Acute Transfusion Reactions Shan Yuan, MD Updated May 19, 2011

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1 Acute Transfusin Reactins Shan Yuan, MD Updated May 19, 2011 I. Acute Hemlytic Transfusin Reactins A. Incidence: 1: 38,000 t 1:70,000 B. Etilgy/Pathphysilgy RBC antigen RBC antibdy reactin usually due t ABO incmpatibility Other cmmnly implicated allantibdies: Kell, Kidd, Rh Usually due t mistransfusin r clerical errrs Ag-Ab activates the fllwing systems: Neurendcrine: Ag-Ab XIIa prductin/activatin f Bradykinin Hyptensin sympathetic vascnstrictin f renal, splanchnic, pulmnary and cutaneus vascular beds Cmplement: Ag-Ab activated cmplement n RBCs intravascular hemlysis with free Hgb and RBC strma (cntributes t ATN?) r C3b RE system Cagulatin: - Intrinsic cascade by XII r RBC strma DIC cnsumptin cagulpathy with bleeding - Prductin f anaphylatxins degranulatin f mast cells release f histamine and sertnin Primary cncerns: Renal ischemia due t hyptensin, renal vascnstrictin and intravascular thrmbi which may lead t ATN DIC C. Signs/Symptms Usually ccur early during the transfusin. Onset f symptms may nt necessarily by sudden; may be mild and vague Fever r fever and chills (mst cmmn presenting sign, >80%): increase in bdy temperature by 1 C Others signs/symptms: chest pain, back pain, pain at infusin site, nausea, flushing, dyspnea, hemglbinuria, liguria, anuria, bleeding, hyptensin, shck Difficult t recgnize in anesthetized patient may manifest as hyptensin, hemglbinuria, and evidence f DIC D. Actin/Therapy Stp transfusin immediately,; keep IV line pen and administer saline t maintain BP Clerical check at bedside Ntify bld bank, send apprpriate specimens Primary gals f therapy: Treat hyptensin

2 Prmte renal bld flw (in adults: maintain urine utput at 100ml/hr fr hrs) Use f smtic r diuretic agents (fursemide) Lw dse dpamine t increase CO, dilate renal vasculature If DIC develps treat with bld prducts fr bleeding,?anticagulatin E. Lab evaluatin Clerical check Evaluatin f patient s pre- and pst- transfusin specimens Lk fr free Hgb r bilirubin Visual check fr hemlysis valuable: eye can detect 5-10 ml f hemlysis Repeat ABO, Rh DAT, eluate and cmpare with pre-transfusin specimen if psitive Repeat crssmatch with RBC unit r segment If immune mediated hemlysis suspected, perfrm antibdy screen n new specimen and phentype segment retained frm the transfused unit. Labratry evaluatin f patient Fllw Hgb and Hct Lk fr free Hgb in free urine, r/ intact RBCs Check uncnjugated bilirubin (5 t 7 hurs pst reactin) Haptglbin n patient s pre- and pst- transfusin specimens Urine hemsiderin Cagulatin labs t mnitr fr DIC If bacterial cntaminatin suspected, gram stain/culture unit and patient If clerical check nt OK, free Hgb present, pst DAT psitive, r patient s cnditin suspicius, further investigatin is warranted If DAT negative, n evidence f clerical errr, and n new allantibdy identified, immune mediated hemlysis unlikely. cnsider nn-immune hemlysis (differential) Bacterial cntaminatin f dnr unit Sepsis with Clstridia. Spp. Mechanical damage f dnr unit Heat damage due t faulty bld warmer Mechanical damage due t pressure infusin pump, small bre needle, extracrpreal circulatin Hemlysis due t hyptnic slutins, dextrse slutins, medicatins R/O myglbinemia Drug-induced hemlysis: penicillin, quinidine, -methyldpa, cephalsprins, sulfnamines, rifampicin (DAT+ but eluate negative) II. Febrile Nn-Hemlytic Transfusin Reactin (FNHTR)

3 A. Incidence: 1:17 t 1:200 in RBCs, 1:3 t 1:100 in platelets (mst frequently reprted reactin) B. Etilgy/Pathphysilgy Due t elevated levels f pyrgenic cytkines (IL-1, IL-6, TNF-) in the transfusin recipient. Pssible mechanisms: - Recipient cells (leukcytes, endthelial cells, etc.) may be stimulated directly r indirectly by infused freign cells r plasma cnstituents t prduce pyrgenic cytkines - Dnr leukcytes may be stimulated in viv t prduce cytkines upn infusin int the recipient - Dnr leukcytes in the cmpnent bag may be stimulated t prduce pyrgenic cytkines during strage C. Signs/Symptms Temperature rise f 1 C/2 F r mre in assciated with transfusin (usually during r shrtly after transfusin, but may ccur up t 2 hurs after cmpletin f transfusin) May be assciated with chills and rigrs, r chills and rigrs withut fever Fever may be blunted with premedicatatin Nt life threatening, but causes patient discmfrt D. Actin/Evaluatin Diagnsis f exclusin Patients respnd t antipyretics (severe rigrs may require Demerl) Usual evaluatin required; imprtant t r/ HTR r bacterial cntaminatin If the fever is quite high r accmpanied by hyptensin, r if the clinical picture is very suspicius fr sepsis, make sure the bld bag and the patient are cultured. Prevent with leukcyte-reduced bld prducts fr patients with tw FNHTRs r a mre severe first reactin; cnsider premedicatin with antipyretics III. Transfusin Related Acute Lung Injury (TRALI) A. Incidence: 1:5,000 t 1:190,000 B. Etilgy/Pathphysilgy Dnr antibdies t HLA r granulcyte antigens f the recipient leading t increase in permeability f the pulmnary micrcirculatin (capillary leakage) rarely antibdies in the recipient s circulatin interact with the transfused granulcytes Multiparus female dnrs are at high risk fr develping anti-hla Pssible tw-hit mdel: First hit is recipient cnditin such as sepsis r trauma that activates pulmnary capillary endthelium and primes recipient neutrphils, bth resulting in sequestratin f these cells in the pulmnary vasculature

