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好中球増多

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
患者向け説明資料

概要・推奨   

  1. 末梢血好中球数(桿状核球分葉核球)が7,000~8,000/μl以上を好中球増多とする。
  1. 好中球増多症は一次性(腫瘍性)増多と二次性(反応性)増多に分類される。好中球増多の原因の大部分は二次性のものであることを念頭においてアプローチする。
  1. 好中球増多以外の白血球分画、赤血球、血小板に異常を認める場合は骨髄増殖性腫瘍の可能性を考慮する
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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。

病態・疫学・診察

疫学情報・病態・注意事項  
  1. 好中球増多は非常によくみられる血球異常で、通常、末梢血好中球数(桿状核球+分葉核球)が7,000~8,000/μl以上を好中球増多とする。
  1. 末梢血白血球数が5万/μl以上で、未熟な好中球系細胞(後骨髄球、骨髄球、ときに前骨髄球、骨髄芽球)が出現する場合を類白血病反応と呼ぶ(これよりも少ない白血球数でも類白血病反応と呼ぶこともある)。
  1. 好中球増多は、①産生亢進、②骨髄から末梢血への遊出の亢進、③辺縁プールから循環プールへの移行の亢進、④血液から組織への移行の低下、⑤これらの原因の複合、――により生ずる。
  1. 生体内の好中球の約1/2が骨髄中に貯蔵され、前駆細胞とともに大きな貯蔵プールが存在する。必要時には、この大きな好中球貯蔵プールが迅速に反応して、数時間で循環血液中の好中球を3倍のレベルにまで増加させることができる
  1. 骨髄中で約7~14日で骨髄芽球から分葉核好中球に成熟する。桿状核好中球と分葉核好中球が末梢血中に出ていく。
  1. 末梢血中を約半日循環した後に組織に出て、組織間を1~4日遊走した後にアポトーシスに至る。
  1. 左方移動は、桿状核好中球の比率が増加した状態であるが、通常は後骨髄球や骨髄球を認める。
  1. 好中球増多症は一次性(腫瘍性)増多と二次性(反応性)増多に分類され、好中球増多の原因の大部分は二次性のものである。<図表><図表>
  1. 好中球数だけでは一次性、二次性を鑑別できない。
  1. 好中球増多以外の白血球分画、赤血球、血小板の異常に注目する。これらに異常を認める場合は一次性(骨髄増殖性腫瘍)の可能性を考慮する。<図表>
  1. 二次性(反応性)好中球増多では、原因疾患を明らかにすることが大切である。
  1. 反応性好中球増多の原因は多岐にわたるが、急性細菌感染症が最も頻度が高く、発熱を伴った好中球増多ではまず急性感染症を念頭に置く。
  1. 原因不明の軽度の好中球増多で喫煙者であれば、喫煙が原因である可能性を考え、禁煙を指示して経過観察する。
  1. 精査しても好中球増多の原因が確定できない場合は、悪性腫瘍が潜在している可能性も念頭に置いて経過観察する。
 
  1. 入院患者の3万/μl以上の白血球増多の原因として感染症、ストレス、炎症、産科疾患が多い(O)
  1. 教育病院である総合病院に1年間に入院した造血器腫瘍以外の原因により白血球数が3万/μl以上であった成人173例(成人入院患者の0.59%)について後方視的に検討した[1]
  1. 白血球数の平均値は37,700/μlで、最も多かったものは88,000/μlで、14例(8.0%)が5万/μlを超えていた。大部分(134例)の症例で、白血球数が3万/μl以上であったのは1日だけで、白血球数が2日以上3万/μl以上であった患者の死亡率は有意に高かった(61.5% vs 31.3%、P=0.001)が、白血球増多の程度と死亡率には関連がなかった。白血球増多の原因としては、感染症が最も多く83例(47.9%)で、虚血/ストレス 48例(22.7%)、炎症 12例(6.9%)、産婦人科領域疾患 12例(6.9%)であった。全体では66人(38.1%)が入院中に死亡し、高齢、感染症、敗血症が死亡と関連していた。
問診・診察のポイント  
 
