Urine prothrombin fragments (F1+2) as a diagnostic tool for arterial and venous thrombosis

The diagnosis of a thrombotic event, either an arterial or venous thrombosis,
is often made in the event of a high clinical probability in combination with
positive results of blood tests and imaging techniques which confirm the
clinical suspicion.1-3
Individuals in whom thrombotic events are suspected immediately face invasive
diagnostic tests to exclude and/ or confirm the possibility of thrombotic
events.
However if a diagnostic tool could be developed to exclude thrombotic events in
a relatively less invasive, inexpensive and patient friendly manner, both the
patient as well as the national health care system could potentially benefit.
Furthermore urine testing (especially 24 hour measurements) to date have proven
to have more diagnostic accuracy compared to plasma samples which tend to
fluctuate in time (e.g endocrine parameters).4
To date thrombin generation markers, particularly ddimer, are routinely used as
part of the work-up of venous thrombo-embolism (VTE). Previously these markers
were also shown to reliably predict the risk of both myocardial infarction (MI)
and stroke. 5,6
Recently levels of prothrombin fragments, F1+2 were assessed in urine samples
of patients who had undergone a total hip replacement surgery. Blood sampling
took place prior to surgery and 3 days after the surgery. Increased urine F1+2
levels, were seen in patients who postoperatively suffered from deep vein
thrombosis, whereas low levels of F1+2 were seen in individuals who suffered
from bleeding complications after surgery. 7
Urine prothrombin fragments, like plasma prothrombin fragments, reflect the
presence of thrombin generation, and could potentially replace blood sampling
in patients with a suspicion of thrombotic events. Since Prothrombin is a
marker of thrombin generation and is increased in the event of thrombotic
events. Since prothrombin fragments F1+2 are excreted in the urine they can
reliably be measured in a urine sample.
We hypothesize that prothrombin fragments in urine can be used to exclude
thrombotic events in patients suspected of venous or arterial thrombotic events

Primary objective: To investigate whether urine prothrombin fragments are
increased in individuals suffering from VTE (i.e. PE or DVT) or a myocardial
infarction compared to healthy matched controls.
Secondary objective: to investigate whether increased levels of urine F1+2
coincide with increased plasma levels of d-dimer and F1+2 in case of VTE and
increased levels of troponine T, CKMB, d-dimer and F1+2 in plasma samples in
case of MI.

This study has a cross-sectional design and will include 20 patients, aged 18
years and older with an objectively proven diagnosis of VTE (DVT or PE) and 20
patients with objectified diagnosis of MI. Furthermore 20 healthy volunteers
will serve as control subjects. The patients will be enrolled at the department
of vascular medicine of the Academic Medical Centre and the departments of
Internal medicine and Cardiology of the Slotervaart Hospital in Amsterdam after
informed consent has been obtained.
A urine sample will be obtained within 48 hours after the diagnosis has been
made in which urine levels of microalbimun and creatinin as well as urine
d-dimer and F1+2 levels will be determined. Simultaneously a blood sample will
be obtained also within 48 hours after diagnosis has been made in which the
d-dimer, and F1+2 levels will be determined. All other medical procedures such
as imaging, blood sampling and treatment will be performed according to routine
medical care.
The duration of the study be approximately 1 year or until a sufficient amount
of participants has been reached.

The study does not carry much risk, the only burden may be time consumption
which is in proportion to the potential value of the study for the researchers.
No personal benefit can be obtained by participants of the study.