9/7/2014. Introduction. Transfusions: What, When, How Peggy McMahon, DVM. Transfusion therapy. Goal of RBC transfusions

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1 Transfusions: What, When, How Peggy McMahon, DVM Providing the best quality care and service for the patient, the client, and the referring veterinarian. Introduction Blood product use has become increasingly popular in general practice and specialty veterinary facilities within the past 25 years Objectives of this lecture Types of transfusions Indications to transfuse and what product to use Techniques in transfusions Risks of transfusions Transfusion therapy Goal of RBC transfusions Blood products are often divided into their components Maximize benefit Minimize volume Avoid waste Decrease risk of transfusion reaction Whole blood Packed red blood cells Plasma products Improve oxygen delivery to and oxygen uptake by cells in the peripheral tissues through increased blood hemoglobin concentration. RBC transfusion Arterial hemoglobin 98% oxygen delivery Tissue hypoxia = insufficient amount of O2 is delivered to the tissues to meet metabolic demands: Low cardiac output (stagnant hypoxia) Low Hb saturation (hypoxic hypoxia) Decreased Hb concentration (anemic hypoxia) Blood transfusions indicated for anemic hypoxia 1

2 Transfusion trigger Adaptive mechanisms of anemia Causes of anemia The Hb level at which an animal s oxygen delivery has decreased enough that anaerobic metabolism occurs Critically ill humans HCT 21% No animal data HCT 15-18% a guideline Animals with heart disease, respiratory disease, or acute blood loss may have higher trigger Body senses that there is decreased oxygen concentration in tissues 1) Increase in afferent sympathetic nerve activity from aortic chemoreceptors 2) Increase in cardiac output 3) Hierarchical increase in organ blood flow to vital organs (heart and brain) 4) Increase in blood oxygen extraction Increase in 2,3-DPG To transfuse or not to transfuse? Doses for treating anemia There s an app for that Hematocrit or hemoglobin Chronicity Acute vs chronic Clinical presentation Weakness or fatigue, dull mentation, pallor, tachycardia, tachypnea, and bounding femoral pulses Doses - Many formulas published, none validated 1mL %PCV rise kg BW 2mL % PCV rise kg BW Volume to be transfused (VT) (ml) 90 ml dog kg BW ([desired PCV patient PCV]/ PCV of donor blood) Most commonly cited, most accurate if donor PCV >80% Most accurate if donor PCV ~45% Thought to be most accurate because donor PCV measured %PCV% rise x 1.5 x kg bodyweight Works best if donor PCV ~60% 2

3 Whole blood Fresh whole blood: When? No processing Contains all cellular and plasma components of blood Red blood cells Clotting factors (if not stored) Platelets (if not stored) WBCs and all other components of plasma Fresh whole blood at room temperature is considered safe for use for 4 to 6 hours Employee donor programs may provide a convenient source Storage 1-6 C Shelf life days, depending on anticoagulant Approximate dose 10-20m/kg Most common blood product traditionally used Beneficial with low blood volume or blood volume loss >50% Patient requires multiple components (prbc, clotting factors, platelets) Anticoagulant rodenticide ingestion with severe hemorrhage Most commonly used platelet transfusion product in veterinary medicine Treatment of choice for acute anemic thrombocytopenic patients that are bleeding, but if non-anemic, may lead to polycythemia and volume overload FWB for platelets Packed red blood cells FWB is the product most veterinarians have available to them to supply a limited number of platelets FWB platelets are less activated than platelets obtained via centrifugation for concentrate Dose of 10 ml/kg of FWB is expected to raise the platelet count about 10,000/mL, generally considered to be minimal, but may be life-saving Platelet survival time 1-2 hours post-transfusion Red blood cells only When? Normal blood volume Chronic disease, hemolysis, and bone marrow dysfunction or in situations where volume overload is a concern due to its lower oncotic pressure Product of choice in normovolemic animals Dose 10-15ml/kg Storage similar to whole blood Questionable efficacy after days 3

