Transfusion Medicine Brooks 2021.pdf

Transfusion Medicine AIMEE BROOKS, DVM, MS, DACVECC Goals of this lecture Understand: Why to transfuse When to transfuse What to transfuse How much to transfuse How to transfuse/monitoring during Complications/risks of transfusion Blood banking/donor selection (briefly!) “FYI” = I will NOT...

Transfusion Medicine AIMEE BROOKS, DVM, MS, DACVECC Goals of this lecture Understand: Why to transfuse When to transfuse What to transfuse How much to transfuse How to transfuse/monitoring during Complications/risks of transfusion Blood banking/donor selection (briefly!) “FYI” = I will NOT ask you a test question on this info WHY transfuse? Severe anemia causing clinical signs Coagulopathies: replace functional coagulation factors, fibrinogen Replace blood components (platelets, albumin) Salt water ≠ blood! Why NOT to transfuse? Not without potential risk/harm! Transfusion reactions Immunosuppressive Proinflammatory Finite resource ($$) http://capecodvets.blogspot.com/2013/08/severe-allergicreactions-in-dogs.html WHAT to transfuse? Fresh whole blood Packed red blood cells (pRBCs) Fresh frozen plasma (FFP) Frozen plasma Cryoprecipitate Cryo-poor plasma (cryosupernatant) Platelet products (platelet rich plasma (PRP), platelet concentrate, etc.) Albumin products WHAT:(Fresh) whole blood All components of normal blood (rbcs, wbc, platelets, proteins) When would you use it? Massive hemorrhage (replace that which is lost) Multiple components (anemic and coagulopathic) Platelets: used to say lost after 4-6h, but now think may last longer in fridge Labile clotting factors (VIII, V) lost after 8h Availability –may be only product you have! WHAT can we transfuse? Packed red blood cells (pRBCs) Spin FWB and separate into plasma and pRBCs Contains RBCs, maybe WBCs (±leukoreduction), minimal plasma Most common RBCs in blood banks Use for RBC loss alone (IMHA) and less need for volume Use in conjunction with other products (FFP, platelets) in lieu of (F)WB Stored at 1-6°C (fridge) for 20-37d (depending on preservative) Older pRBCs  increase storage lesions Leukoreduction (FYI) Remove WBCs from blood prior to storage  (filters, washing, centrifugation, apheresis) Reduce immunomodulation and non-hemolytic febrile reactions? Reduce some storage lesions? Seems positive in vitro and in vivo  studies demonstrating improvement in morbidity/mortality still lacking Downsides: lose blood with processing Difficult when blood volume already small (cats) Cost of filters raise cost of blood (~ $35) Storage lesions (FYI) Physical changes Reduced deformability Spheroechinocytes Microparticle formation Cells more likely to stick to endothelium Chemical changes Decreased ATP, 2,3-DPG Increased K+, ammonia Oxidative damage to RBCs --Balancing use of resources (use oldest unit first) with possible patient harm – ongoing debate as to clinical significance of “harm” from this in human and vet med WHEN to transfuse RBCs? No one “transfusion trigger” PCV for all patients  Where I get twitchy: acute (<20-25%) vs. chronic anemia (<12-15%) Clinical signs of anemia present  Tachycardia, pallor, weakness/exercise intolerant, elevated lactate, tachypnea, +/- hypotensive Suspect >25-30% acute whole blood loss Other patient factors: Cardiovascular dz, traumatic brain injury, anesthesia, etc, may mean you need transfusion at higher PCV General guidelines for acute bleeding:  Estimated blood loss >30% of blood volume  PCV < 20% in acute bleeding episode  Lactate > 4mmol/L despite volume resuscitation https://www.petcoach.co/question/?i d=140236 Antigens and Antibodies “Blood types”  Marker on RBC surface that can be recognized by antibodies of the recipient’s immune system  Individual should be tolerant of “self”-like antigens Naturally occurring alloantibodies  Acquired at or shortly after birth  Of variable clinical significance (not all antibodies cause significant/severe reactions, but some do!) Acquired alloantibodies  Acquired after exposure to an antigen (previous transfusion, giving birth, etc.) Alloantibodies (against other RBC types, natural or acquired) vs. Autoantibodies (against own RBCs) Blood types Species Dog Cat Blood type groups (most antigenic in RED): DEA 1, 3, 4, 5, 6, 7, 8 Dal, Kai 1/Kai 2 A, B, AB Mik (DEA 1 formerly divided into 1.1, 1.2) Equine