Leukodepleted Whole Blood Using a High
Transcrição
Leukodepleted Whole Blood Using a High
'. .' Infusionstherapie Originalarbeit Infusion Therapy Infusionslher und Transfusionsmedizin .nd Transfusion Medicine . Original Article Transfusionsrned 1999;26:339-343 Received: April 3. 1998 Accepted: J.nu.ry Evaluation of Proinflammatory 27. 1999 Cytokines in Prestorage Leukodepleted Whole Blood Using a High..Performance Inline Filter A. Bontadini F. Fruet M. C. Ruscitto S. Manfroi R. Conte Servizio di Immunoematologia e Trasfusianale, Policlínica S. Orsola-Malpighi, Bologna Key Words Leukodepletion. Filtration . Whole blood . Proinflammatory cytokines Schlüsselwõrter leukodepletion . Filtration . Vollblut . Proinflammatorische Zytokine Summary Zu$ammenfassung Background: The efficiency of prestorage leukodep!etion of whole blood on the production of proinflammatory cytokines (ll-1P, Il-5, IL-8 and TNF-a) was compared in two groups of nonfíltered and filtered whole bIcado Ma- Hintergrund: In dieser Studie wurde die Auswirkung einer Leukozytendepletion ver Lagerung von Vollblutkon- terial and Methods: Ten experiments were performed. 1n each experiment we took two whole blood units drawn serven auf .die Produktion proínflammatorisc~er kine (ll-1~, Il-6, Il-8 und TNF-a) untersucht. und Methoden: Insgesamt wurden 10 Untersuchungen durchgeführt. Für jede Untersuchung wurden aos einem Pool 2 Vollblutkonserven hergestelli. Eine der Konserven from a pool. In one group lhe units were immediately filtered by lhe new inline filter Biofil integral on NPBI Com- wurde poflex line-Filter auf dem NPBI-Compoflex-System system while in lhe second group they were maintained, without leukodepletion at +4 oCo Results: The filter showed a mean IOg10 depletion of 3.86 :!:0.08 (CV 2.1%) with a mean absolute number of leukocytes in lhe postfiltration units of 0.29 :t 0.049 x 106 and a RBC recovery of 92.5 :!:1.1%. Il-6 and TNF-a remained at concentrations less than 1 pg/ml in lhe samples dufing lhe storage period both in lhe contraI and filtered units. IL-1f3 was not significantJyhigher on days O and 35 in lhe two groups while IL-8was observed to be increased at day 35 in 2 out of lhe 10 experiments (620 and 415 pg/mt respectively). Conclusions:The inline filter Bjofilin combination with an NPBI Compoflex system has a high performance in lhe leukodep/etion of whole b/ood. Proinnammatory cytokines have a concentration in whole )Iood less than described in platelet concentrates, and )restorage leukodepletionseems to preveni cytokine ac:umulation. Zyto- Material u~gehend mil einem neuen Bíofil-integral-ín- gefiftert, wãhrend die zweite Konserve ohne leukozytendepletion hei +4 °C gefagert wurde. Ergebnisse: Die gefilterten Prãparate zeigten eine 10glO-Depletion von 3,86:t 0,08 (CV 2,1%) mil einer mittleren absoluten Leukozytenzahl von O,29:t 0,049 x 106 une!' einer Erythrozyten-Recovery von 92,5:!: t 1%. Díe Werte für Il-6 und TNF-a blieben wãhrend der lagerung in den gefilterten und ungefilter- ten Produkten unter 1 pg/ml. Für Il-1p zeigte sich zwischen Tag O und 35 ke-in signifikanter Unterschied in beiden Gruppen. Bei Il-8 hingegen zeigte sich ein Anstieg an Tag 35 in 2 der 10 Experimente (620 bzw. 415 pg!ml). SchluBfolgerungen: Der untersuchte Inline-Filter (Biom) ist