Transfusion Flashcards
What is contained in cryoprecipitate
- vWF
- FXIII
- FVIII
- Fibrinogen
What is the shelf life of platelet concentrates
5 days
What is the definition of massive transfusion
Transfusion of:
- Patient’s blood volume in 24h
- 50% of patient’s blood volume in 3 hours
- 1.5 mL/kg/min (90 mL/kg/h) of blood products for 20 min
- 150% of patient’s blood volume regardless of time
What are the storage conditions of: fresh whole blood, stored whole blood, pRBC, FFP, frozen plasma, liquid plasma (refrigerated plasma), cryoprecipitate, cryopoor plasma, platelet-rich plasma, platelet concentrate, lyophilized platelets, canine albumin
- FWB: up to 24 at room temperature under agitation (with preservatives)
- Stored WB: 28-35 days at 2-6°C (with preservatives) ; platelets active for 21 days
- pRBC: 35-42 days at 2-6°C (with preservatives)
- FFP: <-30°C for 1 year
- Frozen plasma: <-30°C for 5 years
- Liquid plasma: 2-6°C for 14 days
- Cryoprecipitate: <-30°C for 1 year
- Cryo-poor plasma: <-30°C for 1 year
- PRP: room temperature under agitation for 5 days
- Platelet concentrate: room temperature under agitation for 5 days ; or cryopreserved in DMSO -> -80°C for 1 year or -20°C for 6 months
- Lyophilized platelets: room temperature for 1 year
- Canine albumin: room temperature for 2 years
What coagulation factors are lost between FFP and frozen plasma / during storage of whole blood?
- Storage of frozen plasma: factors VIII and X
- Storage of whole blood: factors V and VIII
What is the formula to calculate volume of pRBC to transfuse based on the desired PCV
V (mL) = [(desired PCV - patient PCV) / donor unit PCV] * blood volume (L/kg) * BW (kg)
(Or V = desired PCV rise * 1.5 * BW)
What is the formula to calculate dose of canine albumin to transfuse based on the desired albumin
Dose (g) = 10 * (desired albumin - patient albumin) * BW (kg) * 0.3
What are platelet-containing blood products? By how much do they raise platelets?
- Fresh whole blood
- Stored whole blood
- Platelet rich plasma
- Platelet concentrate (fresh or cryopreserved)
- Lyophilized platelets
10 mL/kg of fresh whole blood raises PLT by 10x10^9/L
1 unit of PRP contains 80x10^9 platelets
What is the max delay between collection and freezing for FFP
8 hours
How much plasma is required to increase albumin by 1 g/dL
45 mL/kg
What type of hypersensitivity can happen with transfusion of human albumin to dogs
Type III hypersensitivity
What is the CPD:blood ratio for blood collection
About 1:7-1:8 (63-70mL in 450-500mL of blood)
What are indications for cryoprecipitate transfusion
- Hemophilia A
- vWD
- Hypofibrinogenemia
Name 3 canine RBC antigens
- DEA (dog erythrocyte antigen)
- Kai
- Dal
For what DEA blood groups can dogs have naturally occurring alloantibodies
DEA 3, DEA 5, DEA 7
What blood groups can cause an AHTR in sensitized dogs
DEA 1, DEA 4 (but >99% dogs are positive), Dal
What are the 3 breeds with the most Dal negative dogs
- Dalmatians (12%)
- Dobermand Pinschers (42%)
- Shih Tzus (57%)
What are blood groups where negative phenotype is more prevalent than positive
DEA 3 and DEA 5
(DEA 1 and DEA 7 are variable but can be close to 50%)
What breeds have more type B cats
- Devon Rex
- Cornish Rex
- British Shorthair
- Exotic Shorthair
- Turkish Van
What naturally occurring alloantibodies do cats have
- Type A cats have no or weak (IgG and IgM) naturally occurring anti-B alloantibodies
- Type B cats have strong IgM naturally occurring anti-A alloantibodies
- Cats can have naturally occurring anti-Mik alloantibodies
What is the breed over-represented for type AB cats
Ragdoll
True or false: Blood typing is required for plasma products in cats
True.
Cats have naturally occurring alloantibodies which will be present in the plasma of donors (not true for dogs)
What is the recommended time post-transfusion after which a crossmatch is recommended in dogs and cats
4 days in dogs, 2 days in cats
But some antibodies can develop before that and some will develop later (might still be recommended to repeat crossmatch just before a future transfusion)
What type of immunologic reaction is used in blood typing methods for dogs and cats
Hemagglutination
Briefly described crossmatching methods
- Standard tube method: donor RBC mixed with recipient serum (ideally, otherwise EDTA plasma is fine) in a tube and it is observed for hemolysis and agglutination (semi-quantified). Can be enhanced with addition of antiglobin.
