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

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Transfusion medicine and vascular biology<br />

0832<br />

AN AUDIT OF RED CELL CONCENTRATE, FRESH FROZEN PLASMA AND CRYOPRECIPITATE<br />

USE WITHIN THE WEST OF SCOTLAND: A 5-YEAR REPEAT ANALYSIS<br />

J. Laird, R. Soutar<br />

West <strong>of</strong> Scotland Blood Transfusion Centr, GLASGOW, United Kingdom<br />

Background. The Regional Haematology Audit Group covers a population<br />

<strong>of</strong> 3 million (<strong>the</strong> area <strong>of</strong> <strong>the</strong> regional transfusion centre). An audit<br />

was undertaken in 2000 analysing use <strong>of</strong> plasma products and was published:<br />

discrepancies in use were identified between hospitals and <strong>the</strong><br />

following represents a repeat analysis over <strong>the</strong> interim 5-year period.<br />

Aims. The main aim was to show a change in FFP and cryoprecipitate use<br />

between <strong>the</strong> 2 study periods in order to assess <strong>the</strong> effectiveness <strong>of</strong> modifications<br />

introduced following <strong>the</strong> last audit. Additional areas evaluated<br />

were <strong>the</strong> assessment <strong>of</strong> Rhesus status on prescription <strong>of</strong> FFP and <strong>the</strong><br />

laboratory systems in place to recognise those requiring methylene bluetreated<br />

FFP (MBTFFP). Methods. A questionnaire was distributed to all 15<br />

regional hospitals with an 87% response rate. This compared April 2004-<br />

March 2005 with <strong>the</strong> same period 1999-2000. Results. The results showed<br />

a decline in blood product use during this period despite a 2.9% increase<br />

in bed numbers within <strong>the</strong> region. Since 2000, <strong>the</strong>re was a 9.1% reduction<br />

in red cell transfusions, but an even greater reduction in FFP (17%)<br />

and cryoprecipitate (20%) used. Using bed numbers as a surrogate reflection<br />

<strong>of</strong> activity, a mean <strong>of</strong> 13.65 red cell units were issued per bed (range<br />

7.68-21.32, SD 4.51) in 2000, compared to11.99 in 2005 (range 5.15-<br />

17.91, SD 3.34) p=0.046. Repeat analysis identified a substantial change<br />

in practice in previously outlying hospitals in terms <strong>of</strong> blood product use;<br />

two hospitals, shown to have excessive use <strong>of</strong> both FFP and cryoprecipitate<br />

in <strong>the</strong> initial study (presumed due to automatic issue in 'crashpacks')<br />

now compare favourably to <strong>the</strong> rest <strong>of</strong> <strong>the</strong> region This practice<br />

has now been discontinued at both institutions and as a result <strong>the</strong>y are<br />

mainly responsible for <strong>the</strong> observed reduction in use within <strong>the</strong> area.<br />

Resultant savings <strong>of</strong> around £250,000 per annum have been estimated<br />

due to this alteration in practice. A marked difference in blood product<br />

use between <strong>the</strong> two cardiac surgery centres was observed, which was<br />

thought to be attributable to regular use <strong>of</strong> thromboelastography in one.<br />

Interestingly, 15% <strong>of</strong> centres still continue to take Rhesus D status into<br />

consideration on FFP issue whilst 23% consider it in females <strong>of</strong> childbearing<br />

age, contrary to recent guidance from <strong>the</strong> BCSH. It was also observed<br />

that no standard laboratory procedures were in place for <strong>the</strong> issue <strong>of</strong><br />

MBTFFP and only 50% <strong>of</strong> <strong>the</strong> hospitals with potential use <strong>of</strong> this product<br />

had it in stock. Conclusions. At a time when national FFP use is rising,<br />

we have shown a reduction in red cell, FFP and cryoprecipitate use. The<br />

report demonstrates that effective audit can improve and change clinical<br />

practice - something that is <strong>of</strong>ten questioned.<br />

0833<br />

TRANSFUSION-RELATED ACUTE LUNG INJURY (TRALI) FOLLOWING INTRAVENOUS<br />

IMMUNOGLOBULIN (IVIG) INFUSION<br />

G.A. Zakout, 1 J.E. Tighe, 1 D. Culligan, 1 M.A. Greiss2 1 2 Aberdeen Royal Infirmary, ABERDEEN; Aberdeen Blood Transfusion Center,<br />