hinsichtlich der leukozytendepletion sehr effizient. Die Konzentration proinflammatorischer Zytokine scheint von Thrombozu liege~, díe leukozytendepletion ín Vollblutkonserven unter denen zytenkonzentraten vor Lagerung der Prãparate latiDo zu verhindern. . , :-i:,:,'.:::,;- scheínt die Zytokinakkumu- ' ;;, "':; , .':~2;at " t\\'u t>Jgs of aboul SOO /111. One unil ,,"asimmcdiately filtercd whilc lhe scc0nd was malnlained \\'ilhoul kukoc)'le depletion; both unilS were slored aI a temperature of 4 °c. '1l1eefficiency of lhe filtcr and lhe cano ccnlralion of c)'loki~es aI diffcrenllimes of slorage was evaluated, Introduction Leukoreduelion of ecllular blood eomponenls mar províde severa! advanlages. including reduced risk of primary alloim. \Ve us~d the new filler Bioril in combination with an NPBI Componex munízation and ilS eonsequenees. removal of eell.associaled s)'slem (Biofi!. Medolla. Ilaly). designcd by lhe manufaclurer for high.ef. viruscs, and immune modulation following lhe lransfusion óf fleiene)' leukocyle removaJ in whok blood, The filtration procedure was performed following lhe manufacturer's instructions. We started filtration homo!ogous blood [1-5J, within I h eram harvesting, AlI filtralion processes were drivelÍ by gravil\', Febrile nonhcmolytie transfusíon reactions (FNHTRs) ma}' No pre. and poslfiltration rinsing of filter wilh salinc sOlution VIasix:;. also be relaled 10lhe leukoeytesin lhe blood eomponents and formed Dor VIasan)' pressure applied during the fillration procedure. The are usually attributed to immune meehanisms 'involving al- distaDa: Ixlween pre- and postfiltralion whoJe blood cell bags VIasabout loantibodies to white-blood cells (WBCs) [6-8J. However, 120 em. several studies have reeenl!y demonstraled that a variely of We cvaluated lhe pre- and ~Ifi!lration volumes of whole blood by di. viding lhe nel volume by the specificity gravity (1.05). Both pre- and posto pyrogenic and proinflammalory cytokines sueh as IL-lp, IL-6, filtralion samples were analyzed by automated counling procedures to IL-8, TNF-a are present ínpIatelet concentrates stored for up evaluate hemoglobin and lhe plateJet counls (Genius 5eac, Florence. to 5 days at roem temperature. Because of their biologícal ae- !taly); funhermore. lhe postfillration specimens wilh a low concenlralio'o tívíties, many of these are patential mediators of FNHTRs if of WBCs were counled by Nageotte ehambér'analysis (16,17). transfused in sufficiently high amounts. Hence, FNHTRs ap- BrieOy. 100 fll of lhe samples were mixed wilh 900 JlI of Turk's solution, EvaJu.alion by lighl mieroscope was pcrformed by Iwo invesligators pear to be reIated to lhe lével of cytokines in plalelet concen- counting one fullgrid of lhe Nageolte chamber (50111),and lhe final Te. I trates, and somedata showedlhat prestorage leukodepletion I I I I I storage. The increase ofthe cytokine leve! eram dar Oto dar 3 ís significant, suggesting that cytokines were generated during storage and not during blood donatíon ar componenl prepa- 100.999 aC'COrding to lhe seIlsitivity of lhe lechnique RBC r~o\'ery fatiGo. However, il must be stated that whole blood units w:ilh a low number of leukocytes have a generalIy low conce~tratíon of cytokines, even after 5 days of storage (11r Whíle cytokines