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TRANSFUSIONS IN PRACTICE
PART1:TREATMENT OF ANEMIA AND BLOOD BANK MANAGEMENT
KRISTIN WELCH,DVM,DACVECC
DVM STAT 24/7 2019

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Why Consider Transfusions in Practice?
-Blood typing supplies are inexpensive
-Cross match kits are available
-No special equipment needed to store purchased blood units
-24 hr shipment available through animal blood banks

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Why Consider Transfusions in Practice?
-In some cases, referral is not possible...
- Too unstable
- Cost constraints
- Location

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Indications for Transfusion
-Anemia
-Coagulopathy
-Thrombocytopenia / thrombocytopathia
-Hypoproteinemia

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Most Common Indication for Transfusion
-Anemia
1. Acute blood loss
2. IMHA
3. Chronic anemia

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Acute Blood Loss Anemia
-Healthy animals can tolerate <= 20% loss of blood volume
-Peracute blood loss may have normal PCV for hours...only indication is low TS
-Many animals will have normalization of organ perfusion with crystalloids alone

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Increased Destruction
-Hemolytic anemias
-pRBC are lifesaving
-No evidence that blood adds "fuel to the fire"
-No evidence that transfused cells are destroyed more rapidly than patient's cells

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Decreased Production
-Bone Marrow Directed Anemia
- Destruction of RBC precursors in the marrow
- Pure red cell aplasia
- Erythroid maturation arrest
- Bone marrow directed IMHA
-Slow drop in PCV associated with a subtle onset of clinical signs
-Transfused RBC have near normal RBC lifespan
- 110 days in dogs
- 70 days in cats

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Chronic Nonregenerative Anemia
-Case by case basis
-Much lower PCV may be tolerated without evidence of hypoxemia
-If anesthetic or surgical event anticipated, transfusion may be required

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When to Consider Transfusion?
-Continued blood loss
-Evidence of hypoxemia
- Markers to look for?
-Planned anesthetic procedure (PCV < 20-25%)
Tachycardia Tachypnea increases Lactate

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Possible Side Effects
-Infectious disease transmission -Fatal hemolytic transfusion reactions
-Transfusion related lung injury (TRALI) -Transfusion related circulatory overload (TACO) -Transfusion related immunomodulation (TRIM)

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TRALI
-ARDS occurring <4-6 hrs after transfusion
- Dyspnea - Hypoxemia
- PaO2:FIO2 < 300; SpO2 <90% on room air
- Non cardiogenic pulmonary edema
- Bilateral pulmonary infiltrates
- No evidence of left atrial hypertension (ie. not volume overload!)
-Incidence as high as 0.08%
-#1 cause of transfusion related mortality in people

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TACO-Transfusion Associated Circulatory Overload
-Volume of blood infused causes acute hypervolemia and cardiogenic pulmonary edema

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TRIM-Transfusion Related Immunomodulation
-Transfusions are immunosuppressive and pro- inflammatory
- HLA proteins and immunologically active donor WBCs
--> immunosuppression
- Cellular factors from deteriorating donor WBC -->
endothelial cell and neutrophil activation
- increased incidence of infection in transfused ICU patients
- Transfused transplant patients have improved outcome

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Evidence Against Liberal Transfusions
-Increased risk of:
- Infection
- Earlier reoccurrence of malignancy
- Myocardial infarction
- Stroke
- Organ failure
- Death
CRIT study.CCM 2003
TRICC study.CCM 1999

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Fact or Fiction?
-Do transfusion triggers exist?
- PCV
- Lactate
- Membranes, CRT, HR, BP

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Options
-Packed red blood cells
-Fresh whole blood
-Stored whole blood

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Packed Red Blood Cells
-Benefits:
- Specific component therapy for anemia - Readily available
- National blood banks
- In house blood bank
-Downsides:
- Only provides RBCs...

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Fresh Whole Blood
-Benefits:
- Provides healthy platelets
- Provides coagulation factors
- Improved survival in human trauma victims over stored whole blood
-Downsides:
- Possible increased risk of disease transmission
- Possible increased risk of transfusion reactions
- Not available for purchase from animal blood banks
- Large volume

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Stored Whole Blood
-Benefits:
- Can be stored at 4°C for <= 35 days - Improved hemostasis over component therapy
-Downsides:
- Decreased platelet function within 5 hrs at 4°C
- Decreased factor V and VIII within 12-18 hrs at 4°C

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Canine Blood Types
->12 DEA groups
-Most important DEA = DEA 1.1
- Acute hemolytic transfusion reaction
-Other reported transfusion reactions
- DEA 4 - Dal antigen in Dalmatians