Gold standard, only test looking for hemolysis. - Gel tube assay: donor’s RBC and recipient’s plasma mixed and allowed to migrate through a gel ; agglutinated RBCs get held at the top.
Sensitivity for incompatibilities is not good. - Immunochromatographic strip: donor’s RBC and recipient’s plasma are mixed and allowed to migrate along a strip containing antiglobulin ; RBCs that are coated with antibodies bind to antiglobulin at detection line. Better accuracy.
How to assess hemolysis in a blood unit? What is the acceptable limit for transfusion
% hemolysis = (100-Hct)*(plasma Hb/total Hb)
Can do visually but not reliable
Should be less than 1%
What pathogens should canine and feline blood donors be screened for
- Canine:
- Anaplasma phagocytophilum
- Anaplasma platys
- Babesia canis vogeli
- Babesia Gibsoni
- Bartonella henselae
- Bartonella vinsonii var. berkhoffi
- Ehrlichia canis
- Mycoplasma hemocanis
+/- Brucella canis
+/- Hepatozoon canis
+/- Leishmania donovani (in Foxhounds and travellers)
+/- Rickettsia felis
+/- Neorickettsia risticii
+/- Trypanosoma cruzi
Technically Dirofilaria immitis not part of it because cannot transmit heartworm to recipient but can carry Wolbachia and interfere with diagnostic testing + donor would not be considered healthy -> so should still screen
(Ideally for main pathogens both serology and PCR recommended)
- Feline:
- Anaplasma phagocytophilum
- Bartonella henselae
- Mycoplasma hemofelis
- FIV antibody
- FeLV antigen and PCR
+/- Anaplasma platys
+/- Cytauxzoon felis
+/- Mycoplasma haemominutum
+/- Mycoplasma turicensis
+/- Ehrlichia canis
+/- Neorickettsia risticii
What immunoglobulins are involved in AHTR vs DHTR
- IgM for acute (intravascular hemolysis)
- IgG for delayed (extravascular hemolysis)
What is considered an acute vs. delayed transfusion reaction
- Acute = within 24h
- Delayed = after 24h and within 28 days
You have a type AB feline patient with severe hemorrhage due to rodenticide toxicity (PCV 16%). You have type A and type B pRBC and FFP available. What do you transfuse, with what pre transfusion testing?
- Type A pRBC - do major crossmatch first if clinically able (as for any cat)
(Can wash RBC but no recommendation in TRACS guidelines. Technically washed type B pRBC would be ok.) - Type A FFP - not enough evidence to recommend minor crossmatch (unless typing of plasma not available)
What is the most prevalent transfusion reaction
Febrile non-hemolytic transfusion reaction (FNHTR)
What is the trigger of a FNHTR? What could theoretically help prevent it?
Antigens present on leukocytes / platelets (mostly histocompatibility leukocyte antigens) + cytokines released in store blood
Leukoreduction could help prevent it (mixed results)
List immune and non-immune transfusion reactions
- Immune:
- AHTR
- DHTR
- FNHTR
- Allergic reaction
- Anaphylaxis
- TRALI
- Transfusion-associated graft-versus-host disease (TR-GVHD) - Non-immune:
- Transfusion-associated sepsis / transfusion-transmitted infection
- TACO
- Non-immune hemolysis (freezing, prolonged storage, mechanical damage by pump, incompatible fluids)
- Citrate toxicity
- Transfusion related hyperammonemia
- Hypotensive transfusion reaction (due to bradykinin release)
- FNHTR (if induced by free cytokines in blood product)
What is the time frame for AHTR, DHTR, allergic reaction, FNHTR, TRALI, TACO
- AHTR = within 24 hours
- DHTR = between 24h and 28 days
- Allergic reaction = usually within 1h of initiation of transfusion, can be up to 4h after cessation
- FNHTR = during or within 4h of cessation of transfusion
- TRALI = During or within 6h of cessation of transfusion
- TACO = During or within 6h of cessation of transfusion
What are criteria for a FNHTR
- Temperature > 39°C with increase in temperature > 1°C from pre transfusion temperature
- During transfusion or within 4h of completion
- Rule out external warming, underlying patient condition
- Rule out AHTR, TRALI, transfusion-related infection
What are criteria for TRALI
- Hypoxemia (PF ratio <300, SpO2 < 90%)
- During or within 6h of transfusion
- Bilateral pulmonary edema on radiographs with no evidence of circulatory overload
- Type I TRALI = no concomitant ARDS risk factors / Type II TRALI = concomitant risk factors or pre-existing mild ARDS (PF 200-300) with deterioration of respiratory status following transfusion while it had been stable for at least 12h before
What is the “two-hit” theory in pathogenesis of TRALI
