Massimo Gallerani1*, Roberto Reverberi2, Raffaella Salmi1, Michael H Smolensky3 and Roberto Manfredini4 
Author Affiliations
1 Internal Medicine, Azienda Ospedaliera-Universitaria, Ferrara, Italy 
2 Immunohematological and Transfusional Service, Azienda Ospedaliera-Universitaria, Ferrara, Italy 
3 Department of Biomedical Engineering, The University of Texas at Austin, Austin, USA 
4 Clinica Medica, Azienda Ospedaliera-Universitaria, Ferrara, ItalyBackground: Since available data are not univocal, the aim of this study was to explore the existence of a seasonal variation in platelet count.
Methods: The study was based on the database of the Italian Association of Blood Volunteers (AVIS), section of Ferrara, Italy, 2001–2010. Hematological data (170,238 exams referring to 16,422 donors) were categorized into seasonal and monthly intervals, and conventional and chronobiological analyses were applied.
Results: Platelets and plateletcrit were significantly higher in winter-autumn, with a main peak in December-February (average +3.4% and +4.6%, respectively, P <0.001 for both).
Conclusions: Although seasonal variations have been reported for several acute cardiovascular diseases, it is extremely unlikely that such a slight increase in platelet count in winter alone may be considered as a risk factor.Biomedical Engineeringm.gallerani@ospfe.i

Gallerani, Massimo

Manfredini, Roberto

Reverberi, Roberto

Salmi, Raffaella

Smolensky, Michael H.

