The Risk Factors for Death within 6 Months After Ischemic Stroke in Patients with Cancer



      While the intravenous recombinant tissue plasminogen activator (rt-PA) therapy for acute ischemic stroke patients with cancer is recommended when survival of ≥ 6 months is expected, the risk factors for death and stroke recurrence within 6 months after stroke are not well known. Thus, we aimed to identify markers for death and recurrence risks within six months from stroke onset in patients with cancer.

      Materials and Methods

      In a retrospective cohort study, the subjects comprised acute ischemic stroke patients with cancer hospitalized at St. Marianna University hospital from 2008 through 2019. To evaluate the associations between the clinical factors within 24 h of the initial stroke and death or stroke recurrence events within 6 months from stroke onset, Logistic analysis and Cox proportional hazards regression analysis was used respectively. Next, the optimal cutoff point of markers for different mortality groups was determined using the receiver operating characteristic curve analysis and cumulative outcome rate of each group was compared using the Kaplan–Meier method.


      Among 194 patients with cancer who developed acute stroke, 167 were ultimately selected for analysis. 47 subjects (28.14%) passed away within 6 months following stroke onset, and 20 subjects (11.98%) had stroke recurrence. High D-dimer levels, low fibrinogen levels, high Glasgow prognostic scores (GPS), and multiple vascular territory infarctions was independently associated with death, where higher death rate was significantly confirmed in the group with D-dimer levels of ≥3.95 mg/dl, fibrinogen levels <277.5 mg/dl and GPS scores of 2. Low fibrinogen level, lack of antithrombotic therapy, and the presence of metastasis were associated with stroke recurrence.


      When patients with cancer suffer stroke, D-dimer levels, fibrinogen levels, GPS, and multiple vascular territory infarctions would be associated with the risk of death within 6 months. Low fibrinogen levels, lack of antithrombotic therapy, and the presence of metastasis correlated with high risk of stroke recurrence.

      Key Words


      rt-PA (recombinant tissue plasminogen activator), GPS (Glasgow prognostic scores), QOL (quality of life), DVT (deep vein thrombosis), NIHSS (National Institutes of Health Stroke Scale), HT (hypertension), DL (dyslipidemia), DM (diabetes mellitus), CKD (chronic kidney disease), AF (atrial fibrillation), HbA1c (hemoglobin A1c), eGFR (estimated glomerular filtration rate), TOAST (the trial of ORG 10172 in acute stroke treatment), WBC (white blood cell count), Hb (hemoglobin level), Plt (platelet count), TP (total protein), Alb (albumin), Cr (creatinine), CRP (C-reactive protein), PT/INR (prothrombin time/international normalized ratio), APTT (activated partial thromboplastin time), SPSS (statistical package for the social sciences), ROC (the receiver operating characteristic), NBTE (nonbacterial thrombotic endocarditis), AUC (The area under the curve), DIC (disseminated intravascular coagulation), mRS (modified Rankin scale)
      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 to Journal of Stroke and Cerebrovascular Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Cestari DM
        • Weine DM
        • Panageas KS
        • et al.
        Stroke in patients with cancer: incidence and etiology.
        Neurology. 2004; 62: 2025-2030
        • Navi BB
        • Reiner AS
        • Kamel H
        • et al.
        Association between incident cancer and subsequent stroke.
        Ann Neurol. 2015; 77: 291-300
        • Khorana AA
        Venous thromboembolism and prognosis in cancer.
        Thromb Res. 2010; 125: 490-493
        • Lee MJ
        • Chung JW
        • Ahn MJ
        • et al.
        Hypercoagulability and mortality of patients with stroke and active cancer: the OASIS-CANCER study.
        J Stroke. 2017; 19: 77-87
        • Navi BB
        • Singer S
        • Merkler AE
        • et al.
        Recurrent thromboembolic events after ischemic stroke in patients with cancer.
        Neurology. 2014; 83: 26-33
        • Powers WJ
        • Rabinstein AA
        • Ackerson T
        • et al.
        American Heart Association Stroke Council. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association.
        Stroke. 2018; 49: e46-e110
        • Yoo J
        • Nam HS
        • Kim YD
        • et al.
        Short-term outcome of ischemic stroke patients with systemic malignancy.
        Stroke. 2019; 50: 507-511
        • Navi BB
        • Kamel H
        • Sidney S
        • et al.
        Validation of the stroke prognostic instrument-II in a large, modern, community-based cohort of ischemic stroke survivors.
        Stroke. 2011; 42: 3392-3396
        • Adams Jr, HP
        • Bendixen BH
        • Kappelle LJ
        • et al.
        Classification of subtype of acute ischemic stroke.
        Stoke. 1993; 24: 35-41
        • Navi BB
        • Singer S
        • Merkler AE
        • et al.
        Cryptogenic subtype predicts reduced survival among cancer patients with ischemic stroke.
        Stroke. 2014; 45: 2292-2297
        • Kim SG
        • Hong JM
        • Kim HY
        • et al.
        Ischemic stroke in cancer patients with and without conventional mechanisms: a multicenter study in Korea.
        Stroke. 2010; 41: 798-801
        • Schwarzbach CJ
        • Schaefer A
        • Ebert A
        • et al.
        Stroke and cancer: the importance of cancer-associated hypercoagulation as a possible stroke etiology.
        Stroke. 2012; 43: 3029-3034
        • Seok JM
        • Kim SG
        • Kim JW
        • et al.
        Coagulopathy and embolic signal in cancer patients with ischemic stroke.
        Ann Neurol. 2010; 68: 213-219
        • Kim K
        • Lee JH
        Risk factors and biomarkers of ischemic stroke in cancer patients.
        J Stroke. 2014; 16: 91-96
        • Kuderer NM
        • Ortel TL
        • Francis CW
        Impact of venous thromboembolism and anticoagulation on cancer and cancer survival.
        J Clin Oncol. 2009; 27: 4902-4911
        • Nierodzik M
        • Karpatkin S
        Hypercoagulability preceding cancer. Does hypercoagulability awaken dormant tumor cells in the host?.
        J Thromb Haemost. 2005; 3: 577-580
        • McMIillan DC
        The systemic inflammation -based Glasgow prognostic score: a decade of experience in patients with cancer.
        Cancer Treat Rev. 2013; 39: 534-540
        • McMIillan DC
        Systemic inflammation, nutritional status and survival in patients with cancer.
        Curr Opin Clin Nutr Metab Care. 2009; 12: 223-226
        • Asakura H
        • Takahashi H
        • Uchiyama T
        • et al.
        DIC subcommittee of the Japanese Society on Thrombosis and Hemostasis. Proposal for new diagnostic criteria for DIC from the Japanese Society on Thrombosis and Hemostasis.
        Thromb J. 2016; 14 (28): 42
        • Fujinami J
        • Ohara T
        • Kitani-Morii F
        • et al.
        Cancer-associated hypercoagulation increases the risk of early recurrent stroke in patients with active cancer.
        Cerebrovasc Dis. 2018; 46: 46-51
        • Harvey RL
        • Roth EJ
        • Yarnold PR
        • et al.
        Deep vein thrombosis in stroke. The use of plasma D-dimer level as a screening test in the rehabilitation setting.
        Stroke. 1996; 27: 1516-1520
        • ten Wolde M
        • Kraaijenhagen RA
        • Prins MH
        • Buller HR
        The clinical usefulness of D-dimer testing in cancer patients with suspected deep venous thrombosis.
        Arch Intern Med. 2002; 162: 1880-1884