transfuzia pediatriaSi

1. transfuziapediatriaSi Tbilisi, saqarTvelo seqtemberi/oqtomberi, 2010 Christopher J. Gresens, M.D. VP & Medical Director, Clinical Services BloodSource

2. Ppediatriuli transfuziologia mizani-am moxsenebis bolos monawileebs unda SeeZloT... Camoayalibon, rodis da rogor unda Catardes transfuzia axalSobileSi nayofis da axalSobilis hemolizuri daavaadebis, fetalur/neonataluri aloimunuri hemolizuri anemiis diagnostirebis da marTvis principebis codna.

3. Ppediatriuli transfuziologia-ZiriTadi sakiTxebi • ganviTarebis da imunologiis safuZvlebi • neonataluri transfuzia • fetalur/neonataluri hemolizuri daavadeba • fetalur/neonatalurialoimunuri Trombocitopenia

4. Ppediatriuli transfuziologia ganviTarebis da imunologiis safuZvlebi

5. ganviTareba da imunologiaplacenta da dedis antisxeulebis roli normalur pirobebeSi mxolod dedisIgG (da araIgM, IgA, anIgE) gadis placentas IgG IgE IgA IgM

6. Dembrionaluri da fetaluri ganviTarebis periodebi ganviTareba da imunologia From K.L. Moore, The Developing Human (3rd ed.), 1982.

7. ganviTareba da imunologia kvercxujredis implantacia da adreuli ganviTareba From F.H. Netter’s Reproductive System, 1984.

8. ganviTareba da imunologia placentis da fetaluri membranebis ganviTareba From F.H. Netter’s Reproductive System, 1984.

9. ganviTareba da imunologia placentaruli sisxlis mimoqceva From F.H. Netter’s Reproductive System, 1984.

10. ganviTareba da imunologia placentis anatomia From F.H. Netter’s Reproductive System, 1984.

11. DganviTareba da imunologia placenta da dedis antisxeulebis roli dedis IgG transportirebaxorcieldeba aqtiuri trasportirebis saxiT da iwyeba gestaciis me-14 kviras.

12. ganviTareba da imunologiaplacenta da dedis antisxeulebis roli dedis IgG gadis placentas da iwvevs nayofis da axalSobilis hemolizur daavadebas da fetalur/neonatalur aloimunur Trombocitopenias. Mom’s IgG Fetal Circulation

13. ganviTareba da imunologiaimunologia PLATELET (or RED CELL) Platelet or red cell destruction occurs due to the interaction between: (1) Antigen, (2) IgG, and (3) Reticuloendothelial Fc receptor.

14. Ppediatriuli transfuziologia Nneonataluri transfuziologiis praqtikuli sakiTxebi

15. Nneonataluri transfuziis praqtikuli sakiTxebi • Nneonataluri transfuziis sixSire transfuzia utardeba bevr hospitalizebul axalSobils, maT Soris … • … Zalian dabali masis mqone dRenakl axalSobilebs • transfuziis mizezebia Tanaarsebuli paTologia dRenaklTa anemia (pirveli 2-3 kviris manZilze) samedicino manipulaciebiT ganpirobebuli, mag: flebotomia • sxva procedurebi

16. Nneonataluri transfuziis praqtikuli sakiTxebi • maSin, rodesac pediatrebisTvis “axalSobili”aris pacienti asakiT < 28 dRe, sisxlis bankisTvis “neonataluri transfuzia”moiazreba pacientebSi asakiT< 4 Tve • sisxlis konservirebis bevri meTodi (autologiuri donacia/trasfuzia) ar aris praqtikuli neonatologiaSi • transfuziis dros axalSobilebs aqvT arasasurveli Sexeba mraval donorTan

17. Nneonataluri transfuziis praqtikuli sakiTxebi (gagrZeleba) • axalSobilebSi transfuziasTan dakavSirebul riski aris iseTive,rogorc sxva SemTxvevaSi, gansakuTerebiT… • …siTxiT gadatvirTva da … • … riski didi raodenobiT kaliumis, citratis miRebis, an iseTi nivTierebebis, romlebic Sedian antikoagulanti-damcavis SemadgenlobaSi

18. Nneonataluri transfuziis praqtikuli sakiTxebi (gagrZeleba) • “tipiuria” 10-to-15 mL/kg transfuzia 2--3 saaTis manZilze, Cveulebriv kargi amtanobiT xasiaTdeba, miuxedavad sisxlis produqtis xandazmulobis an damzadebis tipisa. • Tumca masiuri transfuzia mag> 20 mL/kg SedarebiT mokle drois periodSi (mag. kardiopulmonaruli Suntirebis an CanacvlebiTi transfuziis dros) SesaZlebelia gaxdes ufro problematuri …