European Journal of Medical Research

English

PubMed

Massimo Gallerani

Roberto Reverberi

Raffaella Salmi

Michael H Smolensky

Roberto Manfredini

Crossref

EUROPEAN JOURNAL OF MEDICAL RESEARCHGallerani et al. European Journal of Medical Research 2013, 18:31http://www.eurjmedres.com/content/18/1/31RESEARCH Open AccessSeasonal variation of platelets in a cohort ofItalian blood donors: a preliminary reportMassimo Gallerani1*, Roberto Reverberi2, Raffaella Salmi1, Michael H Smolensky3 and Roberto Manfredini4AbstractBackground: Since available data are not univocal, the aim of this study was to explore the existence of a seasonalvariation in platelet count.Methods: The study was based on the database of the Italian Association of Blood Volunteers (AVIS), section ofFerrara, Italy, 2001–2010. Hematological data (170,238 exams referring to 16,422 donors) were categorized intoseasonal and monthly intervals, and conventional and chronobiological analyses were applied.Results: Platelets and plateletcrit were significantly higher in winter-autumn, with a main peak inDecember-February (average +3.4% and +4.6%, respectively, P <0.001 for both).Conclusions: Although seasonal variations have been reported for several acute cardiovascular diseases, it isextremely unlikely that such a slight increase in platelet count in winter alone may be considered as a risk factor.Keywords: Platelet count, Seasons, Chronobiology, Blood donorsBackgroundA broad spectrum of cyclic variations in physiologic andbiologic variables exists, depending on both endogenousand environmental effects. Arterial blood pressure risesduring winter, due to increased sympathetic activity, de-creased loss of fluids and sodium, and elevated blood vol-ume [1]. Again, blood lipids show a significant winter peakindependent of age, gender, body mass index (BMI), diet,and physical exercise [1]. As for rheological and hemostaticparameters, a winter peak has been found in young healthyvolunteers for plasma viscosity, red blood cell (RBC)deformability, whole blood viscosity, hemoglobin (Hb),hematocrit (HCT), mean corpuscular volume (MCV), fi-brinogen, plasminogen activator inhibitor-1 (PAI-1), lowdensity lipoprotein cholesterol (LDL-C), and tryglicerides[2]. On the contrary, no significant seasonal variations wereobserved for RBC aggregation, total cholesterol, and whiteblood cell count (WBC). Again, in subjects with and with-out coronary artery disease, significantly higher values ofBMI, glucose, LDL-C, triglycerides, lipoprotein (a), fibrino-gen, platelet count (PLT), and lower HDL-C, were found incolder months compared with warmer months [3].* Correspondence: m.gallerani@ospfe.it1Internal Medicine, Azienda Ospedaliera-Universitaria, Ferrara, ItalyFull list of author information is available at the end of the article© 2013 Gallerani et al.; licensee BioMed CentrCommons Attribution License (http://creativecreproduction in any medium, provided the orHowever, reports on platelets are not univocal, and limitedto small populations. Thus, we aimed to explore the exist-ence of a seasonal variation in PLT in a large cohort ofblood donors in Italy.MethodsThe study, conducted with the approval of the local institu-tional committee for human research, was based on thedatabase of AVIS (Associazione Volontari Italiani Sangueor Italian Association Blood Volunteers) donors, section ofFerrara, Italy, from January 2001 to December 2010. Foreach donor, and prior to each donation, accurate medicalhistory was obtained and a visit was arranged (to avoidacute diseases or contraindicating conditions), and a checkof Hb level (which could not be <12.5 and <13.5 gr/dl, forwomen and men respectively). Samples were analyzed by aprovincial reference center, with continuous quality con-trols. A Sysmex XE-2100 analyzer (Sysmex CorporationProduction, 1-5-1 Wakinohama-Kaigandori, Chuo-ku,Kobe 651–0073, Japan) was used, which is capable of pro-viding automatic determination of RBC, WBC, reticulo-cytes, erythroblasts, PLT, mean platelet volume (MPV),platelet distribution curve width (MPV) PDCW, andplateletcrit (PTC). The analyzer was placed in atemperature-controlled environment with air conditioning,al Ltd. This is an Open Access article distributed under the terms of the Creativeommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andiginal work is properly cited.Gallerani et al. European Journal of Medical Research 2013, 18:31 Page 2 of 4http://www.eurjmedres.com/content/18/1/31to exclude or minimize seasonal fluctuation of thetemperature at which the measurement was performed.Each blood sample was categorized by date into four 3-month intervals (spring: 21 March to 20 June; summer: 21June to 20 September; autumn: 21 September to 20 Decem-ber; winter: 21 December to 20 March), and into twelve1-month intervals, for seasonal and monthly analysis, re-spectively. The distribution of PLT by season was tested foruniformity in all groups by the χ2 test for goodness of fit.For monthly analysis, partial Fourier analysis was applied(ChronoLab) [4]. This method selects the harmonic, or thecombination of harmonics, that best explain the variance ofthe time-series data. The percentage of the overall variabil-ity of the data about the arithmetic mean that is attributableto the fitted rhythmic function (cosine curve by the methodof least squares) estimates the goodness of fit of theapproximating model, and the F-test statistic is used to testthe zero-amplitude null hypothesis (absence of periodicity).The method calculates the peak and trough time, indicat-ing, respectively, the absolute maximum and minimumvalues during the year. Significance levels were set atP <0.05.ResultsWe analyzed 170,238 consecutive samples referring to16,422 different donors (10,922 men, mean age 43.8 ±11.5 yrs). Of these samples, 139,638 were from men(mean age 44.3 ± 11.2 yrs), and 30,610 from women(mean