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Home , Transfusion medicine

Transfusion

Justine A. Lee, DVM, DACVECC, DABT Garret Pachtinger, VMD, DACVECC CEO, VetGirl COO, VetGirl [email protected] [email protected]

Copyright 2014 © VetGirl, LLC Introduction

Justine A. Lee, DVM, DACVECC, DABT CEO, VetGirl

Dr. Lee’s financial disclosure Introduction

Garret Pachtinger, VMD, DACVECC

COO, VetGirl Sponsorship

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" No'need'to'raise'your'hand!' " Type'in'ques3ons' " Emailed'to'you'48'hours'aLer'the'webinar' " Ac3ve'par3cipa3on'='no'quiz' " Watching'video'later,'must'complete'quiz' " ELITE'members'only' " Email'/'contact'with'ANY'ques3ons' " [email protected]' " [email protected]' Call in from Smart Phone! Why transfuse?

! Underlying causes of : ! loss ! ! Decreased production

! Why is anemia significant?

! Decreased O2 delivery to tissues (DO2)

Oxygen content: CaO2

CaO2 = [1.34 X Hg X SaO2] + 0.003 X PaO2

! Does your IMHA patient need blood or oxygen?

! SaO2 = 100%

! PaO2 = 100% ! HCT = 12% Transfusion trigger Transfusion trigger*

! HCT ! Human: 25% vs. Veterinary: 20%

! Chronicity

! Normovolemia

! Rate of ongoing losses Clinical signs

! Clinical signs? ! Tachycardiac ! Tachypneic ! Hypotension unresponsive to IVF ! Hypovolemic shock ! Pulse quality ! Pallor

Feline In-house blood donors

! Healthy ! CBC ! Indoor only! ! CHEM ! No exposure to other cats! ! UA ! T ! >10# 4 ! Fecal ! Large/lean ! Toxoplasma gondii ! 1-7 yo ! Mycoplasma ! UTD (Haemobartonella) ! FELV/FIV ! Bartonella spp ! ! Heartworm ! Blood type ! FIP? Canine In-house blood donors

! > 1 year ! Good temperament ! Healthy ! Physical exam ! > 25 kg ! CBC ! UTD ! Chemistry ! No concurrent meds ! UA ! Preventative meds ! Tick titers ! E. canis/equi ! B.canis/gibsonii ! Heartworm ! Blood type Download the ACVIM Consensus free! Canine blood typing

! 13 different blood types

! Dog Erythrocyte Antigen (DEA) 1.1, 1.2, 3,4,5,7

! DEA 1.1, 1.2, and 7: most antigenic

! DEA 1.1 more immunogenic than 1.2 ! Very antigenic ! Positive: has antigen on RBC surface ! Negative: antigen missing on surface Universal Donor

! True universal donor: (-) for all but DEA 4+

! Most universal donors: DEA 1.1, 1.2, 7 (-)

! New blood type Dal ! Dal may be missing in an unknown proportion of Dalmatians

Canine blood typing

Percentage % Blood types Positive Negative DEA 1.1 1.1 (A1) 33-45 55-67 1.2 (A2) 7-20 35-60 DEA 3B 5-10 90-95 DEA 4C 87-98 2-12 DEA 5D 12-22 78-88 DEA 7Tr 8-45 55-92 DEA 1.1 negative

! DEA 1.1 (-) can be given to (-) or (+)

! Universal donor

! Use when medical conditions preclude testing ! Hypovolemic or hemorrhagic shock ! IMHA ! autoagglutination DEA 1.1 positive

! Highly antigenic

! Can still use as blood donors

! Use for 1.1 + dogs ONLY!