19. Nneonataluri transfuziis praqtikuli sakiTxebi (gagrZeleba) • Mmasiuri transfuziisTvis gamoiyeneba, RBC romelic aris: • CPDA-1 antikoagulant-damcavis Semcveli (an garecxili) • < 7 dRe(an garecxili) uaryofiTi HgbS • (CanacvlebiTi transfuziis dros) rekombinirebulia AB jgufis plazmasTan,h ematokritis misaRebi maCvenebelia ( 40 – 50% is farglebSi) [SeniSvna: xSirad, rogorc mosaxerxebeli, gamoiyeneba O -jgufis RBC; Tumca es yovelTvis ar aris aucilebeli]

20. Nneonataluri transfuziis praqtikuli sakiTxebi (gagrZeleba) • RBC-is transfuziis gaidlaini< 4 Tvis asakis pacientebSi. Cvenebebia: • hematokriti < 20% retikulocitebis dabali koncentracia da anemiis simptomebi • hematokriti < 30% im pacientebSi romlebic:iReben < 35% O2 niRbiT • iReben O2 nazaluri miliT • imyofebian meqanikur ventilaciaze-mudmivi dadebiTi wnevis da/an wyvetil reJimze, saSualo wneva < 6 cm H2O • mniSvnelovani apneiT an bradikardiiT • mniSvnelovani taqikardiiT an taqipneiT • wonaSi cudi mateba (Continued on next slide)

21. Nneonataluri transfuziis praqtikuli sakiTxebi (gagrZeleba) hematokriti < 35%,pacienti aris: • > 35% O2-ze • Mmeqanikur ventilaciaze Semdegi reJimiT-mudmivi dadebiTi wnevis/wyvetili ventilaciis saSualo wneviT> 6 – 8 cm H2O hematokriti < 45%,pacienti aris: • eqstrakorporalur membranul oqsigenaciaze • daavadebuli gulis cianoturi mankiT From P.D. Mintz (ed.) Transfusion Therapy: Clinical Principles and Practice, 2nd ed. AABB Press, Bethesda, MD, 2005.

22. Ppediatriuli transfuziologia Ffetalur/neonataluri hemolizuri daavadeba Hemolytic Disease of the Fetus/Newborn (HDF/N)

23. HDF/N – klinikuri SemTxveva • 26 wlis qali, G2P1. • Ppirveli fexmZimoba iyo fiziologiuri, amJamad aris gestaciis 22 kviraze wiTeli ujredebis mimarT antisxeulebis titris perinatalurma skriningma aCvena anti-D-s maRali titri (1:2048) da anti-E (1:1)-s dabali titri • ultrabgeriTi kvleviT gamovlinda nayofis hidrofsi (erTi kviris win Catarebul kvlevaze darRvevebi gmovlenili ar iqna). • Mmeanma moiTxovaSesabamisi RBC, saSvilosnosSida transfuziisTvis.

24. HDF/N – klinikuri SemTxveva • hospitalisTvis mowodebuli RBC akmayofilebda Semdeg parametrebs: • Group O, Rh(D)-negative, E-negative • CMV-neg., dasxivebuli, da Senaxvamdeleikoreducirebuli. • CPDA-1 antikoagulant-damcavi, xandazmuloba < 5--7 dRe skriningi Catarebulia namglisebur eriTrocitebze (hospitalis transfuziis samsaxuris mier) dayofilia or porciad, TiTo 120 mL (mxolod erTi porcia iqna dasxivebuli) • “hemokoncentrirebulia”- Hct of 80% + 2%

25. HDF/N – Case Study • Nnayofis Tavdapirveli hemoglobinis koncentracia iyo 2.9 g/dL; • Nnayofma warmatebiT gadaitana tranfuzia (transfuziis Semdeghemoglobinis koncentracia ar aris Semowmebuli analizis aRebis teqnikuri problemis gamo) • II saSvilosnosSida transfuzia Catarda gestaciis 23 kviras imave principiT. (hemoglobinis maCvenebelma momimata 6.9 dan 16.0 g/dL).

26. HDF/N – Case Study • III da VI saSvilosnosSida transfuziebi Catarda gestaciis 25, 28, 32, da 35 kviras analogiuri principiT. • Ddaibada drouli axalSobili,normaluri hemoglobiniT (mniSvnelovani neonataluri paTologiebis gareSe).

27. HDF/N – mimoxilva • Ffetaluri/neonataluri hemolizuri daavadeba (HDF/N) aris dedis antisxeulebiT ganpirobebuli nayofis/axalSobilis RBC –is daSla; • Ddedis sensibilizacia Cveulebriv xdeba wina orsulobis an transfuziis dros • erT dros SemTxvevaTa daaxloebiT 95% ganpirobebuli iyo anti-RhO(D).