4 Leukocyte reduced RBCs RBC storage lesions Decreases the incidence of nonhemolytic transfusion reactions and the immunomodulation that has been seen after transfusion Can be performed either before storage or at the time of administration Available for purchase through commercial blood banks as leukoreduced prbc (Hemosolutions) Now more readily available for canine blood, and has been shown to be associated with smaller increases in WBCs, fibrinogen, and C-reactive protein levels in recipients than with than nonleukoreduced transfusions Standard in human medicine Series of biomechanical and biochemical alterations in the RBC Evolves from a biconcave disc to a deformed spheroechinocyte, which results in lower surface- to-volume ratio, increased cell viscosity, and increased osmotic fragility Diminished oxygen transport ensues Stored RBCs demonstrate increased aggregation, believed to be secondary to loss of negatively charged RBC surface sialic acid residues and increased adherence to endothelial cells, which contributes to a reduction in microvascular flow Abrogated by prestorage leukodepletion, Depletion of ATP affects cell membrane integrity Depletion of RBC 2,3-DPG shift of the oxyhemoglobin dissociation curve to the left and impaired oxygen off-loading to the tissues Media accumulates hydrogen ions, potassium (from RBC hemolysis), proinflammatory cytokines, histamine, complement, and lipid Autotransfusion RBC lifespan post-transfusion Collection and subsequent reinfusion of the patient s own shed blood No risk of immunological reaction Collect blood lost into either the thoracic or abdominal cavity and then filtering and re-infuse it Use standard transfusionadministration sets with filters Contraindications: possibility of contamination with urine, bacteria, or bile, and relatively contraindicated in the presence of diffuse neoplasia In the absence of bleeding and hemolysis, at least 70% of transfused erythrocytes survive 24 hours and transfused erythrocytes may thereafter be expected to have a near normal life span 4

5 Blood types DOGS Blood types DOGS DEA = dog erythrocyte antigen 20 antigen specificities in 13 groups were originally identified DEA 1.1, DEA 1.2, DEA 3, DEA 4, DEA 5, and DEA Can be routinely identified by typing DEA 1 system is most important because of its high degree of antigenicity after the first transfusion. Natural antibodies are present in some dogs for DEA 3, DEA 5, and DEA 7, and in occasional dogs for less common antigens Newer antigen, Dal, exists at high frequency With the tube agglutination method or the card (RapidVet), autoagglutination can prevent accurate typing. We use DEA 4+ blood because 98% of dogs are DEA 4+ Universal donor in dogs Negative DEA 1.1, DEA 1.2, DEA 3, DEA 5, and DEA Positive DEA 4 Significant naturally occurring alloantibodies are not seen in dogs. Antigen-antibody reactions are less likely on initial transfusion Natural antibodies to DEA 3, DEA 5, and DEA 7 can result in transfusion reactions Usually mild or delayed Significantly shorter survival time of the transfused red blood cells (RBCs) may be seen Blood types DOGS Blood types - CATS A, B, AB B cats have strong anti-a alloantibodies A to B cat A cats may have weak anti-b alloantibodies shortened RBC survival if a B donor is used AB cats have no alloantibodies MiK antigen, most cats MiK negative cats may have naturally occurring alloantibodies 5

6 Blood types - CATS Blood types - CATS Which blood product for AB cats? Type A AB cats have no alloantibodies against types A or B Should receive either AB or A blood products if they need a transfusion because of the strong anti-a antibodies present in B serum. RBC lifespans after transfusions: Type A to A cat 36 days Type B to A cat 2 days Type A to B cat 1.3 hours and also likely death of cat Crossmatch Who should be crossmatched? Detects the serologic compatibility between the anemic recipient and potential donor Major cross-match Detects antibodies in the recipients plasma that can cause a hemolytic reaction to donor RBCs Minor cross-match Dogs If transfusion history unknown If >3 days since transfusion If a hemolytic reaction was noted during the first transfusion If donor DEA 7 type unknown Cats ALWAYS before all transfusion types Both typing and crossmatching Identification of antigens such as MiK with naturally occurring antibodies and the potential for a potential fatal transfusion reaction In-house typing methodologies are not perfect Typing and crossmatching on the first transfusion helps to identify any missed type incompatibilities in cats 6

7 Plasma products Albumin, globulin, clotting proteins, anticoagulants, platelets Fresh frozen plasma (FFP) Fresh frozen plasma Fresh plasma Platelet-Rich Plasma vwf rich plasma Platelet concentrate Frozen, Lyophilized Cryoprecipitate Cryoprecipitate-poor plasma (CPP) Human serum albumin (HAS) Canine albumin Intravenous immunoglobulin (IVIG) Plasma separated from WB and frozen within 8 h 1y in freezer -20 to -30 C Coagulation factors, anticoagulation factors (i.e. antithrombin), alphamacroglobulin, albumin Labile clotting factors V and VIII Nonlabile factors generally include the vitamin K-dependent factors II, VII, IX, and X Dose ml/kg, 15-30ml/kg for vwf Fresh frozen plasma (FFP) Frozen plasma (FP) Indications Coagulation disorders resulting in active hemorrhage Prophylaxis before invasive surgery in an animal with a known significant clotting factor deficiency Exceptions to patients actively hemorrhaging Heat stroke Liver failure Plasma separated from WB and frozen >8h after collection FFP >12 months old but <5 years old stored -20 to - 30 C Uses Can use for in anticoagulant rodenticide toxicity due to preservation of non-labile factors II, VII, IX, X Contains albumin Dose ml/kg 7

