12th Congress of the European Hematology ... - Haematologica

12 th Congress of the European Hematology Association
ferences were observed in the propagation phase of TG as indicated by
a reduction in Vmax (3.9-fold for PRP, p=0.008 and 3.7-fold, p=0.006 for
PFP) by the end of shelf life. Conclusions. MPs contained in platelet concentrates
make a significant contribution to TG potential, that is comparable
with procoagulant activity supported by platelet concentration
of 50×10 9 /L. MP-dependent procoagulant activity does not increase with
platelet storage, but decreases in parallel with platelet function.
0835
POLYETHYLENE GLYCOL PRECIPITATION AND ION EXCHANGE CHROMATOGRAPHY
ELIMINATE A TSE-MODEL AGENT SPIKED INTO THE INTRAVENOUS IMMUNOGLOBULIN
PRODUCTION PROCESS
J.M. Diez, S. Caballero, R. Gajardo, J.I. Jorquera
Instituto Grifols S.A., PARETS DEL VALLES, Spain
Introduction. The variant Creutzfeldt-Jakob disease (vCJD) is a transmissible
spongiform encephalopathy (TSE) mainly present in United
Kingdom (UK). The agent (PrPSc) is a prion essentially found in the Central
Nervous System, however it can also be detected in the lymphatic
system and non-neural tissues at much lower concentration. The vCJD
agent has never been detected in blood with methods capable of detecting
it in other tissues, so if present, the concentration must be very low.
No case of vCJD has ever been reported by plasma-derived products,
despite the four cases of possible transmission of the vCJD agent related
with blood cell transfusions. There is no evidence of vCJD transmission
by plasma products in spite of active surveillance specially among
haemophilic patients. Many different published studies (Foster P.R. Vox
Sang., 2004; 87 (suppl.2), S7-S10) indicate that the production processes
of plasma-derived products remove TSE-model agents. Aims. Grifols
has studied the capacity of the 8% PEG (polyethylene glycol) precipitation
step and the DEAE Sephadex treatment followed by several filtrations
of Flebogamma’s production process to eliminate an experimental
TSE agent. Methods. PEG precipitation and DEAE Sephadex treatment
followed by filtrations were studied on a laboratory scale model.
Hamster adapted Scrapie strain 263K was spiked into intermediate
process material to determine PrPSc removal through the purification
process, for each step studied. Two different spikes were used, clarified
hamster brain homogenate and detergent treated hamster brain
homogenate. Two runs were performed for each type of spike and
process step. PrPSc was detected by western blot. Results. PEG precipitation
removed an average of 3.6 log10/mL PrPSc, 3.40 log10/mL PrPSc
when clarified hamster brain homogenate was used and 3.70 log10/mL
PrPSc when detergent treated hamster brain homogenate was used.
DEAE Sephadex treatment followed by several filtrations removed an
average > 4.8 log10/mL PrPSc, > 4.98 log10/mL PrPSc when clarified
hamster brain homogenate was used and > 4.62 log10/mL PrPSc when
detergent treated hamster brain homogenate was used, with the absence
of any detectable PrPSc in the resultant material. Conclusions. The results
obtained show a great removal capacity of PEG precipitation and DEAE
Sephadex treatment followed by several filtrations for the TSE-model
studied. The overall clearance would be > 8.4 log10/mL PrPSc for the
manufacturing process. These results indicate that the Flebogamma production
process has a high potential to eliminate TSE agents, in case
they were present.
0836
FATAL TRANSFUSION ASSOCIATED GRAFT VERSUS HOST DISEASE IN GOODPASTURES
SYNDROME TREATED WITH CYCLOPHOSPHAMIDE
K. Amrein, 1 U. Posch, 2 G. Lanzer, 2 C. Högenauer3 1 UBT, GRAZ; 2 Department of Transfusion Medicine (UBT), GRAZ; 3 Department
of Internal Medicine, GRAZ, Austria
Introduction. Transfusion associated graft versus host disease (TA-
GVHD) is a rare but commonly fatal complication of transfusion of cellular
blood products. It may even arise in apparently immuno-competent
individuals, if viable donor-derived T-lymphocytes escape the recipient’s
immune system due to complete or incomplete HLA match and
attack his organs. Case Report. A 54-year-old man with newly diagnosed
Goodpasture’s syndrome was transfused with twenty-four leukocyte
depleted but not irradiated units of red blood cells. He was considered
immunocompetent at admission but received cyclophosphamide pulse
therapy during the hospitalisation. Two weeks after the first transfusion
he developed severe persisting watery diarrhea, fever, generalised erythema
and jaundice. Blood counts became increasingly leuco-, lymphoand
neutropenic with moderate anemia and thrombopenia. The patient
died of cardiovascular failure in septic shock on day 47 after admission.
312 | haematologica/the hematology journal | 2007; 92(s1)
Results. Sigmoidoscopy on the 31st day after the first transfusion
showed diffuse colitis with multiple ulcerations. Biopsies showed lymphocytic
infiltration in the crypts and disappearance of crypts consistent
with a diagnosis of graft versus host disease. There was no evidence of
viral or parasitic infections. Gastroduodenoscopy several days later
revealed severe hemorrhagic jejunitis, duodenitis and gastritis with multiple
small ulcerations. The patient and 13 blood donors were typed for
HLA A*B*Cw*DRB1*3*4*5* and DQB1* using low resolution PCR SSP.
Two donors were found to be matched for 5 respectively 8 out of 12 tested
HLA antigens with the patient, one female donor turned out HLA
haploidentical with him. PCR HLA typing however revealed no evidence
for chimerism in the patient`s peripheral blood (Figure 1). Conclusions.
The therapy with cyclophosphamide might have critically contributed
to the patient’s susceptibility. As there is no causative therapy
for TA-GvHD, the indication for preventive irradiation of cellular blood
products in high risk groups is out of question. Additionally, the indication
for patients at questionable risk, for example those who are receiving
potent immunocompromising drugs or suffer from a potentially predisposing
disease must be considered. In doubt, irradiation should be
undertaken to prevent this serious condition.
Figure 1. Course of hemoglobin, leukocyte and bilirubin.
0837
REPORTING ADVERSE REACTIONS ASSOCIATED WITH BLOOD TRANSFUSION
C. Politi, E. Zervou, O. Marandidou, M. Hatzitaki, L. Papayiannis,
E. Kantidaki, G. Martinis, P. Damaskos
Coordinating Haemovigilance Centre (SKAE, ATHENS, Greece
Background. One of the objectives of SKAE and its six regional bases
(PEDIA) is the collection and analysis of side effects and incidents associated
with blood transfusion. SKAE is submitting recommendations to
the National Authorities for the improvement of safety and quality of
transfusion. Methods. Reporting is voluntary and codified using standard
forms for individual cases and aggregate hospital data. The type, severity
and imputability of adverse reactions are analysed in relation to the
associated blood product and the degree of morbidity along the lines of
the European Directive 2005/61/EC, the Guide of the Council of Europe
and European Haemovigilance Network standards. Reports are initially
gathered by PEDIA and analysed by SKAE. For further information
SKAE may communicate with local or regional haemovigilance officers.
Table 1. Haemovigilance data: 1997-2005.
Results. Hospitals reporting represented 17-18% of national totals of
blood units and omponents in 1997-2000, increasing to 83% in 2005
(45-50% overall). All adverse reactions 9:10,000 blood products, serious
0.65:10,000. Near misses not included. Associated with RBCs 72%, plasma
9%, platelets 2.5%. Infectious factors caused 12% of serious reac-