28. HDF/N – mimoxilva • ganviTarebul qveynebSi1968 wels Rh immune globulin (RhIg) is danergvam mniSvnelovnad Seamcira anti-D –iT ganpirobebuli daavadebebis ricxvi • RhIg-Tan erTad, dainerga bevri sxva axali meTodi HDF/N diagnostirebisa da mkurnalobisTvis (mag ultrabgeriTi kvleva, Wiplaris sisxlis transabdominaluri aspiracia)

29. HDF/N – istoriuli mimoxilva • HDF/N –Tan asocirebuli paTologiuri cvlilebebi eqimebis mier pirvelad aRwerili iyo me-17 saukuneSi • 1939: Levine/Stetson aRweres transfuziis Semdgomi reaqcia: qalbatons mSobiarobis Semdeg gadaesxa meuRlis sisxli (maTi azriT, dedis imunizacia meuRlis RBC-is mimarT moxda via fetus); • 1940: Landsteiner/Wiener • kurdRlebsa da zRvis goWebs Cautares sensibilizacia Rhesus monkey RBC-is mimarT,Semdeg gamoiyenes Srati, rom eCvenebinaT, rom deda iyo Rh-negative, da mama Rh-positive.

30. HDF/N – daavadebis meqanizmi Mom’s IgG Fetal Circulation • Ddedis antisxeulebi Slian nayofis RBC; • Pplacentarul bariers gadis mxolod IgG (IgM, IgA da IgE -ara); • HDF/N-Si, IgG antisxeulebi mimarTulia mamisgan damemkvidrebuli fetaluri RBC-is sawinaaRmdegod.

31. HDF/N –dedis sensibilizacia da Rh(D) • Cveulebriv. Rh-negative dedis pirveli mSobiarobisas dabadebuli Rh-positive axalSobili ar aris daavadebuli (radgan ar moxda “sruli“ imunizacia) • Ggestaciis, mSobiarobis dros (rodesac placenta scildeba saSvilosnos)fetaluri RBC-aRwevs dedis sisxlis momoqcevaSi

32. HDF/N – dedis sensibilizacia da Rh(D) fetaluri ujredebi, romlebic atareben mamisgan miRebul Rh antigens, astimulireben dedis organizmSi anti-D –s warmoqmnas From A.D.A.M. Website, 2001.

33. HDF/N –dedis sensibilizacia daRh(D) • Yyoveli Semdegi D antigenis mqone nayofi avaddeba • Ddedis anti-D gaivlis placentas, miuerTdeba Rh-positive RBC, da gamoiwvevs retikoloendoTeliaruli sistemis mier maT daSlas, anemiis ganviTarebas From A.D.A.M. Website, 2001.

34. HDF/N – faqtorebi, romlebic ganapirobeben simZimesantigenebis eqspresia • Mmolekuluri biologiis meSveobiT dadginda, rom fexmZime qalebis umravlesobis sisxlSi aris fetaluri ujredebi; • Uumetesad, deda/nayofis hemoragia umniSvneloa, Tumca dedis sensibilzacia SeuZlia 1.0 mL fetalur RBC. • Aaloimunizebul qalebSi, deda/nayofis hemoragia iwvevs dedis antisxeulebis mniSvnelovan zrdas, mZime gamosavals.

35. HDF/N – faqtorebi, romlebic ganapirobeben simZimesmaspinZlis faqtori • Kkompleqsuri genetikuri faqtorebi ganapirobeben individis unars warmoqmnan antisxeulebi antigenis sapasuxod • Rh(D)-negative pirebSi, 1 erTeuli Rh(D)-positive RBC-is transfuziis Semdeg, 80% mde izrdeba anti-Rh(D) aloantisxeulebis raodenoba. • Tu Rh(D)-negativededas, Rh(D)-positivepozitiuri mSobiarobis Semdeg ar Cautarda imunizacia RhIG –iT, aloimunizaciis riski 10%-ia (rCeba sakmaod maRali).

36. HDF/N – faqtorebi, romlebicganapirobeben simZimesantisxeulebis specifiuroba • Rh(D) xasiaTdeba yvlaze maRali eqspresiulobiT RBC antigenebs Soris • Aamis gamo Rh(D)-negative qalebs usxamen mxolod Rh(D)-negative RBC • sxva Rh antigenebi (e.g., C, E, and c) arin Zlieri imunogenebi (Tumca ufro susti vidre D), da iwveven saSulo da mZime HDF/N; • Rh Aantigenis ar arsebobisas, big-K miiCneva klinikurad yvelaze mniSvnelovnad

37. HDF/N – faqtorebi, romlebicganapirobeben simZimesantisxeulebis specifiuroba Antibody Causes of HDF/N CommonRareNever Anti-D Anti-FyaAnti-Lea Anti-D + CAnti-s Anti-Leb Anti-D + EAnti-MAnti-I Anti-CAnti-NAnti-IH Anti-EAnti-S Anti-P1 Anti-c Anti-e Anti-K

