= ‘At present, 33 blood group systems representing over NB.00 antigens are listed by the International Society of B00 Transfusion, map '°St of them have been cloned and sequenced, BAB The genes of these blood group systems are autosomal, BAB — eg antigen wD antigen is the precursor to the ABO blood group eM rtigens. wf present in all RBCs irrespective of the ABO system. mm srtigen deficiency is known as the "Bombay By ecoype (h/h, also known as Oh) do not express H- gD: tigen on their RBCs. gs H-antigen acts as precursor, its absence means the gal bsence of antigen Aand B 9 2 croup O phenotype results from mutations in ABO G5: cause a loss of glycosyl transferase activity Pt BOGS8 ‘TRANSFUSION MEDICINE BLOOD GROUPS Rhesus system = second most important blood group system after ABO. ‘=consists of 50 defined blood group antigens out of which only five are important. = the status is indicated as either Rh-positive (D-antigen present) or Rh-negative (O-antigen absent) In contrast to the ABO system, anti-Rh antibodies are, normally, not present in the blood of individuals with D- negative RBCS, unless the circulatory system of these individuals has been exposed to D-positive RBCs. >These immune antibodies are immunoglobulin G (196) in nature and hence, can cross the placenta. Prophylaxis is given against Rh immunization using anti-D Ig for pregnant Rh- negative mothers who have given birth to Rh-positive child. MNS antigen system =frst described by Landsteiner and Levine in 1927 is based on two genes: Glycophorin A and Glycophorin 8. = under control of an autosomal locus on chromosome 4 and also under control of a pair of co-dominant alleles LM and LN. > Anti and anti-N antibodies are usually !gM types and rarely, associated with transfusion reactions. Lutheran system = comprised of four pairs of allelic antigens representing single amino acid substitution in the Lutheran glycoprotein at chromosome 19, > Antibodies against this blood group are rare and generally not considered clinically significant. Kell system = the third most potent immunogenic antigen after ABO and Rh system, and are defined by an immune antibody, anti-Klt was first noticed in the serum of Mrs. Kellacher, She map HCE t0 the erythrocytes of her newborn infant resulting in hemolytic reactions, ince then 25 Kell antigens have been discovered pay Nti-K antibody causes severe hemolytic disease of the map (f'S and newborn (HOFN) and haemolytic transfusion reactions (HTR). BBD uty system say first isolated in a patient called Duffy who had mee 2MOPhIa. MB. also known as Fy glycoprotein and is present in the MB® surface of RBCS. It is a nonspecific receptor for several chemokines and ma 2°. 2 FecepLOK for human malarial parasite, Plamodium vivax. = BD. Antigens Fya and Fyb on the Duffy glycoprotein can result in four possible phenotypes, namely Fy(a+b-), map (24D, Fyfa-b4, and Fyfa-b-). The antibodies are IgG subtypes and can cause HTR. p@idd system known as Jk antigen, it is a glycoprotein, present on the membrane of RBCs and acts as a urea transporter in M® Cs and renal endothelial cells. —_ MMB Kidd antibodies are rare but can cause severe sap ansfusion reactions. 9 5, 2se antigens are defined by reactions to an antibody g@® designated as anti-Jka, discovered in the serum of eA Mis, Kidd who delivered a baby with HDFN. A was the fist antigen to be discovered by Kidd blood group system, subsequently, two other antigens Jkb M® and Jk3 were found eqs garwal et acaried out a study on automated analysis 2 of blood groups in north Indian donor population ap 1 832" that the common blood groups n order of frequency were: B, O, A, and AB; 944% being Rh- positive > In minor blood groups, the most commonly appearing phenotypes were Le (a-b-) for Lewis, Fy(atb+) for Duffy, Jk(@tb4) for Kidd, and M+N+ for MNS system IMPORTANCE OF BLOOD GROUPS Structural lesions of red blood cell = Of the 33 blood group system antigens, five are defined by their carbohydrate structures (ABO, H, PiPk, |, GLOB); two are obtained from the plasma (LE,CH/RG). > The remaining 23 are characterized by the protein sequence of the RBC membrane proteinfive major proteins (D1, Rh, RhAG, MNS, GE, and CO) among them are expressed at higher levels and function as membrane transporters, whereas the functional importance of rest of 17 antigens is unknown. >The proposed functions of other antigens are mostly receptor/ligand signaling, enzymatic activity, and glycocalyx formation. >The null phenotype of any system (nonfunctional copy of a gene caused by a genetic mutation), however, shows no immune system abnormalities when compared with mice except for a blunted neutrophil response on exposure to bacterial ipopolysaccharide ‘STORAGE OF BLOOD COMPONENTS: =Blood components and products are stored in compliance with the storage temperature requirements specified for that particular component Based on AABB and FDA requirements, you must wait 56 days between whole blood donations. Platelet (apheresis) donors may donate more frequently. This is because the body replenishes platelets and plasma more quickly than red cells. = Platelets will return to normal levels within about 72 hours of donating, 141]* Plasma will return to normal levels within a couple of days. BBEASONS FOR DEFERRAL "Anyone who has ever used needles to take wm —_-UDS, steroids, or any substance not prescribed bya doctor Ven who have had sexual contact with other men in mm the past 12 months =, = @vien and women who have ever engaged in sex for @ Money or drugs ®, nyone with a positive test for HIV (AIDS virus) rnyone who has had babesiosis or Chagas disease @‘nyone who has taken Tegison for psoriasis 2 @pV7E WhO has risk factors for Creutzfeld-Jakob disease (CJD) or who has a blood relative with CID MAnyone who has risk factors for vCJD (variant), including: = \nyone who spent three months or more in the United Kingdom from 1980 through 1996 @ snyone who received a blood transfusion in the United @ = Kingdom or France from gp 0 to the present cyone who has spent five years in Europe from 1960 to the present. LOOD COMPONENTS & Cryoprecipitate is prepared from plasma and contains fibrinogen, von Willebrand factor, factor Vill factor Xill and fibronectin. = the only adequate fibrinogen concentrate available for intravenous use. available in pre-pooled concentrates of five units JRANSFUSION REACTIONS: Acute (<24 hours) > pain at site lumbar pain hives, urticaria, edema Fever, chills dyspnea, stridor (laryngeal bronchospasm) constricting chest pain Hypotension (A drop. of at least 10 mmHg, in systolic or diastolic arterial BP- during transfusion) vvvy .gema and vv Delayed Reactions (>24hours) >commonly occurs about 4-8 days after blood transfusion, = may develop 3-4 weeks after transfusion DONOR’s FACTORS antibodies in thedonor plasma _reactiveto recipient leukocyte antigens reign plasma proteins =production of inflammatory mediators during storage PATIENT'’s FACTORS antibodies developed fr. previous transfusion or pregnancy =angiotensin converting enzyme (ACE) inhibitor drugs =antibodies to leukocyte antigens reacting w/ leukocytes IATROGENIC (Hospital) ERRORS Attending Physician's Factors : = transfusion- related volume overload RETRIEVAL, TRANSPORT, & HANDLING OF BLOOD BAGS =properly signed out. =carfied inside STYROFOAM CONTAINER or with thermal insulation inserts =KEEP HANDLING of the bag to a MINIMUM, =Maintain blood components in a controlled temperature environment until it i transfusion, = THAWING IN WATER OR NEVER ALLOWED, to avoid is ready for UNDER THE FAUCET IS Contamination, 142|Red blood cells should be compatible with LV, lutions: = 5% dextrose inwater (may induce hemolysis) = Lactated ringers (may induce clotting in BT set ‘or bag) = Use only 0.9% NaC! for injection, = No medications should be added to bag or line. SSSseseae @ Blood warming: only temperature - monitored devices gp '0U'd be used ifthe following indications are present: ‘Adults receiving blood >50 mi/kg/hr. Children receiving blood >15 ml/ka/hr. Infants undergoing exchange transfusion. Rapid blood infusion through CVP lines. Patients with cold agglutinins Pressure devices, Blood pressure cuffs, are not recommended = unequal pressure applied on bags a. cause leakage b. induce hemolysis * Only devices designated for this purpose should be used, OSSGCC8 Microaggregate Blood filters must always be used gpi""°" fusing blood components to prevent: 2) alloimmunization to WBC =D b) HLA antigens ©) CMV transmission. ME LIMITS. RANSFUSION MUST BE STARTED WITHIN 30min = Laboratory must be notified on the "TIME TRANSFUSION STARTED". = If transfusion cannot be performed, blood bag MUST BE RETURNED TO THE LAB within 30min > to avoid deterioration or disintegration of blood cells or components VFS TFRRTR8 @® ROSSMATCHING Crossmatched blood (2nd bag & more), that is not transfused within 3 days, = should be CROSSMATCHED AGAIN, especialy if the patient had received transfusion on the 1st day, AAs soon as the transfusion is started, the following time allotment must be strictly followed: a) Components (& whole blood) should be infused within 4 hours. ) Fresh Frozen Plasma — infused within 2 hours. ©) Platelet - should be infused on Fast Drip. ACTIONS TO BE TAKEN ON REACTIONS: *** Disconnect the intravenous line from the needle. 