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

tions (most bacterial, 2 malaria, 6 viral - 4 HIV, 1 HCV and 1 HBV). Long
term morbidity in 13% of serious adverse reactions. 2 fatalities (1 ABO
incompatibility, 1 hyperhaemolysis syndrome), 6 TRALI, 12 incorrect
blood products. Allergic (41%) and NHFTR (54%) in 2005 were mostly
in multitransfused patients. Conclusions/Recommendations. Reporting
improved and hospitals’ participation increased to 83% in 2005. The
reports of incorrect blood component transfused and TRALI increased
after 2004 in part because of increased awareness of these transfusion
side effects. Allergic reactions and NHFTR remain high. Improved
patient identification, leukoreduction, phenocompatibility and strategy
for bacterial sepsis reduction. Continuous training for better reporting
and cooperation.
0838
COMPARISON OF VON WILLEBRAND FACTOR, FACTOR VIII AND ADAMTS13 IN PLASMA
PRODUCTS USED IN THE TREATMENT OF THROMBOTIC THROMBOCYTOPENIC PURPURA
K. Devreese, 1 H.B. Feys, 2 L. Noens, 1 H. Deckmyn, 2 K. Vanhoorelbeke2 1 2 Ghent University Hospital, GHENT; IRC, K.U.Leuven Campus Kortrijk,
KORTRIJK, Belgium
Introduction. Attention has recently turned to the composition of plasma
products used in the treatment of thrombotic thrombocytopenic
purpura (TTP). In Belgium, two virus inactivated fresh-frozen plasma
(FFP) products are available: solvent/detergent (SD) treated pooled plasma
(SD-FFP) and methylene blue/light (MB) treated single plasma units
(MB-FFP). The use of MB-FFP in TTP patients is only anecdotal and
seems less effective. Materials and Methods. Plasma levels of factor VIII,
von Willebrand factor antigen and activity (VWF:act) were measured
with routinely used methods. ADAMTS13 antigen (ADAMTS13ag) was
measured with a commercial polyclonal and a non-commercial monoclonal
antibody-based ELISA. ADAMTS13 activity (ADAMTS13act) was
measured by proteolysis of FRETS-VWF73, a fluorogenic substrate for
the metalloprotease. Five production batches of SD-FFP (Octaplas,
Octapharma, Vienna, Austria) and 198 single donor units of MB-FFP
(Red Cross-Flanders Blood Services, Brugge, Belgium) were analysed.
The plasma of 40 healthy volunteers was analysed in parallel. The pooled
plasma of these 40 healthy volunteers was used as reference for selected
activity assays, whereas standard human plasma, as provided by the
manufacturer, was referred to when using the commercial ADAMTS13
ELISA kit. Results. MB treatment alters levels of all measured plasma proteins.
Although statistically significant, the differences were, however,
minor. SD-FFP contains less VWF:act, ADAMTS13act and
ADAMTS13ag (only with the monoclonal-based ELISA) compared to
the normal volunteers and MB-FFP. Interestingly, ADAMTS13ag measured
with the polyclonal ELISA shows higher levels. Conclusions. The
quantitative differences in ADAMTS13ag levels with both methods give
rise to further investigations regarding the protein structure of
ADAMTS13 in both plasma products. Although the ADAMTS13 activity
in SD-FFP is lower than in MB-FFP, the clinical outcome in TTP
patients has been shown to be better with SD-FFP. Hitherto unidentified
plasma proteins may contribute to the pathophysiology of TTP and
explain the reported difference in clinical efficacy. A randomized clinical
trial should be conducted to find out which plasma product is best
suited to treat TTP patients.
0839
A CASE OF TRALI AFTER THE INFUSION OF CRYOPRESERVED UMBILICAL CORD BLOOD
CELLS
I. Krsnik, C. Regidor, R. Cabrera, E. Ojeda, G. Bautista, R. Forés,
E. Ruiz, Y. Gutiérrez, J. García Marco, C. Vallejo, I. San Juan, S. Gil,
M.N. Fernández
Hospital Puerta de Hierro, MADRID, Spain
Introduction. Transfusion-related acute lung injury (TRALI) is an uncommon
complication reported after the infusion of most blood components.
We describe a case of TRALI following the infusion of cryopreserved
umbilical cord blood (UCB) cells. Case report. A 34-year-old
woman with an AML in second complete remission was admitted for a
cord blood transplant. Cardiac and pulmonary tests were normal. The
day of infusion she was afebrile with a blood pressure of 120/85 mmHg,
SpO2 98%, a cardiac frequency of 78 bpm and a central venous pressure
(CVP) of 6 cm. She was pancytopenic and biochemistry was normal. A
chest-X-ray two days before the infusion was normal. No blood products
had been given in the previous 48 hours. She received 100 mg of
hydrocortisone and 2 mg of dexchlorphenylamine IV pre-infusion,
according to our protocol. The UCB unit had been fractionated before
12 th Congress of the European Hematology Association
cryopreservation (final volume, 27 mL) and diluted post-thawing with
30 mL of 5% human albumin in normal saline. The product was infused
over 15 minutes through a central line. Total volume: 57 mL, DMSO 2.7
mL, red blood cells 12.5 mL and total nucleated cell count 1.524×10 9 . The
patient complained of thoracic discomfort but oxygen saturation
remained normal, as well as blood pressure, cardiac frequency or CVP.