38. HDF/N – faqtorebi, romlebicganapirobeben simZimes ABO sistemis gavlena • rodesac dedas da nayofs Soris aris mniSvnelovani ABO (mag deda=O,nayofi=A) SeuTavsebloba, imunizaciis sixSire Rh(D) naklebia • ABO SeuTavsebloba garkveul wilad icavs Rh(D) imunizaciisgan (? –nawilobriv imiT, rom xdeba dedis organizmSi nayofis Rh(D) pozitiuri RBC-is daSla, sanam isini moaxdenen dedis sensibilizacias.

39. Hemolysis occurs when mom’s IgG attaches to specific antigens on the fetal RBCs The antibody-coated cells are removed from circulation by macrophages of spleen HDF/N –paTogenezihemolizi, anemia da eriTropoezi PLT/RBC

40. HDF/N – paTogenezihemolizi, anemia da eriTropoezi • RBC-is destruqciis xarisxi damokidebulia antisxeulebis titrze/specifiurobaze, aseve fetaluri RBC-is antigenebis raodenobaze. • fetaluri RBC-is destruqcia iwvevs kompensatorulad eriTropoezis gaZlierebas Zvlis tvinSi, elenTasa da RviZlSi.

41. HDF/N – paTogenezihemolizi, anemia da eriTropoezi

42. HDF/N – paTogenezihemolizi, anemia da eriTropoezi From Robbins Pathologic Basis of Disease (5th ed.), 1994. • Spleen and liver become enlarged, resulting in portal hypertension and hepatocellular damage; • Severe anemia, along with reduced plasma protein production by liver can result in hydrops fetalis.

43. HDF/N – paTogenezihemolizi, anemia da eriTropoezi • mZime SemTxvevebSi hidrofsi SesaZlebelia ganviTardes gestaciis 18-20 kviras. • Bbolo dromde hidrofsi iTvleboda fatalur daavadebadc(dRes axalSobilTa umetesoba warmatebiT ikurneba). • RBC –is destruqcia grZeldeba dabadebis Semdegac,cradgan jer kidev cirkulireben dedis IgG,cTumca hemolizis xarisxi iklebs.

44. HDF/N – paTogenezihiperbilirubinemia • The RBC-is destruqciis Sedegad gamoiyofa hemoglobini, romelic gardaiqmneba arapirdapir bilirubinad • In utero, arapirdapiri bilirubini gaivlis placentas da sabolood metabolirdeba dedis RviZlSi (ar iwvevs nayofis klinikur paTologias). • Ddabadebis Semdeg bilirubinis akumulacia iwvevs seriozul problemebs, ramdenadac neonatalur RviZls ar aqvs unari efeqturad moaxdinos bilirubinis metabolireba/gamoyofa

45. HDF/N – paTogenezihiperbilirubinemia From DM Harmening’s Modern Blood Banking (4th ed.), 1999.

46. HDF/N – paTogenezihiperbilirubinemia • mZime da saSualo hemolizis dros arapirdapiri bilirubinis donem SeiZleba miaRwios c.n.s-isTvis toqsiur dones( > 18 mg/dL); • Mmkurnalobis gareSe SesaZlebelia Camoyalibdes tvinis permanentuli dazianeba (kernicterus).

47. HDF/N – paTogeneziSummary From F.H. Netter’s Reproductive System, 1984.

48. HDF/N – diagnostireba da marTva • Ddiagnostireba da marTva moiTxovs fexmZime pacientis, meanis, mamis da laboratoriis mWidro TanamSromloba • Pprocesis safuZvelia sisxlis testireba da klinikuri meTvalyureoba Sesabamis periodebSi • mniSvnelovani problemis aRmoCenisas adeqvaturi Careva (saSvilosnoSida transfuzia)

49. HDF/N –diagnostireba da marTvasisxlis banki (serologia) • “tipireba da antsxeulebis skriningi” tardeba pirveli antenataluri vizitis dros (sasurvelia pirvel trimestrSi). es moicavs: • ABO da Rh testireba (D antigenze), da kidev ufro mniSvnelovania … • … testireba ara-ABO aloantigenebze.

50. HDF/N – diagnostireba da marTvaserologiuri testirebaantisxeulebis gansazRvra • Pprenatalurma testirebam unda SesZlos klinikurad mniSvnelovani IgG antisxeulebis gansazRvra 37º C-ze; • gamoiyeneT> 2 skrining ujredi • Aantisxeulebis raodenobis gazrdisTvis aucilebeli niadagebi (e.g., LISS an albumini)aseve Zalian mniSvnelovania.