ABERDEEN, United Kingdom<br />

Background. Transfusion related acute lung injury is an uncommon life<br />

threatening complication <strong>of</strong> blood product transfusion. It is defined in <strong>the</strong><br />

recent Canadian consensus conference on TRALI as a new episode <strong>of</strong><br />

acute lung injury (ALI) that occurs during or within 6 hours <strong>of</strong> completed<br />

transfusion, and which is not temporally related to a competing aetiology<br />

<strong>of</strong> ALI. The Serious Hazards <strong>of</strong> Transfusion (SHOT) data from<br />

<strong>the</strong> United Kingdom showed an incidence <strong>of</strong> 70 confirmed cases per 16<br />

to 17 million-blood components transfused. However, <strong>the</strong> true incidence<br />

<strong>of</strong> TRALI remains unknown mainly due to <strong>the</strong> previous lack <strong>of</strong> standardisation<br />

<strong>of</strong> its definition and under recognition. Virtually all plasma-containing<br />

blood products have been implicated, particularly when <strong>the</strong>y are<br />

sourced from female donors. Despite <strong>the</strong> ample amount <strong>of</strong> leucocyte<br />

antibodies in IVIG, this blood product has rarely been reported to cause<br />

TRALI. Aim. To report an adverse event to IVIG that has rarely been<br />

reported on literature review. We also highlight that TRALI is a clinical<br />

ra<strong>the</strong>r than a laboratory diagnosis. Methods. A 55-year-old patient with<br />

angioimmunoblastic T-cell lymphoma (AITL) was admitted 3 weeks<br />

after his first cycle <strong>of</strong> oral fludarabine and cyclophosphamide with severe<br />

pneumonia. Three days following his clinical and radiological recovery<br />

12 th <strong>Congress</strong> <strong>of</strong> <strong>the</strong> <strong>European</strong> <strong>Hematology</strong> Association<br />

from pneumonia, he was given prophylactic IVIG as he had secondary<br />

hypogammaglobulinemia, which is an unusual finding in AITL (polyclonal<br />

increase in immunoglobulins is commonly found). He developed<br />

non-cardiogenic pulmonary oedema 40 minutes into <strong>the</strong> IVIG infusion.<br />

This manifested itself by a drop in O2 saturation to 77% and bilateral<br />

pulmonary infiltrates on a chest X-ray. His O2 saturation improved to<br />

91% on 15 L/min oxygen and he made a complete recovery within 12<br />

hours <strong>of</strong> onset. Results. Testing in our regional Blood Transfusion Centre<br />

revealed a positive direct granulocyte immun<strong>of</strong>luorescence (GIF),<br />

which persisted for 11 weeks following <strong>the</strong> TRALI event, and a negative<br />

indirect GIF assay. This suggests <strong>the</strong> presence <strong>of</strong> granulocyte-bound<br />

ra<strong>the</strong>r than free antibodies. A crossmatch between <strong>the</strong> patient’s granulocytes<br />

and IVIG was positive. No anti-HLA Class I or II antibodies were<br />

detected on standard complement-dependent cytotoxicity (CDC) and<br />

ELISA assays respectively, in ei<strong>the</strong>r <strong>the</strong> patient or <strong>the</strong> residual IVIG<br />

infused. Summaryand Conclusions. TRALI still remains a challenging diagnosis<br />

despite <strong>the</strong> proposed guidelines for defining it. The same consensus<br />

panel that proposed <strong>the</strong> definition agrees that TRALI is a clinical and<br />

radiographic diagnosis ra<strong>the</strong>r than a laboratory one. Based on this, our<br />

patient fulfilled <strong>the</strong> clinical diagnostic criteria. AITL is commonly associated<br />

with autoimmune phenomena secondary to marked immune activation<br />

evidenced by increased expression <strong>of</strong> an array <strong>of</strong> cytokines. A significant<br />

proportion <strong>of</strong> patients have circulating autoantibodies. There is<br />

at least 1 case report in which antigranulocyte antibodies were noted in<br />

association with AITL. Such phenomena can ‘prime’ neutrophils, which<br />

upon exposure to <strong>the</strong> IVIG infused are activated resulting in endo<strong>the</strong>lial<br />

damage and capillary leak. IVIG has rarely been reported to cause TRALI.<br />

We postulate that <strong>the</strong> immune dysregulation associated with AITL predisposed<br />

to <strong>the</strong> development <strong>of</strong> TRALI following IVIG in this case.<br />