A, C, D, K, P, Q, U 7 blood systems (big letter); each is a gene that can have multiple alleles/factors (little letter – 34 so far) A(a,b,c), Ca, Ka, P(a,b), Q(a, b, c) (T system: research) (Horses lack “donkey factor”) Natural “No” Alloantibodies? (Some DEA 3, 5, and 7 neg dogs have natural alloantibodies against these blood types, but may only cause delayed reactions) Yes “No” (Weak alloantibodies to Ca) “Ideal” donor: DOES NOT EXIST Negative for Aa and Qa At minimum DEA 1 – Ideally, DEA 3, 5, 7 DEA 4+ (98% of dogs) In-house blood typing Immunochromatographic strip typing: A line impregnated with antibodies against the blood type appears more “red” as RBCs wicking up the strip become trapped in that area Card typing: Card is impregnated with antibodies against the blood type of interest. Agglutination = positive for that blood type. Autoagglutination will interfere Severe anemia may make “red” line hard to see Dog receiving the blood transfusion (recipient) DEA 1+ Canine Compatible! Donor blood DEA 1 + Dog receiving the blood transfusion (recipient) DEA 1 + Canine Compatible! Donor blood DEA 1 - Dog receiving their FIRST blood transfusion (recipient) DEA 1- Canine Compatible! (no alloantibodies in dogs) at birth But within a few days, this dog will now develop antibodies to DEA 1 antigen Donor blood DEA 1 + Dog receiving a subsequent blood transfusion (recipient) DEA 1- Canine NOT COMPATIBLE!! Donor blood DEA 1+ Immune mediated destruction! Cat receiving a blood transfusion (recipient) A A Type A A A Feline Compatible – looks like “self” Donor blood A A Type A A A Cat receiving a blood transfusion (recipient) B B Type B B B Feline NOT COMPATIBLE!!! Donor blood A A Type A A A Immune mediated destruction! What if I don’t have B cat blood? (FYI) XENOTRANSFUSION! Cats don’t have pre-existing antibodies to DOG blood Antibodies develop within 4-7d ◦ Will have delayed transfusion reaction (drop in PCV, fever, icterus) ◦ If try to give again, potentially fatal reaction Can give ONCE in cat’s life as a life-saving measure; buys time to fix cause of anemia or find B blood Crossmatching: blood type isn’t everything RBCs have other antigens beyond those screened by blood typing Dal and Kai in dogs, Mik in cats, many undiscovered Animals can develop antibodies against any RBC antigen if previously transfused Major crossmatch: Donor RBCs and recipient plasma Minor crossmatch: Donor plasma and recipient RBCs Can be used in place of blood typing for specific pairings Exotics Autoagglutination may make it difficult to crossmatch (ex. IMHA) depending on technique used Standard crossmatching takes time, often > 1 hour Minor crossmatch: Donor plasma and recipient RBCs R Major crossmatch: Donor RBCs and recipient plasma R D D Agglutination Compatible: No agglutination Not compatible : Agglutination Compatible: No agglutination Not compatible : Agglutination Newer “cage-side” crossmatching Positive outcome (aka incompatible result) is still caused by antibodies binding to RBCs, but reducing the number of wash steps/procedures and increasing the “readability” of the output makes these techniques more user-friendly and possibly less impacted by auto-agglutination How much to transfuse? Stable patient: aim to raise PCV 5-10% PCVdesired –PCVrecipient × blood volume(mL/kg) × (BW(kg)] PCVdonor Actively bleeding patient: treat similar to colloid for resuscitation, if bolusing, ideally use FWB or use RBC:plasma in a 1:1 ratio https://www.info.gov.hk/gia/genera l/201309/04/P201309040641_phot o_1058172.htm How much to transfuse?—short cuts Stable patient: aim to raise PCV 5-10% For dog pRBCs, BWkg x 1.5 will raise recipient PCV by 1% X2 for FWB Older texts will say “1ml/kg pRBCs to raise PCV by 1%”, but more recent studies in dogs show 1.5ml/kg is more accurate For feline FWB, BWkg x 2 will raise PCV by 1% Reality: often dosed by “unit” Example 30 kg lab, IMHA, PCV 15% Aim to raise PCV to 20% (can always give more!) 30 kg x 1.5 = 45mL of pRBCs will raise PCV by 1%. Want to raise by 5% 45mL x 5 = 225 mL. pRBCs come in 125 and 250 mL units, so…. Give 250 mL unit. Reassess. WHAT can we transfuse? Fresh frozen plasma (FFP) FFP: Used or frozen within 8h of collection Kept at frozen at -20 to -30°C for <1 year Contains all coag factors, vWF, fibrin, anti-coag factors, albumin, etc. Most commonly used to treat coagulopathies (Vit K antagonist rodenticides, hemophilia, liver failure, vWD) DOES NOT CONTAIN PLATELETS!!! 