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Vol. 35, No. 1, 2013
Issue release date: February 2013
Cerebrovasc Dis 2013;35:64–72

Relationship between Plasma D-Dimer Level and Cerebral Infarction Volume in Patients with Nonvalvular Atrial Fibrillation

Matsumoto M. · Sakaguchi M. · Okazaki S. · Furukado S. · Tagaya M. · Etani H. · Shimazu T. · Yoshimine T. · Mochizuki H. · Kitagawa K.
aStroke Center, Departments of bNeurology, cTraumatology and Acute Critical Medicine and dNeurosurgery, Osaka University Graduate School of Medicine, and eDivision of Stroke Medicine, Osaka National Hospital, Osaka, Japan

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Background: Plasma D-dimer level may reflect the activity of thrombus formation in the left atrium of patients with nonvalvular atrial fibrillation (NVAF). Proper anticoagulation with warfarin dramatically decreases the rate of cerebral embolism, reduces stroke severity and subsequent risk of death, as well as the level of D-dimer in NVAF patients. However, the predictive value of D-dimer level on cerebral embolism severity has not been examined. Thus, the purpose of this study was to investigate the association between plasma D-dimer level at admission and infarct size in NVAF patients. Methods: We identified 124 patients with consecutive ischemic stroke and NVAF who were admitted within 48 h of symptom onset. We measured infarction volume from CT taken after 3 ± 1 days from the onset. Plasma D-dimer levels were measured at the time of admission. Relationships were analyzed between infarction volume and plasma D-dimer levels, cardiovascular risk factors, preadmission medications and admission conditions. We also assessed the influence of D-dimer level on functional outcome in patients with preadmission modified Rankin Scale (mRS) score of 0–1 and patients by tertile of D-dimer level (≤0.83, 0.83–2.16 and ≥2.16 µg/ml). Results: Infarction volume significantly correlated with D-dimer level (r = 0.309, p < 0.001), systolic blood pressure (r = 0.201, p = 0.026), diastolic blood pressure (r = 0.283, p = 0.002), National Institutes of Health Stroke Scale (NIHSS) score on admission (r = 0.546, p < 0.001) and mRS score at discharge (r = 0.557, p < 0.001). Multivariate regression analyses showed that the D-dimer level was significantly associated with infarction volume after adjusting for age, sex, current smoker or not, prothrombin time-international normalized ratio ≥1.6, diastolic blood pressure, CHADS2 score and NIHSS score on admission. In patients with a preadmission mRS score of 0–1 (n = 108), D-dimer level was significantly associated with NIHSS score at admission (r = 0.318, p < 0.001) and mRS score at discharge (r = 0.310, p = 0.001). Patients in the highest D-dimer tertile group showed worse outcome than those in the middle (p = 0.041) and lowest (p < 0.001) tertiles. Conclusions: Plasma D-dimer level on admission is significantly related to infarction volume and functional outcome, following cardioembolic stroke in NVAF patients.

