The CLL-phenotype cells found in the general population and in subjects with lymphocytosis have features in common with CLL cells. CLL requiring treatment develops in subjects with CLL-phenotype MBL and with lymphocytosis at the rate of 1.1% per year.

2008 Massachusetts Medical Society
PMID 18687638  N Engl J Med. 2008 Aug 7;359(6):575-83. doi: 10.1056/NE・・・
著者: Luis M Vilá, Graciela S Alarcón, Gerald McGwin, Holly M Bastian, Barri J Fessler, John D Reveille, Lumina Study Group
雑誌名: Arthritis Rheum. 2006 Oct 15;55(5):799-806. doi: 10.1002/art.22224.
Abstract/Text OBJECTIVE: To determine if lymphopenia is associated with clinical/immunologic manifestations, disease activity, and disease damage in systemic lupus erythematosus (SLE).
METHODS: The study group comprised 591 patients with SLE participating in a multiethnic, longitudinal outcome study. Cumulative clinical/immunologic (per American College of Rheumatology criteria) and pharmacologic treatment variables were obtained at enrollment (T0) and last visit (TL). Lymphopenia (<1,500/mm3) was scored only when clinically attributable to SLE and not to medications or other causes. Lymphocyte counts were expressed in 4 categories per the Systemic Lupus Activity Measure (SLAM): normal (> or =1,500/mm3), mild (1,000-1,499/mm3), moderate (500-999/mm3), and marked (<500/mm3). Disease activity was assessed with the SLAM and the Physician's Global Assessment (PGA). Disease damage was determined with the Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI). The relationship of lymphopenia with cumulative clinical/immunologic and pharmacologic treatment variables was first examined, then the association between the SLAM, PGA, and SLICC-DI scores with different categories of lymphopenia was examined by generalized estimating equation (GEE) regression analyses. Ethnicity, age, and sex were entered into all regression models.
RESULTS: At T0 and TL, lymphopenia was found to be positively associated with renal involvement, leukopenia, anti-double-stranded DNA antibodies, anti-Ro antibodies, and the use of glucocorticoids, azathioprine, and methotrexate, but was negatively associated with photosensitivity. On GEE analyses, marked lymphopenia at T0 and moderate and marked lymphopenia for all visits were independently associated with higher SLAM, PGA, and SLICC-DI scores.
CONCLUSION: Lymphopenia is associated with several clinical/immunologic manifestations in SLE. Moderate and marked lymphopenia are associated with higher disease activity and damage accrual.

PMID 17013840  Arthritis Rheum. 2006 Oct 15;55(5):799-806. doi: 10.100・・・
著者: Micah T McClain, Lawrence P Park, Bradly Nicholson, Timothy Veldman, Aimee K Zaas, Ron Turner, Robert Lambkin-Williams, Anthony S Gilbert, Geoffrey S Ginsburg, Christopher W Woods
雑誌名: J Clin Virol. 2013 Dec;58(4):689-95. doi: 10.1016/j.jcv.2013.09.015. Epub 2013 Sep 28.
Abstract/Text BACKGROUND: Leukocyte counts and differentials are commonly acquired in patients with suspected respiratory viral infections and may contribute diagnostic information. However, most published work is limited to a single timepoint at initial presentation to a medical provider, which may correspond to widely varying points in the course of disease.
OBJECTIVES: To examine the temporal development and time-dependent utility of routine leukocyte differentials in the diagnosis of respiratory viral infections.
STUDY DESIGN: We analyzed data from recent experimental human challenges with influenza A/H3N2, human rhinovirus (HRV), and respiratory syncytial virus (RSV). Routine clinical lab cell counts and differentials were measured daily from the time period immediately prior to inoculation through the eventual resolution of symptomatic disease.
RESULTS: Approximately 50% of challenged individuals developed symptoms and viral shedding consistent with clinical disease. Subpopulations of WBC showed marked differences between symptomatic and asymptomatic individuals over time, but these changes were much more profound and consistent in influenza infection. Influenza-infected subjects develop both relative lymphopenia and relative monocytosis, both of which closely mirror symptom development in time. A lymphocyte:monocyte ratio of <2 correctly classifies 100% of influenza (but not RSV or HRV) infected subjects at the time of maximal symptoms.
CONCLUSIONS: Leukocyte differentials may suggest a viral etiology in patients with upper respiratory infection, but are not sufficient to allow differentiation between common viruses. Timing of data acquisition relative to the disease course is a key component in determining the utility of these tests.

Published by Elsevier B.V.
PMID 24140015  J Clin Virol. 2013 Dec;58(4):689-95. doi: 10.1016/j.jcv・・・

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ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから