Thrombocytosis as a Predictor of Serious Bacterial Infection in Febrile Infants.

BACKGROUND: Most of the febrile infants <90 days old will have no more than a mild viral infection but there is a substantial minority that will be diagnosed as having serious bacterial infection at a reported prevalence of 10-14%. A simple, readily available, inexpensive diagnostic marker that yields results quickly and also accurately identifies bacterial infections in febrile infants would be of great value in management of these infants. This study aims to assess the role of thrombocytosis in predicting serious bacterial infection in young febrile infants beyond neonatal period. METHODS: A hospital based cross-sectional observational study was conducted from May 2016 to April 2017 on 76 febrile infants of age group 29-90 days in Kanti Children's Hospital. RESULTS: The incidence of serious bacterial infection was found 43 (56.6%). Thrombocytosis, elevated C-reactive protein and pyuria were significantly higher in serious bacterial infection cases (p value <0.05). Thrombocytosis alone had the sensitivity of only 53.5%, but had specificity of 90.9%. Elevated C-reactive protein had the best sensitivity (81.4%). Combination of leukocytosis, elevated C-reactive protein, pyuria and thrombocytosis had better sensitivity (93.0%) than these parameters alone. The overall ability of platelet count to identify infants with SBI was only moderate (AUC: 0.722). Elevated C-reactive protein was found to have better ability to identify infants with serious bacterial infection (AUC: 0.846). CONCLUSIONS: Thrombocytosis is a common finding in young infants diagnosed with serious bacterial infection. It has however, moderate ability in identifying infants with serious bacterial infection. Combining thrombocytosis with elevated C-reactive protein, leukocytosis and pyuria has better sensitivity in diagnosing serious bacterial infection than these individual parameters alone. Hence, combining these parameters may help in early prediction of febrile young infants at risk of serious bacterial infection.

Antibiotics impair murine hematopoiesis by depleting the intestinal microbiota.

Bone marrow suppression is an adverse effect associated with many antibiotics, especially when administered for prolonged treatment courses. Recent advances in our understanding of steady-state hematopoiesis have allowed us to explore the effects of antibiotics on hematopoietic progenitors in detail using a murine model. Antibiotic-treated mice exhibited anemia, thrombocytosis, and leukopenia, with pronounced pan-lymphopenia as demonstrated by flow cytometric analysis of peripheral blood. Bone marrow progenitor analysis revealed depletion of hematopoietic stem cells and multipotent progenitors across all subtypes. Granulocytes and B cells were also diminished in the bone marrow, whereas the number of CD8+ T cells increased. Reductions in progenitor activity were not observed when cells were directly incubated with antibiotics, suggesting that these effects are indirect. Hematopoietic changes were associated with a significant contraction of the fecal microbiome and were partially rescued by fecal microbiota transfer. Further, mice raised in germ-free conditions had hematopoietic abnormalities similar to those seen in antibiotic-treated mice, and antibiotic therapy of germ-free mice caused no additional abnormalities. The effects of antibiotics were phenocopied in Stat1-deficient mice, with no additional suppression by antibiotics in these mice. We conclude that microbiome depletion as a result of broad-spectrum antibiotic treatment disrupts basal Stat1 signaling and alters T-cell homeostasis, leading to impaired progenitor maintenance and granulocyte maturation. Methods to preserve the microbiome may reduce the incidence of antibiotic-associated bone marrow suppression.

Platelet counts, MPV and PDW in culture proven and probable neonatal sepsis and association of platelet counts with mortality rate.

OBJECTIVE: To determine frequency of thrombocytopenia and thrombocytosis, the MPV (mean platelet volume) and PDW (platelet distribution width) in patients with probable and culture proven neonatal sepsis and determine any association between platelet counts and mortality rate. STUDY DESIGN: Descriptive analytical study. PLACE AND DURATION OF STUDY: NICU, Fazle Omar Hospital, from January 2011 to December 2012. METHODOLOGY: Cases of culture proven and probable neonatal sepsis, admitted in Fazle Omar Hospital, Rabwah, were included in the study. Platelet counts, MPV and PDW of the cases were recorded. Mortality was documented. Frequencies of thrombocytopenia (< 150000/mm3) and thrombocytosis (> 450000/mm3) were ascertained. Mortality rates in different groups according to platelet counts were calculated and compared by chi-square test to check association. RESULTS: Four hundred and sixty nine patients were included; 68 (14.5%) of them died. One hundred and thirty six (29%) had culture proven sepsis, and 333 (71%) were categorized as probable sepsis. Thrombocytopenia was present in 116 (24.7%), and thrombocytosis was present in 36 (7.7%) cases. Median platelet count was 213.0/mm3. Twenty eight (27.7%) patients with thrombocytopenia, and 40 (12.1%) cases with normal or raised platelet counts died (p < 0.001). Median MPV was 9.30, and median PDW was 12.30. MPV and PDW of the patients who died and who were discharged were not significantly different from each other. CONCLUSION: Thrombocytopenia is a common complication of neonatal sepsis. Those with thrombocytopenia have higher mortality rate. No significant difference was present between PDW and MPV of the cases who survived and died.

