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Respiratory syncytial virus infection is strongly correlated with decreased mean platelet volume

Open AccessPublished:March 01, 2013DOI:https://doi.org/10.1016/j.ijid.2013.01.012

      Summary

      Background

      To date, infections have usually been associated with elevations of the mean platelet volume. We correlated infection with respiratory syncytial virus (RSV) with changes in mean platelet volume (MPV).

      Methods

      A consecutive series of patients with positive and negative rapid RSV assays and viral cultures, as well as children under 10 years of age with bronchoscopy for pneumonia or airway obstruction, were compared.

      Results

      The MPV was significantly lower in patients with positive versus negative rapid RSV assays (9.7 ± 0.8 vs. 10.5 ± 0.9 fl, p < 0.001), as well as viral cultures (9.9 ± 1.0 vs. 10.5 ± 1.0 fl, p < 0.001). Children with RSV undergoing bronchoscopy (n = 7) also had significantly lower MPV than children without RSV (n = 79) (8.8 ± 1.0 vs. 10.2 ± 1.1 fl, p < 0.004). An MPV <8.9 fl had a sensitivity of 71% and specificity of 49% for RSV in children undergoing bronchoscopy.

      Conclusions

      We conclude that infection with RSV is associated with decreased MPV and this may be clinically useful in children undergoing bronchoscopy.