! Waste + units for + dogs Feline blood type groups

! A, B, AB, Mik

! Type A more common

! Type B strong anti-A antibodies # fatal transfusion reaction! *B students dont like A students*

! Type A weak anti-B antibodies # shortened half life of RBC (2 days vs. 29-39 days) Feline blood typing

Percentage Percentage % % Type A Type B Type A Type B Abyssinian 86 14 Himalayan 93 7 Birman & 84 16 Japanese 84 16 Somali Bobtail British 60 40 Maine Coon 98 2 Shorthair Burmese 100 0 Nor. Forest 93 7 Cornish Rex 66 34 Persian 84 14 Devon Rex 59 41 Scottish 82 18 Fold DSHA XX XX Siamese/ 100 0 Tonkinese Percentage (%) Percentage (%)

Purebred Domestic shorthair* Type A Type B Type A Type B cats

USA Northeast 99.7 0.3 Abyssinian 84 16

North 99.6 0.4 Am. 100 0 Central shorthair

Southeast 98.5 1.5 Birman* 82 18

Southwest 97.5 2.5 British 64 36 shorthair*

West Coast 95.3 4.7 Burmese 100 0 Blood compatibility

! Pre-transfusion testing ! Prior to infusion of donor products

! Testing of donor

! Selection of appropriate donor units ! Blood type ! Blood crossmatching Blood typing cards

! In-practice blood typing kit ! Based on agglutination reaction that occurs when rbc which contain DEA 1.1 antigen on their surface interact with a murine monoclonal antibody specific to DEA 1.1

! Laboratory gel-test

DMS Laboratories 2 Darts Mill Road Flemington, NJ 08822 1-800-567-4367

Blood Typing: Canine

DEA 1.1 -

DEA 1.1 + DEA 1.1 +

DEA 1.2 +

Feline blood typing

Type A

Type AB

Type B

Blood crossmatching

! Detects serological incompatibility by identifying antibodies in donor or recipient plasma against recipient or donor RBCs.

! Major* vs. minor crossmatch ! MAJOR: patient plasma with donor RBC ! MINOR: donor plasma with patient RBC

* More important to determining survival of transfused RBCs Crossmatching

! Autocontrol (recipient RBC + plasma): rules out autoagglutination

! Any hemolysis or agglutination in major or minor = incompatibility

! Minor BCM – should be compatible in dogs but is of lesser significance in that canine donor plasma should not contain significant antibodies. Crossmatching

! Dogs lack significant naturally occurring alloantibodies # can be safely transfused without a BCM prior to the 1st transfusion!

! 4-7 days to develop antibodies! Crossmatching

! Since cats have naturally occurring alloantibodies and may experience a severe reaction to their first transfusion, a BCM should be performed prior if blood typing is not available.

Crossmatching Technique So what now?

! Consider using blood typing cards for patients receiving acute transfusions (i.e., hemoabdomen, trauma)

! Consider CM when multiple transfusions will be given over one week (i.e., IMHA)

! Consider blood typing cards for FFP use PRESERVING BLOOD Anticoagulant preservatives

! Goal: ! Maintain rbc viability ! Lengthen survival of rbcs post-transfusion ! Am Assoc (AABB) standards: 75% of RBC must survive > 24 hours to be acceptable and successful.

! Longer storage: viability decreases Anticoagulant preservatives

! CPDA-1 (Citrate-Phosphate-Dextrose- Adenine) ! RBC 2,3-DPG & ATP better maintained ! Good anticoagulant-preservative solution ! WB: stored 28 days ! Canine pRBC: 21 days ! Ratio: 1 ml CPDA-1 to 7-9 ml blood Anticoagulant preservatives

! CPD (Citrate-Phosphate-Dextrose) ! pRBC: 21 days ! Ratio: 1 ml CPD1 to 7-9 ml blood

! ACD (Acid-Citrate-Dextrose) ! pRBC: 21 days (dogs and cats) ! Ratio: 1 ml ACD to 7-9 ml blood

Anticoagulant preservatives

! Heparin ! Not generally recommended! ! 625 U/50 mls

! Additive Solutions (i.e., Adsol, Nutricel, Optisol) ! Protein-free solution added to red blood cells after plasma removed from unit of WB ! pRBC: 28 days (canine)

Goals of fluid

! Increase oxygen delivery ! Increase & maintain organ tissue perfusion ! Maintain blood pressure ! Maintain euvolemic state ! Correct electrolyte or acid-base imbalances ! Treat for hypoproteinemia Blood products