have becn most extensívely studied in platelel concentrates, only few data TeCerto packed red bIood cells (RECs) and whoIe blcxxL There seems to be no definilive ron- I I naúons: days O ("ithin 6 h after blood donarion), 5ml of blood Ic:mpcrature. frigcralion for baclerial cultures sloragc:. A quantitalive :or 30 mio at room temperature, mixing in a single unir ., was Iransferred aod 35. IOmin) at to tubc:s for re- eru:yme immunoassay 35 days of (Endogen. was uscd to analyze lhe IL-lp. IL-6. IL-8. and Standard curves were plolted by using r~eombi- with oIhers. tesl is specific The detection lev- Mean. standard de\iation (50). and coefficient of varialion (CV) were . uscd 10show lhe results in a concisc fashion. 5lalÍ5licaJ analysis was performed we toek two who1c: lhe whole blood was divided equally inlO for Slatist;cal Analysis \"Iyusing a paired t tese 10 compare in lhe Iwo groups of unils and at lhe differenl \Vere considered significan! lhe times of for r < 0.05. Results I blood units drawn frem one pool. units of whoJc blood of the same (2.000xg and TNF-a < 5pglml. storag.e. Oifferenees lhe expcrimenl,two determi- 14.21.28. eis of lhe tests uscd are: IL-Ip < 1 pglml. IL-6 < 1 pgJml. IL.8 < 2 pglml. MateriaIs and Methods Jf cclls Ihroughout for cytokine 1.3.7. were taken from ali units after sandwich and does nol cioss-react Icvels of cytokines ~roup were pooJed in a singlc bago After thorough were cenlrifuged laken aI the following ~nd storcd at -80 °C unlil analysis. Samples for one c;10kine IL-6,IL-8,andTNF-a.,whichare alsoprobabJyimplicatedin samples of 450 ml were laken from healthy donors and colleclcd in I an NPBI Componex system. To mainlain the same volume and numbc:r x vÓlume ~tfiltra. nant C:-10kines diluled tO appropriale working ranges. According 10 lhe manufacturer"s instruclions. each ELlSA FNHTR, in two groups of filtered and nonfiltered whole blood units drawn eram one pool 50 as to ensure that the only differencewaslhenumberof leukocytesín lhe bags [15J. I Blood and unfiltered) and lhe supc:malanl Woburn. MA. USA) TNF-a concenlralions. as a filter of packed . In each experiment device. sampJes were times in balh bags (fillered room RBCs. In arder to improve our knowledge on lhe production of proinfIammatory cytokines in RBCs, we evaluated IL1~, ten experiments. " x 100- storage For anal~= age WBC reduction ín whole blood and claimed by lhe manu- We pcrformed ,j ,\ performed, as follows: (hemoglobin x volume prefiltration) By using a sterile connecling cJusion as to whethcr difCerent storage temperalures can decrease celIul~r metaboJism and thus cytokine synthesis (12-14]. II facturer to perform a Icukodepletion wa.s measured lion)Jhcmoglobin I nation In lhe presenl sludy wc lested lhe new filler Biofil in combiwith an NPBI Compol1exsystem, designed for prestorI ,\ sults were expressed as mean of lhe Iwo evaJualions. We calculated lhe fi. nal WBC cona:nlralions as follows: (numbér of counled cells x IO)/vol. ume counled. were 10is lhe dilulion of lhe sampJe. The accuracy of lhe melhod employed was confirmed by dilution studies. A sample of WBCswas serially diluled by adding WBC-<:lepleted packed RBCs 10 reach a final dilulion of I(}-{).OlWBCslfll. We evaluated lhe WBC roncenlration of lhe samples by lhe Nageotte