Israel Potasman, Moti Grupper
Leukemoid reaction: spectrum and prognosis of 173 adult patients.
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.
Tomoyuki Kawada
Smoking-induced leukocytosis can persist after cessation of smoking.
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.
Takakazu Higuchi, Fumio Omata, Kenji Tsuchihashi, Kazuhiko Higashioka, Ryosuke Koyamada, Sadamu Okada
Current cigarette smoking is a reversible cause of elevated white blood cell count: Cross-sectional and longitudinal studies.
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.
John M Granger, Dimitrios P Kontoyiannis
Etiology and outcome of extreme leukocytosis in 758 nonhematologic cancer patients: a retrospective, single-institution study.
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.
Yair Herishanu, Ori Rogowski, Aaron Polliack, Rafael Marilus
Leukocytosis in obese individuals: possible link in patients with unexplained persistent neutrophilia.
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.
Y Shoenfeld, Y Gurewich, L A Gallant, J Pinkhas
Prednisone-induced leukocytosis. Influence of dosage, method and duration of administration on the degree of leukocytosis.
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.