Thrombocytosis is associated with Mycobacterium tuberculosis infection and positive acid-fast stains in granulomas.

Mycobacterium tuberculosis infection is associated with thrombocytosis. We sought to determine if this information might be valuable in evaluating granulomas using acid-fast stains (AFS). Fifty-eight patients with culture-confirmed M tuberculosis infection were compared with 75 patients with atypical mycobacterial infection and 48 patients negative for mycobacteria. Thrombocytosis (platelet count >360 × 10(3)/µL [360 × 10(9)/L]) was significantly more common in patients with M tuberculosis (50%) than those with either atypical mycobacterial infection (12%) or negative for mycobacteria (4%, P < .001 for each). In 67 patients, histologic evaluation of tissue samples showed granulomatous inflammation; 37 (55%) had positive AFS results. Of 19 patients with thrombocytosis, 16 (84%) had a positive AFS result compared with 21 (44%) of 48 without thrombocytosis (P = .003). Fifteen of 16 M tuberculosis cases with thrombocytosis had positive AFS findings on histologic evaluation; the single negative case had a platelet count of 362 × 10(3)/µL (362 × 10(9)/L). However, 3 of these cases of positive results on staining were initially diagnosed as negative and only recognized as positive on review. We conclude that patients whose specimens were sent for mycobacterial culture and thrombocytosis had an increased risk for M tuberculosis. Patients with granulomas and thrombocytosis are more likely to have a positive AFS result usually showing M tuberculosis. Finally, patients with initially negative AFS results and thrombocytosis deserve to have additional evaluation of the AFS specimens.

Q fever as a cause of fever of unknown origin and thrombocytosis: first molecular evidence of Coxiella burnetii in Brazil.

We report a case of Q fever in a man who presented with fever of 40 days duration associated with thrombocytosis. Serological and molecular analysis (polymerase chain reaction) confirmed infection with Coxiella burnetii. A field study was conducted by collecting blood samples from the patient's family and from the animals in the patient's house. The patient's wife and 2 of 13 dogs showed seroreactivity. Our data indicate that C. burnetii may be an underrecognized cause of fever in Brazil and emphasize the need for clinicians to consider Q fever in patients with a febrile illness, particularly those with a history of animal contact.

Reactive thrombocytosis in febrile young infants with serious bacterial infection.

OBJECTIVE: to estimate the incidence of reactive thrombocytosis among febrile young infants and to asses the utility of platelet count as a potential predictor of serious bacterial infection (SBI). DESIGN: retrospective study between January 2005 and December 2008. SETTING: tertiary care pediatric unit. PARTICIPANTS: all infants 29 to 89 days of age, admitted with rectal temperature > 38oC without a focus of infection. MAIN OUTCOME MEASURES: the results of the sepsis evaluation on admission were recorded. SBI included all cases of occult bacteremia, urinary tract infection, bacterial meningitis, pneumonia, bacterial gastroenteritis and infections of the soft tissues and bones. RESULTS: of the 408 infants studied, 103 (25.2%) had SBI. Platelet count was significantly higher in infants with SBI compared to those without (median 513000 /mm3 [interquartile range 455,000-598,000/mm3] vs median 398000/mm3; [interquartile range 313,000-463,000/mm3]; P<0.001). Thrombocytosis had only moderate ability in predicting SBI (area under the curve: 0.74, 95 % CI 0.70-0.79). The combination of platelet count >450,000/mm3, WBC >15,000/mm3, Creactive protein >2 mg/dL, and pyuria >10 WBC/hpf would lead to misclassification of 4 infants with SBI (3.9% of SBIs; negative likelihood ratio 0.08). CONCLUSION: reactive thrombocytosis was a frequent finding in young infants with SBI. Thrombocytosis >450,000 cells/mm3, in combination with leucocytosis, elevated CRP and pyuria, may help in early recognition of febrile young infants at risk for SBI.

