Blood transfusion. .., . , .()

Topic modulesBlood blank practicesIndication to blood transfusionComplicationAlternative strategies for management of blood loss during surgery

Blood blank practices

Human red cell membrane : least 300 different antigenfortunately, only the ABO and the Rh systems are important in the majority of blood transfusionHistory Hct. Infection : Hepatitis B,C syphillis HIV-1,2 HTLV-I,II

#Crossmatching (50 min)Confirms ABO and Rh typingDetects antibodies to the other blood group systemsDetects antibodies in low titers or those that do not agglutinate easilyBlood blank practices

Blood blank practices# Antibody screen : Indirect Coombs test (45 mins) the subject serum + red cells ( antigenic composition) ----- red cell agglutination # Type&screen # Emergency transfusion

T&S -determines ABO and Rh status and the presence of most commonly encountered antibodies risk of adverse rxn is 1:1000 -takes about 5 minsT&C -determines ABO and Rh status as well as adverse rxn to even low incidence antigens risk of rxn is 1:10,000 -takes about 45 mins

Type and screen vs Type and crossmatch

Type and screen vs Type and crossmatchT&S:Type O red cells are mixed with pt serum Antibody screenT&C Type O red cells are mixed with pt serum Antibody screenDonor red cells are then mixed with the pts serum to determine possible incompatibility:

Blood blank practices

All units RBC @ PRC 1unit (250 ml Hct.70%) --platelet@ 1 unit (50-70 ml, stored at 20-24c for 5 days) --plasma @ FFP --cryoprecipitate @ high conc. Of factor VII, fibrinogen

Intraoperative transfusion practicesPRC Ideal for patients requiring red cells but not volume replacement Only one Increase O2 carrying capacity

AGE BLOOD VOLUME Neonates Premature 95 ml/kg Full-term 85 ml/kg Infants 80 ml/kg Adults Men 75 ml/kg Women 65 ml/kg Allowable blood loss = EBV*( Hct Hct)/ Hct Hct. 30% not magic number Jehovah s witness

Practice guideline$$ case series : reports of Jehovah witness; some may tolerate very low Hb< 6-8 g/dl in the perioperative period without an incresae in mortality

Practice guideline

$$ In healthy, normovolemic individual, tissue oxygenation is maintained and anemia tolerated at Hct as low as 18-25%(Hb 6-8gm%)

$$ RBC transfusion is rarely indicated when Hb> 10 g/dl and is almost always indicated when Hb< 6 g/dl

American Society Anesthesiologist : 1996

Intraoperative transfusion practices2. FFP ( initial therapeutic dose : 10-15 ml/kg ) isolated factor deficiencies reverse warfarin therapy correction of coagulopathy associated with liver disease used in patients who are received massive blood transfusion with microvascular bleeding Complications (PATCH) Platelets dec,Potassium inc., ARDS, Acidosis,Temp dec., Citrate intoxication, Hepatiti >1 BV/ 24 HR> 50 % BV within 3 hrs > 150 ml/min

antithrombin III deficiency TTP ( Thrombotic thrombocytopenic purpura ) Do not use for volume

Intraoperative transfusion practices3. PLATELETS **thrombocytopenia or dysfunction platelets in the presence bleeding * prophylactic : plt.counts below 10,000-20,000 * prophylactic preoperative : plt.counts below 50,000 *Microvascular bleeding in surgical patient with platelets < 50,000 *Neuro/ ocular surgery > 75,000

Intraoperative transfusion practices3. PLATELETS *Massive transfusion with microvascular bleeding with platelets < 100,0002 BVs = 50,000

*Qualitative dysfunction with microvascular bleeding (may be > 100,000)

Intraoperative transfusion practices3. PLATELETS 50 ml: 0.5- 0.6 x 10 9 platelets (some RBCs and WBCs)

Single donor apheresis OR Random donor (x 6)

Intraoperative transfusion practices

4. CRYOPRECIPITATE 10 ml: fibrinogen (150-250 mg), VIII (80-145 U), fibronectin, XIII

1U/ 10kg fibrinogen 50 mg/dL (usually a 6- pack)

Hypofibrinogenemia (congenital or acquired)

Microvascular bleeding with massive BT (fibrinogen < 80-100mg/dL)2 BVs = < 100 mg/dL

Bleeding patients with vWD (or unresponsive to DDAVP)