chamber method and ploued lhe data obtained as a function of lhe expecled' concentration. The correlation coefficienls ca!culated from Ihese data ranged eram 0.997 reduced lhe cytokine levels in lhe blood componenl5 [9, IOJ. Accumulation of leukocyte-derived cytokines appears to be proportional to the leukocyte contenl in lhe plateJet concentrates, and preslorage WBC reduction should reduce lhe acI cumulationofcytokínesin lhe platelets fram dar Otodar 5 of I ! ~ The results of lhe 10experiments performed are shown as lhe loglOWBC depletion, RBC recovery and platelet reduction, and expressed as mean :t 50 of 10 experiments in each group. The hematologicaldata are summarized in table I. ..-,,' .::.~ ...'(,)d~:::':~~'~~"",,~ ..-..'.. i J I Table 1. Ilcrn~lol()gic~lú:lla(lfl'rc."ndp(ls!. Absolule Postli1tralion Prcfillralion Hcmalological paramcler; fill r~ljon unils mean :t 5D \\'BC counl WBOI'I mean :t SD range 2.190.29xIOQ I. 'XJ-.3 DO 0.29:t 0.05 x tO'> 0.21-D.38 4.290:t 527 :\.4 00- 0.5:t 0.1 O.4-D.S 3.86.:t 0.08 3.85-.1.96 :; . 'XX) 10glOdcpkllon CV.% 2.1 Volume. ml 515.0:t 25.6 485.0--5800 482.0:t g/dl 10.9:t 1.6 9.9-13.4 1O.8:t 0.7 RBC reco\ery. % Plalclets x 10" 0.73 :t 0.10 0.62-D80 Hemoglobln. . Tab. 2. Conccnlrations of proinnammalor)' I cylOkines IL-8. TNF.cx)' during lhe sroragc(IL-I. period IL-6. in liltcrcd and unfiltered unils. Day O 7 1-1 I 28 .\:' 'IL.l. IL-I: range Blood unir fillercd nol liltered fillered no! liltercd liltered nol lillered filtercd no! liltcred filtered nol filtcred filtered no! fillered filtcred not liltered filtcred no! fillercd IL-Ib 3.4 :t 1.0 33 :tO.9 4.5 :t 1.6 4.2:t 1.4 .1.1:t 1.6 4.4 :t 21 3.6:t I.7 4.4 :t 1.1 4.5 :t 1.8 4.4 :t 21 4.0 :t I.7 -I.7:t 1.6 -I.0:t IA 6.1 :t 1.6 6.4 :t 2.1 7.3:t 21 IL-6 <1 <1 <1 <1 <I <1 <] <1 <1 <1 <] <1 <] <I <I <1 31.3 450.0--530.0 9.7-13.0 92.5 :!: 1.] 91.2-94.0 0.05 :!:0.01 O.O3-D.OS IL.g< TNF -a 3.4:t 0.9 1.1 3.9:t 1.8 5.1:t 4.2:t 0.9 5.0:t 2.2 10.6:t 7.2 5.0:t 1.8 9.6.:t 6.9 8.7:t 5.2 6.6:t 2.5 9.2:t 6.9 42.0:t 59.0 7.8:t 3.2 61.0:t 95.0 7.4:t 3.5 J02.0:t 164.0 < I < 1 < 1 < 1 < 1 < I < 1 < 1 < 1 < 1 < I <I <1 <.1 < 1 <1 IL-6.IL-S. Th'F-a are cxpres.sed as pgJml. p>O.05. cIL-8: p > 0.05. WBC Reduc/ion and RBC Recovery In lhe prefiltration units lhe absolute number of leukocytes ""as 2.19:t 0.29 x 109 while in lhe postfíltr~tion s.amples lhe mean WBC countlJlI was 0.5:t 0.1 with a mean number of ,residual WBCs in lhe units of 0.29:t 0.049 x Iet. The mean loglOdeplelion was 3.86:t 0.08 (CY 2.1%). The mean volume of lhe prefiltration units was 515 :t 25.6 ml while that of lhe poslfiltration units was 482 :t 313 ml. Hemo. globin was evalualed in lhe samples before and afterJiltration by an aulomated counler to calculale RBC recovery. The he. moglobin couot was 1O.9:t1.6gldl and 1O.8:t0.7 g/dl in lhe pre- and postfiltralion samples. respectively. and lhe RBC re. :overy was 925:t 1.1%. Plare/erReduction and TImeof Filrfnrion me mean abs~lute number of platelets in lhe prefiltration .vhole blood units was 0.73:t 0.1 x 1011while in lhe poslfiltraíon units it was 0.054:t 0.01x 1011wilh a mean deplelion of /2.6 :t 4.1%. The time of filtration with a continuous constant now ranged from 10 to 11 mio. Cnokine Derermillarion Cytokine concentrations obtained in lhe lwo different groups on lhe days O, 1,3. 