-Dogs do NOT have pre-existing antibodies
-Pregnancy does not cause sensitization

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-Some dalmations lack an IgG antigen on RBC - Dal antigen
- Readily sensitized to Dal positive blood
- All non-dalmation blood transfusions
- Not detected by typing
- DEA 4 negative dogs can be sensitized
- Most dogs in US are DEA 4+

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Canine Blood Typing
-In-house tests
- Rapid Vet-H Canine Cards
- Alvedia Quick Test DEA 1.1
-Reference laboratories
-Animal blood banks

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Rapid Vet Cards
-Difficult to interpret with severe anemia
-Unable to use in autoagglutination
www.rapidvet.com

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Alvedia Quick Test
-Reliable with severe anemia
-CAN use with autoagglutination
www.alvediaVET.com

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What About Autoagglutination?
-Negates any typing using the cards
-Alvedia Quick Test still valid
-Laboratory to wash RBC before typing
- Turnaround time makes this impractical in an emergency setting

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Feline Blood Types
-AB blood group system
- Type A
- Type B
- Type AB
-Mik antigen
-Cats have naturally occurring alloantibodies
-All feline donors MUST be typed

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Feline Blood Types
-Siamese are type A
-Most DSH are type A - Geographic variations
-NEVER assume a cat's blood type- type ALL cats
-Type B cats have STRONG anti-A antibodies
- Neonatal isoerythrolysis -Type AB cats should receive A blood

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Feline Blood Typing
-In-house tests
- Rapid Vet-H Feline Cards
- Miss AB cats
- Autoagglutination
- Alvedia Quick Test A+B
- Rapid Vet-H Gel Test
-Reference laboratories
-Animal blood banks

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Crossmatching
-Major Crossmatch
- Donor RBC, patient plasma
-Minor Crossmatch
- Donor plasma, patient RBC

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When to Crossmatch?
-Dogs
- Any dog with a transfusion history
- Transfusion >4 days ago
- Adult dog with unknown history
- Any dog that hemolyzes their 1st transfusion
- Suspicious...

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When to Crossmatch?
-Cats
- Cats that can't be typed
- Any cat with a previous transfusion history
- More recent recommendations...all cats?

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-Major Crossmatch compatible feline transfusions
- Increase in PCV was greater with major
crossmatched blood when compared to non- crossmatched transfusions
- Alloantibodies
- Mik antigen

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-Major Crossmatch compatible feline
transfusions - No significant difference in incidence of transfusion reactions in crossmatched vs. non-crossmatched
- 17% vs. 29% (p=0.16)
- No significant difference in % change in PCV

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-Non-AB incompatibility was detected in 15% of transfusion naïve cats
- In these transfusion naïve cats, 74% had 1+ incompatibility; 26% had 2-3+ incompatibility
- Mik?
-Febrile transfusion reactions noted more commonly in non-crossmatched vs. crossmatched transfusions
- 10.1% vs. 2.5% (overall in 5%)

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Crossmatch in Practice?
-In-house
- DMS Laboratories Rapid Vet-H Companion Animal
Crossmatch
- Cursory slide method- Major
- 1 drop donor blood with recipient plasma
- Agglutination?

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Gel-based Crossmatch

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What About Autoagglutination?
-*Autoagglutination precludes in-house crossmatching
- Wash cells 3 x in 0.9% saline
- Send blood to lab for crossmatch with stems from 2-3 type-specific blood units- Send blood to Animal Blood Resources International
- Receive the requested number of crossmatched units

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Where to obtain blood products?
-Planned Autologous transfusion
- Obtain 1 unit of blood from patient with a planned surgical procedure >4 weeks in advance
- Not practical in MOST cases

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Where to obtain blood products?
-Autotransfusion
- Immediately transfuse blood from body cavity
hemorrhage < 1 hr old
- Surgical or trauma
- AVOID in malignant hemorrhage, possible infection
- Requires use of a blood administration filter
- Risks

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Autotransfusion
-1 year FS German Shepherd
- Anticoagulant Rodenticide
- Presents with PCV 20%, TS 3.1 g/dL, tachypnea, muffled lung sounds, pale, tachycardic
- Diagnosed with large volume hemothorax - PT out of range, PTT out of range - Treatment?
- Vitamin K1
- FFP to correct PT/PTT
- Autotransfused 500 ml blood from hemothorax
- Discharged in 36 hours - Normal PT/PTT - PCV 30%, TS 5.2 g/dL

