Evaluation of Complete Blood Count Indices (NLR,PLR,MPV/PLT,and PLCRi) in Healthy Dogs,Dogs With Periodontitis,and Dogs With Oropharyngeal Tumors as Potential Biomarkers of Systemic Inflammatory Response
Restricted accessResearch articleFirst published online December, 2017
Evaluation of Complete Blood Count Indices (NLR,PLR,MPV/PLT,and PLCRi) in Healthy Dogs,Dogs With Periodontitis,and Dogs With Oropharyngeal Tumors as Potential Biomarkers of Systemic Inflammatory Response
The aim of the study was to retrospectively assess complete blood count (CBC) indices of dogs with periodontitis (PD; n = 73) and dogs with oropharyngeal tumors (OT; n = 92) in comparison to CBC indices of healthy dogs (HD; n = 71). Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio, mean platelet volume to platelet ratio, and platelet large cell ratio index (PLCRi) were evaluated as biomarkers of systemic inflammatory response provoked by PD and OT. Results of multivariable polytomous logistic regression analysis indicated no significant associations between CBC indices and PD. Both NLR and PLCRi were significantly higher in dogs with OT when compared to HD and dogs with PD and could, therefore, indicate a tumor-associated systemic inflammatory response. Additional studies of CBC indices, along with other biomarkers of systemic inflammatory response, are recommended to validate them as reliable indicators of clinical disease activity.
D’AiutoFParkerMAndreouG. Periodontitis and systemic inflammation: control of the local infection is associated with a reduction in serum inflammatory markers. J Dent Res. 2004;83(2):156–160.
7.
PassojaAPuijolaIKnuuttilaM. Serum levels of interleukin-10 and tumour necrosis factor-alpha in chronic periodontitis. J Clin Periodontol. 2010;37(10):881–887.
8.
RawlinsonJEGoldsteinREReiterAMAttwaterDZHarveyCE. Association of periodontal disease with systemic health indices in dogs and the systemic response to treatment of periodontal disease. J Am Vet Med Assoc. 2011;238(5):601–609.
9.
D’AiutoFParkarMNibaliLSuvanJLessemJTonettiMS. Periodontal infections cause changes in traditional and novel cardiovascular risk factors: results from a randomized controlled clinical trial. Am Heart J. 2006;151(5):977–984.
10.
DeBowesLJ. The effects of dental disease on systemic disease. Vet Clin North Am Small Anim Pract. 1998;28(5):1057–1062.
11.
GlickmanLTGlickmanNWMooreGEGoldsteinGEGoldsteinGSLewisHB. Evaluation of the risk of endocarditis and other cardiovascular events on the basis of the severity of periodontal disease in dogs. J Am Vet Med Assoc. 2009;234(4):486–494.
12.
PavlicaZPetelinMJunterPErzenPCrossleyDASkalericU. Periodontal disease burden and pathological changes in organs of dogs. J Vet Dent. 2008;25(2):97–105.
13.
RoxburghCSMcMillanDC. Cancer and systemic inflammation: treat the tumour and treat the host. Br J Cancer. 2014;110(6):1409–1412.
14.
BalkwillFMantovaniA. Inflammation and cancer: back to Virchow?Lancet. 2001;357(9255):539–545.
CoussensLMWerbZ. Inflammation and cancer. Nature. 2002;420(6917):860–867.
17.
QinBMaNTangQ. Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were useful markers in assessment of inflammatory response and disease activity in SLE patients. Mod Rheumatol. 2016;26(3):372–376.
18.
PosulEYulmazBAktasGKurtM. Does neutrophil to lymphocyte ratio predict active ulcerative colitis?Wien Klin Wochenschr. 2015;127(7-8):262–265.
19.
YurtdasMYaylaliYTKayaYOzemirMOzkanIAldagN. Neutrophil to lymphocyte ratio may predict subclinical atherosclerosis in patients with psoriasis. Echocardiography. 2014;31(9):1095–1104.
