A huge shout out to Kenichiro Yagi, ICU supervisor/Blood bank manager/PetEd educator, and veterinary technician extraordinaire, for an incredible blog on “The Bloody Truth: Facts About Transfusion Medicine That May Not Actually Be True!

By Kenichiro Yagi, BS, RVT, VTS (ECC, SAIM)

While veterinary transfusion medicine and blood banking has become more commonplace, there are many questions surrounding their use. Newly gained evidence further clarifies already known concepts while others confirm long time suspicions, and others yet teach us something new. Let’s take a moment to update our knowledge!

#1 The First Transfusion is “Free”
Compatibility testing for canine blood transfusions has traditionally been omitted in the interest of swift transfusions and financial considerations from a notion that “first transfusions are free for dogs”. Virtually all canines have no naturally occurring alloantibodies against Dog Erythrocyte Antigen (DEA) 1, a blood type responsible for acute hemolytic transfusion reactions, and the first transfusion will not result in an immunologic complication even when given without blood type matching or cross matching.

The Truth: The first mismatched transfusion leads to sensitization, or development of antibodies over approximately 4 days, leading to delayed hemolytic transfusion reactions and priming the patient for severe acute hemolytic reactions, possibly anaphylaxis, in subsequent mismatched transfusions. A patient may at times present with inaccurate or uncertain transfusion history in emergencies (rescued, adopted, brought in by pet sitter, etc), and blood type matching and cross matching is important. The first transfusion has hidden fees. Read all fine prints before use.
Cats have naturally occurring alloantibodies against blood types different from self, and the first mismatched transfusion causes mild (type B to A transfusions) to severe (type A to B transfusions, Mik antigen mismatch) reactions. Nothing comes free when dealing with cats.

#2 DEA 1 Negative is the Universal Blood Type (Canine)
Giving “universal” blood is ideal when time required for compatibility testing is felt as a critical delay in a life-or-death situation. Universal blood comes from a donor with a blood type compatible with blood types of any other member of the same species, eliminating concerns of an immunologic reaction related to red blood cell antigens.

The Truth: In dogs, blood negative in DEA 1, an antigen responsible for acute hemolytic transfusion reactions when given to previously sensitized patients (see #1), may be considered universal. However, there are other antigens described (DEA 3, 4, 5, 6, 7, and 8. Dal, N-Acetyl-neuraminic/N-glycolyl-neuraminic acid, type C, D1/D2) with varying degrees of prevalence and breed incidences which are responsible for delayed or acute hemolytic transfusion reactions on first or sensitized exposure. Blood typing is currently limited to DEA 1 with commercially available in-house kits and a few DEA through reference laboratories because of a lack of typing sera. This makes claims for universal compatibility very difficult, and we should consider donors negative in every testable erythrocyte antigen to be the “least antigenic” or “least immunogenic” donors.

#3 RBC Products Should be Administered with an Infusion Pump
“Can blood be given through an infusion pump?” is a common and highly debated topic in both human and veterinary care. Delivering RBC products through an infusion pump provides accurate control over the transfusion rate and volume but has been theorized to damage RBCs reducing the effectiveness of the transfusion.

The Truth: Two veterinary studies have been recently published evaluating in vivo RBC survival time with common transfusion methods in the dog and cat. The canine study (McDevitt 2011) observed:
• 100% chance of survival to 49 days post transfusion with gravity delivery (no pump)
• 50% chance of survival to 49 days with a volumetric pump (typical peristaltic IV pump)
• 0% chance of survival beyond 24 hours with a syringe pump

The infusions with syringe pumps were performed through an 18µm pore size filter instead of a 170-260µm administration set, and this is suspected to be the largest contributing factor to the low survival rate. The feline study observed no significant difference in survival time up to 42 days post transfusion between gravity delivery and syringe pump infusions despite the filter pore size difference (Heikes 2014).

Those convinced use gravity delivery as their method for canine transfusions with careful monitoring of transfusion rate through frequent drip rate checks as the current best evidence-based practice. Others await further evidence before changing their practices as experience argues effectiveness of transfusions delivered through mechanical infusion devices. The good news: nobody is debating over transfusion methods for cats.

#4 Premedication Reduces Chances of Reactions
Premedication, the administration of antihistamines, glucocorticoids, or antipyretics in anticipation of immunologic complications, is traditionally practiced in transfusion medicine to prevent type I hypersensitivity immunologic reactions (allergic reactions) and febrile non-hemolytic transfusion reactions (FNHTR) caused by inflammatory mediators.

