Hindawi Publishing Corporation
Thrombosis
Volume 2011, Article ID 150750, 6 pages
doi:10.1155/2011/150750
Research Article
Urinary Prothrombin Fragment 1+2 in relation to
Development of Non-Symptomatic and Symptomatic Venous
Thromboembolic Events following Total Knee Replacement
Lars C. Borris,
1
Morten Breindahl,
2
Michael R. Lassen,
3
and
´
Akos F. Pap
4
1
Department of Orthopaedics,
˚
Arhus University Hospital, Nørrebrogade 44, 8000
˚
Arhus C, Denmark
2
Neonatalklinikken GN5023, Rigshospitalet, Blegdamsvej 9, 2100 København, Denmark
3
Department of Orthopaedics, Nordsjællands Hospital Hørsholm, Usserød Kongevej 102, 2970 Hørsholm, Denmark
4
Bayer HealthCare AG, Aprather Weg 18a, 42096 Wuppertal, Germany
Correspondence should be addressed to Lars C. Borris, larsborr@rm.dk
Received 12 November 2010; Accepted 16 February 2011
Academic Editor: David H. Farrell
Copyright © 2011 Lars C. Borris et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Prothrombin fragment 1+2 is excreted in urine (uF1+2) as a result of in vivo thrombin generation and can be a marker of
coagulation status after an operative procedure. This study compared uF1+2 levels in patients with symptomatic and non-
symptomatic venous thromboembolism (VTE) after total knee replacement (TKR) and in event-free sex- and age-matched
controls. Significantly higher median uF1+2 levels were seen in the VTE patients on days 1, 3, and the day of venography (mostly
day 7) after TKR compared with controls. The uF1+2 levels tended to be high in some patients with symptomatic VTE; however,
the discriminatory efficacy of the test could not be evaluated. In conclusion, this study showed that patients with VTE tend to have
significantly higher uF1+2 levels compared with patients without events between days 1 and 7 after TKR surgery. Measurement of
uF1+2 could provide a simple, non-invasive clinical test to identify patients at risk of VTE.
1. Introduction
Venous thromboembolism (VTE) is a common consequence
of orthopaedic surgery and occurs more frequently after total
knee replacement (TKR) than after total hip replacement
(THR) [1]. Anticoagulation therapy is recommended in
the perioperative period, although the optimal duration of
treatment and the optimal timing of the first dose remain
unresolved [1]. Patients at high risk of VTE will benefit from
appropriate thromboprophylaxis after hospital discharge [1].
Therefore, a non-invasive clinical test would be a valuable
tool for surgeons to identify the TKR patients who are
specifically at a risk of venous thromboembolic events.
During the conversion of prothrombin to thrombin,
the prothrombin fragment 1+2 (F1+2, molecular weight
∼31,000 D [2]) is formed as a by-product [3]. Therefore,
the coagulation status can be determined by measuring
F1+2 levels in plasma [4, 5]. Due to its molecular size,
F1+2 is excreted in urine (uF1+2). It has previously been
reported that measurements of uF1+2 by an enzyme-
linked immunosorbent assay (ELISA) can be used to iden-
tify patients at risk for symptomatic and asymptomatic
VTE and symptomatic arterial vascular events after THR
[6, 7]. Furthermore, in patients who experienced bleeding
complications after THR, a significantly less pronounced
coagulation response with low median uF1+2 levels was seen
in the postoperative period compared with sex- and age-
matched control patients and THR patients with venous
thromboembolic events [7].
The present study was performed to assess whether
measurements of uF1+2 would also be useful in patients
undergoing TKR to differentiate between patients who are
at risk for VTE or bleeding. This study showed that patients
with VTE tend to have significantly higher uF1+2 levels when
compared with patients without events between days 1 and 7
after TKR surgery.