The Role of Factor XIII Activation Peptide and D-dimer Values for the Diagnosis of Cerebral Venous Thrombosis (CVT)
Condition: Cerebral Venous Thrombosis
MeSH terms: Thrombosis; Venous Thrombosis
Study type: Observational

Summary: 
      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.
    

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.
    

Intervention name(s): ELISA Test
Intervention type(s): Other
Intervention description(s): assess the overall accuracy of D-dimer values and FXIII activation peptide (FXIII-AP), using a newly developed ELISA test
Observational model: Case-Only
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Consecutive patients with clinical suspicion of CVT at the emergency department of the
        University Hospital (tertiary care clinic)
      
Keywords: cerebral venous thrombosis; stroke; coagulation