Red cell distribution width and the risk of cerebral vein thrombosis: A case–control study

Published:November 04, 2016DOI:


      • Extreme levels of RDW are associated with the risk of CVT.
      • The association persists after adjustment for hemorheological parameters.
      • The association persists after adjustment for renal function and inflammation.
      • RDW interacts with oral contraceptives and thrombophilia.



      Red cell distribution width (RDW) is a marker of cardiovascular diseases and venous thromboembolism, but its role in cerebral vein thrombosis (CVT) is unknown.


      To investigate whether high values of RDW are associated with an increased risk of CVT.


      A case–control study of CVT patients (≥18 years-old) referred to our center contrasted with healthy individuals. Odds ratios (ORs) were calculated for RDW values >90th percentile by multivariable logistic regression and adjusted for demographic characteristics, hemorheological parameters, renal function, fibrinogen and CRP. Quartiles based on the distribution of RDW values were used in an additional model to assess a dose–response relationship. The risk of CVT associated with the combined presence of high RDW and either thrombophilia abnormalities or oral contraceptive use was also estimated.


      143 cases (median age 36 years, 18–79) and 352 controls (42 years, 18–80) were investigated. RDW values >90th percentile (>14.6%) were associated with an increased risk of CVT (OR 2.44, 95% CI 1.39–4.28). The association remained after further adjustment for hemorheological parameters (OR 3.73, 95% CI 1.72–8.09), inflammatory markers (OR 3.77, 95% CI 1.72–8.25) and renal function (OR 3.62, 95% CI 1.53–8.55). The risk appeared restricted to these extreme levels (>14.6%), as there was no graded association between values of RDW and CVT risk over quartiles. There was a synergistic effect on the risk of CVT for the combination of high RDW and thrombophilia abnormalities (OR 33.20, 95% CI 6.95–158.55) or oral contraceptive use (OR 37.99, 95% CI 8.78–164.45).


      Values of RDW >90th percentile are associated with CVT.


