Elevated factor VIII and von Willebrand factor levels predict unfavorable outcome in stroke patients treated with intravenous thrombolysis

Noémi Klára Tóth, Edina Gabriella Székely, Katalin Réka Czuriga-Kovács, Ferenc Sarkady, Orsolya Nagy, Levente István Lánczi, Ervin Berényi, Klára Fekete, I. Fekete, L. Csiba, Z. Bagoly

Research output: Contribution to journalArticle

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Abstract

Introduction: Plasma factor VIII (FVIII) and von Willebrand factor (VWF) levels have been associated with the rate and severity of arterial thrombus formation and have been linked to outcomes following thrombolytic therapy in acute myocardial infarction patients. Here, we aimed to investigate FVIII and VWF levels during the course of thrombolysis in acute ischemic stroke (AIS) patients and to find out whether they predict long-term outcomes. Materials and methods: Study population included 131 consecutive AIS patients (median age: 69 years, 60.3% men) who underwent i.v. thrombolysis with recombinant tissue plasminogen activator (rt-PA). Blood samples were taken on admission, 1 and 24 h after rt-PA administration to measure FVIII activity and VWF antigen levels. Neurological deficit of patients was determined according to the National Institutes of Health Stroke Scale (NIHSS). ASPECT scores were assessed using computer tomography images taken before and 24 h after thrombolysis. Intracranial hemorrhage was classified according to the European Cooperative Acute Stroke Study (ECASS) II criteria. Long-term functional outcome was determined at 90 days after the event by the modified Rankin scale (mRS). Results: VWF levels on admission were significantly elevated in case of more severe AIS [median and IQR values: NIHSS < 6:189.6% (151.9-233.2%); NIHSS 6-16: 199.6% (176.4-250.8%); NIHSS >16: 247.8% (199.9-353.8%), p = 0.013]; similar, but non-significant trend was observed for FVIII levels. FVIII and VWF levels correlated well on admission (r = 0.748, p < 0.001) but no significant correlation was found immediately after thrombolysis (r = 0.093, p = 0.299), most probably due to plasmin-mediated FVIII degradation. VWF levels at all investigated occasions and FVIII activity before and 24 h after thrombolysis were associated with worse 24 h post-lysis ASPECT scores. In a binary backward logistic regression analysis including age, gender, high-sensitivity C-reactive protein, active smoking, diabetes, and NIHSS > 5 on admission, elevated FVIII and VWF levels after thrombolysis were independently associated with poor functional outcomes (mRS = 3) at 90 days (immediately after thrombolysis: FVIII: OR: 7.10, 95% CI: 1.77-28.38, p = 0.006, VWF: OR: 6.31, 95% CI: 1.83-21.73, p = 0.003; 24 h after thrombolysis: FVIII: OR: 4.67, 95% CI: 1.42-15.38, p = 0.011, VWF: OR: 19.02, 95% CI: 1.94-186.99, p = 0.012). Conclusion: Elevated FVIII activity and VWF antigen levels immediately after lysis and at 24 h post-therapy were shown to have independent prognostic values regarding poor functional outcomes at 90 days.

Original languageEnglish
Article number721
JournalFrontiers in Neurology
Volume8
Issue numberJAN
DOIs
Publication statusPublished - Jan 23 2018

Fingerprint

Stroke
Factor VIII
von Willebrand Factor
National Institutes of Health (U.S.)
Tissue Plasminogen Activator
Intracranial Hemorrhages
Thrombolytic Therapy
factor VIII, von Willebrand factor drug combination
Thrombosis
Myocardial Infarction
Tomography
Population
Von Willebrand antigen
Therapeutics

Keywords

  • Acute ischemic stroke
  • Factor VIII
  • Intracerebral hemorrhage
  • Therapy outcome
  • Thrombolysis
  • Von Willebrand factor

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Elevated factor VIII and von Willebrand factor levels predict unfavorable outcome in stroke patients treated with intravenous thrombolysis. / Tóth, Noémi Klára; Székely, Edina Gabriella; Czuriga-Kovács, Katalin Réka; Sarkady, Ferenc; Nagy, Orsolya; Lánczi, Levente István; Berényi, Ervin; Fekete, Klára; Fekete, I.; Csiba, L.; Bagoly, Z.

In: Frontiers in Neurology, Vol. 8, No. JAN, 721, 23.01.2018.