age 40.8 ± 12.9 yrs, P <0.001). The average num-ber of donations was 9.9 ± 7.3 for men and 5.5 ± 4.6 forwomen. PLT, PTC, and MPV were parameters consid-ered for calculations. The actual monthly platelet values,media ± SD, are shown in Figure 1.Figure 1 Monthly distribution of platelet count (PLT, media ± SD) in aThe seasonal analysis showed higher values of PLT(Figure 2) and PCT in winter to autumn than in summer(average +3.4% and +4.6%, respectively, P <0.001 for both).MPV was slightly higher in spring, but such variation wasnot statistically significant (average +0.4%, P = 0.416)(Table 1).Chronobiologic analysis yielded a rhythmic variation,with a significant winter peak (December to February) forPLT (total, P <0.001; men, P <0.001; women, P = 0.001; 40to 59 years, P = 0.024), ≥60 years: P = 0.001), and PTC(total, P <0.001; men, P <0.001; women, P = 0.001; 40 to 59years, P <0.001; ≥60 years, P = 0.003). No significant vari-ation was found for MPD.DiscussionAn adequate supply of circulating platelets is essential tomaintain vascular integrity and to facilitate thrombusformation at sites of vascular injury, and there is evi-dence that genetic factors, gender and age [5], but alsoinfectious diseases, such as H. pylori, may play a role indetermining PLT count [6].Several studies have investigated the existence of sea-sonal variability in hematological parameters. Data col-lected in four Asian countries showed lower Hb valuesduring summer in areas with marked seasonal variationin outdoor temperature, but no differences in those witha constant high temperature [7]. As for HCT, a reviewon 18 studies calculated that it was on average 3% lower(0 to 7%) in summer than in winter [8]. A summer highin HCT deferral rates was reported in a study based onthe American Red Cross database [9]. As for PLT, a lim-ited number of studies are available. On one hand, a cir-cadian periodicity was reported for both PLT andcohort of blood donors in Italy.Figure 2 Seasonal distribution of platelet count (PLT, media ± SD) in a cohort of blood donors in Italy.Gallerani et al. European Journal of Medical Research 2013, 18:31 Page 3 of 4http://www.eurjmedres.com/content/18/1/31platelet aggregability [10]. The highest number of plate-lets was found in the afternoon, while an increased ag-gregation was observed in the morning, just when thePAI-1 activity is highest [11,12]. No univocal results onthe existence of seasonal variation are available. Findingsincluded reports of PLT increase in the coldest months[13], but also PLT increase in summer, with consistentinfluences by geographical variation in China [14]. Onthe other hand, an autumn to winter preference hasbeen reported for a series of acute cardiovascular dis-eases [15–18], and this excess winter risk has been esti-mated for pulmonary embolism in 14% [19].The present study shows slight, but significant, sea-sonal variation in PLT and PTC in healthy subjects, char-acterized by an autumn to winter peak. This is inagreement with the study by Buckley et al., whoreported a seasonal variation in PLT count, characterizedby a peak during the autumn and winter months and a2% overall variance [20]. It is possible that the coldtemperature may explain these differences, since a mildsurface cooling can also increase the packed cell volumeTable 1 Seasonal variation of platelet count (PLT), plateletcritblood donors in ItalyNumber PLT (× 10^(total = 172,836) average ±Winter 40,465 235.8 ± 5Spring 43,056 229.7 ± 4Summer 44,208 227.1 ± 4Autumn 45,107 235.0 ± 5*F = 312.08, P<0.001; **F = 214.445, P <0.001; ***F = 1.024, P = 0.416.(7%) and PLT and MPV (15%) [21], and experimentalstudies on rats found that diminished PGI2 synthesis/re-lease associated with diminution in the sensitivity ofplatelets to PGI2 after cooling may explain platelethyperaggregability [22].This preliminary study has several limitations: (a) thedonors’ database did not include variables potentially in-fluencing PTC, that is, diet or drugs, and (b) no plateletfunctionality data nor (c) meteorological parameterswere available. However, a potential strength derivesfrom the large number of samples available.ConclusionIn conclusion, at least in our cohort of healthy donors, aslight but significant increase in PLT count was ob-served. However, although it is still uncertain whether ornot thrombocytosis may be associated with clotting dis-ease [23,24], it is unlikely that such a slight increasealone, at least in healthy subjects, may play a role in thecomplex relationship between winter and cardiovasculardiseases.(PTC), and mean platelet volume (MPV) in a cohort of9/L)* PTC (%)** MPV (fL)***SD average ± SD average ± SD0.8 0.263 ± 0.059 11.43 ± 1.009.0 0.258 ± 0.057 11.47 ± 0.988.5 0.251 ± 0.058 11.45 ± 1.000.4 0.262 ± 0.061 11.45 ± 0.99Gallerani et al. European Journal of Medical Research 2013, 18:31 Page 4 of 4http://www.eurjmedres.com/content/18/1/31AbbreviationsAVIS: Italian Association of Blood Volunteers; BMI: Body mass index;Hb: Hemoglobin; HCT: Hematocrit; LDL-C: Low density lipoproteincholesterol; MCV: Mean corpuscular volume; MPV: Mean platelet volume;PAI-1: Plasminogen activator inhibitor-1; PLT: Platelet count; PTC: Plateletcrit;RBC: Red blood cell; WBC: White blood cell count.Competing interestsThe authors declare that they have no competing interests.Authors’ contributionsMG, RR, RM participated in study’s conception and design, interpretation ofdata, drafting the article and revising it critically for important intellectualcontent, and final approval. RR and MG handled the original database. RSand MHS participated in the interpretation of data, drafting the article andrevising it critically for important intellectual content, and final approval. Allauthors read and approved the final manuscript.AcknowledgementsWe thank Florio Ghinelli, MD, President of Ferrara Section, for allowing us theaccess to the AVIS database, and Mrs Chiara Gallerani and Mrs Agata Foglifor precious help in handling it. This paper was supported, in part, by ascientific grant from the University of Ferrara (FAR-Fondo Ateneo Ricerca).Author details1Internal Medicine, Azienda Ospedaliera-Universitaria, Ferrara, Italy.2Immunohematological and Transfusional Service, AziendaOspedaliera-Universitaria, Ferrara, Italy. 