Advertisement

Combined prognostic significance of white blood cell count and D-dimer on in-hospital outcomes of acute ischemic stroke

  • Author Footnotes
    1 Drs Peng and Huang contributed equally and are joint first authors.
    Dan Peng
    Footnotes
    1 Drs Peng and Huang contributed equally and are joint first authors.
    Affiliations
    Department of Neurology and Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China
    Search for articles by this author
  • Author Footnotes
    1 Drs Peng and Huang contributed equally and are joint first authors.
    Yaqian Huang
    Footnotes
    1 Drs Peng and Huang contributed equally and are joint first authors.
    Affiliations
    Department of Neurology and Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China
    Search for articles by this author
  • Yi Wang
    Affiliations
    Department of Neurology and Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China
    Search for articles by this author
  • Zhichao Huang
    Affiliations
    Department of Neurology and Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China
    Search for articles by this author
  • Yafang Zhu
    Affiliations
    Department of Neurology and Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China
    Search for articles by this author
  • Rongfang Shi
    Affiliations
    Department of Neurology and Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China
    Search for articles by this author
  • Yongrong Sun
    Affiliations
    Department of Neurology and Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China
    Search for articles by this author
  • Yan Qin
    Affiliations
    Department of Neurology and Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China
    Search for articles by this author
  • Yongjun Cao
    Correspondence
    Corresponding author. Department of Neurology and Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, 1055# Sanxiang Road, Suzhou 215004, China. Fax: +86 512 68284303
    Affiliations
    Department of Neurology and Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China
    Search for articles by this author
  • Xia Zhang
    Correspondence
    Corresponding author. Department of Neurology and Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, 1055# Sanxiang Road, Suzhou 215004, China. Fax: +86 512 68284303
    Affiliations
    Department of Neurology and Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China
    Search for articles by this author
  • Author Footnotes
    1 Drs Peng and Huang contributed equally and are joint first authors.
Published:October 19, 2022DOI:https://doi.org/10.1016/j.numecd.2022.10.008

      Highlights

      • WBC combined D-dimer has a tendency to improve the predictive power for poor in-hospital outcomes of AIS patients.
      • WBC∗D-dimer has multipliable interaction on in-hospital mortality and pneumonia in AIS.
      • High WBC and high D-dimer level are associated with poor prognosis and pneumonia in AIS.

      Abstract

      Background and aims

      The prognostic significance of combination of white blood cell (WBC) and D-dimer on acute ischemic stroke (AIS) remains to be explored. We aimed to investigate the combined effect of WBC and D-dimer levels on in-hospital outcomes of AIS patients.

      Methods and results

      801 AIS patients were included. Patients were divided into four groups according to the cut-point identified by receiver operating characteristic (ROC) curve of D-dimer (1.105 μg/L) and WBC (7.05 × 109/L): LWLD (low WBC count and low D-dimer), LWHD (low WBC count and high D-dimer), HWLD (high WBC count and low D-dimer), and HWHD (high WBC count and high D-dimer). HWHD group had the highest cumulative incidence of in-hospital mortality (hazard ratio, 5.79; 95%CI, 1.71–19.58, P = 0.006). Patients in HWHD group were 4.14 fold more likely to have in-hospital pneumonia (odds ratio, 4.14; 95%CI, 2.09–8.21; P < 0.001), compared with those in LWLD group. The area under curve (AUC) of the combination of WBC and D-dimer levels for in-hospital mortality and pneumonia was larger than that of WBC and D-dimer alone (0.920 vs. 0.900 vs. 0.915; 0.831 vs. 0.829 vs. 0.807).