20.
BhattiIPeacockOLloydGLarvinMHallRI. Preoperative hematologic markers as independent predictors of prognosis in resected pancreatic ductal adenocarcinoma: neutrophil-lymphocyte versus platelet-lymphocyte ratio. Am J Surg. 2010;200(2):197–203.
21.
KwonHCKimSHOhSY. Clinical significance of preoperative neutrophil to lymphocyte versus platelet-lymphocyte ratio in patients with operable colorectal cancer. Biomarkers. 2012;17(3):216–222.
22.
ChoSYYangJJYouE. Mean platelet volume/platelet count ratio in hepatocellular carcinoma. Platelets. 2013;24(5):375–377.
23.
BaltaSDemirkolSUnluMArslanZCelikT. Neutrophil to lymphocyte ratio may be predict of mortality in all conditions. Br J Cancer. 2013;09(12):3125–3126.
24.
AsherVLeeJInnamaaABaliA. Preoperative platelet to lymphocyte ratio as an independent prognostic marker in ovarian cancer. Clin Transl Oncol. 2013;13(7):499–503.
25.
CedresSTorrejonDMartinezA. Neutrophil to lymphocyte ratio (NLR) as an indicator of poor prognosis in stage IV non-small cell lung cancer. Clin Transl Oncol. 2012;14(11):864–869.
26.
HaddadCRGuoLClarkeSGuminskiABackMEadeT. Neutrophil to lymphocyte ratio in head and neck cancer. J Med Imaging Radiat Oncol. 2015;59(4):514–519.
27.
SummersCRankinSMCondliffeAMSinghNPetersNPetersAM. Neutrophil kinetics in health and disease. Trends Immunol. 2010;31(8):318–324.
28.
SagivJYMichaeliJAssiS. Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer. Cell Rep. 2015;10(4):562–573.
29.
KusumantoYHDamWAHospersGAMeijerCMulderNH. Platelets and granulocytes, in particular the neutrophils, form important compartments for circulating vascular endothelial growth factor. Angiogenesis. 2003;6(4):283–287.
30.
BrandauSDumitruCALangS. Protumor and antitumor functions of neutrophil granulocytes. Semin Immunopathol. 2012;35(2):163–176.
31.
GregoryADHoughtonAM. Tumor-associated neutrophils: new targets for cancer therapy. Cancer Res. 2011;71(7):2411–2416.
32.
FridlenderZGAlbeidaSM. Tumor-associated neutrophils: friend or foe?Carcinogenesis. 2012;33(5):949–955.
33.
HernbergM.Lymphocyte subsets as prognostic markers for cancer patients receiving immunomodulative therapy. Review. Med Oncol. 1999;16(3):145–153.
34.
HernbergMMattilaPSRissanenM. The prognostic role of blood lymphocyte subset distribution in patients with resected high-risk primary or regionally metastatic melanoma. J Immunother. 2007;30(7):773–779.
35.
Ray-CoquardICropetCVan GlabbekeM; European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Lymphopaenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas and lymphomas. Cancer Res. 2009;69(13):5383–5391.
36.
SchmidtHSuciuSPuntCJ; American Joint Committee on Cancer Stage IV Melanoma; EORTC 18951. Pretreatment levels of peripheral neutrophils and leucocytes as independent predictors of overall survival in patients with American joint committee on cancer stage IV melanoma: results of the EORTC 18951 biochemotherapy trial. J Clin Oncol. 2007;25(12):1562–1569.
37.
AnituaEAndiaIArdanzaBNurdenPNurdenAT. Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost. 2004;91(1):4–15.
38.
George-GayBParkerK. Understanding the complete blood count with differential. J Perianest Nurs. 2003;18(2):96–114.
39.
KlingerMHJelkmannW. Role of blood platelets in infection and inflammation. J Interferon Cytokine Res. 2002;22(9):913–922.