3Department of BiomedicalEngineering, The University of Texas at Austin, Austin, USA. 4Clinica Medica,Azienda Ospedaliera-Universitaria, Ferrara, Italy.Received: 25 February 2013 Accepted: 10 September 2013Published: 17 September 2013References1. Manfredini R, Manfredini F, Malagoni AM, Boari B, Salmi R, Dentali F, AgenoW: Chronobiology of vascular disorders: a “seasonal” link betweenarterial and venous thrombotic diseases? J Coagulation Disorders 2010,2:61–67.2. Frölich M, Sund M, Russ S, Hoffmeister A, Fischer HG, Hombach V, KoenigW: Seasonal variations of rheological and hemostatic parameters andacute-phase reactants in young, healthy subjects. Arterioscler Thromb VascBiol 1997, 17:2692–2697.3. Mavri A, Guzic-Salobir B, Salobir-Pajnic B, Keber I, Stare J, Stegnar M:Seasonal variation of some metabolic and haemostatic risk factors insubjects with and without coronary artery disease. Blood CoagulFibrinolysis 2001, 12:359–365.4. Mojon A, Fernandez JR, Hermida RC: Chronolab: an interactive softwarepackage for chronobiologic time series analysis written for theMacintosh computer. Chronobiol Int 1992, 9:403–412.5. Daly ME: Determinants of platelet count in humans. Haematologica 2011,96:10–13.6. Matsukawa Y, Kitamura N, Iwamoto M, Kato K, Mizuno S, Gon Y, ShirinskayaN, Takeuchi J, Sawada S: Helicobacter pylori upregulates peripheralplatelet counts mainly in female patients. Acta Haematol 2011,126:172–175.7. Ikeda M, Watanabe T, Koizumi A, Koizumi A, Fujita H, Ikeda M: Seasonalvariation in hemoglobin concentration in non-agricultural populationsunder various climatic conditions. Human Biol 1986, 58:189–196.8. Thirup P: Haematocrit: within-subject and seasonal variation. Sports Med2003, 33:231–243.9. Sebok MA, Notari NP, Chambers LA, Benjamin RJ, Eder AF: Seasonaltemperature variation and the rate of donor deferral for low hematocritin the American Red Cross. Transfusion 2007, 47:890–894.10. Chrushiel P, Goch A, Banach M, Mikhailidis DP, Rysz J, Goch JH: Circadianchanges in the hemostatic system in healthy men and patients withcardiovascular diseases. Med Sci Monit 2009, 15:RA203–RA208.11. Andreotti F, Davies GJ, Hackett DR, Khan MI, De Bart AC, Aber VR, Maseri A,Kluft C: Major circadian fluctuations in fibrinolytic factors and possiblerelevance to time of onset of myocardial infarction, sudden cardiacdeath and stroke. Am J Cardiol 1988, 62:635–637.12. Bridges AB, McLaren M, Scott NA, Pringle TH, McNeill GP, Belch JJ: Circadianvariation of tissue plasminogen activator and its inhibitor, vonWillebrand factor antigen, and prostacyclin stimulationg factor in menwith ischaemic heart disease. Br Heart J 1993, 69:121–124.13. Elwood PC, Beswick A, O’Brien JR, Renaud S, Fifield R, Limb ES, Bainton D:Temperature and risk factors for ischaemic heart disease in theCaerphilly prospective study. Brit J Hematol 1993, 70:520–523.14. Peng L, Yang J, Lu X, Okada T, Kondo T, Ruan C, Wu Y, Xin X: Effects ofbiological variations on platelet count in healthy subjects in China.Thromb Haemost 2004, 91:367–372.15. Manfredini R, Manfredini F, Boari B, Bergami E, Mari E, Gamberini S, Salmi R,Gallerani M: Seasonal and weekly patterns of hospital admissions fornonfatal and fatal myocardial infarction. Am J Emerg Med 2009,27:1096–1102.16. Gallerani M, Manfredini R, Ricci L, Cocurullo A, Goldoni C, Bigoni M, FersiniC: Chronobiological aspects of acute cerebrovascular diseases.Acta Neurol Scand 1993, 87:482–487.17. Gallerani M, Boari B, Smolensky MH, Salmi R, Fabbri D, Contato E, ManfrediniR: Seasonal variation in occurrence of pulmonary embolism: analysis ofthe database of the Emilia-Romagna region, Italy. Chronobiol Int 2007,24:143–160.18. Manfredini R, Boari B, Manfredini F, Salmi R, Bossone E, Fabbri D, Contato E,Mascoli F, Gallerani M: Seasonal variation in occurrence of aortic diseases:the database of hospital discharge data of the Emilia-Romagna region,Italy. J Thorac Cardiovasc Surg 2008, 135:442–444.19. Dentali F, Ageno W, Rancan E, Donati A, Galli L, Squizzato A, Venco A,Mannucci PM, Manfredini R: Seasonal and monthly variability in theincidence of venous thromboembolism: a systematic review and ameta-analysis of the literature. Thromb Haemost 2011, 106:439–447.20. Buckley MF, James JW, Brown DE, Whyte GS, Dean MG, Chesterman CN,Donald JA: A novel approach to the assessment of variations in thehuman platelet count. Thromb Haemost 2000, 83:480–484.21. Keatinge WR, Coleshaw SR, Cotter F, Mattock M, Murphy M, Chelliah R:Increases in platelet and red cell counts, blood viscosity, and arterialpressure during mild surface cooling: factors in mortality from coronaryand cerebral thrombosis in winter. BMJ 1984, 289:1405–1408.22. Jeremy JY, Mikhailidis DP, Hutton RA, Dandona P: The effect of cooling onin vitro vascular prostacyclin and platelet thromboxane A2 synthesis:relevance to cold-induced pathology. Microcirc Endothelium Lymphatics1988, 4:3–20.23. Coon WW, Penner J, Clagett P, Eos N: Deep venous thrombosis andpostsplenectomy thrombocytosis. Arch Surg 1978, 113:429.24. Ho KM, Yip CB, Duff O: Reactive thrombocytosis and risk of subsequentvenous thromboembolism: a cohort study. J Thromb Haemost 2012,10:1768–1774.doi:10.1186/2047-783X-18-31Cite this article as: Gallerani et al.: Seasonal variation of platelets in acohort of Italian blood donors: a preliminary report. European Journal ofMedical Research 2013 18:31.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color ﬁgure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submit