8 Controversies in plasma use Administration of plasma Hypoalbuminemia Plasma to increase serum albumin 45 ml/kg needed to raise the serum albumin by 1 g/dl Coagulopathy with no signs of bleeding Coagulatopathy before surgery with no signs of bleeding Gently in room temperature warm Filter is essential for all blood product transfusions to remove clots and cellular In-line blood filter ( µm pores) and drip chamber is incorporated into standard transfusion administration sets. Pediatric microaggregate filter with 40 µm pore size is useful for administering small volumes of blood to cats and small dogs via syringe. 2-4 ml/kg/hr in the dog and 1-2 ml/kg/hr in the cat over 4-6h Stop synthetic colloids during administration Risk of volume overload Controversies in plasma use Cryoprecipitate DIC - Controversial, no prospective studies Not currently recommended with no active bleeding Pancreatitis Thought to help replace alpha-macroglobulins and maintain albumin levels Recent canine retrospective study evaluated the use of FFP with pancreatitis found no improvement in mortality was seen with plasma administration Made by slow thawing and centrifugation of FFP supernatant removed cold insoluble proteins, which are a concentrated form of factor VIII (hemophilia A), von Willebrand factor (vwf), and fibrinogen remain Indicated for the management of patients with vwd, factor VIII deficiency (Hemophilia A), hypofibrinogenemia and dysfibrinogenemia For vwd and fvii deficiency, CP is transfused at 1U/10 kg, over minutes, and repeated every 4-12 hours as needed If CP is not available, FFP may suffice, but is suboptimal Can then be refrozen, shelf life 10 months When active hemorrhage from specific deficiency in vwf and Dosing 1 unit of cryoprecipitate for every 10 kg of body weight 8

9 Cryoprecipitate-poor plasma (CPP) Human serum albumin (HSA) This is the supernatant removed in the process of making cryoprecipitate Can use with coagulation deficiencies of II, VII, IX, or X resulting in active hemorrhage that does not require vwf Dosing is similar to that for FFP or FP for coagulopathy. With the current availability of canine albumin, the use of a potentially antigenic human product is not recommended due to severe immunogenic reactions Canine albumin Human immunoglobulin (IVIG) Lyophilized product, each bottle contains 5 g albumin Uses Treatment of hypotension or hypovolemia in the septic patient with severe hypoalbuminemia Albumin deficit = 0.3 BW (kg) x 10 x (albumin desired - current albumin) Storage 3 years at 20 to 24 C Albumin is responsible for 50% of total plasma protein concentration and 80% of plasma COP Raise serum albumin to g/dl, and to provide synthetic colloid in addition to maintain a COP of mmhg Polyvalent IgG that has been extracted and pooled from the plasma from multiple donors Blockade of Fc receptors on monocyte-macrophage system suppression of antibody production and Suppression of antibody production and binding Modification of complement activation Uses Immune-mediated thrombocytopenia (ITP), immune-mediated hemolytic anemia, nonregenerative anemias, cutaneous diseases, polyradiculoneuritis, myasthenia gravis, and sudden acquired retinal degeneration Dosing Extrapolated from human medicine, and is currently recommended at 0.5 g/kg 9

