Blood transfusion

Topic modules 1.Blood blank practices 2.Indication to blood transfusion 3.Complication 4.Alternative strategies for management of blood loss during surgery

Blood blank practices 1.Human red cell membrane : least 300 different antigen 2.fortunately, only the ABO and the Rh systems are important in the majority of blood transfusion 3.History Hct. Infection : Hepatitis B,C syphillis HIV-1,2 HTLV-I,II

#Crossmatching (50 min) 1)Confirms ABO and Rh typing 2)Detects antibodies to the other blood group systems 3)Detects antibodies in low titers or those that do not agglutinate easily 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 mins T&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

T&S: Type O red cells are mixed with pt serum Antibody screen T&C Type O red cells are mixed with pt serum Antibody screen Donor red cells are then mixed with the pt’s serum to determine possible incompatibility :

Blood blank practices All units – PRC 1unit (250 ml Hct.70%) 1 unit (50-70 ml, stored at 20-24c for 5 days) FFP high conc. Of factor VII, fibrinogen

Intraoperative transfusion practices 1.PRC Ideal for patients requiring red cells but not volume replacement Only one – Increase O 2 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 ตั้งต้น –Hct ที่ยอมรับได้ )/ Hct เฉลี่ย 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

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Intraoperative transfusion practices FFP 2. FFP ( initial therapeutic dose : 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 practices 3.PLATELETS 3. 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 practices 3.PLATELETS 3. PLATELETS *Massive transfusion with microvascular bleeding with platelets < 100,000 2 BVs = 50,000 *Qualitative dysfunction with microvascular bleeding (may be > 100,000)

Intraoperative transfusion practices 3.PLATELETS 3. PLATELETS 50 ml: x 10 9 platelets (some RBC’s and WBC’s) Single donor apheresis OR Random donor (x 6)

Intraoperative transfusion practices 4. CRYOPRECIPITATE 10 ml: fibrinogen ( mg), VIII ( U), fibronectin, XIII 1U/ 10kg  fibrinogen 50 mg/dL (usually a 6- pack) Hypofibrinogenemia (congenital or acquired) Microvascular bleeding with massive BT (fibrinogen < mg/dL) 2 BVs = < 100 mg/dL Bleeding patients with vWD (or unresponsive to DDAVP)

Alternative strategies for management of blood loss during surgery 1)Autologous transfusion 2)Blood salvage & refusion 3)Normovolemic 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

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

TRANSFUSION ! Nonhemolytic 1-5 % transfusions Causes -Physical or chemical destruction of blood: freezing, heating, hemolytic drug -solution added to blood -Bacterial contamination : fever, chills, urticaria –Slow transfusion, diphenhydramine, antipyretic for fever Hemolytic –Immediate: ABO incompatibility (1/ 12-33,000) with fatality (1/ ,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 Effects Acute 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 AHTR Chills, fever Facial flushing Hypotension Renal failure DIC Chest pain Dyspnea Generalized bleeding Hemoglobinemia Hemoglobinuria Shock Nausea Vomitting Back pain Pain along infusion vein

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

Laboratory investigation for AHTR sample from blood bag Repeat ABO, Rh, Ab screening Patient sample Pre Tx sample Repeat ABO, Rh, Ab screening Post Tx sample Repeat ABO, Rh, Ab screening, DAT, CBC, UA, Bilirubin, BUN, Cr, Coagulation screening Repeat 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 Ab’s against RBC membrane Ag Related to future delayed hemolytic reactions and difficulty crossmatching

Europe: All products leukodepleted USA: Initial FDA recommendation now reversed pending objective data (NOT  length of stay for  expense) Febrile reactions –Recipient Ab reacts with donor Ag, stimulates pyrogens (1-2 % transfusions) – % of platelet transfusions –Slow transfusion, antipyretic, meperidine for shivering

TRALI ( Transfusion related acute lung injury) –Donor Ab reacts with recipient Ag (1/ 10,000) –noncardiogenic pulmonary edema –Supportive 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 O 2 metabolites Endothelial damage Interstitial edema and fluid in alveoli

Transfusion-related Acute Lung Injury (TRALI) Acute and severe type of transfusion reaction Symptoms and signs Fever Hypotension Tachypnea Dyspnea Diffuse pulmonary infiltration on X-rays Clinical of noncardiogenic pumonary edema

Transfusion-related Acute Lung Injury (TRALI) Therapy and Prevention Adequate respiratory and hemodynamic supportive treatment If TRALI is caused by pt. Ab  use LPB If 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 donors –BMT, LBW neonates, Hodgkin's disease, exchange Tx in neonates

Transfusion-associated Graft-versus-Host Disease ( TA-GVHD) Pathophysiology Infusion of Immunocompetent Cells (Lymphocyte) Patient at risk proliferation of donor T lymphocytes attack against patient tissue

Graft-versus-Host Reaction Signs & 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! Alloimmunization –50 % of repeated platelet transfusions –Ab-dependent elimination of platelets with lack of response –Use single donor apheresis –Signs & Symptoms mild  slight fever and Hb severe  platelet refractoriness with bleeding Post-transfusion purpura –Recipient 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, APCs –Modification T helper/suppressor ratio –Allogeneic lymphocytes may circulate for years after transfusion

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

INFECTIOUS COMPLICATIONS I. 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, % 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 weeks 70 % patients become chronic carriers, % develop cirrhosis

HIV Current risk 1/ ,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 only Problem in immunocompromised, although 80 % adults have serum Ab WBC filtration decreases risk of transmission CMV -ve blood: –CMV -ve pregnant patients, LBW neonates, CMV -ve transplant recipient, –CMV-ve/ HIV +ve

II. Bacterial Contamination unlikely in products stored for > 72 hours at 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. Protozoal Trypanosoma cruzi (Chaga’s disease) Malaria Toxoplasmosis Leishmaniasis

Serological Testing for Infectious markers HIV – Ag Anti – HIV HBsAg Anti – HCV Test for syphilis

METABOLIC COMPLICATIONS Citrate toxicity Citrate (3G/ unit WB) binds Ca 2+ / Mg + Metabolized liver, mobilization bone stores Hypocalcemia ONLY if > 1 unit/ 5 min or hepatic dysfunction Hypotension more likely due to  cardiac output/ perfusion than  calcium (except neonates) Worse with hypothermia/ hepatic dysfunction

Hyperkalemia After 3 weeks, K + is mmol/l Only mmol per unit PRBC/ WB Concern with > 1 unit/5 infants

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

2, 3 DPG Depleted within 96 hours of storage O 2 Hb DC to left Restored within hours of transfusion

E. REFERENCES Practice Guidelines for Blood Component Therapy (ASA Task Force). Anesthesiology 1996; 84: Safety of the Blood Supply. JAMA 1995; 274: Infectious Disease Testing for Blood Transfusions (NIH Consensus Conference). JAMA 1995; 274: