Favorable response of pediatric stem cell recipients to human protein C concentrate substitution for veno-occlusive disease

• Published in: Pediatric transplantation 2007-02, Vol.11 (1), p.49-57
• Main Authors: Eber, S. W., Gungor, T., Veldman, A., Sykora, K., Scherer, F., Fischer, D., Grigull, L.
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; beta-Thalassemia - therapy; Biological and medical sciences; bone marrow transplantation; Bone marrow, stem cells transplantation. Graft versus host reaction; chemotherapy; Child; Female; Fibrinolytic Agents - therapeutic use; Humans; Leukemia - therapy; Male; Medical sciences; Neuroblastoma - therapy; Plasminogen Activator Inhibitor 1 - blood; protein C; Protein C - metabolism; Protein C - therapeutic use; Stem Cell Transplantation; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Treatment Failure; Treatment Outcome; Vascular Diseases - drug therapy; Vascular Diseases - therapy; veno-occlusive disease
• ISSN: 1397-3142; 1399-3046
• DOI: 10.1111/j.1399-3046.2006.00612.x

:  Plasminogen activator inhibitor 1 is known to be elevated in patients with hepatic VOD after intensive chemotherapy. To re‐establish endogenous fibrinolysis and to inhibit thrombin formation, we used non‐APC (zymogen) to normalize PAI‐1 levels. As a consequence of thrombin formation inhibition and the consecutive inhibition of the coagulation cascade, this treatment is expected to reduce the elevated D‐dimer level. Six pediatric stem cell recipients with moderate or severe VOD after busulfan or total body irradiation conditioning regimen are reported here who were therapy‐refractory to defibrotide or rt‐PA therapy. All patients had low levels of PC activity (16–39%). The administration of PC (60–240 IU/kg) led to a rapid and sustained rise in PC activity (target level >80%) with near normalization of prothrombin and partial thromboplastin time in all patients. Elevated PAI‐1 levels declined. Five of the six patients showed a good clinical response with prompt resolution of clinical, sonographic, and laboratory signs of hepatic blood flow obstruction, while one patient with severe VOD, as well as concomitant liver GVHD and CMV disease, had a slow but detectable response to PC therapy. All patients survived.