7, 14,21, 28, and 35 are summarized in lable 2. lL-6 and TNF-o: \Vere nol detected in lhe samples during lhe storage penod, neither in lhe control unils Dor in lhe fillered unit$.. The concentralions of bolh proinf1aminatory cytokines were less than 1 pglml in a1l samples tested. Our results did not show any s~nificativc difference of IL11~ concentrations in both groups during storagc lime. Moreover, IL-l~ was no! significantly higher in lhe twogroups when comparing dar O and dar 35 (p > 0.05). Its concentration in lhe fiJtered and unfiltered unils was 3.4:t 1.0pg/ml and 3.3 :t 0.9 pg/ml, respectively, at dar O and 6.4 :t 2.1 pg/ml and 7.3 :t 2.2 pglml, respectively, at dar 35. Io two out of lhe ten experiments, lhe leveI of IL-8 in t~e un- i ..~,,;';:.: .,~.},)i;;'/.~::;'>..: . '. '::;\::{~. <;.j.;{;i'~>:'. '. . ... ':., ;.,;;~.~; 111 I 1, I 1;1 fillcrcd unit was significantly highcr aI dar 35 in comparison wilh lhe levelsal the days O, 1,3.7, and 14.AI lhe slorage dar 21 weobscrved in one experimenl an increase of the !L-8conccnlralion (250pglml) that reached lhe highest quanlity at dar 35 with a concentration of 620 pglml whife in anothcr experimenllhe IL-8 conccntration was 156pglml and 415 pglml at the days 21 and 35, respectively. In lhe olheI eight experimenls lhe concentration of IL-8 did not increase during storage lime and lhe quantities were similar in the two groups wilhout significative difference (p > 0.05). BaCleria/ eu/fures In neilher of lhe samples laken from whole blood units afIeI 35 days of storage growth of bacterial cultures could be s~own. Discussion In Ihis study we evaluated lhe efficiency of lhe new filter Biofil in combination with'lhe NPBI Compot1ex bag designed by lhe manufacturer for fillration of whoIe blood after harvesling. The WBC counting melhod for lhe postfillration unils was lhe Nageotte chamber validated by lhe BEST group [16.17]. The results showed that this filter is able to reduce WBCs by 10glO3.86:t 0.08 (CV 2.1%) with a mean number of residual WBCs in lhe postfi!tration units of 0.29:t 0.049 x 1()6.In ali experiments lhe mean absoIute number of leukocytes in lhe postfiltration unit was less than 0.5 x 1()6.confirming a high reproducibility performance comparable to that described in filtersforpackedRBCs[5]. . The recovery of RBCs was92.5 :t 1.1% and thus similar to data previously rcportcd usingfilters for packed RECs. This is in accordance with lhe AABB standards that require a rescoe of at least 80% of lhe original RBCs [18J and with lhe new guidelines regarding leukoreduction of blood recently promulgaled by lhe US Food and Drug Administration which reporl Ihat leukodepletion devices should not sacrifice more Ihan 15% of lhe therapeutic blood eIements. ' The number of platelets is reduced in lhe postfillration unil.S, wilh a mean depletion of92.6 :f:4.1% in comparison to lhe absolule number of platelets in lhe prefiltration units. This datum is important because packed RBCs separated from lhe plasma afIeI centrifugation are depleted fram WBCs and platelets, assuring an optimal blood component in aIJoimmunized patients with a higb tireI of anti-HLA that must be transfused with'rnore units of packed RBCs. / In pIate/et concentrares high leveIs of prointJammalory