transfusion (component not stated), the platelet count dropped to <10 x 109/L, although there was no haemorrhage. Chemotherapy was curtailed because of the thrombocytopenia. HPA-1a and HLA antibodies were identified, and she was treated with random platelets, IVIgG, and steroids. The platelet count reached 50 x 109/L in 10 days. Case 3 was a 67-year old woman who was transfused because of a gastro-intestinal haemorrhage secondary to oesophagitis. She had had 2 pregnancies, but had never been transfused. Five to nine days after transfusion, she developed purpura/bruising, and the platelet count dropped from 171 x 109/L to <10 x 109/L. Anti-HPA-1a was identified, plus platelet autoantibodies and HLA antibodies. She was treated with random platelets, intravenous imunoglobulin and steroids. The platelet count was > 50 x 109/L when checked at day 22, and was normal by day 26. The reporter commented that the apparently slow recovery time probably reflected infrequent checking of the platelet count after the acute phase.
COMMENTARY
It seems increasingly likely that the incidence of PTP is decreasing in the era of universal LD. In the first 3 years of SHOT reporting, prior to universal LD, there were a total of 32 reported cases (11, 11 and 10 cases/year respectively). In the 2 years since LD was implemented, the number of reported cases has dropped to 6 and 3 in 1998-99 and 1999-2000 respectively. The most likely mechanism for this reduction is the observed removal of 90% of platelets from red cell components by leucocyte depleting filters. Such filters also reduce the load of platelet microparticles in red cell components. It is of interest that 2 of the 3 cases reported this year, and 2 of 6 cases reported last year were receiving platelet as well as red cell transfusions, and were thus exposed to large amounts of antigen. The role of leucocyte removal in preventing PTP is less clear. The classical description of PTP is of a patient whose primary sensitisation occurred months or years earlier, perhaps by transfusion but more usually by pregnancy. It is rare to know whether the patient developed HPA antibodies at the time of this first exposure. The transfusion which precedes the acute thrombocytopenia thus acts as a secondary immune stimulus, with possibly little or no requirement for donor-derived antigen presenting cells.
Post Transfusion Purpura SHOT Annual Report 2000 / 2001 RECOMMENDATIONS
G We would urge hospitals to continue to report PTP cases to help confirm whether its likelihood is reduced by universal LD.
G As recommended in the 1998-99 report,39 the presence of HPA antibodies should be considered in platelet-dependent patients who become refractory to random donor platelets, once HLA antibodies have been excluded as the cause of the refractoriness. In addition HPA antibodies must be sought in HLA alloimmunised patients if there are poor responses to HLA selected platelets.
17.
TRANSFUSION-ASSOCIATED GRAFT-VERSUS-HOST DISEASE
Definition
Transfusion-associated graft-versus-host disease was defined as the development of the classical symptoms of fever, rash, liver dysfunction, diarrhoea and pancytopenia occurring 1-6 weeks following transfusion, without other apparent cause. The diagnosis was usually supported by skin/bone marrow biopsy appearances and/or the presence of circulating donor lymphocytes.
One case, which was fatal, was reported during 1999-2000, the first newly reported case in the UK for 2 years. This case was a 14-year-old girl with relapsed acute lymphoblastic leukaemia (ALL). She was being treated with the UKALL R2 protocol, which does not contain purine antagonists such as fludarabine. Although ALL is not currently an indication for gamma irradiated blood components,1 all red cells and platelets had been gamma irradiated by the hospital in a specific blood irradiator once the diagnosis was made. The intended midplane dose used was >30 Gy, and radiation-sensitive labels were used on each batch. However, at presentation with relapse, she had received 2 units of red cells and 2 units of platelets which were not irradiated. Just over 2 weeks after receiving these non-irradiated units, she developed all the classical features of GVHD –skin rash, diarrhoea, deranged liver function, pancytopenia and infection. Biopsies of skin and bowel were consistent with the diagnosis, which was confirmed by demonstration of 3 bands on variable number tandem repeat (VNTR) analysis. The patient’s HLA type was HLA A3,28; B27,44; DRB1 04,13 B3 01 B4 01; DQ 0302, 0603. Implicated donors were not recalled for HLA typing.
Treatment with methyl prednisolone was commenced within 2 days of the onset of symptoms, and a decision was taken to proceed to stem cell transplantation as ‘rescue’ therapy. She was pre-conditioned for this using fludarabine, melphalan and CAMPATH but she died of infection the day after stem cell infusion.
COMMENTARY
• This case confirms that current leucocyte depletion processes, even when performed under optimal conditions before blood storage, and with full quality monitoring, cannot always prevent TA-GVHD in susceptible patients. In the 1999-00 SHOT report,9 a similar case was described of TA-GVHD in a woman with myeloma who had received only leucocyte-depleted red cells. It should be borne in mind that although LD processes are highly consistent, the possibility of an occasional unit failing the LD process cannot be excluded. It is not practical to perform low level leucocyte counting on 3 million components/year, so processes are monitored using statistical techniques. The current UK specification of < 5 x 106/unit in 99% of units with >95% statistical confidence reflects this. However, it is possible that LD affords partial protection from TA-GVHD, and may be enough to protect patients with normal immune function whose only risk factor is chance haplotype sharing with the donor. No cases of TA-GVHD in patients have with normal immune function have been reported since universal LD was introduced, compared with 5/12 cases in the previous 3 years. Whole blood filtration reduces the T cell load by > 4.5 logs, and platelet filtration by >3.5 logs.44 However, the leucocyte load in platelets is already pre-reduced during processing, and the final leucocyte levels in red cells and platelets is comparable.
• Of 13 TA-GVHD cases in the 5 years of SHOT reporting, 6 have occurred in patients with B cell malignancies (3 non-Hodgkin’s lymphoma, 1 Waldenstrom’s macroglobulinaemia, 1 myeloma, and this case of ALL). These patients now appear to be the most susceptible group not recommended for irradiated components under current BCSH Guidelines.1
Transfusion-associated graft-versus-host disease SHOT Annual Report 2000 / 2001 receive irradiated components when these were indicated. Fortunately, no cases of TA-GVHD have resulted from these omissions.
• The investigation and management of this case once symptoms appeared was exemplary. However, it illustrates the fact that there is currently no proven treatment for TA-GVHD.
RECOMMENDATIONS
• The issue of whether some or all patients with B cell malignancies should receive irradiated components should be again reviewed. In addition, as the current BCSH guideline1 recommends, each new chemo- or immuno- therapeutic regime should be assessed for the possibility of its causing TA-GVHD. Both of these recommendations might best be achieved by a complete review of the BCSH guidelines.
• Hospitals should have systems in place to ensure that patients who need irradiated components always get them. Mechanisms for achieving this include flagging such patients on the hospital computer, and the use of the BCSH/NBS card and leaflet ‘Information for patients needing irradiated blood’. (See appendix 13 for a pre-publication version updated for 2002). There may be a role for hospital pharmacies in reminding staff that recipients of purine analogues require irradiated components.