問診:
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文献 

著者: Israel Potasman, Moti Grupper
雑誌名: Clin Infect Dis. 2013 Dec;57(11):e177-81. doi: 10.1093/cid/cit562. Epub 2013 Aug 30.
Abstract/Text BACKGROUND: The prognosis of patients with leukemoid reaction (LR) depends mainly on their underlying illness. Our aim was to investigate the etiologies and prognosis of a mixed group of patients with LR.
METHODS: We identified 173 patients who had ≥30.0 × 10(9) leukocytes/µL without hematologic malignancies. Causes of LR and factors contributing to death were analyzed.
RESULTS: Patients with LR constituted 0.59% of all admitted adults. The median age was 75 years, but 20 patients were aged <40 years. There was no difference in LR prevalence by gender (female/male = 88/85). Average white blood cell (WBC) count was 37.7 × 10(9)/µL. Fourteen patients (8.0%) had a WBC count of >50.0 × 10(9)/µL. The median duration of LR was 1 day, but 39 patients had prolonged LR (>1 day). Infection was the most common cause of LR (n = 83, 47.9%; 95% confidence interval, 40.7-55.4), followed by ischemia/stress (27.7%), inflammation (6.9%), and obstetric diagnoses (6.9%). Higher WBC counts were significantly associated with positive blood cultures (P = .017) or a positive Clostridium difficile toxin (P = .001). Antibiotics were prescribed for 140 patients (80.9%). Sixty-six patients (38.1%) died during hospitalization. Those with prolonged LR had an in-hospital mortality rate of 61.5%. Factors found to be highly correlated with death were age (odds ratio [OR] = 1.051, P < .001), any infectious diagnosis (OR = 2.574, P = .014), and sepsis (OR = 3.752, P = .001).
CONCLUSIONS: LR carries a grave prognosis, especially among the elderly and those with sepsis. LR was found to have multiple etiologies including infections, stress, inflammation, and obstetric diagnoses.

PMID 23994818  Clin Infect Dis. 2013 Dec;57(11):e177-81. doi: 10.1093/・・・
著者: Tomoyuki Kawada
雑誌名: Arch Med Res. 2004 May-Jun;35(3):246-50. doi: 10.1016/j.arcmed.2004.02.001.
Abstract/Text BACKGROUND: Associations between smoking and leukocytosis or elevated hemoglobin concentrations in the blood need to be validated using multivariate analysis.
METHODS: A total of 2,511 male subjects aged 25-62 years participated in an annual health examination held at their workplace. The relationship between white blood cells (WBC) and hemoglobin (Hb) levels in blood and smoking status was then evaluated using a cross-sectional survey and multiple logistic regression analysis. Age, body mass index (BMI), smoking and drinking status, diastolic blood pressure, and physical activity were used as covariate factors.
RESULTS: Odds ratios (ORs) and 95% confidence intervals (95% CIs) of WBC of >9,000 counts/mm3 of total blood for current smokers and ex-smokers with a period of 5-9.9 years since smoking cessation vs. that of nonsmokers were 12.1 (7.0-21.0) and 3.8 (1.2-12.0), respectively. OR (95% CI) of Hb level >16 g/dL of total blood for current smokers vs. nonsmokers was 1.6 (1.1-2.3). Significant ORs for elevated Hb level in total blood were also observed for age (OR, 1.0; 95% CI, 0.9-1.0), BMI >25 (OR, 2.2; 95% CI, 1.6-3.1), and diastolic blood pressure of >90 mmHg (OR, 2.2; 95% CI, 1.5-3.2).
CONCLUSIONS: Current smoking is associated with increase in WBC count and Hb levels in total blood, the former relationship recognized in subjects who have stopped smoking for 5-9.9 years. Obesity and aging are inversely related with Hb level in blood.

PMID 15163468  Arch Med Res. 2004 May-Jun;35(3):246-50. doi: 10.1016/j・・・
著者: Takakazu Higuchi, Fumio Omata, Kenji Tsuchihashi, Kazuhiko Higashioka, Ryosuke Koyamada, Sadamu Okada
雑誌名: Prev Med Rep. 2016 Dec;4:417-22. doi: 10.1016/j.pmedr.2016.08.009. Epub 2016 Aug 9.
Abstract/Text While cigarette smoking is a well-recognized cause of elevated white blood cell (WBC) count, studies on longitudinal effect of smoking cessation on WBC count are limited. We attempted to determine causal relationships between smoking and elevated WBC count by retrospective cross-sectional study consisting of 37,972 healthy Japanese adults who had a health check-up between April 1, 2008 and March 31, 2009 and longitudinal study involving 1730 current smokers who had more than four consecutive annual health check-ups between April 1, 2007 and March 31, 2012. In the cross-sectional study, younger age, male gender, increased body mass index, no alcohol habit, current smoking, and elevated C-reactive protein level were associated with elevated WBC count. Among these factors, current smoking had the most significant association with elevated WBC count. In subgroup analyses by WBC differentials, smoking was significantly associated with elevated counts of neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Ex-smoking was not associated with elevated WBC count. In the longitudinal study, both WBC and neutrophil counts decreased significantly in one year after smoking cessation and remained down-regulated for longer than next two years. There was no significant change in either WBC or neutrophil count in those who continued smoking. These findings clearly demonstrated that current smoking is strongly associated with elevated WBC count and smoking cessation leads to recovery of WBC count in one year, which is maintained for longer than subsequent two years. Thus, current smoking is a significant and reversible cause of elevated WBC count in healthy adults.