10 not disconnect the unit from the IV set. = Attach a new IV set and prime with saline and reconnect the line. pen the line toa slow drip. > In certain cases, such as a mild urticarial reaction or repeated chill-fever reactions, it may be possible to restart the blood transfusion after evaluation and treatment of the patient. NURSING STATION RESPONSIBILITIES, STOP transfusion NOTIFY BLOOOD BANK/MD = Recheck ID Monitor Vital signs reat sx per MD orders =Do not discard the unit of blood that has been discontinued = necessary for investigation =The blood bag together with attached tubing and intravenous fluids should be saved for further investigations, = Notify the Blood Bank of transfusion reaction & and briefly describe the nature of the reaction. = Delay the transfusion of addi itional units until the possible reason for r 143 |Chapter 5 Transfusion Medicine Routine Transfusion Therapy «Blood products should not be transfused on a unit basis in children 144 |Base thi ic re ne volume Of transfusion products on weight to avoid over or under resuscitation later tranetusinn toe Ge stusions are needed, consider having the blood bank split a unit and save portions of t for ca traf on 24 h maximum); this will help avoid multiple donor exposures foe aan 7 blood cell (RBCs) that have been in storage for > 14 days has been associated with increased risk in critically ill children; isk of i fects Seer isk of immunologic, vasoregulation, and adverse hypercoagulation ef Estimated volume per unit of blood products is as follows: Packed red blood cells (PRBCS): 300 mL/unit Whole blood: 450-500 mL/unit * Fresh frozen plasma (FFP): 250-300 mL/unit * Platelets: 40-50 mL/unit ° Cryoprecipitate: 10-12 mL/unit + PRECs * 7 es volume of 10-15 ml/kg can be given quickly over minutes or over a 4-hour period, depending on the situation “The following equation can be used to determine the volume of PRBCs to transfuse; it quires the current hematocrit (HCT) level and the child's estimated blood volume (EBV; see Table 5-1 for average total blood volumes by age) desired HT - present HCT* x EBV HCT of PREC (avg 60%5=7ORT "ACT OF wine BOOT AOS=A5¥5 3B *HCT of whole blood 40%-45% Pediatric Surgery and Medicine for Hostile Environments Table 5-1. Blood Volume by Age Blood Volume (mL/kg) Premature infant 100 Full-term neonate 85 Older infant 75 >12mo0 70-75 *Transfusing a pediatric patient with 4 cc/kg will increase hemoglobin by 1 a/dL *Transfusing 1 unit in an adult patient willraise hemoglobin by 1 g/dL. (or HCT by 3%) + FFP *Transfuse FFP 10-15 mL/kg °f close, round up or down to the closest unit * Routine FFP transfusion rates should not exceed 1 mL/ ka/min because of the risk of hypotension caused by low ionized calcium during the FFP infusion > This complication can be treated with 10 mg/kg CaCl or 100 mg/kg calcium gluconate IV over 5~10 minutes * For patients with massive bleeding who are at risk for death secondary to hemorthage, give FFP as fast as possible, paying attention to ionized calcium levels because large volumes of plasma and red cells will decrease ionized calcium concentrations ° For patients with known clotting factor deficiencies, 10-15 ml/kg of FFP will rise factors levels 15%-20% + Platelets 14s |aioe vrs have @ volume of 6-10 random donor units S 9 OF | unit/5 kg of body weight > Equivalent to about 5~10 mL/kg, >» Increases platelet count by approximately 50,000/ mm3 + Cryoprecipitate “An excellent source of fibrinogen and factor Vill factor Xil, and Von Willebrand's factor ° Administering 1-2 bags for every 5-10 kg willraise fibrinogen levels 60-100 mg/dL Table 5-1. Blood Volume by Age ‘Age Blood Volume (mL/kg) Premature infant 100 Full-term neonate 85 Older infant 75 > 12 mo 70-75 39 Transfusion Medicine Massive Transfusion Therapy for Severe Hemorthagic Shock + The principles of damage-control resuscitation developed for adults are generally applicable in massively bleeding children ° Current policies regarding hemorrhagic-shock resuscitation, regarding the use of whole blood and recombinant factor Vila, are appropriate to guide therapy for children with severe injuries + A’massive transfusion” in a child is when approximately one circulating blood volume is replaced within 24 hours * Consider using massive transfusion strategies when a child is anticipated to need more than two traditional 15 ml/kg transfusions of PRBCs during one resuscitation (equivalent to about > 6-8 PRBC units for an adult) + Some clinical parameters may predict the need for a massive transfusion during active bleeding * Severe tachycardia or hypotension for age Base deficit > 6 * Lactate = 4 mmol/L *Intemational normalized