      Keywords

      1. Introduction

      The mean platelet volume (MPV) is a laboratory value that is defined as the mean volume of a large number of platelets as measured on automated hematology machines. MPV is associated with many factors including platelet age (younger platelets are larger), and is measured to help evaluate abnormalities in platelet function or number. MPV has also been associated with a wide variety of different medical and non-medical conditions. Elevations of the MPV have been described in smokers,
      • Varol E.
      • Icli A.
      • Kocyigit S.
      • Erdogan D.
      • Ozaydin M.
      • Dogan A.
      Effect of smoking cessation on mean platelet volume.
      high elevation living,
      • Vij A.G.
      Effect of prolonged stay at high altitude on platelet aggregation and fibrinogen levels.
      diabetes,
      • Demirtunc R.
      • Duman D.
      • Basar M.
      • Bilgi M.
      • Teomete M.
      • Garip T.
      The relationship between glycemic control and platelet activity in type 2 diabetes mellitus.
      obese patients,
      • Yazici M.
      • Kaya A.
      • Kaya Y.
      • Albayrak S.
      • Cinemre H.
      • Ozhan H.
      Lifestyle modification decreases the mean platelet volume in prehypertensive patients.
      • Coban E.
      • Yilmaz A.
      • Sari R.
      The effect of weight loss on the mean platelet volume in obese patients.
      and wine drinkers.
      • Tozzi Ciancarelli M.G.
      • Di Massimo C.
      • De Amicis D.
      • Ciancarelli I.
      • Carolei A.
      Moderate consumption of red wine and human platelet responsiveness.
      In addition, elevated MPVs are seen in patients who have thrombocytopenia,
      • Bessman J.D.
      • Williams L.J.
      • Gilmer Jr., P.R.
      Mean platelet volume. The inverse relation of platelet size and count in normal subjects, and an artifact of other particles.
      • Demirin H.
      • Ozhan H.
      • Ucgun T.
      • Celer A.
      • Bulur S.
      • Cil H.
      • et al.
      Normal range of mean platelet volume in healthy subjects: insight from a large epidemiologic study.
      • Bessman J.D.
      • Gilmer P.R.
      • Gardner F.H.
      Use of mean platelet volume improves detection of platelet disorders.
      hypothyroidism,
      • Yilmaz H.
      • Ertugrul O.
      • Ertugrul B.
      • Ertugrul D.
      Mean platelet volume in patients with subclinical hypothyroidism.
      congestive heart failure,
      • Ertas G.
      • Kozdag G.
      • Emre E.
      • Akay Y.
      • Ural D.
      • Hebert K.
      Effect of enhanced external counterpulsation treatment on mean platelet volume in patients affected by ischemic chronic heart failure.
      right ventricular enlargement,
      • Varol E.
      • Icli A.
      • Uysal B.A.
      • Ozaydin M.
      Platelet indices in patients with acute pulmonary embolism.
      acute pulmonary embolism,
      • Varol E.
      • Icli A.
      • Uysal B.A.
      • Ozaydin M.
      Platelet indices in patients with acute pulmonary embolism.
      stroke,
      • Bath P.
      • Algert C.
      • Chapman N.
      • Neal B.
      Association of mean platelet volume with risk of stroke among 3134 individuals with history of cerebrovascular disease.
      acute myocardial infarction,
      • Ozdemir O.
      • Soylu M.
      • Alyan O.
      • Geyik B.
      • Demir A.D.
      • Aras D.
      • et al.
      Association between mean platelet volume and autonomic nervous system functions: increased mean platelet volume reflects sympathetic overactivity.
      unstable angina,
      • Pizzulli L.
      • Yang A.
      • Martin J.F.
      • Luderitz B.
      Changes in platelet size and count in unstable angina compared to stable angina or non-cardiac chest pain.
      and hypoxic chronic obstructive pulmonary disease.
      • Onder I.
      • Topcu S.
      • Dokmetas H.S.
      • Turkay C.
      • Seyfikli Z.
      Platelet aggregation size and volume in chronic obstructive pulmonary disease.
      Higher MPVs are associated with autoimmunity in general,
      • Confino-Cohen R.
      • Chodick G.
      • Shalev V.
      • Leshno M.
      • Kimhi O.
      • Goldberg A.
      Chronic urticaria and autoimmunity: associations found in a large population study.
      as well as psoriasis,
      • Karabudak O.
      • Ulusoy R.E.
      • Erikci A.A.
      • Solmazgul E.
      • Dogan B.
      • Harmanyeri Y.
      Inflammation and hypercoagulable state in adult psoriatic men.
      Raynaud's disease,
      • Shemirani A.H.
      • Nagy B.
      • Takats A.T.
      • Zsori K.S.
      • Andras C.
      • Kappelmayer J.
      • et al.
      Increased mean platelet volume in primary Raynaud's phenomenon.
      rheumatoid arthritis, and ankylosing spondylitis, and this correlates with the degree of activity as well as lack of treatment.
      • Yazici S.
      • Yazici M.
      • Erer B.
      • Calik Y.
      • Ozhan H.
      • Ataoglu S.
      The platelet indices in patients with rheumatoid arthritis: mean platelet volume reflects disease activity.
      • Yazici S.
      • Yazici M.
      • Erer B.
      • Calik Y.
      • Bulur S.
      • Ozhan H.
      • et al.
      The platelet functions in patients with ankylosing spondylitis: anti-TNF-alpha therapy decreases the mean platelet volume and platelet mass.
      In contrast, decreases in MPV have most commonly been associated with anemia
      • Lozano M.
      • Narvaez J.
      • Faundez A.
      • Mazzara R.
      • Cid J.
      • Jou J.M.
      • et al.
      [Platelet count and mean platelet volume in the Spanish population].
      and chronic renal failure,
      • Correa Leite M.L.
      Fibrinogen, hematocrit, platelets in mild kidney dysfunction and the role of uric acid: an Italian male population study.
      but have also been described in patients with vascular malformations,
      • Klapman M.H.
      • Sosa V.B.
      • Mattson-Gates G.F.
      • Baker C.N.
      • Sydorak R.M.
      • Ong V.L.
      • et al.
      Smaller platelet volumes associated with vascular malformations.
      as well as acute appendicitis,
      • Bilici S.
      • Sekmenli T.
      • Goksu M.
      • Melek M.
      • Avci V.
      Mean platelet volume in diagnosis of acute appendicitis in children.
      acute pancreatitis,
      • Beyazit Y.
      • Sayilir A.
      • Torun S.
      • Suvak B.
      • Yesil Y.
      • Purnak T.
      • et al.
      Mean platelet volume as an indicator of disease severity in patients with acute pancreatitis.
      ulcerative colitis, and Crohn's disease (which also correlates with the severity of the activity and is reversed with therapy).
      • Yuksel O.
      • Helvaci K.
      • Basar O.
      • Koklu S.
      • Caner S.
      • Helvaci N.
      • et al.
      An overlooked indicator of disease activity in ulcerative colitis: mean platelet volume.
      • Douda T.
      • Bures J.
      • Rejchrt S.
      • Kopacova M.
      • Pecka M.
      • Maly J.
      [Mean platelet volume (MPV) in Crohn's disease patients].
      • D’Halluin P.N.
      • Tribut O.
      • Branger B.
      • Lebreton C.
      • Bretagne J.F.
      • Bentue-Ferrer D.
      • et al.
      RBC 6-TGN and hematological parameters in patients with Crohn's disease treated by azathioprine.
      • Kapsoritakis A.N.
      • Koukourakis M.I.
      • Sfiridaki A.
      • Potamianos S.P.
      • Kosmadaki M.G.
      • Koutroubakis I.E.
      • et al.
      Mean platelet volume: a useful marker of inflammatory bowel disease activity.
      Only a few studies have examined the effects of infection on MPV. In a canine model, endotoxemia was associated with an increase in MPV,
      • Yilmaz Z.
      • Eralp O.
      • Ilcol Y.O.
      Evaluation of platelet count and its association with plateletcrit, mean platelet volume, and platelet size distribution width in a canine model of endotoxemia.
      and in humans, tuberculosis infection has been associated with a higher MPV which decreases with therapy.
      • Tozkoparan E.
      • Deniz O.
      • Ucar E.
      • Bilgic H.
      • Ekiz K.
      Changes in platelet count and indices in pulmonary tuberculosis.
      Increased MPVs are also seen with lower platelet counts in patients with Crimean-Congo hemorrhagic fever.
      • Ekiz F.
      • Gurbuz Y.
      • Basar O.
      • Aytekin G.
      • Ekiz O.
      • Senturk G.C.
      • et al.
      Mean platelet volume in the diagnosis and prognosis of Crimean-Congo hemorrhagic fever.
      Decreases in MPV have also been associated with some infections, including sepsis,
      • Becchi C.
      • Al Malyan M.
      • Fabbri L.P.
      • Marsili M.
      • Boddi V.
      • Boncinelli S.
      Mean platelet volume trend in sepsis: is it a useful parameter?.
      hookworm,
      • Wiwanitkit V.
      • Soogarun S.
      • Saksirisampant W.
      • Suwansaksri J.
      Platelet parameters in subjects infected with hookworm.
      and Trichinella.
      • Matowicka-Karna J.
      • Panasiuk A.
      • Kemona H.
      Estimation of platelet function state in the course of Trichinella spiralis infection.
      Recently, we noticed that some patients with infection with respiratory syncytial virus (RSV) had relatively low MPVs. To investigate this, we examined MPVs in a consecutive series of patients in a variety of settings.