Seasonal variation of platelets in a cohort of Italian blood donors: a preliminary report

Massimo Gallerani1*, Roberto Reverberi2, Raffaella Salmi1, Michael H Smolensky3 and Roberto Manfredini4 
Author Affiliations
1 Internal Medicine, Azienda Ospedaliera-Universitaria, Ferrara, Italy 
2 Immunohematological and Transfusional Service, Azienda Ospedaliera-Universitaria, Ferrara, Italy 
3 Department of Biomedical Engineering, The University of Texas at Austin, Austin, USA 
4 Clinica Medica, Azienda Ospedaliera-Universitaria, Ferrara, ItalyBackground: Since available data are not univocal, the aim of this study was to explore the existence of a seasonal variation in platelet count.
Methods: The study was based on the database of the Italian Association of Blood Volunteers (AVIS), section of Ferrara, Italy, 2001–2010. Hematological data (170,238 exams referring to 16,422 donors) were categorized into seasonal and monthly intervals, and conventional and chronobiological analyses were applied.
Results: Platelets and plateletcrit were significantly higher in winter-autumn, with a main peak in December-February (average +3.4% and +4.6%, respectively, P &lt;0.001 for both).
Conclusions: Although seasonal variations have been reported for several acute cardiovascular diseases, it is extremely unlikely that such a slight increase in platelet count in winter alone may be considered as a risk factor.Biomedical Engineeringm.gallerani@ospfe.i

Texas ScholarWorks

https://eurjmedres.biomedcentral.com/track/pdf/10.1186/2047-783X-18-31?site=eurjmedres.biomedcentral.com

Seasonal variation of platelets in a cohort of Italian blood donors: a preliminary report

Abstract

Similar works

Full text

Available Versions

Crossref

Texas ScholarWorks