PMID 27583199  Prev Med Rep. 2016 Dec;4:417-22. doi: 10.1016/j.pmedr.2・・・
著者: John M Granger, Dimitrios P Kontoyiannis
雑誌名: Cancer. 2009 Sep 1;115(17):3919-23. doi: 10.1002/cncr.24480.
Abstract/Text BACKGROUND: To the authors' knowledge, the literature regarding extreme leukocytosis in solid tumor patients is sparse, consisting of a few case reports and small case series.
METHODS: A total of 3770 consecutive solid tumor patients with a white blood cell count>40,000/microL were retrospectively identified over a 3-year period (2005-2008). Those patients without a secondary cause of their leukocytosis were defined as having a paraneoplastic leukemoid reaction.
RESULTS: A total of 758 (20%) patients with solid tumors and extreme leukocytosis were identified. The etiology of the leukocytosis was hematopoietic growth factors in 522 (69%) patients, infection in 112 (15%) patients, high-dose corticosteroids in 38 (5%) patients, newly diagnosed leukemia in 9 (1%) patients, and paraneoplastic leukemoid reaction in 77 (10%) patients. The patients diagnosed with a paraneoplastic leukemoid reaction typically had neutrophil predominance (96%) and radiographic evidence of metastatic disease (78%), were clinically stable, and had a poor prognosis; 78% either died or were discharged to hospice within 12 weeks of their initial extreme leukocyte count. All of the 8 (10%) patients who survived>1 year received effective antineoplastic therapy.
CONCLUSIONS: Infection was an uncommon cause of extreme leukocytosis in patients with solid tumors. Patients with paraneoplastic leukemoid reactions typically were clinically stable despite having large tumor burdens. However, clinical outcomes were poor unless effective antineoplastic treatment was received.

PMID 19551882  Cancer. 2009 Sep 1;115(17):3919-23. doi: 10.1002/cncr.2・・・
著者: Yair Herishanu, Ori Rogowski, Aaron Polliack, Rafael Marilus
雑誌名: Eur J Haematol. 2006 Jun;76(6):516-20. doi: 10.1111/j.1600-0609.2006.00658.x.
Abstract/Text BACKGROUND: Recently, it was shown that fat tissue produces and releases inflammatory cytokines, and that obesity may be regarded as a state of low-grade inflammation. In this regard, we aimed to establish an association between obesity and persistent leukocytosis.
PATIENTS AND METHODS: We present clinical observations of obese subjects primarily referred for further evaluation of leukocytosis without a cause and validated the link between leukocytosis and elevated body mass index (BMI) in a cross-sectional study.
RESULTS: During 1999-2005, 327 patients were referred for further investigation because of persistent leukocytosis. Of these, 15.3% were asymptomatic obese, mostly females, with mild persistent neutrophilia accompanied by elevated acute-phase reactants. After careful evaluation, no recognized cause for leukocytosis was found other than the fact that the patients were obese. During a mean follow-up of 45.6 months, the leukocytosis and the elevated acute-phase reactants persisted and no new causes for leukocytosis were evident. Furthermore, in a cross-sectional analysis of 3716 non-smoker subjects, 62 were found to have leukocytosis. Compared with the population with a normal white blood count range, these subjects with leukocytosis had higher BMI, serum C-reactive protein (CRP) levels, waist circumference, and neutrophil and platelet count (all P < 0.0005). After logistic regression analysis, only BMI was shown to be associated with leukocytosis (P < 0.0005).
CONCLUSIONS: Obesity is recognized as a possible cause for reactive leukocytosis. Awareness of this 'obesity-associated leukocytosis' may help the clinician to avoid more extensive and unnecessary diagnostic work-up, particularly in similar obese subjects.

PMID 16696775  Eur J Haematol. 2006 Jun;76(6):516-20. doi: 10.1111/j.1・・・
著者: Y Shoenfeld, Y Gurewich, L A Gallant, J Pinkhas
雑誌名: Am J Med. 1981 Nov;71(5):773-8.
Abstract/Text The long-term pattern of prednisone-induced leukocytosis was examined in 80 patients. Our results disclosed an extremely variable leukocytic responses, in which the white blood cell count surpassed 20,000/mm3 as early as the first day of treatment, an increase that persisted for the duration of therapy. Although the degree of leukocytosis was related to the dosage administered, it did appear sooner with higher doses. Leukocytosis reached maximal values within two weeks in most cases, after which the white blood cell count decreased, albeit not to pretreatment levels. The leukocytosis was attributed predominantly to a rise in the polymorphonuclear white blood cells, a phenomenon that coincided with monocytosis, eosinopenia and a variable degree of lymphopenia. It can be concluded that even small doses of prednisone, administered over a prolonged period of time, can induce extreme and persistent leukocytosis. This observation is of consequence especially when infection is suspected, particularly in an immunocompromised host. However, a shift to the left in the peripheral white blood cells, i.e., more than 6 percent band forms, and the appearance of toxic granulation may assist in the differential diagnosis between infection, in which the latter are observed, and corticosteroid-induced leukocytosis, in which they are rare.

PMID 7304648  Am J Med. 1981 Nov;71(5):773-8.

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