The Role of Factor XIII Activation Peptide and D-dimer Values for the Diagnosis of Cerebral Venous Thrombosis (CVT)

The Role of Factor XIII Activation Peptide and D-dimer Values for the Diagnosis of Cerebral Venous Thrombosis

The investigators aim to assess the overall accuracy of D-dimer values and FXIII activation peptide (FXIII-AP), using a newly developed ELISA test, to exclude CVT in patients with clinical suspicion of CVT.

Study Overview

• Status: Completed
• Conditions: Cerebral Venous Thrombosis
• Intervention / Treatment: Other: ELISA Test

Detailed Description

Background

Because of the broad clinical spectrum it is often difficult to establish the diagnosis of cerebral venous thrombosis (CVT). Combined MRI/MRV and contrast-enhanced CT are the most accurate methods for diagnosis of CVT. However these methods are often not available on an emergency basis. This stresses the need for additional widely available tests such as coagulation markers to exclude CVT. The diagnostic value of D-dimer levels for the exclusion of CVT is still under debate. Other potential coagulation markers have not been systematically investigated. The investigators aim to assess the overall accuracy of D-dimer values and FXIII activation peptide (FXIII-AP), using a newly developed ELISA test, to exclude CVT in patients with clinical suspicion of CVT. Consecutive patients with clinical suspicion of CVT at the emergency department of the University Hospital Bern will be included in this study over a two year period. All included patients will receive standard care applied by the treating physician who will follow international recommendations. Patient involvement in the study shall not influence any treatment decision. On admission patients will undergo a complete diagnostic work-up, including a clinical neurological examination, standard laboratory examination including D-dimer values, and brain contrast CT and/or MRI/MRV. In addition, plasma FXIII-AP will be analyzed. FXIII-AP will be analyzed at the Hemostasis Research Laboratory, Department of Hematology, University of Bern, based on a newly developed highly sensitive and specific ELISA method. The investigators will be blinded for the clinical symptoms and diagnosis of the patient. The study will be conducted according to the guidelines of the STARD (Standards for Reporting Diagnostic Accuracy) initiative.

The following primary evaluation criteria will be analysed:1) The overall diagnostic accuracy of FXIII-AP to exclude CVT in patients with clinical suspicion of CVT; 2) The overall diagnostic accuracy of D-dimer to exclude CVT in patients with clinical suspicion of CVT; 3) Roc curves will be calculated.

Prespecified subgroup analyses will be performed according to the clinical presentation: 1) isolated headache; 2) isolated intracranial hypertension (headache and papilledema); 3) Focal neurological deficits and/or seizures and/or disturbances of consciousness. Furthermore, prespecified subgroup analyses will be performed according to modes of onset: 1) acute (symptoms < 48 hours duration); 2) subacute (symptoms > 48 hours and < 7 days duration); 3) chronic (symptoms > 7 days duration).

The following secondary evaluation criteria will be assessed: 1) The overall frequency of CVT in patients with clinical suspicion of CVT; 2) The overall frequency of other diseases in patients with clinical suspicion of CVT; 3) The site of involved veins and sinus in patients with CVT.

Objective

The investigators aim to assess the overall accuracy of D-dimer values and FXIII activation peptide (FXIII-AP), using a newly developed ELISA test, to exclude CVT in patients with clinical suspicion of CVT.

Methods

Consecutive patients with clinical suspicion of CVT at the emergency department of the University Hospital Bern will be included in this study over a two year period. All included patients will receive standard care applied by the treating physician who will follow international recommendations. D-dimer measurement at entry will be performed using a rapid sensitive assay. FXIII-AP will be analyzed at the Hemostasis Research Laboratory, Department of Hematology, University of Bern based on a highly sensitive and specific ELISA method.The investigators will be blinded for the clinical symptoms and diagnosis of the patient.

• Study Type: Observational
• Enrollment (Actual): 401

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1100
    • Department of Neurology, Academic Medical Centre, University of Amsterdam
• Switzerland
  • Bern, Switzerland, 3010
    • Dep. of Neurology, Bern University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Consecutive patients with clinical suspicion of CVT at the emergency department of the University Hospital (tertiary care clinic)

Description

Inclusion Criteria:

• Adults with clinical suspicion of CVT
• Isolated unexplained headache of less than 30 days duration
• Headache associated with focal central neurological deficits of less than 30 days duration
• Headache associated with disturbed consciousness of less than 30 days duration
• Headache associated with epileptic seizures of less than 30 days duration
• Unexplained papilledema of less than 30 days duration

Exclusion Criteria

• Deep venous thrombosis within 3 months prior to admission
• Pulmonary embolism within 3 months prior to admission
• Ischemic stroke within 3 months prior to admission
• Myocardial infarction within 3 months prior to admission
• Other vascular disease within 3 months prior to admission
• Headache due to trauma
• Malignant neoplasia
• Treatment with anticoagulants prior to admission

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1; Patients with clinical suspicion of CVT	Other: ELISA Test; assess the overall accuracy of D-dimer values and FXIII activation peptide (FXIII-AP), using a newly developed ELISA test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The overall diagnostic accuracy of FXIII-AP an D-dimer to exclude CVT in patients with clinical suspicion of CVT	at hospital entry

Secondary Outcome Measures

Outcome Measure	Time Frame
The overall frequency of CVT in patients with clinical suspicion of CVT	at hospital entry
The overall frequency of other diseases in patients with clinical suspicion of CVT	at hospital entry
The site of involved veins and sinus in patients with CVT	at hospital entry

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Collaborators: Schweizerische Herzstiftung
• Investigators: Principal Investigator: Marcel Arnold, MD Prof., Dep. of Neurology, Bern University Hospital

Publications and helpful links

General Publications

• Heldner MR, Zuurbier SM, Li B, Von Martial R, Meijers JCM, Zimmermann R, Volbers B, Jung S, El-Koussy M, Fischer U, Kohler HP, Schroeder V, Coutinho JM, Arnold M. Prediction of cerebral venous thrombosis with a new clinical score and D-dimer levels. Neurology. 2020 Aug 18;95(7):e898-e909. doi: 10.1212/WNL.0000000000009998. Epub 2020 Jun 23.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2009
• Primary Completion (Actual): December 31, 2017
• Study Completion (Actual): December 31, 2017

Study Registration Dates

• First Submitted: June 15, 2009
• First Submitted That Met QC Criteria: June 18, 2009
• First Posted (Estimate): June 19, 2009

Study Record Updates

• Last Update Posted (Actual): October 12, 2018
• Last Update Submitted That Met QC Criteria: October 11, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: stroke; coagulation; cerebral venous thrombosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Venous Thrombosis
• Other Study ID Numbers: 112/09