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PubMed2000

No significant leukocytosis under controlled ovarian stimulation using the LHRH antagonist Cetrorelix and recFSH.

OBJECTIVE: To study the influence of an LHRH (luteinizing hormone releasing hormone) antagonist protocol (Cetrorelix) and the use of recombinant follicle-stimulating hormone (FSH) on the development of leukocytosis, compared to the use of urinary HMG (human menopausal gonadotrophin). DESIGN: Prospective, randomized phase III clinical trial. SETTING: Infertility day clinic, Department of Gynecology and Obstetrics. PATIENTS: Thirty patients undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment following controlled ovarian stimulation using a multiple dose protocol and the LHRH antagonist Cetrorelix. MAIN OUTCOME MEASURE: Differences in white blood cell (WBC) count before stimulation, during the follicular phase and in the midluteal phase. RESULTS: Statistically significant increase in WBC count in the HMG group from the start of stimulation to the midluteal phase. No statistically significant increase in the recFSH group, but only a trend towards higher values was observed. CONCLUSION: The development of a leukocytosis in controlled ovarian stimulation does not depend on the protocol used. Urinary gonadotrophins seem to have a greater potential to increase WBC count compared to recombinant gonadotrophins.

Estradiol↗

PubMed2003

On the mechanism of post-splenectomy leukocytosis in mice.

BACKGROUND: Increased number of peripheral white blood cells (PWBCs) has been noted after removal of the spleen. DESIGN: To clarify the possible mechanisms by which splenectomy affects the PWBC number, the percentage of apoptotic PWBCs, the number and migration rate of peritoneal cells, as well as the 3H-TdR incorporation into PWBCs, were examined in splenectomized, sham-operated and control mice. In addition, the effect of control plasma injected to splenectomized animals on the number of PWBCs was examined. RESULTS: One and two months after splenectomy the PWBC counts significantly increased, whereas the percentage of apoptotic PWBCs and the number of cells in the peritoneal cavity decreased in comparison with that of the control and sham-operated mice. Seventeen days after injection of carboxy-fluorescein diacetate succinimidyl ester (CFSE)-labelled peritoneal cells into the peritoneal cavity of the animals, their number was significantly higher in the peripheral blood and lower in the peritoneal cavity of the splenectomized animals in comparison with that of the control and sham-operated mice. Injection of control plasma into the splenectomized mice prevented the development of postsplenectomy leukocytosis. Finally, 3H-TdR incorporation into nonstimulated and Con A stimulated PBMCs from the splenectomized mice was higher as compared with cells from the control and sham-operated mice. CONCLUSIONS: The results of the study present several mechanisms that may clarify the cause of postsplenectomy leukocytosis.

Animals↗

PubMed1991

Are leukocytosis and lipid peroxidation involved in ischemic or reperfusion injury in cardiac surgery?

We have studied the hypothesis that free-radical generation during cardiac surgery could explain partly the pathophysiology of ischemic or reperfusion injury during cardiopulmonary bypass (CPB). Ten patients undergoing cardiac surgery using CPB were prospectively studied. Malondialdehyde (MDA) was measured as a marker of free-radical-induced lipid peroxidation (LPO) using the thiobarbituric acid method, and leukocytes were counted during ischemia and reperfusion. Both MDA and leukocytes increased significantly, especially after starting reperfusion. There was significant correlation between LPO and leukocytosis (r = 0.8, p less than 0.005). It is concluded that free radicals generated during ischemia and reperfusion lead to an increase of LPO, which is shown for the first time to be associated with leukocytosis in cardiac surgical patients. The implication of this observation is of importance for the treatment strategy using free-radical scavengers in reducing the harmful effects of ischemia and reperfusion in cardiac surgery.

Aged↗

PubMed1981

[Initial treatment of acute childhood leukemia with extreme leukocytosis by blood exchange transfusion -- rheological aspects (author's transl)].

In leukemia patients with extremely high leukocytosis the great number of poorly deformable lymphoblasts compared to normally deformable red cells greatly influences the flow properties of leukemic blood. The increased blood viscosity implies a great risk of disturbance of the microcirculation by leukostasis and bleeding. Removal of large amounts of leukemic cells by exchange transfusion with fresh blood diminished leukemic cell burden and reduced the initial elevated leukocyte counts by more than 50% in 3 patients. In addition, anemia and thrombocytopenia improved and the disturbed plasma coagulation returned to normal. One of the patients with additional risk factors treated by exchange transfusion died 8 months after diagnosis in hematologic release. The two other patients perform well without relapse six and nine months after diagnosis, respectively. Exchange transfusion with 150 ml/kg of fresh blood is considered to be of value to avoid severe early complications as e.g. massive intracerebral hemorrhage observed in 3 other patients and to correct hematological and rheological abnormalities in childhood leukemia with extreme leukocytosis. Possible favourable effects as to long term prognosis have to be awaited.