      2. Methods

      This study was approved by the Institutional Review Board. A consecutive series of patients with positive and negative rapid RSV assays and viral cultures from respiratory specimens, as well as children under 10 years of age with bronchoscopy for pneumonia or airway obstruction, were compared. Searches began in January of 2012 and were conducted retrospectively until either 100 patients were obtained or no more cases were identified in the electronic record back to 2005. Patients with underlying hematologic diseases were excluded.
      MPV was assessed on Sysmex 2100 hematology instrumentation. Reference ranges were 7.7–13.2 fl. The rapid RSV assay was performed using the BinaxNow RSV by Inverness Medical.
      Specimens for viral culture were submitted fresh in sterile containers using viral transport medium VTM-M4 and inoculated onto shell vials of MRC5-CV1 (H&V), Super E-Mix, and R-Mix Too monolayer cultures. Cytopathic effect (CPE) confirmation for RSV and blind staining for RSV were performed at 48 h, 3 days, and 5 days of culture using an indirect fluorescent antibody respiratory stain (Quidel Corp., Santa Clara, CA, USA). Patients who were positive with the rapid test did not have cultures performed. Cultures were done on patients with either no rapid RSV test or in whom the rapid test was negative.
      The statistical analysis was performed using a two-tailed Student's t-test and a significance level of 0.05%.