0834<br />

CONTRIBUTION OF STORAGE-INDUCED PLATELET MICROPARTICLES TO THROMBIN<br />

GENERATION<br />

G. Ivanov, 1 N. Bowen, 1 C. Saunders, 2 P.W. Collins1 1 2 University Hospital <strong>of</strong> Wales, CARDIFF; The Welsh Blood Service, PONTY-<br />

CLUN, United Kingdom<br />

Background. Procoagulant activity <strong>of</strong> platelet microparticles (MPs) has<br />

been extensively described. The number <strong>of</strong> platelet-derived MPs increases<br />

significantly with time during platelet storage. The understanding <strong>of</strong><br />

storage-induced MPs’ contribution to thrombin generation (TG) could be<br />

important in situations when additional procoagulant effect <strong>of</strong> platelet<br />

transfusions is undesirable (e.g. disseminated intravascular coagulation).<br />

Aims. To assess <strong>the</strong> contribution <strong>of</strong> storage-induced platelet MPs to<br />

thrombin generation at <strong>the</strong> beginning and <strong>the</strong> end <strong>of</strong> platelet concentrate<br />

shelf life. Methods. Platelet concentrates used were leucodepleted pooled<br />

preparations, sampled initially at Day 2 and at <strong>the</strong> end <strong>of</strong> shelf life (6 to<br />

8 days, mean 7.25 days, n=13). Platelet concentrates were stored under<br />

standard blood bank conditions, at 22ºC on a lateral shaking device.<br />

After sampling, platelet concentrates were diluted with autologous<br />

platelet-free plasma (PFP) and mixed 1:2 with freshly prepared donors’<br />

PFP containing corn trypsin inhibitor (CTI). This step was introduced in<br />

order to prevent contact activation as well as to replenish plasma clotting<br />

factors that may have been lost during platelet storage. Thrombin<br />

generation was triggered with 0.5 pM TF and recorded using automated<br />

calibrated thrombography. Parameters such as lag, peak thrombin, initial<br />

and maximal velocity <strong>of</strong> TG were studied in platelet-rich (PRP) and<br />

PFP, as well as in PFP filtered through 0.1 µm filter. Initial velocity <strong>of</strong> TG<br />

(Vini) was defined as <strong>the</strong> slope <strong>of</strong> <strong>the</strong> TG curve between 1 and 10<br />

nM/min. Vmax was calculated as <strong>the</strong> maximal velocity <strong>of</strong> TG. Results.<br />

Using low-dose TF trigger in presence <strong>of</strong> CTI, we observed minimal or<br />

no TG in freshly prepared PFP obtained from normal donors. However,<br />

in PFP obtained by centrifugation <strong>of</strong> platelet concentrates, we demonstrated<br />

significant procoagulant activity both at early and late stages <strong>of</strong><br />

storage. All <strong>of</strong> <strong>the</strong> TG parameters tested in MP-containing PFP <strong>of</strong> stored<br />

platelets were not significantly different from those produced by PRP<br />

with a platelet concentration <strong>of</strong> 50×10 9 /L. Fur<strong>the</strong>r increase in platelet<br />

concentration to 100×10 9 /L did not lead to a significant rise in procoagulant<br />

activity. Removal <strong>of</strong> MPs by filtration <strong>of</strong> PFP, derived from Day 2<br />

platelet concentrates, led to a significant prolongation <strong>of</strong> lag time and<br />

reduction in thrombin peak, Vini and Vmax as compared with unfiltered<br />

PFP. TG was completely abolished when PFP from 7 day-old platelets<br />

was subjected to filtration. We observed a significant loss <strong>of</strong> both<br />

platelet-dependent and MP-dependent procoagulant activity in platelet<br />

concentrates stored for 7 days as compared with ones stored for 2 days.<br />

Although all <strong>of</strong> <strong>the</strong> tested parameters pointed to a significant loss <strong>of</strong><br />

thrombin generation potential with platelet storage, most noticeable dif-<br />

haematologica/<strong>the</strong> hematology journal | 2007; 92(s1) | 311

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