Blood Viscosity↗

PubMed2001

Leukocytosis caused by prostaglandin E1 in neonates.

We conducted a retrospective study of neonatal leukocytosis induced by prostaglandin E(1). Among 45 neonates with congenital heart disease, leukocyte counts increased during PGE(1) infusion. We conclude that PGE(1) infusion is a predictable cause of leukocytosis in newborns with congenital heart disease.

Alprostadil↗

PubMed2002

Effects of leukocytosis and macrophage activation on anti-Thy 1.1 glomerulonephritis in the rat.

OBJECTIVE: In anti-Thy 1.1 proliferative glomerulonephritis (GN), glomerular infiltration of polymorphonuclear leukocytes (PMNs) reaches a peak level after 1 h and that of macrophages does so 24 h after induction. However, the roles of PMNs and macrophages in the pathogenesis of anti-Thy 1.1 GN remain unclear. We examined the effects on this model of leukocytosis induced by granulocyte colony-stimulating factor (G-CSF) and of macrophages stimulated by macrophage colony-stimulating factor (M-CSF). MATERIAL AND METHODS: Anti-Thy 1.1 GN was induced in male Wistar rats by intravenous injection of OX-7, a monoclonal antibody to the Thy 1 antigen. G-CSF (10 microg/kg/day), M-CSF (20 microg/kg/day) or vehicle was administered intraperitoneally for 7 days starting 24 h before the injection of OX-7. Histological examination of renal biopsy specimens was performed on Days 1, 5 and 14 after induction. RESULTS: Circulating and glomerular-infiltrating PMNs (RP-3-positive cells) were increased at Day 5 in G-CSF-treated rats compared with controls receiving vehicle, and glomerular mesangiolysis continued at Day 5. The number of proliferating cells positive for proliferating cell nuclear antigen at Day 5 and matrix scores at Day 14 were smaller in G-CSF-treated rats than in control rats. The mesangiolysis score was significantly higher in the G-CSF group than in the control group at Days 5 and 14, but not at Day 1. ED-1-positive cells were increased in number at Day 5 and matrix accumulation decreased at Day 14 in M-CSF-treated rats compared with controls. Serum creatinine level at Day 14 was lower in the M-CSF group, but not in the G-CSF group, compared with the control group. CONCLUSIONS: Activated macrophages may inhibit excess matrix accumulation and ameliorate the recovery of renal function, whereas leukocytosis inhibits the repair of mesangial cell injury in this model.

Animals↗

PubMed2002

Neutrophil gelatinase B and chemokines in leukocytosis and stem cell mobilization.

Leukocytosis is a physiopathological mechanism primarily to combat infections, whereas stem cell mobilization is induced for therapeutical purposes. Both processes are dependent on the balance between leukocyte and stem cell retention and mobilization. The retention is mediated by the specific architecture of the bone marrow, adhesion molecules and the production of chemokines in the bone marrow, which attract escaped immature cells to the marrow. Mobilization is the effect of the action of "peripheral" chemokines, such as interleukin-8 (IL-8 or CXCL8) and the remodeling of the matrix and basement membranes by matrix enzymes, such as gelatinase B (MMP-9). Recent studies lead to the conclusion that neutrophils, IL-8/CXCL8 and gelatinase B/MMP-9 play control roles in leukocytosis and stem cell mobilization. Neutrophils are the predominant circulating leukocyte type and IL-8/CXCL8 is the major neutrophil chemoattractant in humans. Gelatinase B and no gelatinase A is rapidly released from prestored granules after activation of neutrophils by IL-8/CXCL8. Moreover, neutrophils do not produce TIMP-1 and can chemically activate latent progelatinase B. Activated gelatinase B catalyses the aminoterminal truncation of IL-8/CXCL8 into a tenfold more potent chemokine. This implies that, when IL-8/CXCL8 appears in the circulation, the bone marrow is instructed to release neutrophils and concomitantly stem cells. These studies suggest that IL-8/CXCL8 and gelatinase B/MMP-9 are targets for the modulation of stem cell mobilization.

Animals↗

PubMed1969

The occurrence and properties of leukocytosis and lymphocytosis-stimulating material in the supernatant fluids of Bordetella pertussis cultures.