! (pRBC) ! Provides: RBC ! HCT = 80% ! Minimal COP! ! 10-20 ml/kg will raise PCV 10-20% ! Treatment for anemia ! No clotting factors ! Can reconstitute with 0.9% NaCl ! Store at 1-6 C for 28-35 days Dose: pRBCs

! Equation:

ml blood = PCV(target) – PCV(recipient) 80 ml/kg x BW (kg) PCV (donor)

! 10-20 ml/kg ! pRBCs ! FFP ! FP Blood products

! FFP ! Separated from whole blood and frozen at -20 to -30 within 6-8 hours of collection

! Provides: plasma, albumin, all factors (labile, Vit K dept), alpha-macroglobulins

! COP = 20

! Storage: 1 year frozen at -20°C or below

! 10-20 ml/kg

Blood products

! FFP ! Dose: 6-20 ml/kg for

! Dose for albumin: 45 ml/kg increases albumin by 1 g/dl ! 30 kg retriever: 1.3 liters (5-6 units)

! Minimal albumin!!!

Blood products

! FFP ! Dose: 6-20 ml/kg for coagulopathies

! Dose for albumin: 45 ml/kg increases albumin by 1 g/dl ! 30 kg retriever: 1.3 liters (5-6 units)

! Minimal albumin!!!

Blood products

! Frozen plasma (FP) ! Provides: plasma, albumin, stable coagulation factors (Vitamin K dept: II, VII, IX, X)

! COP = 20

! 10-20 ml/kg

! Collected > 6-8 hours from whole blood

! Storage: 5 years frozen at -20C (1 year as FFP, 4 years as FP)

! Waste on Vit K deficiency patients!

Blood products

! Fresh Whole blood (FWB) ! Provides: RBC, plasma proteins, COP 20, all clotting factors, WBC

! (limited)

! HCT: 40%

! 20 ml/kg will raise PCV 10%

! Shelf life: < 8 hours

! Preparation: Use immediately!

Blood products

! Stored Whole blood (SWB) ! Provides: RBC, WBC, Plasma proteins

! Platelets only viable for 2 hours after refrigeration

! Labile coag factors (V, VIII) viable for 24 hrs

! HCT = 40%

! Defined: > 8 hours old and up to 30 days (if using CPDA-1 collection bags) Blood products

! rich plasma and plasma concentrates ! Provides: Platelets, few RBC and WBC

! Some plasma

! Shelf life: 5 days at 22°C

! Intermittent agitation necessary

! Administer following collection and preparation (sit undisturbed for 30 min after harvesting) Platelet Concentrates

! Lyophilized platelets ! Davidow et al, JVECC 2012 ! Fresh platelets vs. lyophilized platelets ! No significant change in platelet count with either product Blood products

! (CRYO) ! Provides: concentration of VIII, vWF, XI, XIII, fibrinogen, fibronectin

! Prepared from FFP, which is thawed at 0-6C # precipitate: cryo

! 12 months frozen at -20C

! Dose: 1 unit/10 kg HBOCs: Oxyglobin

! Oxyglobin ! Ultrapurified ! Bovine ! Stroma free ! LRS base ! Used for treatment of anemia ! 10-30 ml/kg (not to exceed 10 ml/kg/hr) ! 10 ml/kg in dogs will raise Hg 2 g/dl = PCV 6% HBOCs: Oxyglobin

! HBOCs ! $$ ! COP 40 ! ! Fluid overload Good storage ! Interferes with ! Pigmentation changes colometric testing

Protocol for transfusions:

! Evaluate the unit

! Use a filter

! Pick which catheter you give it through

! Pre-treat? ! Diphenhydramine 0.5 mg/kg SQ or IM ! DexSP 0.1 mg/kg IV

Protocol for transfusions:

! Rate dependent on status

! Heart : < 4 ml/kg/hr

! If stable and normovolemic: ! 0.25-0.5 ml/kg for 30 minutes ! If no reaction, increase to 0.5 ml/kg (prbc or WB) or 2-6 ml/kg (FFP)

Protocol for transfusions:

! Monitor for transfusion reaction

! TPR q 1-5 minutes initially, then q. 15 minutes until finished.