10-20mL/kg recommended to start, higher (15-30ml/kg) for vWD FFP used 1:1 with pRBC in massive transfusion prevent dilutional coagulopathy Controversial uses of FFP (FYI): DIC – depends on timing of disease state. Treat the patient (bleeding), not the coag times! Albumin replacement/colloidal support 40mL/kg FFP needed to raise serum Alb by 1.0 g/dL (no ongoing loss!) ~1000mL for a 25kg dog, or 4.5 U, or $960 (plasma cost ALONE) α2macroglobulin in pancreatitis - no evidence, not done in human med To give immunity – yes for FPT, no strong evidence for other diseases (parvo) Prior to invasive procedures—poor relationship with coag values and clinical bleeding, cost vs. benefit? WHAT: Frozen plasma (FP) Frozen plasma (FP) Not frozen completely w/in 8h of collection Frozen >1 yr but < 4y More labile coagulation factors (V, VIII) may be lost in plasma or whole blood if not frozen <8h or stored too long II, VII, IX, X still present, fine for Anti-K rodenticide Albumin still present May be cheaper… WHAT: Cryoprecipitate; Cryo-poor plasma (FYI) Cryoprecipitate FFP thawed just to slushee phase (1-5°C), centrifuged Concentrates cold insoluble proteins  VIII, vWF, fibrinogen, XIII Preferred TX for vWD or hemophilia A (lack of VIII) 1U cryo/10kg BW Additional fibrinogen support in massive transfusion Cryo-poor plasma (CPP) or cryosupernatant is what’s left over Contains II, VII, IX, X and albumin Used for rodenticide or oncotic support, Cheaper for a larger volume WHAT: Albumin (FYI) Albumin – Human serum albumin (HSA) vs Canine More concentrated than FFP Less volume  increased colloidal support and vascular “pull power” BUT HSA is only 80% homologous to canine albumin  Severe reactions in healthy dogs  Less reactions seen in critically ill dogs, still possible. Can only give HSA once EVER to a dog for its entire life – document!! Canine albumin would be great (?) – limited availability, $$ How much? 1.5g/kg, OR: 10 x Δalb x BWkg x 0.3 = grams Alb WHAT:Platelets (FYI except red text) Platelets (F)WB: Most common source in vet med 10 mL/kg FWB will raise plt count by about 10 x 109/L Platelet rich plasma/Platelet concentrate (second spin concentrates the PRP) Stored room temp for 7d, constant rocking. 1U/10kg raise plt by 40 x 109/L Frozen/cryopreserved platelets Stored at -20°C for 6 mo. Less platelets than PRP, but 1U/10kg was effective at reducing active bleeding in thrombocytopenia Lyophilized platelets Freeze-dried platelets. May reduce bleeding; platelets or microparticles? FFP, FP, pRBC are NOT a source of platelets! Should we transfuse platelets? In human med, PRP more widely available: Recommendation to give plts at counts <10x109/L OR < 50x109/L if undergoing invasive procedures In vet med, most often using FWB:  More volume and more antigenic substance $$ concerns Most common cause of bleeding thrombocytopenia in vet med is ITP. Platelets you give will be destroyed! Exceptions: Bleeding into critical areas (brain, lungs) or animal that MUST have urgent surgery (GDV) How do we transfuse? Warm/thaw product to room temp (or body temp for small things) No microwaves! ALWAYS use a filter!! Give blood IV or IO Pump vs. drip: Give plasma SQ or PO for FPT, otherwise IV/IO One study found loss of RBCs in <24h if pump used. Another abstract says it’s fine. Gravity drip is fine, but lacks fine volume control Give alone 0.9% Saline only fluid OK to mix with blood, can combo blood products in same line in an emergency How: Rate? Massive transfusion/volume resuscitation: bolus blood products! Don’t worry about reactions if they are dead! (ideally type cats 1st) Stable patient: give w/in 4 h Start at slower rate (0.5 to 1 ml/kg/hr) for 15-30 min Increase rate to deliver desired volume within 4 h  Longer blood @ room temp, ↑ risk of contamination Concern for volume overload? Split the unit and give each portion over 4-6 hrs Keep 2nd portion refrigerated If >8h for plasma, may start to lose factors How: Monitoring for transfusion reactions Monitor baseline HR, RR, Temp, PCV/TP Start out at the slow rate, monitoring frequently (q515 min) Toxin is in the dose! Tolerated well, increase to desired rate after 10-30 min Still monitor at least hourly thereafter