1. Leukocytosis- and lymphocytosis-stimulating activity was present in fluid cultures of B. pertussis. The activity was found primarily in the culture supernatant fluid. 2. The sequential changes in the leukocyte response were similar to those previously observed following injection of intact bacteria into mice. 3. Activity was destroyed by heat and was diminished, but not abolished, by prolonged treatment with proteolytic enzymes. 4. A water-insoluble fraction of the culture supernatant fluid was isolated which contained virtually all of the activity. The specific activity was more than 100-fold greater than that of the intact bacteria, and injection of microgram quantities produced a response. 5. The distribution of histamine-sensitizing factor followed that of leukocytosis-stimulating activity. In contrast, mouse protective antigen was localized to the bacterial pellet.

Ampicillin↗

PubMed1999

Utility of fever and leukocytosis in acute surgical abdomens in octogenarians and beyond.

BACKGROUND: The study determined the incidence of specific surgical diagnoses in patients age 80 years or older who presented to an emergency department (ED) with acute abdomens and required emergency surgical intervention within 72 hours. The usefulness of an increase in temperature and leukocytosis in the evaluation of each surgical diagnostic group is discussed. METHODS: The study was a retrospective review of ED records and operative reports of patients 80 years or older who were seen from November 1992 to September 1995 at a large midwestern tertiary-care ED with 65,000 annual patient visits. RESULTS: Among the 117 patients who met the inclusion criteria, the most common diagnoses were acute cholecystitis (29 patients), hernia (24), and bowel obstruction (19). The least common diagnoses were Meckel's diverticulum (1 patient), diverticulitis (1), and a carcinoid tumor (1). Temperature increase to more than 37.5 degrees C was statistically more common in patients with acute cholecystitis (13 of 29) and viscus perforation (4 of 11) than in all other patient groups (4 of 77). A leukocyte count of more than 15,500/mm3 was most statistically suggestive of acute cholecystitis (10 of 29 patients), intestinal ischemia (5 of 11), viscus perforation (5 of 11), acute appendicitis (2 of 3), and abscess (1 of 2). Of 115 patients with a recorded temperature and leukocyte count, 35 had a temperature of less than 37.5 degrees C and a leukocyte count of less than 10,500/mm3. CONCLUSION: Acute surgical abdomen in patients 80 years or older has a unique distribution of diagnoses. Although an increase in temperature and marked leukocytosis are not diagnostic of any particular illness, their presence should suggest certain specific surgical illnesses to the practicing clinician. Frequently, elderly patients with acute surgical abdomens present with a normal temperature and leukocyte count.

Abdomen, Acute↗

PubMed1997

Leukocytosis in response to exogenous gonadotrophin stimulation.

Leukocytosis may develop in women undergoing ovulation induction. The production of blood leukocytes and their numbers in circulation are regulated by complex interactions involving endogenous haematopoietic cytokines, such as granulocyte-colony stimulating factor (G-CSF), monocyte-colony stimulating factor (M-CSF), and interleukins. The purpose of this prospective study was to explore the presence of leukocytosis in women who receive urinary menotrophins, and to determine whether haematopoietic cytokines are changed in the stimulation process. Controls were volunteers of the same age range, not taking any medication, who received daily saline injections. Subjects underwent phlebotomy at defined points for determination of complete blood counts, G-CSF, M-CSF, and interleukin-6 concentrations. Baseline white blood cell (WBC) counts were similar in patients and controls. In menotrophin-treated patients the WBC counts rose significantly (4.19 +/- 0.28 to 6.37 +/- 0.71) during the stimulation and peaked in the luteal phase (P = 0.037). In contrast, WBC counts decreased in controls. Other leukocytic lineages were not affected. In treated patients G-CSF concentrations rose significantly (P = 0.028 versus controls), while changes in M-CSF and interleukin-6 were not significant.

Adult↗

PubMed1993

Cervical leukocytosis and abnormal post-coital test: a diagnostic and therapeutic approach.

Inflammatory processes and cell-mediated immunological reactions in the cervix and vagina have been implicated as causal factors in some cases of infertility. This investigation examined whether cervical Papanicolaou (PAP) smears in combination with post-coital tests could reveal infertile patients with asymptomatic cervical leukocytosis. Women (n = 56) attending a hospital-based community infertility clinic were subjected to post-coital tests and simultaneous preparation of cervical PAP smears. Those women (n = 18) with both abnormal post-coital tests and asymptomatic cervical leukocytosis, based on abnormally high numbers of leukocytes in the PAP smear, were randomly divided into two groups. One group (n = 10) received antibiotic therapy and the other (n = 8) received no therapy. In the treated group six women became pregnant within 3 months after treatment; none of the eight untreated patients became pregnant within the same period. These results suggest that cervical PAP smears, in cases with abnormal post-coital tests, are useful in detecting couples whose infertility may be due to simple, undetected, asymptomatic bacterial infections.

