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Thromb Haemost 2016; 116(01): 58-68
DOI: 10.1160/TH15-10-0786
Coagulation and Fibrinolysis
Schattauer GmbH

Efficacy and safety of protein C concentrate to treat purpura fulminans and thromboembolic events in severe congenital protein C deficiency

Marilyn J. Manco-Johnson
1   Children’s Hospital Colorado and the University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
,
Lisa Bomgaars
2   Baylor College of Medicine, Texas Children’s Hospital Hematology Center, Texas Children’s Hospital, Houston, Texas, USA
,
Joseph Palascak
3   University of Cincinnati, Hemophilia Treatment Center, Cincinnati, Ohio, USA
,
Amy Shapiro
4   Indiana Hemophilia & Thrombosis Center, Indianapolis, Indiana, USA
,
John Geil
5   |University of Kentucky Chandler Medical Center, Lexington, Kentucky, USA
,
Sandor Fritsch
6   Baxalta Innovations GmbH, Vienna, Austria
,
Borislava G. Pavlova
6   Baxalta Innovations GmbH, Vienna, Austria
,
David Gelmont
7   Baxalta US Inc., Westlake Village, California, USA
› Author Affiliations Financial support: This study was funded by Baxalta US, Inc.
Further Information

Publication History

Received: 09 October 2015

Accepted after major revision: 27 March 2016

Publication Date:
27 November 2017 (online)

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Summary

Severe congenital protein C (PC) deficiency (SCPCD) is associated with disseminated intravascular coagulation (DIC), purpura fulminans (PF), and vascular thromboembolic events (TE), often leading to organ failure and death. PC replacement therapy offers a safe, effective treatment for thromboembolic complications of SCPCD and secondary prophylaxis for recurrent DIC, PF, and TEs. A prospective, multi-centre, open-label, phase 2/3 study was conducted to demonstrate the safety and efficacy of protein C concentrate for treatment of PF and acute TEs. Fifteen enrolled patients with SCPCD received protein C concentrate; 11 received treatment for acute TEs (PF, 18 events; PF and other coumarin-related vascular thromboembolic events [coumarin-induced skin necrosis; CISN], 1 event; venous thrombosis, 5 events). Predefined efficacy criteria for treatment of acute TEs were compared with a historical control arm (i. e. patients receiving conventional therapy without protein C replacement). PF/CISN was demonstrated by pre-defined primary and secondary efficacy ratings. Primary ratings of protein C concentrate–treated episodes were significantly higher (p=0.0032) than in the historical control. For 19 PF/CISN episodes in 11 patients, 94.7 % of treatments were rated effective and 5.3 % effective with complications (not related to protein C concentrate). In a secondary efficacy rating, all treatments were rated effective (68.4 % excellent; 21.1 % good; 10.5 % fair). For 5/24 vascular thrombosis episodes, 80 % of treatments were rated excellent and 20 % were rated good. No treatment-related adverse events or serious adverse events occurred. In conclusion, protein C concentrate provides an efficacious, safe treatment for PF, CISN, and other TEs in SCPCD patients.

Keywords

Disseminated intravascular coagulation - protein C deficiency - congenital thrombotic disease due to protein C deficiency - purpura fulminans - therapeutics

 

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