BACKGROUND: Therapeutic use and effective function of recombinant urokinase (r-UK) for occluded ports need the presence of plasminogen. METHODS: As a therapeutic proof of principle, we demonstrate that the use of r-UK and autologous plasma effectively reestablishes the function of occluded central venous ports (CVP) resistant to routine management of catheter occlusion. Five patients with occluded ports resistant to the routine management were treated. RESULTS: All patients were successfully treated with thrombolytic therapy using intraluminal instillation of r-UK and autologous plasma. CONCLUSION: Instillation of r-UK and autologous plasma is a safe and effective method for management of CVP occlusion

Anja Borgmann

D Collen

Georg Seifert

Guenter Henze

Hanno Riess

Karl Seeger

MF Glynn

MR Hurtubise

T Wachs

English

PubMed

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Intraluminal instillation of urokinase and autologous plasma: a method to unblock occluded central venous ports

Abstract Background Therapeutic use and effective function of recombinant urokinase (r-UK) for occluded ports need the presence of plasminogen. Methods As a therapeutic proof of principle, we demonstrate that the use of r-UK and autologous plasma effectively reestablishes the function of occluded central venous ports (CVP) resistant to routine management of catheter occlusion. Five patients with occluded ports resistant to the routine management were treated. Results All patients were successfully treated with thrombolytic therapy using intraluminal instillation of r-UK and autologous plasma. Conclusion Instillation of r-UK and autologous plasma is a safe and effective method for management of CVP occlusion.</p