4 Secnd hit is a dnr factr either specific antibdy r anther factr such as a lipid agent f cytkine which triggers the sequestered neutrphils t damage the endthelium, leading t capillary leak C. Signs/Symptms Acute respiratry distress during r shrtly after transfusin (1-6 hurs but has been reprted within 24 hurs) can be fatal Can be accmpanied by fever, chills, and hyptensin (hypertensin seen less frequently) CXR: pulmnary edema/diffuse bilateral pulmnary interstitial infiltrates Nrmal CVP, nrmal/lw pulmnary wedge pressure Diagnsis f exclusin must rule ut cardigenic pulmnary edema May lk like ARDS, but usually reslves in hurs D. Actin/Evaluatin Stp transfusin immediately Respiratry supprt t maintain xygenatin intubatin may be required Patient shuld nt be diuresed diuresis can further cmplicate the patient s clinical status Usual bld bank evaluatin (cnsider assessing patient and/r unit segment fr HLA and granulcyte antibdies) Preventin: Nne generally necessary since the dnr is usually the prblem Cnsider remving implicated dnrs frm the dnr pl and quarantine ther prducts frm the dnr Other measures dnr centers can take: N cnsensus yet. - Using nly male plasma (UK, American Red Crss) - Deferring dnr with anti-hla antibdies frm dnating plasma r platelets IV. Allergic (Urticarial) Transfusin Reactin A. Incidence: 1:33 t 1:100 (secnd mst frequently reprted reactin) B. Etilgy/Pathphysilgy Due t sluble prducts/prteins in dnr plasma Type I hypersensitivity Dse dependent: mre cmmn secndary t FFP and platelet apheresis prduct than RBCs due t the greater vlume f plasma Usually nt dangerus but may cause patient discmfrt and anxiety C. Signs/Symptms Hives r pruritic rash during r shrtly after transfusin Usually withut fever r ther symptms D. Therapy/Evaluatin If lcalized, can mmentarily stp transfusin and administer antihistamine (i.e. Benadryl). If hives/itching abate, can restart transfusin (nly transfusin reactin in which transfusin can be safely restarted) Rutine bld bank evaluatin if reprted

5 Preventin: cnsider premedicatin if repeated allergic reactins r reactins are particularly severe V. Anaphylactic Transfusin Reactins A. Incidence: 1:20,000 t 1:50,000 B. Etilgy/Pathphysilgy Abut 50% reprted cases ccur in patients wh are IgA deficient with anti-iga Abs due t transfusin r pregnancy IgA deficiency: 1 in 700 individuals but this includes many individuals with lw levels f IgA Fr clinically significant anti-iga t develp in an individual, IgA levels must be absent, nt simply decreased levels, Sme reprted cases have been attributed t antibdies t drugs C. Signs/Symptms Cughing, brnchspasm, dyspnea, vmiting, diarrhea, hyptensin, shck, LOC Symptms may be seen after infusin f nly a few mls f bld r plasma D. Therapy/Evaluatin Stp transfusin immediately; keep IV pen Treat anaphylaxis with sub-q epinephrine, IV sterids, etc. Usual bld bank evaluatin, r/ HTR Sensitive quantitatative assays fr IgA and anti-iga Abs nt readily available (send t Natinal Red Crss) Sensitized IgA deficient patients shuld be transfused with cmpnents lacking IgA Rare dnr file must be cnsulted fr IgA deficiency plasma/platelets Deglycerlized/washed RBCs can be used fr red cell transfusin Autlgus dnatin prvides the safest transfusin VI. Bacterial Cntaminatin (Septic Unit) A. Incidence: 1:2,000 t 1:4,000 B. Etilgy/Pathphysilgy Bacteria prliferate during strage Organisms depends n the prduct, and therefre strage temperature RBCs (irn-lving rganisms) - Yersinia entreclitica - Citrbacter Freundii - E. cli - Peusdmmnas species C. Signs/Symptms Platelets - Gram-psitive ccci, skin cntaminants Rapid nset f high fever, rigrs, abdminal cramping, nausea/vmiting May have hemglbinemia/hemglbinuria D. Actin/Evaluatin Stp transfusin immediately

6 Immediate wide-spectrum antibitics and pressure supprt Usual bld bank evaluatin (plus culture bth the unit and the recipient) Disclred prduct Gram stain/culture f prduct nt segment (unless nly segment available) Preventin Careful dnr histry Prper phlebtmy technique Bacterial detectin systems f platelets VII. Circulatry Overlad Vlume sensitive patients CHF symptms during r after transfusin Treatment: xygen +/- diuresis