      3. Results

      A consecutive series of 100 patients with ordered complete blood counts were used as a control group to verify our normal range. These patients had a mean MPV of 10.8 ± 0.9 fl.
      MPV was compared in patients with rapid RSV tests (58 patients) and viral cultures (100 patients). These patients did not have an underlying hematologic disease and were both children and adults (mean age 38 years, range 16–91 years, 112 patients aged <18 years). They included 69 males and 89 females.
      The MPV was significantly lower in patients with positive versus negative rapid RSV assays (9.7 ± 0.8 vs. 10.5 ± 0.9 fl, p < 0.001, n = 100 each), as well as viral cultures (9.9 ± 1.0 vs. 10.5 ± 1.0 fl, p < 0.001). Nevertheless, there was significant overlap between these two groups. Platelet counts were not significantly different between any of these four groups (342 ± 121 vs. 327 ± 171 × 109/l, p = 0.47, and 350 ± 144 vs. 338 ± 158 × 109/l, p = 0.63, respectively). Hemoglobin was not significantly different between these four groups (11.6 ± 1.4 vs. 11.9 ± 1.2 g/dl, p = 0.11, and 12.1 ± 1.8 vs. 11.7 ± 1.0 g/dl, p = 0.07).
      Children with RSV undergoing bronchoscopy (n = 7) also had significantly lower MPV than children without RSV (n = 79) (8.8 ± 1.0 vs. 10.2 ± 1.1 fl, p < 0.004). An MPV <8.9 fl had a sensitivity of 71% and specificity of 49% for RSV in children undergoing bronchoscopy.

      4. Discussion

      We were motivated to do this study by an incidental finding of a very low MPV in a child with RSV. Our results support the idea that infection with RSV is associated with a decrease in MPV regardless of whether the infection is detected by rapid assay or culture. While significant, this difference is unlikely to be large enough to be useful in most clinical settings. However, in children who are undergoing bronchoscopy for presumptive pneumonia or airway obstruction, an MPV <8.9 fl was relatively sensitive and specific for infection with RSV. This change was not due to anemia, since there was no significant difference in hemoglobin between the RSV-positive and RSV-negative patients.
      Measuring MPV can be problematic. MPV increases with prolonged storage in ethylenediaminetetraacetic acid (EDTA)
      • Diaz-Ricart M.
      • Brunso L.
      • Pino M.
      • Navalon F.
      • Jou J.M.
      • Heras M.
      • et al.
      Preanalytical treatment of EDTA-anticoagulated blood to ensure stabilization of the mean platelet volume and component measured with the ADVIA counters.
      and there is variation in the measurement between analyzers, although there is substantial work to standardize this.
      • Latger-Cannard V.
      • Hoarau M.
      • Salignac S.
      • Baumgart D.
      • Nurden P.
      • Lecompte T.
      Mean platelet volume: comparison of three analysers towards standardization of platelet morphological phenotype.
      In this study, all measurements were made at the same hospital on the same analyzer, and specimens were received and processed in the usual fashion without substantial delays in measurement.
      Changes in MPV are quite common in a variety of normal and pathologic conditions. Autoimmune and cardiac conditions and most infections measured to date tend to lead to an elevated MPV. This elevated MPV is often thought to be due to an increase in young platelets that are larger than more mature platelets. In contrast, vascular malformations and inflammatory conditions involving the bowel are often associated with a decrease in MPV. The mechanism of action of this change is not fully understood. Whether fragmentation of the platelets is involved is not known. Nevertheless, the most common cause of a decreased MPV is anemia, which is not known to cause platelet fragmentation. The specific mechanism of action of RSV on MPV is not known. As part of this study we examined the MPV of patients with other types of viral infections and could not demonstrate a consistent relationship between these other viral infections and changes in MPV. Thus we suspect that the effect of RSV on MPV is specific to this virus, at least among the commonly detected viruses in our hospital.
      There are several limitations to this study. We chose to study MPV at the time of specimen collection for RSV. It is possible that the MPV changed over the course of the admission and the illness, and if so, we were not able to document this change. Similarly, our assessments of hemoglobin and platelet count were also performed at the time of specimen collection. It is possible that these variables also could have changed over the course of the illness. In addition, the timing of the specimen collection likely varied between the patients course of illness. We were not able to control for this variable. Finally, interventions by the medical staff to treat the illness were not controlled for in this study.
      In conclusion, we have shown that infection with RSV as determined by both rapid testing and culture is associated with decreased MPV. This may be particularly useful clinically in children undergoing bronchoscopy.
      Conflict of interest: No conflict of interest to declare.

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