Anti-Bacterial Agents↗

PubMed1996

Triple paraneoplastic syndrome of hypercalcemia, leukocytosis and cachexia in two human tumor xenografts in nude mice.

Nude mice bearing the human oral cavity carcinoma cell line OCC-1, and the lung cancer cell line LC-1, developed a triple paraneoplastic syndrome consisting of hypercalcemia, cachexia and leukocytosis. All of these abnormalities disappeared rapidly after surgical resection of the tumors, suggesting their ectopic humoral nature. Search for the factors responsible for the respective abnormalities revealed that the production of parathyroid hormone-related protein and colony-stimulating factors (CSFs), mainly granulocyte-CSF, by the tumors could explain the hypercalcemia and leukocytosis, respectively. With regard to the severe cachexia, the production of two cachexia-associated cytokines, interleukin-6 and leukemia inhibitory factor, was able to explain the syndrome in OCC-1 bearing nude mice; however, the factor responsible in LC-1 bearing nude mice could not be identified. The triple paraneoplastic syndrome that developed in these two animal models could be explained partly by concomitant production of the peptide hormone and cytokines by cancer cells. These animal models may be very useful for the evaluation of diagnostic and therapeutic modalities for humoral abnormalities.

Animals↗

PubMed1988

Determination of blood gases in children with extreme leukocytosis.

The effect of extreme leukocytosis (greater than 300,000/mm3) on the PaO2 of blood stored at 22 degrees and 2 degrees C was studied in two children with leukemia. Arterial blood samples drawn from these patients at 1 and 10 min were compared to blood samples drawn from eight control patients with normal leukocyte counts and PaO2 levels in the same range. One minute after drawing the samples, the PaO2 values at 2 degrees C were significantly higher than those stored at 22 degrees C. Later, there was a rapid and progressive decline in PaO2 values in both samples stored at 2 degrees and 22 degrees C. Rapid consumption of O2 by leukocytes is liable to result in erroneous diagnosis of severe hypoxemia in patients with extreme leukocytosis. Immediate cooling of the samples is insufficient to eliminate this process.

Blood Gas Analysis↗

PubMed1999

Leukocytosis and free fluid are important indicators of isolated intestinal injury after blunt trauma.

BACKGROUND: The detection of isolated intestinal injuries after blunt trauma can be difficult because of subtle signs and symptoms, often leading to delayed diagnosis. We hypothesized that specific clinical indicators could be identified to assist in the diagnosis of these injuries. METHODS: Medical records of all patients with such injuries from 1988 to 1996 were reviewed. The patients were stratified into those operated on within 6 hours of presentation (apparent injury) and those operated on after 6 hours (occult injury), and the data were compared. RESULTS: Forty-six patients with isolated intestinal injuries were identified. There were no differences in the rate of peritonitis or free fluid on abdominal computed tomography, blood loss, intraoperative findings, or morbidity and mortality between groups. Leukocytosis (sensitivity, 84.8%; specificity, 55.2%; p = 0.01) and free fluid on computed tomography were frequently present, however, and their significance was underappreciated in the occult injury group. CONCLUSION: After blunt abdominal trauma in patients without obvious indications for invasive evaluation of the abdomen (e.g., peritoneal lavage, laparoscopy, laparotomy), leukocytosis can indicate an intestinal injury. Additionally, unexplained free fluid on abdominal computed tomography must be aggressively evaluated.

Adolescent↗

PubMed1999

Differential leukocytosis and lymphocyte mitogenic response to acute maximal exercise in the young and old.