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        • Stam J.
        Thrombosis of the cerebral veins and sinuses.
        N Engl J Med. 2005; 352: 1791-1798
        • Ferro J.M.
        • Canhao P.
        • Stam J.
        • Bousser M.G.
        • Barinagarrementeria F.
        • Investigators I.
        Prognosis of cerebral vein and dural sinus thrombosis: results of the international study on cerebral vein and dural sinus thrombosis (ISCVT).
        Stroke. 2004; 35: 664-670
        • Raizer J.J.
        • DeAngelis L.M.
        Cerebral sinus thrombosis diagnosed by MRI and MR venography in cancer patients.
        Neurology. 2000; 54: 1222-1226
        • Martinelli I.
        • De Stefano V.
        • Carobbio A.
        • Randi M.L.
        • Santarossa C.
        • Rambaldi A.
        • et al.
        Cerebral vein thrombosis in patients with Philadelphia-negative myeloproliferative neoplasms. An European Leukemia Net study.
        Am J Hematol. 2014; 89: E200-E205
        • Martinelli I.
        • Sacchi E.
        • Landi G.
        • Taioli E.
        • Duca F.
        • Mannucci P.M.
        High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation and in users of oral contraceptives.
        N Engl J Med. 1998; 338: 1793-1797
        • Dentali F.
        • Crowther M.
        • Ageno W.
        Thrombophilic abnormalities, oral contraceptives, and risk of cerebral vein thrombosis: a meta-analysis.
        Blood. 2006; 107: 2766-2773
        • Saadatnia M.
        • Fatehi F.
        • Basiri K.
        • Mousavi S.A.
        • Mehr G.K.
        Cerebral venous sinus thrombosis risk factors.
        Int J Stroke. 2009; 4: 111-123
        • Evans T.C.
        • Jehle D.
        The red blood cell distribution width.
        J Emerg Med. 1991; 9: 71-74
        • Bucciarelli P.
        • Maino A.
        • Felicetta I.
        • Abbattista M.
        • Passamonti S.M.
        • Artoni A.
        • et al.
        Association between red cell distribution width and risk of venous thromboembolism.
        Thromb Res. 2015; 136: 590-594
        • Lappe J.M.
        • Horne B.D.
        • Shah S.H.
        • May H.T.
        • Muhlestein J.B.
        • Lappe D.L.
        • et al.
        Red cell distribution width, C-reactive protein, the complete blood count, and mortality in patients with coronary disease and a normal comparison population.
        Clin Chim Acta. 2011; 412: 2094-2099
        • Forhecz Z.
        • Gombos T.
        • Borgulya G.
        • Pozsonyi Z.
        • Prohaszka Z.
        • Janoskuti L.
        Red cell distribution width in heart failure: prediction of clinical events and relationship with markers of ineffective erythropoiesis, inflammation, renal function, and nutritional state.
        Am Heart J. 2009; 158: 659-666
        • Cay N.
        • Unal O.
        • Kartal M.G.
        • Ozdemir M.
        • Tola M.
        Increased level of red blood cell distribution width is associated with deep venous thrombosis.
        Blood Coagul Fibrinolysis. 2013; 24: 727-731
        • Rezende S.M.
        • Lijfering W.M.
        • Rosendaal F.R.
        • Cannegieter S.C.
        Hematologic variables and venous thrombosis: red cell distribution width and blood monocyte count are associated with an increased risk.
        Haematologica. 2014; 99: 194-200
        • Zoller B.
        • Melander O.
        • Svensson P.
        • Engstrom G.
        Red cell distribution width and risk for venous thromboembolism: a population-based cohort study.
        Thromb Res. 2014; 133: 334-339
        • Soderholm M.
        • Borne Y.
        • Hedblad B.
        • Persson M.
        • Engstrom G.
        Red cell distribution width in relation to incidence of stroke and carotid atherosclerosis: a population-based cohort study.
        PLoS One. 2015; 10e0124957
        • Demir R.
        • Saritemur M.
        • Ozel L.
        • Ozdemir G.
        • Emet M.
        • Ulvi H.
        Red cell distribution width identifies cerebral venous sinus thrombosis in patients with headache.
        Clin Appl Thromb Hemost. 2015; 21: 354-358
        • Agid R.
        • Shelef I.
        • Scott J.N.
        • Farb R.I.
        Imaging of the intracranial venous system.
        Neurologist. 2008; 14: 12-22
        • Frezzato M.
        • Tosetto A.
        • Rodeghiero F.
        Validated questionnaire for the identification of previous personal or familial venous thromboembolism.
        Am J Epidemiol. 1996; 143: 1257-1265
        • Patel H.H.
        • Patel H.R.
        • Higgins J.M.
        Modulation of red blood cell population dynamics is a fundamental homeostatic response to disease.
        Am J Hematol. 2015; 90: 422-428
