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Dayne Mickelson, MD Surgery Resident February 16, 2012 Who do we transfuse? What do we transfuse? How do children differ from adults? How do we decide when to transfuse in children? Why do we transfuse & what are the risks involved What strategies can we use to reduce transfusion in surgical patients & improve safety • • • • • Neonatology Surgery Trauma Intensive Care / ECMO Heme-Oncology • Agranulocytosis • Sickle cell crisis • Leukemia • Respiratory distress syndrome 4yo F s/p Lap Perf Appy with HCT slowly downtrending. HCT now 21. Tachycardic, mildly symptomatic. UOP decr 6yo M w ALL requiring port replacement for malfunctioning central line -Platelets 37 & INR 1.6 Nationwide pediatric transfusion uncertain. Academic Children's Hospitals - transfusion of either RBCs or platelets = ~5 %. Pediatric Health Information Database (35 centers. ~1 million pts <18yo. From 2001-2003) PRBC transfusions = 4% Platelet transfusions =1% Age <30days - 17.5 % Age 30 days to 2 years - 22.6 % Age >2 years of age - 58.6 % Whole blood - Donor’s blood mixed with an anticoagulant Whole blood components: Red blood cells Plasma Platelets Cryoprecipitate Plasma derivatives: Coagulation factor concentrates Albumin Immunoglobulins PACKED RED BLOOD CELLS (PRBC) • Red blood cells are plasma reduced blood. • One unit contains about ~300 ml. • Hemoglobin content is about 20 gm %. • Stored for 35 days at temperature 2 – 6 C in blood bank refrigerator. Pediatric/Divided RBCs (PEDI-PACK) 1unit PRBC separated into four bags. Each Pedi-Pack contains ~45 to 50 ml of RBCS + ~15 ml of plasma. Minimizes wasting blooded when only small volumes transfused Reduce the recipient's donor FRESH FROZEN PLASMA (FFP) • Whole blood plasma is centrifuged to provide a unit of plasma & platelets. • 1 unit FFP (~200-250 ml) frozen to–25c within 6hrs of collection. • May be stored for up to one year at –25 C. • Contains clotting factors, albumin, immunoglobulins PLATELETS • Whole blood plasma is centrifuged to provide a unit of plasma & a unit of platelets. • 1 unit contains approximately 5.5 x 1010 platelets in 50 – 75 mls of plasma. • May be stored for 5 days at 20 – 24˚C •Same donor or pooled platelets CRYOPRECIPITATE • Cold, insoluble, white precipitate that forms when a unit of FFP is thawed slightly. •1 unit is the amount removed from 1unit of FFP ( ~10 – 20 mls) •Refrozen at - 18˚C & stored for up to 12 months. •Can be fractionated to manufacture factor concentrates. Fibrinogen Factor VIII Factor IX Factor XIII 150 – 250 mg. 100 – 200 Units. 40 – 70 % of original unit of FFP. 20 – 30 % of original unit of FFP. SPECIAL BLOOD PRODUCTS IRRADIATED RED CELLS Exposed to ~2500 rads of Gamma radiation to destroy the lymphocyte’s ability to divide. -Prevents transfusion-associated graft versus host disease (TA-GVHD) -Not sufficient to kill viruses and irradiation does not provide a CMV-safe product -At risk recipients -Immunocompromised -Immunodeficiencies -Marrow or organ transplant recipients -Neonatal exchange transfusions or use of ECMO -Hodgkin's disease -Transfusion from a blood relation / HLA-matched SPECIAL BLOOD PRODUCTS LEUKOREDUCED Filtered to contain less than a known and accepted range of leukocytes -Reduces febrile non-hemolytic transfusion reactions -Prevents alloimmunization -Reduces the transmission of certain infections (notably CMV). -Does not eliminate all lymphocytes or prevent their ability to divide. -Thus can still cause transfusion-associated-graft-versus-host disease (TA-GVHD) CMV-SAFE RED CELLS - CMV-Seronegative & leukoreduced -Reduce the transmission of CMV -For CMV-seronegative recipients with special risks for CMV disease Circulation Fetal Neonatal circulation leads to increased pulmonary vascular resistance with some decrease in oxygenation Erythropoietin Decreases with increased Oxygenation after birth Levels lowest at ~2 weeks old Fetal Hemoglobin (HbF) Highest at birth (60 - 85 % at term, > 90 % pre- term) Fetal Hemoglobin has higher oxygen affinity Impaired oxygen delivery to tissues NEWBORN BLOOD VOLUME Total blood volume of approximately ~80 to 100 mL/kg. -i.e. Extremely low birth weight infant (<750 g) = total blood volume of <75 ml ANEMIA -Iatrogenic withdrawal of blood labs tests -Physiologic Anemia of Infancy, which is accentuated in premature infants. NEWBORNS Total blood volume of approximately ~80 to 100 mL/kg. -i.e. Extremely low birth weight infant (<750 g) = total blood volume of <75 mL. Physiologic Anemia of Infancy -Decr EPO, Decr Hgb, Incr plasma Vol -All infants experience a decline in Hemoglobin Norm BW = Nadir > 9g Hgb @ 6-10 wks VLBW (1-1.5 kg) = Nadir ~8 g Hgb. ELBW (<1.0kg) = Nadir ~7gHgb “The one and only reason to provide a red blood cell transfusion to a human is to restore or maintain the delivery of oxygen to vital organ systems. It’s use for any other reason has no physiologic or medical basis” KR Ward et al in Perioperative Transfusion Medicine, 2006 Tissue Oxygen Delivery Tissue Oxygen Delivery = Arterial O2 Content O2 Saturation Hb concentration Lactate Base Deficit Mixed Venous O2 Sat Oxygen requirement Arterial Blood Gas x Cardiac Output Intravascular Volume Stroke Volume × Heart rate Vasoconstriction Heart rate Blood pressure Cardiac function Capillary Refill CVP Clinicians have sought a (absolute Hgb or HCT value below which a patient needs a transfusion) NOT REALISTIC. No hard & fast Clinical Triggers Hgb level at which transfusion is indicated varies with the clinical setting and the individual’s medical history and physiologic status The physiologic response to anemia in children is different from adults. Few studies of RBC transfusion requirements in children except in patients with sickle cell disease and neonates. Guidelines established by taking standards from adult patients and modifying them according to clinical experience 2007 Trial - PICU pts: restrictive (Hgb ≤ 7 g/dL) or liberal (Hgb ≤9.5 g/dL) thresholds -In stable, critically ill children a hemoglobin threshold of 7 g per deciliter for RBC transfusion can decrease transfusion requirements without increasing adverse outcomes. Lacroix J, Hébert PC, Hutchison JS, et al. Transfusion strategies for patients in pediatric intensive care units. N Engl J Med 2007; 356:1609. These guidelines separate recommendations for Patients <4 months of age Patients >4 months of age Infants (<4mo) are considered separately due unique physiologic factors: • Small blood volume • Decreased production of endogenous EPO • Physiologic anemia of infancy • Immature humoral immune system PACKED RED BLOOD CELLS (PRBC) General transfusion guidelines based principally upon patient's clinical status have been developed by pediatric transfusion medicine specialists Roseff SD, Luban NL, Manno CS. Guidelines for assessing appropriateness of pediatric transfusion. Transfusion 2002; 42:1398. <4 Months >4 Months PLATELETS Guidelines for pediatric platelet transfusion: Age < 4 months: •Platelets < 100,000/mm3 and bleeding. •Platelets < 50,000/mm3 and invasive procedure. •Platelets < 20,000/mm3 and clinically stable. •Platelets < 100,000/mm3 and clinically unstable. Age > 4 months: •Platelets < 50,000/mm3 and bleeding. •Platelets < 50,000/mm3 and invasive procedure. •Platelets < 20,000/mm3 and marrow failure with additional hemorrhagic risk factor. Strauss, Chap 20 Neonatal Transfusion in Anderson, Ness Scientific Basis of Transfusion Medicine http://www.psbc.org/therapy/ffp.htm FRESH FROZEN PLASMA Indications: • Bleeding related to congenital or acquired coagulation factors deficiencies •Bleeding due to coumadine / warfarin therapy. Tx w Vitamin K time permitting. INR ≥ 1.6 before clinically important factor deficiency exists. This corresponds to factor levels <30% of normal. Benefits of FFP transfusion in terms of normalization of coagulation test results Minimal in patients with an INR of less than 1.6-1.7 (PT < 1.7 times normal) http://www.psbc.org/therapy/ffp.htm CRYOPRECIPITATE With the availability of coagulation factors concentrate, most commonly used as replacement therapy for patients with acquired bleeding disorders and low fibrinogen levels (< 100 mg%). -Hemophilia A -Von Willebrand disease -Hypofibrinogenemia -Factor XIII deficiency Consent Matching the blood Type and screened Type and crossmatch Certain specific concerns for this patient? Irradiated, Leukocytes reduced, etc. IV Access, Blood warmer? PACKED RED BLOOD CELLS Amount: • The usual dose is 10–15 ml/Kg •Expected to raise the hemoglobin concentration by 2 to 3 gm/dL •Vary depending on clinical circumstances (20ml/Kg is not uncommon) Infusion Rate: • Administered slowly, at approximately 2.5/mL/kg/hour (10 mL/kg / 4 hrs) •To avoid volume overload •Fast as patient can tolerate for massive loss. •To reduce viscosity add 50 ml normal saline to increase rate FRESH FROZEN PLASMA Amount: • 10 – 15 ml/Kg. Infusion Rate: • Approximately 0.5 ml/Kg/minute PLATELETS Amount: • One unit of platelets / 10 kg • 0.1 unit/kg = raise the platelet count by ~20,000 / mm3 Infusion Rage: • One unit over 10 min. (use 170 μm filter) CRYOPRECIPITATE Dose: -One unit of cryoprecipitate / 10 Kg - Increase the fibrinogen level by 50 mg%. Infusion Rate: Approximately 10 ml/minute. Transfusion Reactions o Febrile o Acute hemolytic reactions