cytokines were detected afIeI 3 days of storage. and their presence is one of the possible causes of FNHTRs. Several studies have shown thal in prestorage leukodepleted platelet concentrates a prevenlion of lhe cytokine accumulation couId be achieved. suggesling that tbis accumulation is caused by cylokine synthesisand secretion or leukocyles in lhe blood componenls. Howcver, in packed RBCs lhe cold slorage condition should have an inhibilory effecI on celfular metaboliSI1lwitha reduc. tiDo in cytokin~ synthesis in contrast 10 platelel concentrales where cytokine'accumulalion occurs. Nonetheless, a (cwsludies have described lhe presence of IL-l~ and IL-8 in slored packed RBCs, though with lowcr concentrations than in platelet concentrales. ln particular, Stack el aI. [11] dcscribed a mean IL-8 concentration of 512:t 543 pg/ml in units of packed RBCs storcd for 42 days in which 20% of lhe uni[s had a concentralion of >1,000pglml and 40% or >500pg/ml: in contrast, lhe group of WBC-filtered units showed a mean IL-8 eoncentration of 49 pglml.Thc results of Smith el aI. [12] wen: also in Iine wilh reduced amounts of IL-8 in leukodepIeted RBCs. ane aim of this study was 10 investigare whelher or nol lhe accumulation of cytokines in whole bIood was prevented 'by lhe prestorage leukodepletion. The results showed Ihal IL-6 and TNF~a were not detected in any unit tesled while IL-lp and IL-8 were detected in low concentrations in units af bolh groups: in only Iwo experirnents in lhe group of unfiltered units we did observe an increment of lhe IL-8 concentration afIeI 35 days of storage with 620and 415 pglml, respeclively. The present data and those reported by Stack et aI. [11]and Smith et aI. [12] suggest considerable variations in lhe measured IL-8 concentrations. MelhodoIogic factors mighl piar a role. and varialions in lhe sensitivity of different commerciaf immunoassay kirscannol be excluded. However, 'biological variabilities of dono r leukocyte characlerislics alIowingnew synthesis ar release of preexisling inlracellular cytokines despjle lhe low slorage temperature should also be considered. A possible effecl of mixing whole blood cells obtained from two donors on activation of ceIls and production 9f cytokines as possible altemative to lhe production of IL-8, is unlikely since lhe slimulation rcquires melabolicalIy active and viable Iymphocyles.However, in blood camponents slored at 4 °C,lymphoc)'les are not proliferative and are induccd 10 apoplosis by cold slorage condilions, which is in contrast 10 plaleJeI concentrales produced eram buffy coals stored at 20 °C [19-21J. In condusion, despite tIl; limited number of experimenls performed, our data suggesl some conclusions. 111enew filler Biofil in combinalion wilh an NPBI Compot1ex system has a high performance in lhe leukodeplelion of whole blood like Ihat described for lhe last gencration of fillers for packed RBCs. Proinflammatory cylokines are presenl in lower concentralions in whofe bJood Ihan in plalelet concentrares; prestorage leukodepletion ofwhoIe blood could be employed in lhe preparalion of blood components in blood banks lha I need filtered packed RBCs for hematological patients. Even though only Iwo experiments in lhe group of unfiltered unils showed an increase of lhe IL-8 cylokine levei, preslorage leukodepletion seems 10 prevenI cytokine accumulalion in cases where lhe danar Ieukocytesdo not reduce their metabolism during cold slorage. 