! If reaction: ! Treat ! Slow down the transfusion ! Discontinue AUTOTRANSFUSIONS Autotransfusions

! When can we autotransfuse?

! VetGirl’s rule: From the chest! ! Dirty, dirty abdomen

! Is the blood sterile? ! Is the blood free of neoplasia? ! Is it end-stage disease? TRANSFUSION REACTIONS Autotransfusions

! Sterile collection of blood (60 mls syringes) ! Filter ! Give back IV via filter ! No need to add preservative ! Hypocalcemia Transfusion reactions

! Immune-mediated ! Hemolytic ! Acute (pre-existing alloantibodies or prior sensitization) ! Hemolytic reactions: Fever, tachycardia, weakness, muscle tremors, vomiting, collapse, hemoglobinemia, hemoglobinuria ! Due to: mismatched transfusion ! Nonhemolytic reactions: urticaria, pruritus, pyrexia, vomiting ! Due to: antibodies to WBC, plt, plasma protein ! Transient ! Delayed (4-21 days post-transfusion)

Transfusion reactions

! Nonimmune-mediated ! Trauma to the rbc: ! Overheating (protein denaturation, increased bacterial growth) ! Freezing of rbc ! Mixing rbc with non-isotonic solutions ! Warming and then rechilling ! Collecting or infusing blood through small needles or catheters

Transfusion reactions

! Nonimmune-mediated ! Bacterial pyrogens and sepsis (improperly collected and stored blood) ! Dark brown to black supernatant plasma: digested hemoglobin from bacterial growth ! Citrate intoxication: hypocalcemia Risks of medicine

! Veterinary medicine reactions: 3%

! Risks: ! Disease transmission (FIP, Leishmania) ! Elyte and acid-base disturbances (hypocalcemia) ! ALI ! Microembolic disease ! ! Immunosuppressive effects* ! 6X more nosocomial ! More sensitive marker of injury severity? Transfusion Reactions

! Hemolytic transfusion reactions (HTR) ! Allergic/anaphylactic reactions (ATR) ! Febrile, nonhemolytic reactions (FNHTR)

! Transfusion-transmitted (TTI) ! Transfusion-related acute lung injury (TRALI) ! Transfusion-associated circulatory overlaod (TACO) Hemolytic Transfusion Reactions

! AlloAB against RBC antigen

! Hemolytic serum

! Hemoglobinuria

! Elevation in body temp

! Vomiting Allergic/Anaphylactic Reactions ! Histamine release ! Treat with diphenydramine ! Vomiting, facial swelling, hives, elevated body temperature Febrile, Non-hemolytic Reactions

! Increase in at least 2 in body temperature during transfusion

! No signs of hemolysis

! Usually due to cellular components (WBCs, platelets, other) ! Leukoreduction

! Usually resolves without intervention ! Slow transfusion rate TTI, TRALI, TACO

! Transfusion-transmitted infections ! Reports in the veterinary literature ! Transfusion-related acute lung injury ! Pulmonary edema/pulmonary vasculitis ! During or within 6 hrs transfusion ! Massive transfusion ! 1 blood vol < 24 hrs, ½ blood vol < 3 hrs, 150% blood vol ! Immune-mediated ! Diuretics not indicated ! No reported cases in veterinary literature

! Transfusion-associated cardiovascular overload ! Hydrostatic pulmonary edema (treat with diuretics) CASE EXAMPLES Buffy, 4 yo FS Cocker, 10 kgs Presenting complaint:

! O noticed the following clinical signs: ! Orange urine ! Lethargy ! Vomited once this week ! Anorexia for 2 days Buffys initial exam

! T: 104.8° F (40.4° C) ! HR: 180

! Panting

! Bounding pulses ! Pallor ! Icterus ! 2/6 heart murmur ! 10 kgs Buffys Big 4/SAG

! Tells you all you need to know in < 1 minute!

