The University of Southampton
University of Southampton Institutional Repository

Use of recombinant tissue plasminogen activator in children with meningococcal purpura fulminans: a retrospective study

Zenz, Werner, Zoehrer, Bettina, Levin, Michael, Fanconi, Sergio, Hatzis, Tassos D., Knight, Geoff, Mullner, Marcus and Faust, Saul N. (2004) Use of recombinant tissue plasminogen activator in children with meningococcal purpura fulminans: a retrospective study Critical Care Medicine, 32, (8), pp. 1777-1780. (doi:10.1097/01.CCM.0000133667.86429.5D).

Record type: Article


Objective: Meningococcal disease causes septic shock with associated disseminated intravascular coagulation and hemorrhagic skin necrosis. In severe cases, widespread vascular thrombosis leads to gangrene of limbs and digits and contributes to morbidity and mortality. Uncontrolled case reports have suggested that thrombolytic therapy may prevent some complications, and the use of tissue plasminogen activator (t-PA) has been widespread. Our aim was to summarize the clinical outcome and adverse effects where systemic t-PA has been used to treat children with fulminant meningococcemia.
Design: International, multiple-center, retrospective, observational case note study between January 1992 and June 2000.
Setting: Twenty-four different hospitals in seven European countries and Australia.
Patients: A total of 62 consecutive infants and children with severe meningococcal sepsis in whom t-PA was used for the treatment of predicted amputations and/or refractory shock (40 to treat severe ischemia, 12 to treat shock, and ten to treat both).
Interventions: t-PA was administered with a median dose of 0.3 mg[middle dot]kg-1[middle dot]hr-1 (range, 0.008-1.13) and a median duration of 9 hrs (range, 1.2-83).
Main Results: Twenty-nine of 62 patients died (47%; 95% confidence interval, 28-65). Seventeen of 33 survivors had amputations (11 below knee/elbow or greater loss; six less severe). In 12 of 50 patients to whom t-PA was given for imminent amputation, no amputations were observed. Five developed intracerebral hemorrhages (five of 62, 8%; 95% confidence interval, 0.5-16). Of these five, three died, one developed a persistent hemiparesis, and one recovered completely.
Conclusions: The high incidence of intracerebral hemorrhage in our study raises concerns about the safety of t-PA in children with fulminant meningococcemia. However, due to the absence of a control group in such a severe subset of patients, whether t-PA is beneficial or harmful cannot be answered from the unrestricted use of the drug that is described in this report. Our experience highlights the need to avoid strategies that use experimental drugs in an uncontrolled fashion and to participate in multiple-center trials, which are inevitably required to study rare diseases.

PDF 40619.pdf - Version of Record
Restricted to Repository staff only
Download (749kB)

More information

Published date: August 2004


Local EPrints ID: 40619
ISSN: 0090-3493
PURE UUID: 1ed81df6-f7bb-4811-94e4-0315417f22dc
ORCID for Saul N. Faust: ORCID iD

Catalogue record

Date deposited: 07 Jul 2006
Last modified: 16 Apr 2017 21:51

Export record



Author: Werner Zenz
Author: Bettina Zoehrer
Author: Michael Levin
Author: Sergio Fanconi
Author: Tassos D. Hatzis
Author: Geoff Knight
Author: Marcus Mullner
Author: Saul N. Faust ORCID iD

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton:

ePrints Soton supports OAI 2.0 with a base URL of

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.