Patients already have primed neutrophils and endothelium from their underlying condition. The transfusion of antibodies, neutrophil antigens, lipids, and CD40 ligand leads to activation of neutrophils and endothelial damage
What type of pumps are suitable for blood products administration
Volumetric piston pumps (when manufacturer approved)
What fluids cannot be administered in the same line are RBC-containing blood products
- Hypotonic fluids
- Hypertonic fluids
- LRS (for all blood products independently of RBC)
What is the incidence of transfusion reactions
3.3-15% of patients
What most commonly triggers transfusion-associated anaphylaxis
Plasma proteins antigens (mostly IgA)
What are criteria for AHTR
New onset of evidence of hemolysis within 24 hours of transfusion:
- Hyperbilirubinemia (icterus of patient or serum, hyperbilirubinemia on biochemistry, bilirubinuria in cats, >2+ bilirubinuria in dogs)
- Hemoglobinemia (visible or identified by biochem machine)
- Hemoglobinuria
- Spherocytosis in dogs
- Erythrocyte ghosts on a smear made immediately after blood collection
+ inadequate increase in PCV
+/- new onset fever > 39.2, tachycardia, hypotension
What bacteria are most commonly involved in transfusion-associated sepsis
Gram-neg (E Coli, Pseudomonas, Serratia, Caulobacter, Ralstonia), Gram-pos (Enterococcus, Proppionobacterium, Corynebacterium, Leucobacter, Bacillus, Staphylococcus)
What are differentials for transfusion reactions causing: fever / vomiting / hypotension / dyspnea
- Fever: AHTR, DHTR, TRALI, transfusion-transmitted infection (sepsis), FNHTR
- Vomiting: AHTR, TTI (sepsis), allergic reaction, hyperammonemia, FNHTR
- Hypotension: AHTR, TTI (sepsis), anaphylaxis, TRALI, hypotensive transfusion reaction (from bradykinin)
- Dyspnea: TACO, TRALI, allergic reaction (for cats), AHTR, TTI (sepsis)
What are the 3 categories of RBC storage lesions with examples and consequences
- Biochemical:
- Decrease in 2,3-DPG -> left shift of Hb dissociation curve
- Accumulation of free hemoglobin (-> scavenger of NO, procoagulant)
- Decrease in pH due to glycolysis (-> acidosis)
- Accumulation of ammonia (-> hyperammonemia)
- Accumulation of free iron (-> oxidative stress) - Biomechanical / morphological:
- Membrane changes of RBC decreasing their deformability (-> decreased survival of RBC)
- Accumulation of microparticles (-> pro-coagulant) - Immunological:
- Accumulation of cytokines (-> pro-inflammatory / immunosuppression)
- Release of phospholipids (-> pro-coagulant)
What are theoretical benefits of leukoreduction
- Lower risk of FNHTR
- Lower risk of immunosuppression from transfusion
- Decreased oxidative stress
- Decreased microparticle formation
- Lower incidence of alloimmunization
-> overall supposed to decrease pro-inflammatory and pro-coagulant effect of pRBC transfusion but limited evidence in veterinary medicine
What patient populations might benefit from transfusion of fresher blood
- Patients with hemolysis (recommend pRBC of 14 days or less)
- Patients with sepsis
- Patients with hepatic insufficiency (recommend pRBC < 7 days)
What filters should be used for administration of blood products to dogs / cats
- Cats: 18-micron micro aggregate filter before syringe pump administration
- Dogs: 170-260 micron in-line filter
What transfusion reactions warrant discontinuation / slowing of transfusion
- Discontinuation:
- AHTR
- TTI (transfusion transmitted infection) - usually not confirmed during transfusion, but if suspected based on patient hemolysis
- TRALI
- Anaphylaxis
- Hypotensive transfusion reaction - Slower rate:
- TACO
- Not enough evidence to slow rate for FNHTR and allergic reaction
What is a transfusion protocol for massive hemorrhage
- pRBC 15 mL/kg with FFP 10-20 mL/kg
- or if available whole blood 20-30 mL/kg
(should be adjusted to patient’s needs based on monitoring)
What are complications of massive transfusion
- Hypocalcemia (Ca gets bound to citrate)
- Hypomagnesemia (Mg gets bound to citrate)
- Hypothermia
- Metabolic alkalosis due to metabolism of citrate
- Metabolic acidosis if citrate can’t be metabolized due to liver failure or if pH of RBC units is low due to storage
- Transfusion reactions
- Thrombocytopenia (dilution effect)
- Coagulopathy if not enough plasma
(- Hyperkalemia reported in humans but unlikely to be an issue in veterinary patients since very little K in RBC)
What are the recommended monitoring timepoints during a transfusion? What should be monitored?