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Where to obtain blood products?
-In house blood donation
-Blood banks

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In House Blood Donation
-Requires diligent record keeping, annual infectious disease testing and dedicated equipment for safe blood handling and storage
-Practical in a large emergency or referral practice with a technician and veterinarian dedicated to blood banking
-Feasible on an emergency basis in practice with preplanning

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Canine Donors
->25 kgs ... donate 450 ml
-No transfusion history
-UTD on vaccines, indoor only
-CBC, chemistry, UA every 6-12 months
-Specific testing:
- Brucella, Babesia, Ehrlichia, Anaplasma, Borrelia, Leishmania
- Regional and breed variations
-PE and PCV/TS prior to every bleeding
- PCV >40% -No more than every 4 weeks

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Feline Donors
-> 4 kgs ... donate 40 ml
-No transfusion history
-UTD on vaccines, indoor only
-CBC, chemistry, UA every 6-12 months -Echocardiogram or proBNP
-Specific testing:
- HW, FeLV, FIV, Mycoplasma haemofelis
-PE and PCV/TS before every bleeding
- PCV >30% -No more than every 4 weeks

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Blood Collection
-Sedation
- Avoid acepromazine, dexmedetomidine
- Dogs - butorphanol / benzodiazapine
- Cats - ketamine/valium

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Blood Collection- Dogs
-Closed collection system
- Containing CPDA
- With or without satellite bags for component separation

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Blood Collection- Cats
-Commercial closed collection system
-Modified closed collection system
- Butterfly catheter, 30 cc syringe, 3- way stopcock, satellite collection bags -Open collection system
- 30 cc syringes with 19 G butterfly
- 1 ml CPDA or citrate per 9 ml blood

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Closed Collection System- Cat

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Blood Collection

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Blood Collection

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Obtaining Component Therapy
-Use of closed collection system & satellite bags
-Centrifugation of FWB within 8 hrs
- pRBC
- FFP / platelet rich plasma
- Cryoprecipitate
- Cryoprecipitate poor plasma

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Blood Product Storage
-What if FFP is thawed for a patient, and the unit is not used?
- Can be refrozen within 2 hrs of thaw and maintains all
factor efficacy
- Frozen plasma
Yaxley PE. Freeze-thaw-cycled FFP. JVECC 20(5) 2010.

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Blood Product Storage
-What if FFP is thawed for a patient, and the unit is
not used?
- Can be refrozen within 2 hrs of thaw and maintains all
factor efficacy
- Frozen plasma
Yaxley PE. Freeze-thaw-cycled FFP. JVECC 20(5) 2010.

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-Filter with 170-260 um pores most
common -Removes RBC and platelet aggregates
-Filter with 20 um pores
-Hemo-Nate

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Administration
-Warming bath for FFP
- 39 C (102.2 F)

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Does Administration Method Alter RBC Survival?

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Administration via Pump - Dog
-Very high proportion of early loss of
transfused RBC at 24 hr post-transfusion
- 4/8 dogs via volumetric pump
- 1/7 dogs via syringe pump
- 0/8 dogs transfused via gravity drip
-Average RBC lifespan 43 days

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Administration via Pump-Cat
- No decrease in circulating number of RBC with
administration using syringe pump/aggregate filter
- Rate of administration
- RBC MCV - Average RBC lifespan 23 days
- Transfused RBC detectable for 6 weeks

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Administration
-IV or IO
- Neonates
-0.9% NaCL can be administered concurrently
-Can add warm 0.9% NaCl to pRBC to increase bolus speed in emergencies

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What's in a Date?
-Age of blood is associated with rate of
transfusion complications
-Rate of transfusion complications 25% (333
transfusion events)
- Fever 12% - Hemolysis 6% -Odds of hemolysis increased significantly for
every additional day of age (OR 1.11)

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What volume to administer?
-Expected rise in PCV
- Whole blood
- 1% for each 2 ml/kg WB administered
- pRBC
- 1% per 1ml/kg pRBC administered

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Premedication
-Overall 15% rate of transfusion reactions (TR)
- 53% fever - 18% vomiting - Significantly associated with type of transfusion
- PRBC >>> Plasma - Immune mediated disease more likely to have TR - Premedication did NOT decrease overall TR
- Did decrease allergic reactions

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Transfusion Monitoring
-Rate is dependent on patient, indication for transfusion, CV status -Monitor for transfusion reactions
-Initial 2-5 ml over 15 minutes
-Entire transfusion volume over 4 hours
-TPR q 5 min for 1st 15 min
-TPR q 15 minutes for 1st hr
-TPR q 1 hr for 4 hours
-PCV/TS 2 hrs after completion of transfusion