        • Salvagno G.L.
        • Sanchis-Gomar F.
        • Picanza A.
        • Lippi G.
        Red blood cell distribution width: a simple parameter with multiple clinical applications.
        Crit Rev Clin Lab Sci. 2015; 52: 86-105
        • Cockcroft D.W.
        • Gault M.H.
        Prediction of creatinine clearance from serum creatinine.
        Nephron. 1976; 16: 31-41
        • Lippi G.
        • Pavesi F.
        • Bardi M.
        • Pipitone S.
        Lack of harmonization of red blood cell distribution width (RDW). Evaluation of four hematological analyzers.
        Clin Biochem. 2014; 47: 1100-1103
        • Tripodi A.
        • Chantarangkul V.
        • Menegatti M.
        • Tagliabue L.
        • Peyvandi F.
        Performance of clinical laboratories for DNA analyses to detect thrombophilia mutations.
        Clin Chem. 2005; 51: 1310-1311
        • Bertina R.M.
        • Koeleman B.P.
        • Koster T.
        • Rosendaal F.R.
        • Dirven R.J.
        • de Ronde H.
        • et al.
        Mutation in blood coagulation factor V associated with resistance to activated protein C.
        Nature. 1994; 369: 64-67
        • Poort S.R.
        • Rosendaal F.R.
        • Reitsma P.H.
        • Bertina R.M.
        A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis.
        Blood. 1996; 88: 3698-3703
        • Tripodi A.
        A review of the clinical and diagnostic utility of laboratory tests for the detection of congenital thrombophilia.
        Semin Thromb Hemost. 2005; 31: 25-32
        • Pengo V.
        • Tripodi A.
        • Reber G.
        • Rand J.H.
        • Ortel T.L.
        • Galli M.
        • et al.
        Update of the guidelines for lupus anticoagulant detection. Subcommittee on lupus anticoagulant/antiphospholipid antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis.
        J Thromb Haemost. 2009; 7: 1737-1740
        • Mannucci P.M.
        • Mannucci T.A.
        RMB J.J. Haverkate F. Factor VIII clotting activity. Kluwer Academic Publishers, Dordrecht1999 (107–13 pp.)
        • van der Griend R.
        • Biesma D.H.
        • Banga J.D.
        Postmethionine-load homocysteine determination for the diagnosis hyperhomocysteinaemia and efficacy of homocysteine lowering treatment regimens.
        Vasc Med. 2002; 7: 29-33
        • Baglin T.
        • Gray E.
        • Greaves M.
        • Hunt B.J.
        • Keeling D.
        • Machin S.
        • et al.
        Clinical guidelines for testing for heritable thrombophilia.
        Br J Haematol. 2010; 149: 209-220
        • Harrell F.E.
        Regression modelling strategies: Springer.
        2001 (572 pp.)
        • Jung C.
        • Fujita B.
        • Lauten A.
        • Kiehntopf M.
        • Kuthe F.
        • Ferrari M.
        • et al.
        Red blood cell distribution width as useful tool to predict long-term mortality in patients with chronic heart failure.
        Int J Cardiol. 2011; 152: 417-418
        • Anderson J.L.
        • Ronnow B.S.
        • Horne B.D.
        • Carlquist J.F.
        • May H.T.
        • Bair T.L.
        • et al.
        Usefulness of a complete blood count-derived risk score to predict incident mortality in patients with suspected cardiovascular disease.
        Am J Cardiol. 2007; 99: 169-174
        • Zorlu A.
        • Bektasoglu G.
        • Guven F.M.
        • Dogan O.T.
        • Gucuk E.
        • Ege M.R.
        • et al.
        Usefulness of admission red cell distribution width as a predictor of early mortality in patients with acute pulmonary embolism.
        Am J Cardiol. 2012; 109: 128-134
        • Allen L.A.
        • Felker G.M.
        • Mehra M.R.
        • Chiong J.R.
        • Dunlap S.H.
        • Ghali J.K.
        • et al.
        Validation and potential mechanisms of red cell distribution width as a prognostic marker in heart failure.
        J Card Fail. 2010; 16: 230-238
        • Dhermy D.
        • Simeon J.
        • Wautier M.P.
        • Boivin P.
        • Wautier J.L.
        Role of membrane sialic acid content in the adhesiveness of aged erythrocytes to human cultured endothelial cells.
        Biochim Biophys Acta. 1987; 904: 201-206
        • Osterud B.
        • Unruh D.
        • Olsen J.O.
        • Kirchhofer D.
        • Owens III, A.P.
        • Bogdanov V.Y.
        Procoagulant and proinflammatory effects of red blood cells on lipopolysaccharide-stimulated monocytes.
        J Thromb Haemost. 2015; 13: 1676-1682
        • Koshiar R.L.
        • Somajo S.
        • Norstrom E.
        • Dahlback B.
        Erythrocyte-derived microparticles supporting activated protein C-mediated regulation of blood coagulation.
        PLoS One. 2014; 9e104200