ratio 2 1.5 * Hemoglobin < 9 g/dl. upon admission + When transfusing through small IV catheters (22 gauge and 24 gauge), bolusing with a 10-20 mL syringe may be the most efficient way to deliver fluids and blood products rapidly + Ifa patient is at risk for massive transfusion, PRBCS, FFP, and platelet transfusion should be initiated in a 1:1:1 ratio® Helps avoid coagulopathy and is associated with reduced mortality from hemorrhage in adults * Use of blood products in this ratio should continue until the life-threatening bleeding has stopped; at this point use more restrictive transfusion criteria, Formulas for calculating volumes of each product should be used + Fresh warm whole blood (FWW8) * if FWWBis available, consider using it as a substitute for PRBCs, FFP, and platelets, ° FWWB can be beneficial in the massively transfused patient Decreases the likelihood of hypothermia > Avoids the deleterious effects of large volumes of old stored RBCs and the accompanying anticoagulants 40 Pediatric Surgery and Medicine for Hostile Environments and preservatives * FWWBis particularly helpful when platelets or other component therapy is unavailable * Risk of transmitting infection and minor blood group incompatibilities is increased *Transfuse 15-20 mL/kg; repeat as necessary * Watch for hypocalcemia and hyperkalemia + Factor Vila has been used to reduce blood loss and restore hemostasis in combat casualties wth coagulopathy associated with hemorrhagic shock * Works best with a pH > 7.1, a platelet count > 50,000/mm3 , and a fibrinogen level > 100 g/L * Has been used successfully in pediatric trauma for patients requiring massive transfusion * Doses 90 na/kg and may be repeated if persistent bleeding occurs secondary to coagulopathy within 1-3 hours 146 |Risks Associated with Pediatric Transfusions + Hyperkalemia {Potassium escapes from RBCs as they age; therefore, older units of PRECs may contain high levels of potassium : Pediatric Patients have small blood volume, so a potassium load results in a higher risk of hyperkalemia Transfusion-associated hyperkalemic cardiac arrest is almost always associated with a low cardiac output state, acidosis, hyperglycemia, hypocalcemia, and hypothermia; all conditions commonly found in patients requiring massive transfusion * Avoiding older blood products and closely monitoring electrocardiogram (ECG) morphology and serum potassium can help avoid hyperkalemic cardiac arrest « Hypocalceria ° Children are particularly prone to hypocalcemia secondary to citrate-containing blood products *Transfusion related hypocalcemia is most likely to be caused by FFP and whole blood because these products contain the most citrate per unit volume > Monitor for hypocalcemia if FFP is transfused > 1 mL/ kg/min 41 Transfusion Medicine » Ca2+ is a potent inotrope in infants and children; severe cardiac depression and hypotension can result from ionized hypocalcemia D Potent inhalational agents dramatically exacerbate this hypotension > Prevention includes limiting the rate of FFP transfusion to < 1 mL/kg/min iffeasible and administering calcium chloride (5 mg/kg) or calcium gluconate (15 mg/kg) = Hypothermia * This isa significant risk given pediatric surface-area-toweight ratios * Consider using blood warmer, especially iflarge volumes will be transfused +The risks of bacterial and viral contamination are the same as in adults + Fluid overload * Patients with chronic anemias (eg, sickle cell anemia) undergoing transfusion are at risk for fluid overload and congestive heart failure © Use slow transfusions (1 cc/kg/h) * Consider administering furosemide (0.25-0.5 mg/kg) midtransfusion or after transfusion Special Preparations (consider if available) = Leukocyte-teduced blood products * Used to prevent febrile, nonhemolytic transfusion reactions * Microaggregate filters prevent febrile transfusion reactions and are useful in patients who have received blood frequently in the past * Leukopore filters are needed to decrease risk of cytomegalovirus transmission and human leukocyte antigen alloimmunization * White blood cell fiers will dramatically slow the rate of a transfusion (may not be appropriate during a transfusion for hefhorrhagic shock because of active bleeding) Further Reading 1. Smith HIM, Farrow SJ, Ackerman JD, Stubbs JR, Sprung 42 Pediatric Surgery and Medicine for Hostile Environments 4. Cardia arrests associated with hyperkalemia during red blood cell transfusion: a case series. Anesth Analg 2008;106:1062-1069, 147References: 1) Henry's Clinical Diagnosis & Management by Laboratory Methods, 23” ed for Clinical Chemis nline.on antinuclear-antibody-ana htips//labtestse