Alternative strategies for management of blood loss during surgeryAutologous transfusionBlood salvage & refusionNormovolemic hemodilution

Blood is still the best possible thing to have in our veins - Woody Allen

Blood transfusion is a lot like marriage. It should not be entered upon lightly, unadvisedly or wantonly, or more often than is absolutely necessary - Beal

TRANSFUSION REACTIONSis any unfavorable transfusion-related event occurring in a patient during or after transfusion of blood components

TRANSFUSION REACTIONS@RBCs !Nonhemolytic 1-5 % transfusions Causes -Physical or chemical destruction of blood: freezing, heating, hemolytic drug -solution added to blood -Bacterial contamination : fever, chills, urticariaSlow transfusion, diphenhydramine , antipyretic for feverHemolyticImmediate: ABO incompatibility (1/ 12-33,000) with fatality (1/ 500-800,000) Majority are group O patients receiving type A, B or AB blood Complement activation, RBC lysis, free Hb (+ direct Coombs Ab test)

Acute Hemolytic Transfusion Reaction Ab (in recipient serum) + Ag (on RBC donor)-Neuroendocrine responses-Complement Activation-Coagulation Activation- Cytokines EffectsAcute hemolytic transfusion reaction Pathophysiology

Acute Hemolytic Transfusion Reactions

Acute onset within minutes or 1-2 hours after transfuse incompatible blood Most common cause is ABO-incompatible transfusion

Signs and Symptoms of AHTRChills , feverFacial flushingHypotensionRenal failureDICChest painDyspneaGeneralized bleeding

HemoglobinemiaHemoglobinuriaShockNauseaVomittingBack painPain along infusion vein

Anesthesia: hypotension, urticaria, abnormal bleedingStop infusion, blood and urine to blood bank, coagulation screen (urine/plasma Hb, haptoglobin)Fluid therapy and osmotic diuresisAlkalinization of urine (increase solubility of Hb degradation products)Correct bleeding, Rx. DIC

Laboratory investigation for AHTRsample from blood bag Repeat ABO, Rh, Ab screeningPatient sample Pre Tx sample Repeat ABO, Rh, Ab screening Post Tx sample Repeat ABO, Rh, Ab screening, DAT, CBC, UA, Bilirubin, BUN, Cr, Coagulation screeningRepeat compatibility test - Pre Tx sample & Donor unit - Post Tx sample & Donor unit

Delayed: (extravascular immune)1/ 5-10,000 Hemolysis 1-2 weeks after transfusion (reappearance of Ab against donor Ag from previous exposure) Fever, anemia, jaundice

Alloimmunization Recipient produces Abs against RBC membrane Ag Related to future delayed hemolytic reactions and difficulty crossmatching

@WBCs!Europe: All products leukodepletedUSA: Initial FDA recommendation now reversed pending objective data (NOT length of stay for expense)

Febrile reactionsRecipient Ab reacts with donor Ag, stimulates pyrogens (1-2 % transfusions) 20 - 30% of platelet transfusionsSlow transfusion, antipyretic, meperidine for shivering

TRALI (Transfusion related acute lung injury)Donor Ab reacts with recipient Ag (1/ 10,000) noncardiogenic pulmonary edemaSupportive therapy

Transfusion-related Acute Lung Injury (TRALI)Pathophysiology Leukocyte Ab in donor react with pt. leukocytes

Activate complements

Adherence of granulocytes to pulmonary endothelium with release of proteolytic enz.& toxic O2 metabolites

Endothelial damage

Interstitial edema and fluid in alveoli

Transfusion-related Acute Lung Injury (TRALI)Acute and severe type of transfusion reaction

Symptoms and signsFeverHypotensionTachypneaDyspneaDiffuse pulmonary infiltration on X-raysClinical of noncardiogenic pumonary edema

Transfusion-related Acute Lung Injury (TRALI)Therapy and PreventionAdequate respiratory and hemodynamic supportive treatmentIf TRALI is caused by pt. Ab use LPBIf TRALI is caused by donor Ab no special blood components

Transfusion-associated Graft-versus-Host Disease ( TA-GVHD) Rare: immunocompromised patients Suggestion that more common with designated donorsBMT, LBW neonates, Hodgkin's disease, exchange Tx in neonates

Transfusion-associated Graft-versus-Host Disease ( TA-GVHD) PathophysiologyInfusion of Immunocompetent Cells(Lymphocyte)

Patient at risk

proliferation of donor T lymphocytes

attack against patient tissue

Graft-versus-Host ReactionSigns & Symptoms

Onset ~ 3 to 30 days after transfusion Clinical significant pancytopenia Other effects include fever, liver enzyme, copious watery diarrhea, erythematous skin erythroderma and desquamation

@Platelets!

Alloimmunization50 % of repeated platelet transfusionsAb-dependent elimination of platelets with lack of responseUse single donor apheresis Signs & Symptomsmild slight fever and Hbsevere platelet refractoriness with bleeding

Post-transfusion purpuraRecipient Ab leads to sudden destruction of platelets 1-2 weeks after transfusion (sudden onset)Rare complication

Immunomodulatory effects of transfusion

Wound infection: circumstantial evidence (? leukocyte filters for immunocompromised)Beneficial effects on renal graft survival (now < NB with CyA)97: 9% graft survival advantage after 5 years Nonspecific overload of RES lymphocytes, APCsModification T helper/suppressor ratioAllogeneic lymphocytes may circulate for years after transfusion

Cancer recurrence (mostly retrospective) Colon: 90 % studies suggest increased recurrenceBreast: 70 % studies Head and neck: 75 % studiesAllogeneic blood products increase cancer recurrence after potentially curative surgical resection - Landers Evidence circumstantial NOT causal

INFECTIOUS COMPLICATIONSI. Viral (Hepatitis 88% of per unit viral risk)

Hepatitis B Risk 1/ 200,000 due to HBsAg, antiHBc screening (7-17 % of PTH) Per unit risk 1/63-66,0000.002% residual HBV remains in negative donors (window 2-16 weeks)Anti-HBc testing retained as surrogate marker for HIV

NANB and Hepatitis C

Risk now 1/ 103,000 (NEJM 96) with 2nd/ 1/ 125,000 with 3rd generation HCV Ab/ HVC RNA tests Window 4 weeks70 % patients become chronic carriers, 10-20 % develop cirrhosis

HIV

Current risk 1/ 450- 660,000 (95) With current screening (Abs to HIV I, II and p24 Ag), window 6-8 weeks (third generation ELISA tests in Europe) sero -ve window to < 16 days

HTLV I, II

Only in cellular components (not FFP, cryo)Risk 1/ 641,000 (window period unknown)Screening for antibody I may not pick up II

CJD (and variant CJD)

CMV

Cellular components onlyProblem in immunocompromised, although 80 % adults have serum AbWBC filtration decreases risk of transmissionCMV -ve blood: CMV -ve pregnant patients, LBW neonates, CMV -ve transplant recipient, CMV-ve/ HIV +ve

II. BacterialContamination unlikely in products stored for > 72 hours at 1-6 0 C gram ve, gram +ve bacteria most frequent Yersinia enterocolitica Produced endotoxin Platelets stored at room temperature for 5 days, with infection rate of 0.25%

III. ProtozoalTrypanosoma cruzi (Chagas disease) MalariaToxoplasmosisLeishmaniasis

Serological Testingfor Infectious markersHIV AgAnti HIVHBsAgAnti HCVTest for syphilis

METABOLIC COMPLICATIONSCitrate toxicityCitrate (3G/ unit WB) binds Ca2+ / Mg+Metabolized liver, mobilization bone storesHypocalcemia ONLY if > 1 unit/ 5 min or hepatic dysfunctionHypotension more likely due to cardiac output/ perfusion than calcium (except neonates) Worse with hypothermia/ hepatic dysfunction

Hyperkalemia

After 3 weeks, K+ is 25- 30 mmol/l Only 8- 15 mmol per unit PRBC/ WBConcern with > 1 unit/5 min @ infants

Acidosis

Acid load after after 3 weeks 30-40 mmol/l (pH 6.6 - 6.9)Metabolic acidosis more likely due to decreased perfusion, hepatic impairment, hypothermiaNaHCO3 or THAM if base deficit > 7-10 mEq/l

2, 3 DPG

Depleted within 96 hours of storageO2 Hb DC to leftRestored within 8- 24 hours of transfusion

E. REFERENCESPractice Guidelines for Blood Component Therapy (ASA Task Force). Anesthesiology 1996; 84: 732-47.Safety of the Blood Supply. JAMA 1995; 274:1368--73.Infectious Disease Testing for Blood Transfusions (NIH Consensus Conference). JAMA 1995; 274: 1374-9.