- 5 min, 15 min, 30 min, 60 min, then every hour, 15 min after transfusion, 1 hour after transfusion, then 24h after transfusion
- Monitor RR, HR, MM colour, CRT, temperature, mentation, BP + clinical signs of transfusion reactions (fever, urticaria, facial edema, tachycardia, tachypnea, weakness, vomiting, hemoglobinuria, hemolyzed serum)
What is approximately the PCV of a pRBC unit with preservatives
~ 60% (without preservatives would be around 80%)
Should a standard tube crossmatch be done with recipient’s serum or plasma? Why?
Ideally serum because fibrinogen in plasma can increase rouleau formation and EDTA can interfere with some hemolytic antibodies.
But most incompatibility crossmatch reactions are agglutination so EDTA plasma is ok otherwise.
True or false: In a patient who has never been transfused previously, a crossmatch can be performed on a blood sample collected a few days before
False. Crossmatches on “old” samples have more risk of being falsely incompatible
List blood typing methods. Why one(s) is/are affected by auto-agglutination?
- Standard tube method (never used) / affected by auto-agglutination
- Typing cards (antibodies lyophilized onto cards) / affected by auto-agglutination
- Gel method / affected by auto-agglutination
- Immunochromatographic method / not affected by auto-agglutination
(For methods that are affected by auto-agglutination, washing the RBC can help)
True or false: Type B kittens are born with naturally occurring alloantibodies against A antigen
False. The alloantibodies develop after birth (at ~4-6 weeks)
What are causes of false type AB results in cats
- Type A Abyssinian and Somali cats
- FeLV positive cats
- Cats with IMHA
- Cats with severe inflammation
- Cats with flea-induced anemia
What is the prevalence of crossmatch incompatibility in transfusion-naive cats
About 15% (unclear clinical significance though)
What is the main reason why a major crossmatch could be impossible to interpret
Auto-agglutination in the recipient
When agglutination cards are used for blood typing, which disease can cause a false DEA 1 positive result?
IMHA because of autoagglutination
What are key factors from the recipient and from the donor that can influence the severity of a transfusion reaction?
Recipient:
- Alloantibody titer –> the higher the titer, the more severe the reaction
- Alloantibody type –> hemolysin (IgM) reactions are worse than agglutinins (IgG) reactions
- Binding affinity –> the higher the affinity of the antibody to the blood group antigen, the more severe the reaction
Donor:
- Antigen expression on RBC surface (IgM is especially good at binding an antigen that is highly expressed)
- Transfusion volume
If blood typing is not possible/not clear in an anemic cat, what is the safest blood product to be administered?
Washed type B red cells
What is the raise in PLT count expected with 10ml/kg o FWB?
10 x 10^9/L
What type of hypersensitivity reaction is acute hemolytic transfusion reaction?
Type II - IgM react with RBC and activate complement
Name 1 reason why fresher blood may be better for IMHA patients
Pro-inflammatory mediators (hemoglobin, microparticles) that accumulate during storage might exacerbate inflammatory response of dogs with IMHA
Which category of patients is at higher risk of citrate toxicity?
Patients with liver disease (citrate metabolized in the liver)
List the steps that should be taken when investigating an acute transfusion reaction
- Confirm species and blood type of donor + recipient
- Confirm expiry date of blood product
- Assess blood product for hemolysis
- Perform crossmatch using pre-transfusion blood from recipient if possible
- Gram stain + culture from blood bag
- Blood culture from recipient
- Check that blood pump. filter and other administration technique are appropriate
True or false:
Crossmatching beyond 4 days after initial transfusion in a dog is not necessary if using the same initially compatible donor.
False. The use of the same compatible donor dog will not assure compatibility for a second transfusion even if the original testing was compatible
True or false:
Type AB plasma can be given to all cats
True
What is the test dose rate for transfusion?
0.25ml/kg/h for 15 min
True or false: Checking PCV 2h post transfusion is more reliable than immediate
False, immediate PCV is just as reliable