Research output: Contribution to journalArticle

Tóth, Noémi Klára ; Székely, Edina Gabriella ; Czuriga-Kovács, Katalin Réka ; Sarkady, Ferenc ; Nagy, Orsolya ; Lánczi, Levente István ; Berényi, Ervin ; Fekete, Klára ; Fekete, I. ; Csiba, L. ; Bagoly, Z. / Elevated factor VIII and von Willebrand factor levels predict unfavorable outcome in stroke patients treated with intravenous thrombolysis. In: Frontiers in Neurology. 2018 ; Vol. 8, No. JAN.
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abstract = "Introduction: Plasma factor VIII (FVIII) and von Willebrand factor (VWF) levels have been associated with the rate and severity of arterial thrombus formation and have been linked to outcomes following thrombolytic therapy in acute myocardial infarction patients. Here, we aimed to investigate FVIII and VWF levels during the course of thrombolysis in acute ischemic stroke (AIS) patients and to find out whether they predict long-term outcomes. Materials and methods: Study population included 131 consecutive AIS patients (median age: 69 years, 60.3{\%} men) who underwent i.v. thrombolysis with recombinant tissue plasminogen activator (rt-PA). Blood samples were taken on admission, 1 and 24 h after rt-PA administration to measure FVIII activity and VWF antigen levels. Neurological deficit of patients was determined according to the National Institutes of Health Stroke Scale (NIHSS). ASPECT scores were assessed using computer tomography images taken before and 24 h after thrombolysis. Intracranial hemorrhage was classified according to the European Cooperative Acute Stroke Study (ECASS) II criteria. Long-term functional outcome was determined at 90 days after the event by the modified Rankin scale (mRS). Results: VWF levels on admission were significantly elevated in case of more severe AIS [median and IQR values: NIHSS < 6:189.6{\%} (151.9-233.2{\%}); NIHSS 6-16: 199.6{\%} (176.4-250.8{\%}); NIHSS >16: 247.8{\%} (199.9-353.8{\%}), p = 0.013]; similar, but non-significant trend was observed for FVIII levels. FVIII and VWF levels correlated well on admission (r = 0.748, p < 0.001) but no significant correlation was found immediately after thrombolysis (r = 0.093, p = 0.299), most probably due to plasmin-mediated FVIII degradation. VWF levels at all investigated occasions and FVIII activity before and 24 h after thrombolysis were associated with worse 24 h post-lysis ASPECT scores. In a binary backward logistic regression analysis including age, gender, high-sensitivity C-reactive protein, active smoking, diabetes, and NIHSS > 5 on admission, elevated FVIII and VWF levels after thrombolysis were independently associated with poor functional outcomes (mRS = 3) at 90 days (immediately after thrombolysis: FVIII: OR: 7.10, 95{\%} CI: 1.77-28.38, p = 0.006, VWF: OR: 6.31, 95{\%} CI: 1.83-21.73, p = 0.003; 24 h after thrombolysis: FVIII: OR: 4.67, 95{\%} CI: 1.42-15.38, p = 0.011, VWF: OR: 19.02, 95{\%} CI: 1.94-186.99, p = 0.012). Conclusion: Elevated FVIII activity and VWF antigen levels immediately after lysis and at 24 h post-therapy were shown to have independent prognostic values regarding poor functional outcomes at 90 days.",
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TY - JOUR

T1 - Elevated factor VIII and von Willebrand factor levels predict unfavorable outcome in stroke patients treated with intravenous thrombolysis

AU - Tóth, Noémi Klára

AU - Székely, Edina Gabriella

AU - Czuriga-Kovács, Katalin Réka

AU - Sarkady, Ferenc

AU - Nagy, Orsolya

AU - Lánczi, Levente István

AU - Berényi, Ervin

AU - Fekete, Klára

AU - Fekete, I.

AU - Csiba, L.

AU - Bagoly, Z.