One hour later she referred shortness of breath. Crepitants could be
heard in both lung bases. Blood pressure had increased to 150/100 mm
Hg; CVP was 9 cm, cardiac frequency 72 bpm and oxygen saturation
dropped to 90%. A chest-X-ray showed bilateral fluffy perihiliar infiltrates.
She was treated with supplementary oxygen, diuretics and
enalapril. In the following hours, blood pressure returned to normal but
she required supplementary oxygen to keep a normal saturation. Temperature
rose to 37.4º C and she complained of pain in the wrists and
ankles with local edema. Twenty hours later she was afebrile, with normal
blood pressure, CVP, oxygen saturation on room air; a chest-X-ray
showed no infiltrates. Further course of the transplantation was uneventful.
Blood cultures taken the day before, the afternoon of the infusion and
from the UCB unit were negative. Discussions. TRALI is a leading cause
of transfusion- related morbidity and mortality. It has been reported
after the infusion of any blood product but usually with more than 50
ml of plasma and exceptionally after cryopreserved bone marrow or
peripheral blood stem cells. A multi-factorial mechanism has been proposed
involving antineutrophil antibodies or a previous lung damage
and the infusion of biologic response modifiers (the two-hit hypothesis).
Our case fulfils the criteria of TRALI: acute onset, hypoxemia, bilaterial
infiltrates and no evidence of circulatory overload, within 6 hours of
the infusion and no temporal relationship to an alternative risk factor.
Bacterial contamination can be ruled out. The volume of DMSO and red
blood cells in this unit was small, but UCB units contain usually mature
granulocytes. We have observed no cases of acute lung injury after any
of the 64 UCB units infused in our centre.
0840
REGULATION OF DLL4 EXPRESSION IN BM-EPCS CONTROLS TUMOUR
NEOANGIOGENESIS
C. Real, 1 C. Igreja, 1 A.P. Elias, 1 C. Borges, 2 A. Duarte, 2 S. Dias1 1 2 IPO/IGC, LISBOA; CIISA, Faculdade de Medicina Veterinária, LISBON,
Portugal
Bone marrow-derived endothelial progenitor cells (BM-EPCs) have
been implicated in adult neoangiogenesis and consequently used as biomarkers
for human pathologies with endothelial damage. The administration
of these cells in human patients temporally improves endothelial
function, although the engraftment of these cells in newly formed
vessels is inefficient. The mechanisms by which these cells promote vessel
regeneration remain largely unclear.In this work, we analysed the
role of the Notch/Delta signalling pathway in EPC function during
tumour neoangiogenesis, by regulating the expression of Notch ligand,
delta-like 4 (Dll4) in these cells. Sublethally irradiated NOD-SCID mice
received either WT or Dll4±BM-EPCs and were subcutaneously inoculated
with tumour cell lines (leukemias and breast cancer). Tumours generated
in Dll4±EPCs transplanted mice presented increased microvessel
density when compared with WT EPCs transplanted mice or non-transplanted
controls, regardless of VEGF expression. Although with
increased vessel number, tumours of Dll4±EPC transplanted mice presented
more hypoxic cells and decreased tumour cell proliferation,
revealing impairment in vessel function. In addition, these tumours present
a diminished expression of PDGF, a vessel stabilizing factor, and
increased expression of Ang2, known as a vessel destabilizing factor.
These results showed that EPCs have a major role in vessel stabilization
in sites of active neoangiogenesis by the regulation of Dll4 expression.
We propose that targeting the Notch/Dll4 pathway on EPCs, modulating
vessel stability, may have therapeutic potential.
0841
CHALLENGES IN TRANSFUSION MEDICINE: NEED OF TRANSFUSION DEPENDENT
PATIENTS WITH MYELODYSPLASTIC SYNDROMES
C.P. Plesnila-Frank, 1 K. Berger, 2 M. Voelkl, 3 W. Schramm4 1 MERG, MUNICH; 2 MERG-Medical Economics Research Group, MUNICH;
3 Celgene GmbH, MUNICH; 4 University of Munich, MUNICH, Germany
Background. With the increasing proportion of elderly individuals in the
population, the prevalence of Myelodysplastic syndromes (MDS) will
likely rise further in the future. For rational resource allocation information
on resource consumption and costs of potential complications (e.g.
haematologica/the hematology journal | 2007; 92(s1) | 313