S J Thorpe1, B J Fox, C D Dolman, J Lawrence, R Thorpe. 1. Division of Haematology, National Institute for Biological Standards and Control, Potters Bar, Herts., UK. sthorpe@nibsc.ac.uk
Abstract
BACKGROUND AND OBJECTIVES: The presence of anti-Rh D in intravenous immunoglobulin (IVIG) products has been claimed to be associated with adverse reactions in recipients. There is currently no regulatory specification to control the level of anti-D in IVIG products and it is unclear what this should be. Two reports of haemolysis occurring in recipients of IVIG manufactured from US plasma provided a rare opportunity to investigate whether high anti-D levels could have induced the haemolysis. MATERIALS AND METHODS: We developed a direct microtitre plate haemagglutination method suitable for screening IVIG products and starting plasma pools for haemagglutinating activity. RESULTS: Of 101 batches of IVIG tested, six were found to contain specific anti-D. Four of these batches had anti-D titres ranging from 64 to 256 (including the two batches each associated with a report of haemolysis) and could be linked, in each case, to a starting plasma pool also positive for anti-D. CONCLUSIONS: Our results show that IVIG products can contain appreciable anti-D levels. To avoid potential problems in recipients, we propose an anti-D titre of 8 as the maximum permissible limit of anti-D in IVIG products for batch acceptance and release. The availability of a reference preparation is essential for control of this proposed requirement.
BACKGROUND AND OBJECTIVES: The presence of anti-Rh D in intravenous immunoglobulin (IVIG) products has been claimed to be associated with adverse reactions in recipients. There is currently no regulatory specification to control the level of anti-D in IVIG products and it is unclear what this should be. Two reports of haemolysis occurring in recipients of IVIG manufactured from US plasma provided a rare opportunity to investigate whether high anti-D levels could have induced the haemolysis. MATERIALS AND METHODS: We developed a direct microtitre plate haemagglutination method suitable for screening IVIG products and starting plasma pools for haemagglutinating activity. RESULTS: Of 101 batches of IVIG tested, six were found to contain specific anti-D. Four of these batches had anti-D titres ranging from 64 to 256 (including the two batches each associated with a report of haemolysis) and could be linked, in each case, to a starting plasma pool also positive for anti-D. CONCLUSIONS: Our results show that IVIG products can contain appreciable anti-D levels. To avoid potential problems in recipients, we propose an anti-D titre of 8 as the maximum permissible limit of anti-D in IVIG products for batch acceptance and release. The availability of a reference preparation is essential for control of this proposed requirement.
Authors: Niels S Vermeer; Sabine M J M Straus; Aukje K Mantel-Teeuwisse; Francois Domergue; Toine C G Egberts; Hubert G M Leufkens; Marie L De Bruin Journal: Drug Saf Date: 2013-08 Impact factor: 5.606