UNLABELLED: Despite the increasing use of exercise in the elderly as a means of improving muscle function, little is known regarding the effects of exercise on the senescent immune system. PURPOSE: The purpose of this study was to determine the effects of acute maximal exercise on blood leukocyte numbers, leukocyte subsets, and the T cell mitogenic response in the elderly. METHODS: Previously sedentary elderly (N = 33, 65.3 +/- 0.8 yr) and young (N = 14, 22.4 +/- 0.7 yr) subjects participated in a modified Balke maximal exercise treadmill test. Venous blood samples were collected pre-, immediately post-, and 20 min postexercise. Blood was analyzed for leukocyte counts, leukocyte subsets via immunofluorescence, and whole blood mitogenesis in response to various doses of mitogens. RESULTS: Whereas VO2max was lower in the elderly, maximal RQ, age-predicted heart rates, and times to fatigue were not different, indicating that both groups achieved relative maximal exercise intensity. There were significant exercise-induced leukocytoses in both the elderly and young made up largely of a lymphocytosis and neutrophilia. The magnitude of the leukocytosis was lower in the elderly and failed to return to pre-exercise levels by 20 min postexercise. Acute maximal exercise increased CD8+ (153% vs 112% in young and old, respectively) and CD4+ (57% vs 22% in young and old, respectively) T cells when measured immediately postexercise. By 20 min postexercise, concentrations in the young were not significantly different from baseline, whereas CD8 cell number was still elevated in the old. The elderly had significantly higher percentages of memory (i.e., CD45RO+) and significantly lower percentages of naive (i.e., CD45RA+) CD4 and CD8 T cells pre-exercise, and the young and old recruited approximately equal numbers of CD8+ naive and memory cells to the blood in response to exercise. In contrast, the aged recruited significantly fewer numbers of CD4+ naive and transitional (CD45RA+RO+) cells. At most doses of Con A and PHA, the lymphoproliferative response was lower in the elderly subjects even though they had significantly higher numbers and percentages of CD3+ cells. Interestingly, immediately postexercise, young (but not old) subjects demonstrated reduced proliferative ability on a per CD3+ cell basis. CONCLUSIONS: These data indicate that several blood leukocyte responses to maximal exercise stress are similar in the young and the old. However, the elderly demonstrate a less resilient leukocytosis and a different lympho-proliferative response following acute maximal exercise.

Adult↗

PubMed1991

Extreme leukocytosis in patients presenting to a pediatric emergency department.

We determined the frequency and clinical significance of white blood cell (WBC) counts greater than or equal to 25,000/microliters in children presenting to an emergency department (ED) and defined a degree of leukocytosis which might be considered extreme in this setting. Records of all patients seen in the ED between February 1985 and December 1986 with WBC counts greater than or equal to 25,000/microliters were identified. Each patient was paired with the chronologically nearest patient with a WBC count between 15,000 and 25,000/microliters. Of the total WBCs obtained, 5.8% were greater than or equal to 25,000/microliters; only 1% were greater than or equal to 35,000/microliters. Eighteen percent of patients with counts greater than or equal to 25,000/microliters had a serious disease, and 6% had bacteremia. Twenty-six percent of patients with counts greater than or equal to 35,000/microliters had a serious disease, and 10% had bacteremia. On the basis of infrequency and severity of illness, we suggest that, in children presenting to a pediatric emergency department, WBC counts greater than or equal to 35,000/microliters be considered extreme leukocytosis.

Adolescent↗

PubMed1999

Correlation of pseudohypoxemia and leukocytosis in chronic lymphocytic leukemia.

Pseudohypoxemia has been reported in leukemic patients with extreme leukocytosis, and it is characterized by a low oxygen saturation on arterial blood gas analysis despite normal saturation on pulse oximetry. We report the case of a 51-year-old man with chronic lymphocytic leukemia and an elevated white blood cell (WBC) count after splenectomy, his progressive postoperative pseudohypoxemia gradually improved as the leukocytosis was lowered by chemotherapy. We believe this is the first report to show a statistically significant correlation between the WBC count and the degree of pseudohypoxemia in a patient with leukemia.

Antibiotics, Antineoplastic↗

PubMed2005

Significance of extreme leukocytosis in the evaluation of febrile children.

BACKGROUND: Emergency department evaluation of young febrile children often includes a white blood cell count. Although a high white blood cell count is associated with an increased likelihood of infection, the clinical significance of extreme leukocytosis (EL), defined as a white blood cell count of > or = 25,000/mm, has not been well-studied. OBJECTIVE: To determine diagnoses associated with EL in febrile children evaluated in a pediatric emergency department and to compare rates of serious bacterial infection in those with EL and in those with more modest leukocytosis (LK) (15,000-24,999/mm). METHODS: A retrospective case-control study of children 2-24 months of age was performed. Those with EL were frequency age- and gender-matched to controls with LK. RESULTS: Sixty-nine patients with EL and 94 patients with LK were included. The mean age was 9.9 months, and 91 (56%) patients were male. The diagnoses were similar between the 2 groups, with otitis media, viral syndrome and pneumonia being the most common. The rates of proven serious bacterial infection were similar between EL (25%; 95% confidence interval, 15-36%) and LK (17%; 95% confidence interval, 10-26%) patients. Using different white blood cell cutoff points did not distinguish between patients with and without serious bacterial infection. CONCLUSION: Young febrile children whose emergency department evaluation revealed EL had diagnoses and rates of serious bacterial infection similar to those of children with LK.

Bacterial Infections↗