Henze Guenter

Seeger Karl

Riess Hanno

Seifert Georg

Borgmann Anja

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BioMed CentralBMC Cancer
ssOpen AcceTechnical advance
Intraluminal instillation of urokinase and autologous plasma: a 
method to unblock occluded central venous ports
Georg Seifert*1, Hanno Riess2, Karl Seeger1, Guenter Henze1 and 
Anja Borgmann1
Address: 1Department of Paediatric Oncology/Haematology, Charité – Universitätsmedizin Berlin, Germany and 2Department of Haematology 
and Oncology, Charité – Universitätsmedizin Berlin, Germany
Email: Georg Seifert* - georg.seifert@charite.de; Hanno Riess - hanno.riess@charite.de; Karl Seeger - karl.seeger@charite.de; 
Guenter Henze - guenter.henze@charite.de; Anja Borgmann - anja.borgmann@charite.de
* Corresponding author    
Abstract
Background: Therapeutic use and effective function of recombinant urokinase (r-UK) for
occluded ports need the presence of plasminogen.
Methods: As a therapeutic proof of principle, we demonstrate that the use of r-UK and
autologous plasma effectively reestablishes the function of occluded central venous ports (CVP)
resistant to routine management of catheter occlusion. Five patients with occluded ports resistant
to the routine management were treated.
Results: All patients were successfully treated with thrombolytic therapy using intraluminal
instillation of r-UK and autologous plasma.
Conclusion: Instillation of r-UK and autologous plasma is a safe and effective method for
management of CVP occlusion.
Background
Regular application of plasma products or chemotherapy
is often complicated by catheter-related problems such as
blockage. Especially in children, an effective and simple
reestablishment of catheter patency is important. Mainte-
nance of catheter function is usually achieved with flush-
ing (sodium chloride and/or heparin) or urokinase
instillation [1,2]. In the majority of cases low-dose uroki-
nase therapy is a safe and efficacious treatment for cathe-
ter occlusion, frequently obviating the need for catheter
removal. However, in some cases of occluded central
venous ports (CVP), r-UK instillation is not effective.
Because effective therapeutic function of r-UK requires the
presence of plasminogen (see Figure 1) contained in
human plasma, we combined autologous plasma and r-
UK for treatment of occluded CVP in adult and paediatric
patients.
Methods
Five patients with occluded CVP were treated. Patient
characteristics are given in Table 1. After up to eight
attempts every 15 minutes with drawing and pressing to
remove the CVP occlusion with sodium chloride and/or
heparin and subsequently with 10 mg recombinant tissue
plasminogen activator (r-tPA) and 5.000 IU r-UK, we used
a combination of 2 ml of the patient's plasma and 10.000
IU r-UK (Medac GmbH, Germany) dissolved in 1 ml
sodium chloride. The plasma was obtained by centrifuga-
Published: 24 April 2006
BMC Cancer 2006, 6:103 doi:10.1186/1471-2407-6-103
Received: 10 November 2005
Accepted: 24 April 2006
This article is available from: http://www.biomedcentral.com/1471-2407/6/103
© 2006 Seifert et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), 
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 3
(page number not for citation purposes)
BMC Cancer 2006, 6:103 http://www.biomedcentral.com/1471-2407/6/103tion at 1100 g for 10 minutes in a sterile syringe. Next, the
combination of autologous plasma and r-UK were slowly
mixed for 2 minutes within a 5 ml- syringe before applica-
tion. The combination was slowly instilled, whereby a
volume slightly above the CVP volume was injected.
Thirty minutes after instillation, success was assessed by
attempting to aspirate the combination and residual clot
with an empty, sterile syringe. Up to three further attempts
of aspiration were made. If the aspiration was successful,
the catheter lumen was immediately flushed with 10 ml
sodium chloride and/or heparin. Informed consent was
obtained from patients, and, if necessary, from parents, as
approved by the Institutional Ethical Committee.
Results
We report on five patients with an CVP occlusion that
could not be managed by routine procedures. All patients
had internal jugular CVPs, which had all been implanted
in a surgical unit. The indications for CVP placement were
regular infusion of plasma products, chemotherapy and
antibiotics. We tested the new method described in this
paper as a last resort before catheter replacement. All
instillations resulted in successful reestablishment of cath-
eter function after approximately 60 minutes of uroki-
nase/plasma instillation. No patient experienced adverse
effects during or after instillation. No bleeding complica-
tions occurred. The entire management procedure was
easy to perform and well tolerated. In one case the instil-
lation of urokinase and plasma failed. The explanted CVP
showed that a silicon particle, which had originated dur-
ing puncture, had occluded the CVP.
Fibrinolytic Systemigure 1
Fibrinolytic System.
Table 1: Patient characteristics.
Initials Age (years) Diagnosis Therapy
NK 6 Hemophilia Factor VIII
AH 3 Hemophilia Factor VIII
HR 67 Hepatocellular Carcinoma Fluorouracil, Folic Acid
MA 51 Colon Carcinoma Fluorouracil, Folic Acid
BH 53 Mammary Carcinoma Fluorouracil, DoxorubicinPage 2 of 3
(page number not for citation purposes)
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Discussion
Catheter occlusion is a common complication of long-
term CVP placement. Therapeutic fibrinolytic agents like
r-UK or r-tPA are used successfully to restore function of
occluded CVP [1,2] Generally one or two instillationsof r-
UK are required in the majority of patients. A 98.1% pat-
ency rate is reported when treating catheter occlusions in
paediatric patients with r-UK at a concentration of 5,000
IU/mL [4] However, after repeated applications of plas-
minogen activators, a clot may become deprived of plas-
minogen. This will result in the failure of further attempts.
Conclusion
The method we have described in this paper is useful in
such situations. We were able to avoid catheter replace-
ment in all five patients with thrombotic catheter occlu-
sions that were treated with r-UK and autologous plasma.
This is especially important for children.
Competing interests
The author(s) declare that they have no competing inter-
ests.
Authors' contributions
Georg Seifert was involved in acquisition of data, drafted
the manuscript and has given final approval of the version
to be published.
Hanno Riess was involved in acquisition of data and
made substantial contributions to conception and design
and has given final approval of the version to be pub-
lished.
Karl Seeger was involved in acquisition of data and criti-
cally revised the manuscript and has given final approval
of the version to be published.
Günter Henze critically revised the manuscript and has
given final approval of the version to be published.
Anja Borgmann was involved in acquisition of data and
has given final approval of the version to be published.
Acknowledgements
None
References
1. Glynn MF, Langer B, Jeejeebhoy KN: Therapy for thrombotic
occlusion of long-term intravenous alimentation catheters.
JPEN J Parenter Enteral Nutr 1980, 4:387-390.
2. Hurtubise MR, Bottino JC, Lawson M, McCredie KB: Restoring pat-
ency of occluded central venous catheters.  Arch Surg 1980,
115:212-213.
3. Collen D, Lijnen HR: Thrombolytic agents.  Thromb Haemost 2005,
93:627-630.
4. Wachs T: Urokinase administration in pediatric patients with
occluded central venous catheters.  J Intraven Nurs 1990,
13:100-102.
Pre-publication history
The pre-publication history for this paper can be accessed
here:
http://www.biomedcentral.com/1471-2407/6/103/pre
pubPage 3 of 3
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KB: Restoring patency of occluded central venous catheters. Arch Surg

KN: Therapy for thrombotic occlusion of long-term intravenous alimentation catheters.

Lijnen HR: Thrombolytic agents. Thromb Haemost

Urokinase administration in pediatric patients with occluded central venous catheters.

http://doaj.org/search?source=%7B%22query%22%3A%7B%22bool%22%3A%7B%22must%22%3A%5B%7B%22term%22%3A%7B%22id%22%3A%2288e8b49e58a6474ab066874670bd6728%22%7D%7D%5D%7D%7D%7D

Intraluminal instillation of urokinase and autologous plasma: a method to unblock occluded central venous ports

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