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Acute Transfusion Reactions
-Non hemolytic febrile transfusion reaction
-Hemolytic transfusion reaction
-Infectious transfusion reactions

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Non Hemolytic Febrile Transfusion Reaction
-Most common transfusion reaction identified
-Occurs within minutes to hours of receiving transfusion
-Usually mild and self limiting
-Likely due to leukocytes and cytokines
- Leukoreduced RBC reduce incidence of febrile
transfusion reactions but not common practice in the US

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Hemolytic Transfusion Reaction
-Due to donor-recipient incompatibility
- Minimized by blood typing all recipients
- If indicated, major and minor crossmatching will indicate incompatibility prior to transfusion
-Due to previous sensitization
- Knowing past transfusion history is critical - Antibodies form in 4-5 days from 1st transfusion -->
crossmatch required with all subsequent transfusions

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Hemolytic Transfusion Reaction
-Due to donor-recipient incompatibility
1. Canine patient with past transfusion history that was not
crossmatched
2. Any cat that was not blood typed before transfusion
3. Cat receiving type-specific blood that has Mik-antigen incompatibility
-As little as 1 ml of incompatible blood can potentially
cause fatal hemolytic transfusion reaction
- Blood typing is critical, especially in cats
- Type B cats have strong anti-A antibodies
- Incompatible transfusion is fatal

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Infectious Transfusion Reactions
-Contaminated blood units
- Out of date
- Incorrect storage temperature
- Non sterile collection technique
- Blood bag sterility compromised
-Donor with infectious disease
- Incomplete donor infectious disease testing
- Not receiving heartworm prevention monthly
- Not up to date on vaccinations

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Recognizing Transfusion Reactions
-Febrile Non-hemolytic transfusion reactions
- Signs
- Fever
- Vomiting
- Urticaria
- Pruritis
- Most commonly respond to slowing the transfusion rate
- May require diphenhydramine, less commonly steroids

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a picture of a dog laying down

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Action Step
Febrile Non-hemolytic transfusion reactions
- Slow rate of transfusion
- If temperature normalizes or stabilizes then can continue transfusion
- If temperature continues to rise, stop transfusion temporarily
- If temperature stabilizes, continue transfusion at a slower rate
- If temperature continues to rise, STOP transfusion and submit blood for a bacterial culture and gram stained blood smear to rule out bacterial contamination

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Action Step
Febrile Non-hemolytic transfusion reactions
- Slow rate of transfusion
- If temperature normalizes or stabilizes then can continue transfusion
- If temperature continues to rise, stop transfusion temporarily
- If temperature stabilizes, continue transfusion at a slower rate
- If temperature continues to rise, STOP transfusion and submit blood for a bacterial culture and gram stained blood smear to rule out bacterial contamination

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Action Step
Non-hemolytic transfusion reactions
- Vomiting, urticaria, pruritis
- Slow rate of transfusion
- Administer 1-4 mg/kg diphenhydramine IM/SQ
- If clinical signs resolve, continue transfusion at current rate
- If clinical signs continue, try slowing transfusion even further - If signs resolve, continue transfusion
- If signs continue, consider repeating diphenhyrdamine or administering corticosteroids - No data to support use of steroids to treat non hemolytic transfusion reactions

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Recognizing Transfusion Reactions
-Acute hemolytic transfusion reaction
- Tachycardia
- Collapse
- Vomiting
- Pyrexia
- Hypotension
- Hemoglobinemia, hemoglobinuria

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Action Step
Acute hemolytic transfusion reaction
- Stop the transfusion immediately
- Submit blood (pre-transfusion) from recipient and blood from donor bag to reference lab or complete in house testing to confirm type/ crossmatch
- Monitor recipient closely with serial PCVs as hemolysis can be severe
- Perform new blood type and crossmatch before another transfusion is administered

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Recognizing Transfusion Reactions
-Delayed hemolytic transfusion reaction
- Extravascular hemolysis occurring 3-21 days after
transfusion
- Drop in PCV sooner than expected
- New hyperbilirubinemia
- New hyperbilirubinuria
-Usually no specific treatment required

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How long will the transfusion last?
-RBC lifespan
- 110 days in dogs - 70 days in cats
-Factors that shorten the RBC lifespan
- Hemolysis
- IMHA
- Transfusion related hemolysis
- Bleeding

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Resources for Transfusion Medicine

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DVM STAT 24/7 2019