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  1. Inoue H, Fujiki A, Origasa H, Ogawa S, Okumura K, Kubota I, Aizawa Y, Yamashita T, Atarashi H, Horie M, Ohe T, Doi Y, Shimizu A, Chishaki A, Saikawa T, Yano K, Kitabatake A, Mitamura H, Kodama I, Kamakura S: Prevalence of atrial fibrillation in the general population of Japan: an analysis based on periodic health examination. Int J Cardiol 2009;137:102–107.
  2. Wolf PA, Dawber TR, Thomas HE Jr, Kannel WB: Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: The Framingham Study. Neurology 1978;28:973–977.
  3. Lip GY, Tse HF, Lane AD: Atrial fibrillation. Lancet 2012;379:648–661.
  4. Tripodi A: D-Dimer testing in laboratory practice. Clin Chem 2011;57:1256–1262.
  5. Manning WJ, Weintraub RM, Waksmonski CA, Haering JM, Rooney PS, Maslow AD, Johnson RG, Douglas PS: Accuracy of transesophageal echocardiography for identifying left atrial thrombi: a prospective, intraoperative study. Ann Intern Med 1995;123:817–822.
  6. Lip GY, Lip PL, Zarifis J, Watson RD, Bareford D, Lowe GD, Beevers DG: Fibrin D-dimer and β-thromboglobulin as markers of thrombogenesis and platelet activation in atrial fibrillation: effects of introducing ultra-low-dose warfarin and aspirin. Circulation 1996;94:425–431.
  7. Gustafsson C, Blombäck M, Britton M, Hamsten A, Svensson J: Coagulation factors and the increased risk of stroke in nonvalvular atrial fibrillation. Stroke 1990;21:47–51.
  8. Inoue H, Nozawa T, Okumura K, Jong-Dae L, Shimizu A, Yano K: Prothrombotic activity is increased in patients with nonvalvular atrial fibrillation and risk factors for embolism. Chest 2004;126:687–692.
  9. Nozawa, T, Inoue H, Hirai T, Iwasa A, Okumura K, Lee JD, Shimizu A, Hayano M, Yano K: D-Dimer level influences thromboembolic events in patients with atrial fibrillation. Int J Cardiol 2006;109:59–65.
  10. Hart RG, Pearce LA, Aguilar MI: Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007;146:857–867.
  11. Schwammenthal Y, Bornstein N, Schwammenthal E, Schwartz R, Goldbourt U, Tsabari R, Koton S, Grossman E, Tanne D: Relation of effective anticoagulation in patients with atrial fibrillation to stroke severity and survival (from the National Acute Stroke Israeli Survey [NASIS]). Am J Cardiol 2010;105:411–416.
  12. Naess H, Brogger J, Waje-Andreassen U, Idicula TT, Thomassen L: Preadmission use of warfarin improves short-term outcome in patients with acute cerebral infarction: The Bergen Stroke Study. Cerebrovasc Dis 2009;28:8–12.
  13. Hylek EM, Go AS, Chang Y, Jensvold NG, Henault LE, Selby JV, Singer DE: Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med 2003;349:1019–1026.
  14. O’Donnell M, Oczkowski W, Fang J, Kearon C, Silvia J, Bradley C , Guyatt G, Gould L, D’Uva C, Kapral M, Silver F, Investigators of the Registry of the Canadian Stroke Network: Preadmission antithrombotic treatment and stroke severity in patients with atrial fibrillation and acute ischaemic stroke: an observational study. Lancet Neurol 2006;5:749–754.
  15. Matsumoto M, Okazaki S, Sakaguchi M, Ohara N, Furukado S, Nagano K, Kuwagata Y, Shimazu T, Yoshimine T, Kitagawa K: Preadmission therapeutic anticoagulation reduces cerebral infarct volume in patients with nonvalvular atrial fibrillation. Eur Neurol 2011;66:277–282.
  16. Nakatani Y, Mizumaki K, Nishida K, Hirai T, Sakabe M, Oda Y, Joho S, Fujiki A, Nozawa T, Inoue H: Anticoagulation control quality affects the D-dimer levels of atrial fibrillation patients. Circ J 2012;76:317–321.
  17. Becattini C, Lignani A, Masotti L, Forte MB, Agnelli G: D-Dimer for risk stratification in patients with acute pulmonary embolism. J Thromb Thrombolysis 2012;33:48–57.
  18. Klok FA, Djurabi RK, Nijkeuter M, Eikenboom HC, Leebeek FW, Kramer MH, Kaasjager K, Kamphuisen PW, Büller HR, Huisman MV: High D-dimer level is associated with increased 15-d and 3 months mortality through a more central localization of pulmonary emboli and serious comorbidity. Br J Haematol 2008;140:218–222.
  19. De Monyé W, Sanson BJ, Mac Gillavry MR, Pattynama PM, Büller HR, van den Berg-Huysmans AA, Huisman MV; ANTELOPE-Study Group: Embolus location affects the sensitivity of a rapid quantitative D-dimer assay in the diagnosis of pulmonary embolism. Am J Respir Crit Care Med 2002;165:345–348.