PY - 2018/1/23

Y1 - 2018/1/23

N2 - Introduction: Plasma factor VIII (FVIII) and von Willebrand factor (VWF) levels have been associated with the rate and severity of arterial thrombus formation and have been linked to outcomes following thrombolytic therapy in acute myocardial infarction patients. Here, we aimed to investigate FVIII and VWF levels during the course of thrombolysis in acute ischemic stroke (AIS) patients and to find out whether they predict long-term outcomes. Materials and methods: Study population included 131 consecutive AIS patients (median age: 69 years, 60.3% men) who underwent i.v. thrombolysis with recombinant tissue plasminogen activator (rt-PA). Blood samples were taken on admission, 1 and 24 h after rt-PA administration to measure FVIII activity and VWF antigen levels. Neurological deficit of patients was determined according to the National Institutes of Health Stroke Scale (NIHSS). ASPECT scores were assessed using computer tomography images taken before and 24 h after thrombolysis. Intracranial hemorrhage was classified according to the European Cooperative Acute Stroke Study (ECASS) II criteria. Long-term functional outcome was determined at 90 days after the event by the modified Rankin scale (mRS). Results: VWF levels on admission were significantly elevated in case of more severe AIS [median and IQR values: NIHSS < 6:189.6% (151.9-233.2%); NIHSS 6-16: 199.6% (176.4-250.8%); NIHSS >16: 247.8% (199.9-353.8%), p = 0.013]; similar, but non-significant trend was observed for FVIII levels. FVIII and VWF levels correlated well on admission (r = 0.748, p < 0.001) but no significant correlation was found immediately after thrombolysis (r = 0.093, p = 0.299), most probably due to plasmin-mediated FVIII degradation. VWF levels at all investigated occasions and FVIII activity before and 24 h after thrombolysis were associated with worse 24 h post-lysis ASPECT scores. In a binary backward logistic regression analysis including age, gender, high-sensitivity C-reactive protein, active smoking, diabetes, and NIHSS > 5 on admission, elevated FVIII and VWF levels after thrombolysis were independently associated with poor functional outcomes (mRS = 3) at 90 days (immediately after thrombolysis: FVIII: OR: 7.10, 95% CI: 1.77-28.38, p = 0.006, VWF: OR: 6.31, 95% CI: 1.83-21.73, p = 0.003; 24 h after thrombolysis: FVIII: OR: 4.67, 95% CI: 1.42-15.38, p = 0.011, VWF: OR: 19.02, 95% CI: 1.94-186.99, p = 0.012). Conclusion: Elevated FVIII activity and VWF antigen levels immediately after lysis and at 24 h post-therapy were shown to have independent prognostic values regarding poor functional outcomes at 90 days.

AB - Introduction: Plasma factor VIII (FVIII) and von Willebrand factor (VWF) levels have been associated with the rate and severity of arterial thrombus formation and have been linked to outcomes following thrombolytic therapy in acute myocardial infarction patients. Here, we aimed to investigate FVIII and VWF levels during the course of thrombolysis in acute ischemic stroke (AIS) patients and to find out whether they predict long-term outcomes. Materials and methods: Study population included 131 consecutive AIS patients (median age: 69 years, 60.3% men) who underwent i.v. thrombolysis with recombinant tissue plasminogen activator (rt-PA). Blood samples were taken on admission, 1 and 24 h after rt-PA administration to measure FVIII activity and VWF antigen levels. Neurological deficit of patients was determined according to the National Institutes of Health Stroke Scale (NIHSS). ASPECT scores were assessed using computer tomography images taken before and 24 h after thrombolysis. Intracranial hemorrhage was classified according to the European Cooperative Acute Stroke Study (ECASS) II criteria. Long-term functional outcome was determined at 90 days after the event by the modified Rankin scale (mRS). Results: VWF levels on admission were significantly elevated in case of more severe AIS [median and IQR values: NIHSS < 6:189.6% (151.9-233.2%); NIHSS 6-16: 199.6% (176.4-250.8%); NIHSS >16: 247.8% (199.9-353.8%), p = 0.013]; similar, but non-significant trend was observed for FVIII levels. FVIII and VWF levels correlated well on admission (r = 0.748, p < 0.001) but no significant correlation was found immediately after thrombolysis (r = 0.093, p = 0.299), most probably due to plasmin-mediated FVIII degradation. VWF levels at all investigated occasions and FVIII activity before and 24 h after thrombolysis were associated with worse 24 h post-lysis ASPECT scores. In a binary backward logistic regression analysis including age, gender, high-sensitivity C-reactive protein, active smoking, diabetes, and NIHSS > 5 on admission, elevated FVIII and VWF levels after thrombolysis were independently associated with poor functional outcomes (mRS = 3) at 90 days (immediately after thrombolysis: FVIII: OR: 7.10, 95% CI: 1.77-28.38, p = 0.006, VWF: OR: 6.31, 95% CI: 1.83-21.73, p = 0.003; 24 h after thrombolysis: FVIII: OR: 4.67, 95% CI: 1.42-15.38, p = 0.011, VWF: OR: 19.02, 95% CI: 1.94-186.99, p = 0.012). Conclusion: Elevated FVIII activity and VWF antigen levels immediately after lysis and at 24 h post-therapy were shown to have independent prognostic values regarding poor functional outcomes at 90 days.

KW - Acute ischemic stroke

KW - Factor VIII

KW - Intracerebral hemorrhage

KW - Therapy outcome

KW - Thrombolysis

KW - Von Willebrand factor

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