If using products over longer transfusion times (e.g. plasma or albumin for colloidal support): Decreased frequency monitoring may be OK if same donor With new donor, monitor closely at start of transfusion Transfusion reactions Immunologic Allergic/anaphylactic (type I) Hemolytic (type II) Delayed RBC destruction Febrile non-hemolytic (FNHTR most common) TRIM (transfusion related immunomodulation) TRALI (transfusion related acute lung injury) Non immunologic Sepsis Massive transfusion complications: Citrate toxicity, hypocalcemia, hypophosphatemia, hypothermia Elevations in ammonia, K Transmission of infectious disease TACO (transfusion associated circulatory overload) Transfusion reactions Vomiting, fever, tachycardia, tachypnea, agitation, weakness/collapse, low BP, urticaria/edema What do you do if you suspect a reaction? STOP the transfusion Assess severity of reaction: mild, moderate, severe? Evidence of hemolysis (serum, pigmenturia) Evaluate possible reason for reaction – product contamination? Concurrent disease state? If suspect anything wrong with UNIT (discolored, etc.) OR reaction was severe, do not restart that unit. Transfusion reactions For mild (FNHTR, urticaria) reactions: Re-start at slower rate Diphenhydramine +/- steroids Continue close monitoring Transfusion reactions For moderate to severe reactions: Diphenhydramine +/- steroids +/- epinephrine Supportive care as needed Restart that unit? --NO Further type/crossmatch if not already performed IV or urine evidence of hemolysis? Renal support, monitoring Blood banking/donor selection (ALL FYI) JUST A FEW WORDS Where do you get products? Commercial blood banks Local blood banking centers/cohort of e-clinics Your own donors (owned by clients or clinic) DonorsHealthy dogs (>27 kg, 1-7 yo) and cats (>4.5kg, 1-7 yo) Larger horses, no mares who have previously foaled Have not ever received a transfusion Screened for infectious disease, coagulopathies, known blood type ACVIM guidelines for donor disease screening UTD on vaccines, year-round HW and flea/tick prevention, yearly bloodwork Good temperament and easy venous access (not obese!) Donor Breeds Greyhounds – “universal” donors, high PCV, easy veins, big dogs Cats - most donors and recipients will be A Exotic and British shorthair cats, Persians, Abyssinians, Scottish folds, may be up to 20-45% type B 6% of USA DSH are B! Can’t tell the type by the breed – ALWAYS type cats! Look for horses that are Aa and Qa negative. Certain breeds (QH, Standardbred, Morgan) more likely to be negative How do I bleed an animal for donation? Check PCV/TP. Dogs > 40%, cats > 35% Cats usually done under sedation or gas anesthesia 15-20% of blood volume can be taken every 3 weeks (standard 450 mL for dogs, 50 mL for cats) OR 16-18 mL/kg Blood must be anticoagulated (14 mL CPDA/100 mL blood) Collect into appropriate bag unless need immediately (collect into syringe with anticoagulant) Horses: vacuum suction into bags improves speed  Suction into sterile glass bottles inactivates platelets and damages RBCs Autotransfusion Salvage procedure if other blood products not available/too slow Re-transfuse blood from a body cavity (abdomen, thorax) A filter should be used Ideally anticoagulate blood if time permits  Cavitary blood is defibrinated already, anticoagulant not critical Cell salvage devices best –wash, filter, and anticoagulate the blood automatically, but not widely available in vet med Avoid if blood is contaminated (septic peritonitis) Use with neoplasia is controversial, but balance risk/benefit Questions? Email: [email protected] References Short et al. Accuracy of formulas used to predict post-transfusion packed cell volume rise in anemic dogs. JVECCS 2012, 22(4) p. 428-434 Small Animal Critical Care Medicine, second edition, by Silverstein and Hopper. Ch 61 and 62 Davidow. Transfusion medicine in small animals. Vet Clin NA SA 2013 43(4) p.735-756 McDevitt et al. Influence of transfusion technique on survival of autologous red blood cells in the dog. JVECCS 2011 21(3) p.209-216 McMichael et al. Effect of leukoreduction on transfusion induced inflammation in dogs. JVIM 2010 24(5) p.1131-1137 Mudge, Acute hemorrhage and blood transfusion in horses. Vet Clin NA Eq 2014 (30) 427-436. Thanks to Dr. Scott Moncrieff for providing template slides and pictures!