    External Resources

  20. Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ: Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001;285:2864–2870.
  21. Brott T, Marler JR, Olinger CP, Adams HP Jr, Tomsick T, Barsan WG, Biller J, Eberle R, Hertzberg V, Walker M: Measurements of acute cerebral infarction: lesion size by computed tomography. Stroke 1989;20:871–875.
  22. Barber M, Langhorne P, Rumley A, Lowe GD, Stott DJ: Hemostatic function and progressing ischemic stroke: D-dimer predicts early clinical progression. Stroke 2004;35:1421–1425.
  23. Ageno W, Finazzi S, Steidl L, Biotti MG, Mera V, Melzi D’Eril G, Venco A: Plasma measurement of D-dimer levels for the early diagnosis of ischemic stroke subtypes. Arch Intern Med 2002;162:2589–2593.
  24. Sacco RL, Shi T, Zamanillo MC, Kargman DE: Predictors of mortality and recurrence after hospitalized cerebral infarction in an urban community: the northern Manhattan stroke study. Neurology 1994;44:626–634.
  25. Castillo J, Leira R, Garcia MM, Serena J, Blanco M, Dávalos A: Blood pressure decrease during the acute phase of ischemic stroke is associated with brain injury and poor stroke outcome. Stroke 2004;35:520–526.
  26. Heuschmann PU, Kolominsky-Rabas PL, Misselwitz B, Hermanek P, Leffmann C, Janzen RW, Rother J, Buecker-Nott HJ, Berger K, German Stroke Registers Study Group: Predictors of in-hospital mortality and attributable risks of death after ischemic stroke: The German Stroke Registers Study Group. Arch Intern Med 2004;164:1761–1768.
  27. Sato S, Yazawa Y, Itabashi R, Tsukita K, Fujiwara S, Furui E: Pre-admission CHADS2 score is related to severity and outcome of stroke. J Neurol Sci 2011;307:149–152.
  28. Hong HJ, Kim YD, Cha MJ, Kim J, Lee DH, Lee HS, et al: Early neurological outcomes according to CHADS2 score in stroke patients with non-valvular atrial fibrillation. Eur J Neurol 2012;19:284–290.
  29. Ohara K, Inoue H, Nozawa T, Hirai T, Iwasa A, Okumura K, et al: Accumulation of risk factors enhances the prothrombotic state in atrial fibrillation. Int J Cardiol 2008;126:316–321.
  30. Barber M, Langhorne P, Rumley A, Lowe GD, Stott DJ: D-Dimer predicts early clinical progression in ischemic stroke: confirmation using routine clinical assays. Stroke 2006;37:1113–1115.
  31. Welsh P, Barber M, Langhorne P, Rumley A, Lowe GD, Stott DJ: Associations of inflammatory and haemostatic biomarkers with poor outcome in acute ischaemic stroke. Cerebrovasc Dis 2009;27:247–253.
  32. Tombul T, Atbas C, Anlar O: Hemostatic markers and platelet aggregation factors as predictive markers for type of stroke and neurological disability following cerebral infarction. J Clin Neurosci 2005;12:429–434.
  33. Squizzato A, Ageno W, Finazzi S, Mera V, Romualdi E, Bossi A, Venco A: D-Dimer is not a long-term prognostic marker following acute cerebral ischemia. Blood Coagul Fibrinolysis 2006;17:303–306.
  34. Krarup LH, Sandset EC, Sandset PM, Berge E: D-Dimer levels and stroke progression in patients with acute ischemic stroke and atrial fibrillation. Acta Neurol Scand 2011;124:40–44.
  35. Lip GY, Blann AD, Farooqi IS, Zarifis J, Sagar G, Beevers DG: Sequential alterations in haemorheology, endothelial dysfunction, platelet activation and thrombogenesis in relation to prognosis following acute stroke: The West Birmingham Stroke Project. Blood Coagul Fibrinolysis 2002;13:339–347.
  36. De Silva DA, Brekenfeld C, Ebinger M, Christensen S, Barber PA, Butcher KS, Levi CR, Parsons MW, Bladin CF, Donnan GA, Davis SM, Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) Investigators: The benefits of intravenous thrombolysis relate to the site of baseline arterial occlusion in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET). Stroke 2010;41:295–299.
  37. Urbach H, Hartmann A, Pohl C, Omran H, Wilhelm K, Flacke S, Schild HH, Klockgether T: Local intra-arterial thrombolysis in the carotid territory: does recanalization depend on the thromboembolus type? Neuroradiology 2002;44:695–699.
  38. Welsh P, Barber M, Langhorne P, Rumley A, Lowe GD, Stott DJ: Associations of inflammatory and haemostatic biomarkers with poor outcome in acute ischaemic stroke. Cerebrovasc Dis 2009;27:247–253.
  39. Katsnelson M, Sacco RL, Moscucci M: Progress for stroke prevention with atrial fibrillation: emergence of alternative oral anticoagulants. Stroke 2012;43:1179–1185.
  40. Langhorne P, Stott DJ, Robertson L, MacDonald J, Jones L, McAlpine C, Dick F, Taylor GS, Murray G: Medical complications after stroke: a multicenter study. Stroke 2000;31:1223–1229.
  41. Hirano K, Takashima S, Dougu N, Taguchi Y, Nukui T, Konishi H, Toyoda S, Kitajima I, Tanaka K: Study of hemostatic biomarkers in acute ischemic stroke by clinical subtype. J Stroke Cerebrovasc Dis. 2012;21:404–410.

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