! PCV 15%/TS 7 g/dL

! Icteric & hemolyzed serum

! BUN 5-15 mg/dL

! Blood glucose 170 mg/dL

Goal #1: Perfusion, perfusion, perfusion

! Start with crystalloids first ! Cheap $ ! Life-saving ! 20-30 ml/kg IV balanced crystalloid over 20 minutes ! Perfusion – keep on IVF! Goal #1: Perfusion, perfusion, perfusion

! Check perfusion values ! If still unstable, re-bolus as needed: ! 10-20 ml/kg IV crystalloids/20 minutes ! 5 ml/kg HES IV/20 minutes Back to Buffy – does she need fluids?

! T: 104.8° F (40.4° C) ! HR: 180

! Panting

! Bounding pulses ! Pallor ! Icterus ! 2/6 heart murmur ! 10 kgs Back to Buffy – does she need fluids?

! 10 kgs, HR 180, pallor

! Bolus 200 mls of crystalloid over 20-30 minutes

! Recheck HR, pulse quality

! HR 160 bpm, bounding pulses Back to Buffy – does she need fluids?

! Rebolus 100-200 mls of crystalloid again!

! Recheck HR, pulse quality

! HR 150 bpm still. Next?

! Bolus 50 mls of HES over 30 minutes!

! HR 120 bpm Oxygen content = CaO2

(0.003 X paO ) ! CaO2= Hgb X 1.34 X SaO2 + 2

! i.e. IMHA with a PCV of 9%

! Does it need RBC or O2?

! Does Buffy need blood or oxygen? Give Buffy a blood transfusion!

! Pros vs. cons of giving antigenic RBC ! Deliver oxygen! ! Stimulate immune system?

! What type should I give? ! Universal donor (A-/DEA 1.1)

! Choices: ! PRBC ! FRESH whole blood ! FFP? ! Oxyglobin PRBC

! Whats in it? RBC only! Perfect!

! Unable to blood type

! 10-20 ml/kg over 1-4 hours, depending on how stable. Fresh whole blood

! Readily available at your clinic!

! Provides: RBC, plasma proteins, all clotting factors, WBC, some platelets, PCV 40%

! Shelf life: < 8 hours

! Preparation: Use immediately!

! 20 ml/kg will raise PCV 10%

Fresh Frozen Plasma (FFP)

! Whats in it: Plasma, albumin, all coagulation factors (Vit K dependent factors, labile coagulation factors), and alpha-macroglobulins

! Does Buffy need it? NO!

! 10-20 ml/kg

Where do we go from here? References:

! Canine and Feline Blood Donor Screening for Infectious Disease Wardrop KJ, Reine NJ, Birkenheuer B, et al. J Vet Intern Med 19[1]:135-142 Jan-Feb'05 ACVIM Consensus Statement

! Clinical Use of Blood Products in Cats: A Retrospective Study (1997-2000). Castellanos I, Couto CG, Gray TL. J Vet Intern Med 2004;18[4]: 529-532.

! transfusions in cats: 126 cases (1999). Klaser DA, Reine NJ, Hohenhaus AE. J Am Vet Med Assoc 2005;226(6):920-923.

! Whole Blood Transfusions In 91 Cats: A Clinical Evaluation J Feline Med Surg 6[3]:139-148 Jun'04 Retrospective Study 27 Refs C. Weingart, U. Giger, B. Kohn *

! Massive transfusions in dogs: 15 cases (1997-2001) Jutkowitz LA, Rozanski EA, Moreau JA, et al. J Am Vet Med Assoc 2002;220(11): 1664-9.

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Dr. Justine Lee ! August 4-6, 2014: International Veterinary Seminars, San Diego, CA ! August 7-10, 2014: Southern Veterinary Conference, Birmingham, AL. (Dr. Justine Lee) ! August 12, 2014: Merck Continuing Education, Chicago, IL. (Dr. Justine Lee) ! August 13, 2014: Merck Continuing Education, Omaha, NE. (Dr. Justine Lee)

Dr. Garret Pachtinger ! August 16-18, 2014: Pennsylvania Veterinary Medical Association Keystone Veterinary Conference in Hershey, PA ! September 5, 2014: Leon Veterinary Conference, Guadalajara, Mexico ! September 24-28, 2014: Southwest Veterinary Symposium, Ft. Worth, Texas