Volume 186 - Issue 8
Potential impact of AUSFTA on Australia's blood supply
Authors: Glen A Kennedy, Judy Cummings and Simon T Durrant
Med J Aust 2007; 186 (8): 427-430. || doi: 10.5694/j.1326-5377.2007.tb00982.x
Published online: 16 April 2007
Published online: 16 April 2007
To the Editor: We read with great interest the article by Bambrick et al relating to the potential impact of the Australia–United States Free Trade Agreement (AUSFTA) on supply of blood products in Australia.1 Our recent experience with Octagam (Octapharma Australia, Sydney, NSW), an intravenous immunoglobulin (IVIg) product produced overseas, highlights some of the quality concerns raised in their article.
Routine practice in our bone marrow transplant unit is to administer IVIg weekly for 100 days after allogeneic stem cell transplantation. Until December 2004, locally produced IVIg, Intragam-P (CSL, Melbourne, Vic), was used exclusively as the IVIg product for these patients. From October 2005, because of limitations in the supply of Intragam-P, the Australian Red Cross Blood Service (ARCBS) also provided Octagam for IVIg replacement therapy in transplant recipients.
It has also been routine practice within our transplant unit to repeat serological tests for a variety of transfusion-transmitted viral infections, including human T-lymphotropic virus type I and type II (HTLV-I and HTLV-II), in all transplant patients 100 days after transplantation. Until 2006, none of our patients had ever tested positive for HTLV-I or HTLV-II antibodies. After the introduction of Octagam, the first two transplant patients who received this product for IVIg replacement tested positive for HTLV-I/HTLV-II antibodies at 100 days after transplant (signal to cut-off [S/CO] ratios, 4.36 and 6.33, respectively).
Subsequent investigation revealed that these results were probably secondary to passive transfer of HTLV antibodies from the IVIg product used. Both patients received Octagam from the same batch, and subsequent testing of this batch was positive for the presence of HTLV-I/HTLV-II antibodies. Of note, both patients tested negative for HTLV-I/HTLV-II antibodies before transplantation (S/CO ratio < 1.00). Their stem cell donors were also negative for HTLV on testing immediately before stem cell donation, and the only other blood product shared between the two patients (platelets from a common donor) also tested negative for HTLV. Follow-up testing for HTLV-I/HTLV-II antibodies at about 12 months after transplantation gave a negative result in both patients (S/CO ratio < 1.00).
Given that Octagam is a plasma (acellular) product processed with appropriate viral inactivation steps,2 we believed it to be extremely unlikely that direct transfer of HTLV virus had occurred. The most likely explanation was the passive transfer of HTLV antibodies. It followed that Octagam must have been sourced from HTLV-positive plasma donors — a practice that is in direct conflict with current ARCBS policy, which specifies that all blood and plasma donors must be screened for HTLV-I and HTLV-II, and that any donors testing positive should be excluded from blood or plasma donation.3 The HTLV-I/HTLV-II serostatus of donors used to source plasma for Octagam are not reported on the product information sheet.2 Testing of one patient sample at the National Serology Reference Laboratory (Melbourne, Vic) suggested the positive serological results in our patients were due to the presence of HTLV-II antibodies. In collaboration with Octapharma, it was subsequently determined that plasma for Octagam was sourced from paid donors from the southern United States, an area where HTLV-I and HTLV-II seropositivity is known to be prevalent among blood donors.4
The clinical implications of our findings are unclear. Our results were reported rapidly to the ARCBS and subsequently to the Therapeutic Goods Administration. Our main concerns are that Octagam plasma is sourced from donors who would normally be excluded from plasma donation within Australia,3 and that there appears to be no current mechanism for addressing this issue. Some of the quality concerns raised by Bambrick et al appear to be not so theoretical after all.
References
- Bambrick HJ, Faunce TA, Johnston K. Potential impact of AUSFTA on Australia’s blood supply. Med J Aust 2006; 185: 320-323.
- Octapharma. Octagam product information sheet. Octapharma Australia Pty Ltd. Approval date Jan 2006. 0_i1091800
- Australian Red Cross Blood Service. Transfusion medicine manual. Chapter 3. Collection and preparation of blood components and plasma-derived blood products. http://www.transfusion.com.au/ResourceLibrary/TMM_ch03_Collection.asp (accessed Mar 2006).
- Murphy EL, Watanabe K, Nass CC, et al. Evidence among blood donors for a 30-year-old epidemic of human T lymphotropic virus type II infection in the United States. J Infect Dis 1999; 180: 1777-1783. 0_i1091807