40.
QuianXTuszynskiGP. Expression of thrombospondin 1 in cancer: a role in tumour progression. Proc Soc Exp Biol Med. 1996;212(3):199–207.
41.
BambaceNMHolmesCE. The platelet contribution to cancer progression. J Thromb Haemost. 2011;9(2):237–249.
SharmaDBrummel-ZiedinsKEBouchardBAHolmesCE. Platelets in tumour progression: a host factor that offers multiple potential targets in the treatment of cancer. J Cell Physiol. 2014;229(8):1005–1015.
44.
WolfHFRateitschakEMRateitschakKHHassellTM. Color Atlas of Dental Medicine: Periodontology. 3rd ed. Stuttgart, Germany: Georg Thieme Verlag; 2005.
45.
OwenLN. TNM classification of tumors in domestic animals. Geneva, Switzerland: World Health Organisation; 1980.
46.
R Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing. 2013. http://www.R-project.org/. Accessed September 17, 2016.
47.
VenablesWNRipleyBD. Modern Applied Statistics with S. 4th ed. New York, NY: Springer; 2002.
48.
ElinavENowarskiRThaissCAHuBJinCFlavellRA. Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer. 2013;13(11):759–771.
49.
MutzMBoudreauxBKearneyMStrodaKGauntSShiomitsuK. Prognostic value of baseline absolute lymphocyte concentration and neutrophil/lymphocyte ratio in dogs with newly diagnosed multi-centric lymphoma. Vet Comp Oncol. 2015;13(4):337–347.
50.
KumarVSharmaA. Neutrophils: Cinderella of innate immune system. Int Immunopharmacol. 2010;10(11):1325–1334.
51.
BhansaliRSYeltiwarRKBhatKG. Assessment of peripheral neutrophil functions in patients with localized aggressive periodontitis in the Indian population. J Indian Soc Periodontol. 2013;17(6):731–736.
DeNardoDGAndreauPCoussensLM. Interactions between lymphocytes and myeloid cells regulate pro-versus anti-tumour immunity. Cancer Metastastasis Rev. 2010;29(2):309–316.
54.
LeeYKimSHHanJYKimHTYunTLeeJS. Early neutrophil to lymphocyte ratio reduction as a surrogate marker of prognosis in never smokers with advanced lung adenocarcinoma receiving gefitinib or standard chemotherapy as first-line therapy. J Cancer Res Clin Oncol. 2012;138(12):2009–2016.
55.
EnganTHannisdalE. Blood analyses as prognostic factors in primary lung cancer. Acta Oncol. 1990;29(2):151–154.
56.
KamathSBlannADLipGY. Platelet activation: assessment and quantification. Eur Heart J. 2001;22(17):1561–1571.
57.
KaiHKitadaiYKodamaM. Involvement of pro-inflammatory cytokines IL-1beta and IL-6 in progression of human gastric carcinoma. Anticancer Res. 2005;25(2A):709–713.
58.
StoneRLNickAMMcNeishIA. Paraneoplastic thrombocytosis in ovarian cancer. N Engl J Med. 2012;366(7):610–618.
59.
GorelickCAndikyanVMackMLeeYCAbulafiaO. Prognostic significance of preoperative thrombocytosis in patients with endometrial carcinoma in an inner-city population. Int J Gynecol Cancer. 2009;19(8):1384–1389.
60.
IshizukaMOyamaYAbeAKubotaK. Combination of platelet count and neutrophil to lymphocyte ratio is a useful predictor of postoperative survival in patients undergoing surgery for gastric cancer. J Surg Oncol. 2014;110(8):935–941.
61.
JosaVKrzystanekMEklundAC. Relationship of postoperative thrombocytosis and survival of patients with colorectal cancer. Int J Surg. 2015;18:1–6.
62.
