*Evaluation of biomarkers in VTE study with capillary blood sample; the EVA-II study*

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are two manifestations
of Venous Thrombo-Embolism (VTE), is the third most common cause of
cardiovascular death, after myocardial infarction and stroke, and has an annual
incidence rate of about 1 per 1000 person-years in general population. Rapid
diagnosis and treatment of VTE is important to the restrict disease progression
and to lower the risk of fatal events.
The GP cannot trust on patient history, symptoms and signs for diagnosis, for
signs and symptoms can be non-specific and frequently nearly absent, e.g.
mimicking a simple leg or respiratory tract infection.
Therefore, the use of a Clinical Decision Rule (CDR) score combined with a
D-dimer test in primary care is recommended. However, referral for imaging in a
hospital setting is only recommended for those with a high CDR score, as well
as those with a positive D-dimer test (regardless of the CDR-score). This
approach is validated as a safe diagnostic strategy in suspected patients to
refrain from referring nearly half of the patients and is written in current
guidelines.
Very recently, novel Point-of-Care test devices have been introduced using a
blood sample from a finger prick enabling appropriate use in GP practice. An
additional advantage is that different frequently-ordered tests in primary care
can be carried out on the same device (CRP, HbA1c etc).

Plasma samples of five devices under study have already been compared with a
routine laboratory assay, STA-R Max, by the members of our study group (the EVA
study). Results of POC measurements have been shown to be comparable with the
routine laboratory results. Before these devices can be introduced for usage in
GP practice, validation of the sensitive D-dimer test using whole blood drawn
by a finger prick procedure in primary care setting is needed.

The primary objective of this study is an analytic validation of D-dimer tests
with capillary whole blood of five different, recently introduced POC
laboratory devices compared with a central routine lab D-dimer assay. Secondary
objective is a clinical validation according to VTE diagnosis, as a Gold
Standard is lacking for D-dimer measurement.

Prospective cohort study in patients suspected of having a VTE who are referred
to a laboratory for a lab D-dimer testing. After written Informed Consent, an
additional blood sample will be extracted from the venipuncture that will be
used for routine D-dimer testing in order to prepare plasma for a central
D-dimer measurement at the Jeroen Bosch Hospital at *s-Hertogenbosch. In
addition, a POC D-dimer test will be done using a capillary blood sample drawn
from a finger prick.
Three months after the blood draw, the GP will be enquired for the diagnosis of
the anonymized patient. The experimental intervention under study is limited to
a 11 mL blood draw in addition to the routine-care blood sample drawn from the
same venipuncture, and a POC D-dimer test using capillary blood drawn from a
finger prick.
For each different POC device, 70 patients will undergo additional testing,
which amounts to 5 x 70 = 350 patients in total.
Inclusion period will consist of 2 months at 10 laboratories with a follow-up
of 3 months.

There is a minimal burden and risk for patients participating in the study, as
the only intervention is to take an additional blood sample of 11 mL from the
same venipuncture as a regular D-dimer test. Patient management will be
completely guided by care as usual and current guidelines under responsibility
of the treating physician.

Het kost de patiënt 20 minutes extra tijd en het risico bij een capillaire
bloedafname is nihiel.