11: II. I I I.i i Ii: ,i . . . . "',; >-;~;; ':.; ,.:~/:~i,;:~:'."~~-', ',. .' ,." , :" . ," ~, í ; . I .:. I I References MN. :; f!robakerDf!: Clinicalsignilie.1ncc 01 while ceUalo ló Dumonl U. [)lIk \Vii. Renull. P. Dranu"'e;n H. Eernissc JG: Alloimmunizalion afieI !c!;,kocyle.dc. p!cled mullipJc tandem donor plalelellranslusion. Vox Sang 19985-1:160--166. 2 Triu!z.i DJ. Vanck K. Ryan DH. 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Transfusion 1993;33{suppl): 53S (abstract). 13 Slack G. Baol L. N"p)'Ch.ink P. Snydcr EL Cylokine generation in storcd. white ccU.reduccd and bacteri"Uy contwú""tcd IUÚts01 rcd cclls. Translu. siDo 1995:35:199--2030 I~ Shan ell A. KristWtssoo M. Rembcrger M. Rin]'den O: GeoclOltion of cytókincs in red cell caneca. Irales doring stOl'Olgcis prcvenlcd by prCSlorage hile ccll reduction. Tn.nsfusioo J997:37:67&-ó..~o J5 Bontadini A. Fru<:tF. Coole R: A """'. 1001in "ohile blood eell redoction for padcd red ccl15:5 Jog ck. pklion. Transfus Mcd 1997:7:29-:'2. e<llcneelor Safer Tramlusion (BEST) Working Pari)' 01 lhe Internalional Sociely aI Blood Trans. lusion (ISBT)oTrans(usion 19%:36:11..:20. 17 Conte R. B'1l\ladini A. Cirillo D. Fruel F: Process eunlrol 01 filtered rcd blood edls: Which coonting melhod7 TrJnslus Med 1997:7:217-219. 18 St.ndard Commillec Amerian Associalion 01 Blood Banks. Standards for Blood Bank and Translusion Savices 1997.18thed. AABR ArlingIDO.Virginia. 1997. 19 Duponl B. Hansen JA. Yoim EJ: Boman mixed. lymphoc)1e culture reaclion: Genetic:s, spccirocily. and biological implicarion$. Adv Immonoll98I:3I: 107-202, 20 Frabclli F. Mosiani D. Marini M. Fanelli C. CoppoIa s.. Ghitsclli L. Tazuri PL. Bonladini A. Tassi C. Conte R: \\ 'bile ali apoplos;s in paeked rcd eclls. Transfusi<1l\1993:38:1082-1039. ]! Helland Go ~oflnes TE, Bergh K. Hogascn K. Bergcrutl L'E, Solheim BG: Elfcd 01 filtmion and slora~e 01 rblc!el coneentralCS on lhe prodUCtion 01 lhe chem,>ta,ins C5.. inlcrlcukin 8, IUmor nccr(1$h C1..Jntl kokotriene B.o Translusion 1993: 38:16-2..'. 2. Kasseler Trm;isfusionsgesprache (vormaIs Hannoveraner Transfusionsgesprãche) Ort: Universitat Gesarnthochschule Kasse!, Hollãndischer Platz, Kassei Termin: 3J4. Marz 2000 Themen:. Praklische Probleme und akluelle Themen der Transfllsionsmedizin 1m Hinblick auf die Aktualitãt werden °dic Themcn erst Endc des Jahres festgelegt. Jedcr kann noch Vorschlage machen. ' . Bisher anvisÍerte Themen: 1. NoveUierte Richtlinien 2. In-linc-Leukozytendepletion - aktueller Stand 3. Eignung von verschiedenen Labormethoden für(Qualitatskontrollen. Ringversuchc usw. 4. Transfusionsvorbereitung bei ilTegularen Antikõrpem 5. Fort- und Weiterbildung - Umsetzung in der Praxis. Weitere Wormationen: OrganisationJAnm~ldung: 'ProL Dr. G. Holzberger DRK-Blutspendedienst Kassel MõnchebergstraBe 57 D-34125 Kassel Te!. +49 561 'ó/93-201, Fax -203 AlImeldung VOllDiskllssioll5beifragen: - ProL Dr. V. Kretschmer Abteilung für Transfusionsmedizin und GerinnungsphysioIogie Klinikum Marburg ConoradistraBe 0-35033 Marburg Te!. +496421 286-6282. Fax -56 55 .,. <o/., ..:..,;o,:.::.:t/~~:,:.;Lo'f~,,~~;~'i:.,