      Conclusions

      The combination of WBC count and D-dimer levels at admission was independently associated with in-hospital outcomes of AIS patients. The addition of WBC to D-dimer levels had a tendency to improve the predictive power for in-hospital mortality and pneumonia.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Nutrition, Metabolism and Cardiovascular Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Zang R.S.
        • Zhang H.
        • Xu Y.
        • Zhang S.M.
        • Liu X.
        • Wang J.
        • et al.
        Serum C-reactive protein, fibrinogen and D-dimer in patients with progressive cerebral infarction.
        Transl Neurosci. 2016; 7: 84-88
        • Yuan B.
        • Yang T.
        • Yan T.
        • Cheng W.
        • Bu X.
        Relationships between D-dimer levels and stroke risk as well as adverse clinical outcomes after acute ischemic stroke or transient ischemic attack: a systematic review and meta-analysis.
        Front Neurol. 2021; 12670730
        • Choi K.H.
        • Kim J.H.
        • Kim J.M.
        • Kang K.W.
        • Lee C.
        • Kim J.T.
        • et al.
        D-Dimer level as a predictor of recurrent stroke in patients with embolic stroke of undetermined source.
        Stroke. 2021; 52: 2292-2301
        • Yao T.
        • Tian B.L.
        • Li G.
        • Cui Q.
        • Wang C.F.
        • Zhang Q.
        • et al.
        Elevated plasma D-dimer levels are associated with short-term poor outcome in patients with acute ischemic stroke: a prospective, observational study.
        BMC Neurol. 2019; 19: 1-8
        • Nam K.W.
        • Kim C.K.
        • Kim T.J.
        • An S.J.
        • Oh K.
        • Mo H.
        • et al.
        Predictors of 30-day mortality and the risk of recurrent systemic thromboembolism in cancer patients suffering acute ischemic stroke.
        PLoS One. 2017; 12e0172793
        • Long H.
        • Nie L.
        • Xiang X.
        • Li H.
        • Zhang X.
        • Fu X.
        • et al.
        D-dimer and prothrombin time are the significant indicators of severe COVID-19 and poor prognosis.
        BioMed Res Int. 2020; 20206159720
        • Cerda-Mancillas M.C.
        • Santiago-Germán D.
        • Andrade-Bravo B.
        • Pedraza-Olivares F.
        • Valenzo-Hernández F.
        • Leaños-Miranda A.
        • et al.
        D-dimer as A Biomarker of severity and adverse outcomes in patients with community acquired pneumonia.
        Arch Med Res. 2020; 51: 429-435
        • You S.
        • Ou Z.
        • Zhang W.
        • Zheng D.
        • Zhong C.
        • Dong X.
        • et al.
        Combined utility of white blood cell count and blood glucose for predicting in-hospital outcomes in acute ischemic stroke.
        J Neuroinflammation. 2019; 16: 1-9
        • Biamonte F.
        • Botta C.
        • Mazzitelli M.
        • Rotundo S.
        • Trecarichi E.M.
        • Foti D.
        • et al.
        Combined lymphocyte/monocyte count, D-dimer and iron status predict COVID-19 course and outcome in a long-term care facility.
        J Transl Med. 2021; 19: 1-10
        • Bu X.
        • Chen J.
        • Wan Y.
        • Xu L.
        Diagnostic value of D-dimer combined with WBC count, neutrophil percentage and CRP in differentiating between simple and.
        Clin Lab. 2016; 62: 1675-1681
        • Wen H.
        • Chen Y.
        The predictive value of platelet to lymphocyte ratio and D-dimer to fibrinogen ratio combined with WELLS score on lower extremity deep vein thrombosis in young patients with cerebral hemorrhage.
        Neurol Sci. 2021; 42: 3715-3721
        • Gu L.F.
        • Gu J.
        • Wang S.B.
        • Wang H.
        • Wang Y.X.
        • Xue Y.
        • et al.
        Combination of D-dimer level and neutrophil to lymphocyte ratio predicts long-term clinical outcomes in acute coronary syndrome after percutaneous coronary intervention.
        Cardiol J. 2021; https://doi.org/10.5603/CJ.a2021.0097
        • Qin Q.X.
        • Cheng X.M.
        • Lu L.Z.
        • Wei Y.F.
        • Wang D.C.
        • Li H.H.
        • et al.
        Biomarkers and potential pathogenesis of colorectal cancer-related ischemic stroke.
        World J Gastroenterol. 2018; 24: 4950-4958
        • Kaplan R.C.
        • McGinn A.P.
        • Baird A.E.
        • Hendrix S.L.
        • Kooperberg C.
        • Lynch J.
        • et al.
        Inflammation and hemostasis biomarkers for predicting stroke in postmenopausal women: the Women's Health Initiative Observational Study.
        J Stroke Cerebrovasc Dis. 2008; 17: 344-355
        • Marta-Enguita J.
        • Navarro-Oviedo M.
        • Muñoz R.
        • Olier-Arenas J.
        • Zalba G.
        • Lecumberri R.
        • et al.
        Inside the thrombus: association of hemostatic parameters with outcomes in large vessel stroke patients.
        Front Neurol. 2021; 12599498
        • Andersson T.
        • Alfredsson L.
        • Källberg H.
        • Zdravkovic S.
        • Ahlbom A.
        Calculating measures of biological interaction.
        Eur J Epidemiol. 2005; 20: 575-579
        • Elberts S.J.
        • Bateman R.
        • Koutsoubis A.
        • London K.S.
        • White J.L.
        • Fields J.M.
        The impact of COVID-19 on the sensitivity of D-dimer for pulmonary embolism.
        Acad Emerg Med. 2021; 28: 1142-1149
        • Koch V.
        • Biener M.
        • Müller-Hennessen M.
        • Vafaie M.
        • Staudacher I.
        • Katus H.A.
        • et al.