10 Platelet products Techniques in administration FWB Platelet-rich plasma (PRP) Platelet concentrate (fresh, frozen) Lyophilized platelets Blood storage additives CPDA-1 ADC Routes - IV, IO, intraperitoneal Drips sets canine Delivery of autologous canine RBCs via mechanical delivery systems is associated with a high risk for early loss of transfused cells Syringe feline In contrast to findings from dogs, transfusion of autologous feline RBCs using a syringe + aggregate filter method does not significantly impact shorten long-term survival of the transfused cells. Risks of transfusion Risks of transfusion: Most common types Reactions have been reported to occur in 8% to 13% of prbc transfusions in dogs and cats Immunologic Nonimmunologic TRIM Nonhemolytic febrile reaction TACO Type I hypersensitivity Hemolytic reactions TRALI TRIM Decreased RBC survival Sepsis Citrate toxicity (hypocalcemia) Hyperammonemia Hypothermia Hyperphosphatemia Hyperkalemia Infectious disease transmission Nonhemolytic febrile reaction Temperature increase of 1 to 2C within 1 to 2 hours of a transfusion Usually caused by antibody reactions against donor leukocyte or platelet antigens and are greatly reduced when leukoreduction filters are used before storage of blood Slow the rate, consider diphenhydramine 2mg/kg IM and/or steroid (e.g., dexamethasone SP mg/kg IV) Transfusion-associated circulatory overload (TACO) Signs of volume overload Tachypnea, weight gain, hemodilution, serous nasal discharge, development of pulmonary edema or pleural effusion 10

11 Risks of transfusion Risks of transfusion Type I hypersensitivity can also occur with any type of blood product Includes pruritus and angioedema, can progress to bronchoconstriction and hypotension, vomiting Slow or stop transfusion Treat with diphenhydramine and a steroid Transfusion-related acute lung injury (TRALI) development of acute lung injury or acute respiratory distress syndrome within 6 hours of blood product administration. Inflammatory mediators within the blood product unit that activate endothelial cells and pulmonary neutrophils leading to capillary leakage and pulmonary edema Greater risk following plasma administration than red blood cell transfusion Only effective prevention of the development of TRALI is to minimize transfusions as much as possible TRALI has not yet been reported in veterinary patients but it would seem prudent to avoid unnecessary blood product administration in all species Risks of transfusion Summary Transfusion related immunomodulation (TRIM) Associated with all blood products Foreign antigens being introduced to animal s immune system, especially to the RBCs Most animal blood not leukoreduced White cells sitting in the stored blood, releasing cytokines, etc. Plasma does not have WBCs Blood product administration may be feasible and can be life saving Transfusion products are not benign and should be ordered judiciously Convenient, commercially available testing kits are available to aid in safe and effective transfusions Proinflammatory responses Immunosuppression 11

12 Questions? References 1. Prittie, J. E. (2010). Controversies related to red blood cell transfusion in critically ill patients. Journal of Veterinary Emergency and Critical Care (San Antonio, Tex. : 2001), 20(2), Short, J. L., Diehl, S., Seshadri, R., & Serrano, S. (2012). Accuracy of formulas used to predict post-transfusion packed cell volume rise in anemic dogs. Journal of Veterinary Emergency and Critical Care, 22(4), Hare, G. M. T. (2014). Transfusion and Apheresis Science. Transfusion and Apheresis Science, 50(1), Hux, B. D., & Martin, L. G. (2012). Platelet transfusions: treatment options for hemorrhage secondary to thrombocytopenia 5. JutkowitzJA,RozanskiEA,MoreauJA,etal.Massivetransfusionsin dogs: 15 cases ( ). Am Vet Med Assoc 2002; 220: Journal of Veterinary Emergency and Critical Care, 22(1), Tocci LJ. Transfusion medicine in small animal practice. Vet Clin North Am Small Anim Pract 2010; 40(3): References 8. Prittie, J. E. (2003). Triggers for use, optimal dosing, and problems associated with red cell transfusions. Veterinary Clinics of North America: Small Animal Practice, 33(6), Weatherton, L. K., & Streeter, E. M. (2009.). Evaluation of fresh frozen plasma administration in dogs with pancreatitis: 77 cases ( ). Journal of Veterinary Emergency and Critical Care, 19(6), McDevitt, R. I., Ruaux, C. G., & Baltzer, W. I. (2011). Influence of transfusion technique on survival of autologous red blood cells in the dog. Journal of Veterinary Emergency and Critical Care, 21(3), Heikes, B. W., & Ruaux, C. G. (2013). Effect of syringe and aggregate filter administration on survival of transfused autologous fresh feline red blood cells. Journal of Veterinary Emergency and Critical Care, 24(2), Nakamura, R. K., Tompkins, E., & Bianco, D. (2012). Therapeutic options for immunemediated thrombocytopenia. Journal of Veterinary Emergency and Critical Care, 13. Davidlow,. D. D. (2013). Transfusion Medicine in Small Animals. Veterinary Clinics of NA: Small Animal Practice, 43(4),

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