Hematological changes in tuberculous spondylitis patients at the Hospital Universiti Sains Malaysia.

In this study, we compared the platelet count with erythrocyte sedimentation rates (ESR) in patients with tuberculous spondylitis to evaluate the correlation. This was a retrospective 3-year study covering January 2004 to December 2006 at the Hospital Universiti Sains Malaysia. Platelet counts, hemoglobin levels, ESR, peripheral blood counts and peripheral blood smears on 17 patients with tuberculous spondylitis were obtained. The ages of the patients ranged from 20- to 70-years-old. The male to female ratio was 3.2:1. The majority of the patients were anemic (88.2%) and 52.9% of the patients had thrombocytosis. All the patients had normal lymphocyte counts and a high in ESR at diagnosis. There was a linear correlation between the platelet count and ESR (r = 0.60, p < 0.01). The platelet count was also significantly correlated with the hemoglobin level (r = -0.6, p < 0.02). The degree of thrombocytosis was related to the degree of inflammation measured by the ESR. Thrombocytosis also correlated with the hemoglobin level. We suggest that evaluating hematological values in suspected cases of tuberculosis should be considered. The presence of hematological changes should raise the suspicion of tuberculosis in spondylitis patients.

Elevation of serum thrombopoietin precedes thrombocytosis in acute infections.

To clarify the mechanisms underlying thrombocytosis secondary to infections, we longitudinally studied serum levels of thrombopoietin (TPO) and interleukin (IL)-6 in 15 infants and young children with prominent thrombocytosis (platelets >700 x 10(9)/l) following acute infections and 116 age-matched controls using an enzyme-linked immunosorbent assay. The subjects included nine patients with bacterial infections, three with viral infections and three with non-determined pathogens. TPO values in the controls were 2.24 +/- 0.87 fmol/ml (mean +/- SD) with a 95% reference interval of 0.85-4.47 fmol/ml. In the first week of infection, platelet counts were normal, but TPO values increased (approximately 10.73 fmol/ml). TPO levels peaked on day 4 +/- 2 at 6.44 +/- 2.37 fmol/ml and then fell gradually. When platelet counts peaked in the second and third weeks, TPO levels were similar to the controls. IL-6 levels in the first week rose and dropped more rapidly than TPO. Serum TPO values were significantly correlated with C-reactive protein levels (r = 0.688, P < 0.001) and IL-6 levels (r = 0.481, P = 0.027). These results suggest that TPO contributes to thrombocytosis following infections in conjunction with IL-6, arguing for additional regulatory mechanisms of blood TPO levels.

Effect of busulfan on oncornavirus-like activity in platelets and chromosomes in polycythemia vera and essential thrombocythemia.

The effect of busulfan therapy on the activity of oncornavirus-like particles and chromosome patterns in patients with polycythemia vera and essential thrombocythemia was studied. Three patients had pretreatment platelet counts greater than 1 million/microliter, abnormal bone marrow karyotypes, and electron microscopic and biochemical evidence of oncornavirus. The results demonstrated that in all 3 patients virus-like particles and reverse transcriptase-like activity could no longer be found in the platelets within 2-4 weeks after the initiation of busulfan treatment. The platelet count was still elevated at this point for each patient, although the count returned to normal levels within 2-3 weeks after virus-like activity was no longer detectable. The chromosome patterns, characterized by aneuploidy (30-50%) before treatment, improved after therapy.

Analysis of platelets from patients with thrombocythemia for reverse transcriptase and virus-like particles.

A preliminary analysis of an RNA-directed DNA polymerase was made and a C-type virus-like particle was identified in platelets from 2 patients with the myeloproliferative disorder thrombocythemia (primary, essential, hemorrhagic, or idiopathic thrombocythemia). Platelet homogenates were centrifuged through a sucrose equilibrium density gradient. Both endogenous and exogenous DNA polymerase activity was found at a density of 1.19 g/ml. No activity was seen at comparable densities in control gradients. Electron micrographs of thin sections of these platelets revealed a particle with the morphologic characteristics of a C-type virus; however, the diameter of this particle was about 80 nm, slightly lower than that commonly found for C-type particles. Critical-point dried specimens, from the fractions of the sucrose gradient at which DNA polymerase activity was found, contained particles of the same size and morphology as those in the thin sections.