        Diagnostic performance of D-dimer in predicting venous thromboembolism and acute aortic dissection.
        Eur Heart J Acute Cardiovasc Care. 2021; 10: 559-566
        • Wang J.
        • Feng A.
        • Xu J.
        • Liu Y.
        • Li F.
        • Sun Y.
        • et al.
        D-Dimer and its combination with blood lipid on prognosis of patients with acute ischemic stroke.
        J Stroke Cerebrovasc Dis. 2020; 29105394
        • Liu Y.
        • Li F.
        • Sun H.
        • Sun Y.
        • Sun H.
        • Zhai Y.
        • et al.
        Combined prognostic significance of D-dimer level and platelet count in acute ischemic stroke.
        Thromb Res. 2020; 194: 142-149
        • Furlan J.C.
        • Vergouwen M.D.
        • Fang J.
        • Silver F.L.
        White blood cell count is an independent predictor of outcomes after acute ischaemic stroke.
        Eur J Neurol. 2014; 21: 215-222
        • Gong X.
        • Zou X.
        • Liu L.
        • Pu Y.
        • Wang Y.
        • Pan Y.
        • et al.
        Prognostic value of inflammatory mediators in 1-year outcome of acute ischemic stroke with middle cerebral artery stenosis.
        Mediat Inflamm. 2013; 2013850714
        • Qu X.
        • Shi J.
        • Cao Y.
        • Zhang M.
        • Xu J.
        Prognostic value of white blood cell counts and C-reactive protein in acute ischemic stroke patients after intravenous thrombolysis.
        Curr Neurovascular Res. 2018; 15: 10-17
        • Antoniazzi A.M.
        • Unda S.R.
        • Klyde D.M.
        • Miller R.
        • Lam S.
        • Fluss R.
        • et al.
        Sterile leukocytosis predicts hemorrhagic transformation in arterial ischemic stroke: a national inpatient sample study.
        Cureus. 2021; 13e14973
        • Ge Y.L.
        • Liu C.H.
        • Wang N.
        • Xu J.
        • Zhu X.Y.
        • Su C.S.
        • et al.
        Elevated plasma D-dimer in adult community-acquired pneumonia patients is associated with an increased inflammatory reaction and lower survival.
        Clin Lab. 2019; 65https://doi.org/10.7754/Clin.Lab.2018.180720
        • Li S.
        • Luo Y.
        • Wang W.
        • Lu J.
        • Hu M.
        • Sun Q.
        • et al.
        A novel multiparameter scoring model for noninvasive early prediction of ischemic colitis: a multicenter, retrospective, and real-world study.
        Clin Transl Gastroenterol. 2021; 12e00370
        • Liu D.
        • Zhu Y.
        • Chen W.
        • Li J.
        • Zhao K.
        • Zhang J.
        • et al.
        Relationship between the inflammation/immune indexes and deep venous thrombosis (DVT) incidence rate following tibial plateau fractures.
        J Orthop Surg Res. 2020; 15: 1-8
        • Jayarangaiah A.
        • Kariyanna P.T.
        • Chen X.
        • Jayarangaiah A.
        • Kumar A.
        COVID-19-Associated coagulopathy: an exacerbated immunothrombosis response.
        Clin Appl Thromb Hemost. 2020; 261076029620943293
        • Robson S.C.
        • Shephard E.G.
        • Kirsch R.E.
        Fibrin degradation product D-dimer induces the synthesis and release of biologically active IL-1 beta, IL-6 and plasminogen activator inhibitors from monocytes in vitro.
        Br J Haematol. 1994; 86: 322-326
        • Zhou D.
        • Yang P.Y.
        • Zhou B.
        • Rui Y.C.
        Fibrin D-dimer fragments enhance inflammatory responses in macrophages: role in advancing atherosclerosis.
        Clin Exp Pharmacol Physiol. 2007; 34: 185-190
        • Frantzeskaki F.
        • Armaganidis A.
        • Orfanos S.E.
        Immunothrombosis in acute respiratory distress syndrome: cross talks between inflammation and coagulation.
        Respiration. 2017; 93: 212-225
        • Zarbock A.
        • Singbartl K.
        • Ley K.
        Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregation.
        J Clin Invest. 2006; 116: 3211-3219
        • von Brühl M.L.
        • Stark K.
        • Steinhart A.
        • Chandraratne S.
        • Konrad I.
        • Lorenz M.
        • et al.
        Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo.
        J Exp Med. 2012; 209: 819-835
        • Franck G.
        • Mawson T.L.
        • Folco E.J.
        • Molinaro R.
        • Ruvkun V.
        • Engelbertsen D.
        • et al.
        Roles of PAD4 and NETosis in experimental atherosclerosis and arterial injury: implications for superficial erosion.
        Circ Res. 2018; 123: 33-42
        • Gaul D.S.
        • Stein S.
        • Matter C.M.
        Neutrophils in cardiovascular disease.
        Eur Heart J. 2017; 38: 1702-1704
        • Marta-Enguita J.
        • Navarro-Oviedo M.
        • Rubio-Baines I.
        • Aymerich N.
        • Herrera M.
        • Zandio B.
        • et al.
        Association of calprotectin with other inflammatory parameters in the prediction of mortality for ischemic stroke.
        J Neuroinflammation. 2021; 18: 1-13
        • Semerano A.
        • Strambo D.
        • Martino G.
        • Comi G.
        • Filippi M.
        • Roveri L.
        • et al.
        Leukocyte counts and ratios are predictive of stroke outcome and hemorrhagic complications independently of infections.
        Front Neurol. 2020; 11: 201
        • Yu Z.
        • Zhou H.
        • Shan B.
        • Fu J.
        • Zhu H.
        • Feng Q.
        • et al.
        Clopidogrel increases risk of pneumonia compared with aspirin in acute ischemic minor stroke patients.
        J Thromb Thrombolysis. 2021; 52: 301-307