o Delayed hemolytic o Transfusion-related lung injury (TRALI) o Allergic & Anaphylatic reactions Transmission of Infection Dilution Coagulopathy Jaundice Overall pediatric risk Transfusion Rxn = ~1% IMMUNE MEDIATED ACUTE HEMOLYTIC REACTION -Due to incompatible ABO RBCs between the administered blood and the patient. PREVENTION -Misidentified patient or Specimin -Error in Type and Crossmatching DONOR RECIPIENT A A · B Rh Positive Rh Negative Rh Rh Positive Negative · · O AB AB · · B O · · · · · · · COMPLICATIONS Febrile Reaction: -May be the first sign of an immune mediated hemolytic transfusion reaction. -May be a sign of bacterial contamination of the blood product. -The transfusion should be Stopped & exclude a hemolytic reaction or sepsis -Not due to hemolysis = presence of cytokines produced by leukocytes. -Treatment : • Stopping the transfusion • Antipyretic Therapy • Leukocyte Reduction or Pre Treat with Antipyretic COMPLICATIONS Transfusion Related Acute Lung Injury (TRALI) Dyspnea, b/l pulmonary edema, hypotension, and fever within 6 hours of completion of transfusion. Due to antibodies in donor's blood against patient WBC. Activation of host leukocytes = pulmonary capillary trapping. Incidence ~1:5,000 but rarely reported in pediatric transfusions Treatment: Supportive COMPLICATIONS Transfusion Associated Graft–Vs–Host Disease (GVHD) Immune reaction of donor T cells against immunodefecient recipient & premature infants. Related donors. Occurs 4-30 days after transfusion, and is usually fatal. Irradiated blood products may prevent TA-GVHD GRAPHICS Risk of infection following transfusion of blood products Whole blood or red blood cell products* Hepatitis B 1:58,000 to 1:269,000 (see note below for 2011 estimates) Hepatitis C 1:1,000,000 to 1:2,000,000 HTLV 1:1,900,000 HIV 1:1,500,000 to 1:2,000,000 Solvent/detergent-treated plasma products Hepatitis C Inactivated Hepatitis B Inactivated HIV Inactivated Hepatitis A Not inactivated• Parvovirus B19 Not inactivated• Platelet products With automated bacterial culturing methods in place, septic transfusion reactions are estimated to occur at a rate of 1:50,000 transfused platelet apheresis units. Cytomegalovirus (CMV) infection The risk of CMV infection is rare in recipients with selected conditions (eg, bone marrow or solid organ transplants) who are at risk for severe morbidity from CMV infection and who receive CMV reduced risk products. Two methods to supply CMV reduced risk products, which appear to have equal efficacy are: CMV seronegative cellular components (red cells, platelets) or leukoreduced components. Numbers reported in this table are estimates derived from multiple sources within the United States, where blood is routinely screened for infection with syphilis, - IDENTIFY PT & SAMPLE - ALL UNITS SCREENED FOR: HIV Hepatitis B and C viruses Human T-cell leukemia virus West Nile virus Chagas disease Treponema - IDENTIFY SPECIAL RECIPIENTS - Immunocompromised Benefits of Transfusion Protocols Decrease transfusion and improve consistency of care Improved patient outcomes with reduced transfusion Require a multidisciplinary approach Tailor to pediatric patient group • Autologous transfusion • Donation may cause iatrogenic anemia • Direct donors • Pharmacologic: Iron, Folate, Erythropoietin • Intraoperative hemodilution & blood salvage • Hemoglobin/Platelet substitutes Roseff SD, Luban NL, Manno CS. Guidelines for assessing appropriateness of pediatric transfusion. Transfusion 2002; 42:1398. Holland LL, Brooks JP. Toward rational fresh frozen plasma transfusion: The effect of plasma transfusion on coagulation test results. Am J Clin Pathol 2006; 126(1):133-139 Lacroix J, Hébert PC, Hutchison JS, et al. Transfusion straegies for patients in pediatric intensive care units. N Engl J Med 2007; 356:1609. Slonim AD, Joseph JG, Turenne WM, et al. Blood transfusions in children: a multi- institutional analysis of practices and complications. Transfusion 2008; 48:73. Gibson BE, Todd A, Roberts I, et al. Transfusion guidelines for neonates and older children. Br J Haematol 2004; 124:433. Strauss, Chap 20 Neonatal Transfusion in Anderson, Ness Scientific Basis of Transfusion Medicine Teruya,, J.. Indications for red blood cell transfusion in infants and children. UpToDate. January 2012 Teruya,, J.. Administration and complications of red cell transfusion in infants and children. UpToDate. January 2012 Teruya,, J.. Red cell transfusion in infants and children: Selection of blood products. UpToDate. January 2012 Blood Book Information http://www.bloodbook.com/products.html#CMV Puget Sound Blood Center: http://www.psbc.org/home/index.htm