KurtMOnalIKSayilirAY. The role of mean platelet volume in the diagnosis of hepatocellular carcinoma in patients with chronic liver disease. Hepatogastroenterology. 2012;59(117):1580–1582.
63.
KaramanKBostanciEBAksoyE. The predictive value of mean platelet volume in differential diagnosis of nonfunctional pancreatic neuroendocrine tumors from pancreatic adenocarcinomas. Eur J Intern Med. 2011;22(6):95–98.
MangalpallyKKSiqueiros-GarciaAVaduganthanMDongJFKleimaNSGuthikondaS. Platelet activation patterns in platelet size subpopulations: differential responses to aspirin in vitro. J Thromb Thrombolysis. 2010;30(3):251–262.
66.
ThompsonCBJakubowskiJAQuinnPGDykinDValeriCR. Platelet size and age determine platelet function independently. Blood. 1984;64(6):1372–1375.
67.
De LucaGSantagostinoMSeccoGG. Platelet large cell ratio in the extent of coronary artery disease: results from a large prospective study. J Thromb Thrombolysis. 2010;30(4):426–433.
68.
SeretisCSeretisFLagoudianakisEPolitouMGemenetzisGSalemisNS. Enhancing the accuracy of platelet to lymphocyte ratio after adjustment for large platelet count: a pilot study in breast cancer patients. Int J Surg Oncol. 2012;2012:653608:7.
69.
Al-RasheedA. Elevation of white blood cells and platelet counts in patients having chronic periodontitis. Saudi Dent J. 2012;24(1):17–21.
70.
McKeeLC. Excess leukocytosis (leukemoid reactions) associated with malignant diseases. South Med J. 1985;78(12):1475–1482.
71.
SakkaVTsiodrasSGiamarellos-BourboulisEJGiamarellouH. An update on the etiology and diagnostic evaluation of leukemoid reaction. Eur J Inter Med. 2006;17(6):394–398.
72.
SchniewindBChristgenMHauschildAKurdowRKalthoffHKlompHJ. Paraneoplastic leukemoid reaction and rapid progression in a patient with malignant melanoma: establishment of KT293, a novel G-CSF-secreting melanoma cell line. Cancer Biol Ther. 2005;4(1):23–27.
73.
WatabeAFukumotoSKomatsuTEndoYKodosawaT. Alterations in lymphocyte subpopulations in healthy dogs with aging and in dogs with cancer. Vet Immunol Immunopathol. 2011;142(3-4):189–200.
74.
TefferiA. Blood eosinophilia: new paradigm in disease classification, diagnosis and treatment. Mayo Clin Proc. 2005;80(1):75–83.
75.
SamoszukM. Eosinophils and human cancer. Histol Histopathol. 1997;12(3):807–812.
76.
HutterJWvan der VeldenUVaroufakiAHuffelsRAHoekFJLoosBG. Lower numbers of erythrocytes and lower levels of haemoglobin in periodontitis patients compared to control subjects. J Clin Periodontol. 2001;28(10):930–936.
77.
YamamotoTTsuneishiMFurutaM. Relationship between decrease of erytrocyte count and progression of periodontal disease in a rural Japanese population. J Periodontol. 2011;82(1):106–113.
78.
AgarwalNKumarVSGujjariSA. Effect of periodontal therapy on haemoglobin and erythrocyte levels in chronic generalized periodontitis patients: an interventional study. J Indian Soc Periodontol. 2009;13(1):6–11.
79.
RaiBKharbS. Effect of scaling and root planning in periodontitis on peripheral blood. Internet J Dent Sci. 2007;6:1.
80.
AljohaniHA. Association between hemoglobin levels and severity of chronic periodontitis. JKAU Med Sci. 2010;17(1):53–64.
81.
Havemose-PoulsenAWestergaardJStoltzeK. Periodontal and haematological characteristics associated with aggressive periodontitis, juvenile idiopathic arthritis, and rheumatoid arthritis. J Periodontol. 2006;77(2):280–288.