The Truth: A number of human studies and a systematic review observed no difference in incidence of allergic reactions or FNHTR (Marti-Carvaial 2010). Some clinicians reason that premedication is detrimental, potentially masking early symptoms of immunologic complications delaying required interventions for treatment, and advocate against it. Human evidence is not always directly translatable into veterinary practice, though expectations of similar physiological mechanisms exist. Studies evaluating premedication for hemolytic transfusion reactions are not apparently available. Any argument for benefits is theoretical, and is no justification for forgoing proper compatibility testing.

#5 Blood Products must be Warmed Prior to Administration
Warming of blood products to prevent hypothermia in the recipient is considered during blood product administration.

The Truth: Concerns for hemolysis of erythrocytes when warming during transfusion exist, and studies point towards little to no difference in markers for hemolysis in vitro when blood is warmed to typical body temperature. However, at non-emergency administration rates, blood reaching the patient through the line placed in a room temperature environment easily equilibrates prior to reaching the patient, and will not significantly affect the body temperature (Chiang 2011).

With that said, patients with concerns of hypothermia should have their blood products warmed. In the case of rapid or large volume transfusions, evenly warming the blood to 35-37°C and not exceeding 42°C is appropriate. Warming with heated IV extension sets or inline IV fluid warmers closest to the patient as possible will minimize heat loss. Hypothermia is also a documented complication in massive transfusions. Aside from these situations, warming effort directed at the patient is most effective in treating hypothermia without causing risk of damage to the RBCs.

#6 pRBC Requires Dilution with Saline for Administration
Previously published packed red blood cell (pRBC) administration protocols may call for dilution of pRBCs with saline reducing the viscosity of the RBC suspension, increasing flow rates, and reducing hemolysis.

The Truth: While administration of undiluted pRBC increased plasma hemoglobin level by as much as 270% (details of this human study design were not available), dilution was more relevant when pRBC was prepared without additive solutions of today. pRBC was often prepared as a solution of 80% PCV, viscous enough to cause flow and hemolysis issues. Majority of pRBC preparations these days use a predetermined amount of additive solution resulting in pRBC units of 60-70% PCV. There typically is no significant viscosity issue at this level. Additionally, reduced transfusion volume of pRBC provides an advantage for patients at risk of fluid overload (IMHA, CKD, for example), and the additional dilution volume is best avoided. The PCV of the specific pRBC unit being administered should be considered when employing dilution.

#7 Plasma is Indicated for Use in Hypoproteinemia
Plasma contains many proteins of interest, namely hemostatic proteins, albumin, and immunoglobulins. Hypoproteinemia, specifically hypoalbuminemia, occurs in many critically ill patients with protein-losing disorders including protein-losing enteropathies, protein-losing nephropathies, liver failure, trauma, burn wounds, etc. This leads to a loss of intravascular colloid osmotic pressure (COP), and subsequent consequences. Administration of plasma products (fresh frozen plasma, frozen plasma, or cryosupernatant) have been used as a method in supplementing albumin for COP.

The Truth: The amount of plasma required to raise the patient’s albumin level by 1g/dL is approximately 40-50mL/kg, equivalent to 1.1L (9.5 units) of plasma for a 50 lb (22.7kg) patient. This is cost prohibitive and pose a large immunologic and circulatory overload risk to the patient. Synthetic colloids provide higher COP for the volume infused without associated immunologic risks. In addition, whether increasing the albumin level to a normal value (>2g/dL) will lead to increased chances of a positive outcome is still unclear, and difficult to advocate. Treatment for hypoproteinemia is directed at the underlying cause.

#8 Plasma from Parvo Survivors Help Parvo Patients
Canine parvovirus (CPV) infections cause severe gastroenteritis and lead to dehydration, shock, disseminated intravascular coagulation, bacterial translocation and sepsis when left untreated. With aggressive treatment, the mortality rate can be reduced to between 0% and 30% from 90%. Clinicians have theorized that administration of plasma containing antibodies against CPV will aid in recovery.

The Truth: A study evaluating use of a single dose of plasma containing CPV antibodies in its efficacy versus saline placebo saw no significant effect in reducing clinical signs and viremia, or speeding recovery (Bragg 2012). The efficacy of the treatment remains in the realms of anecdotal evidence. Proven key elements of an effective therapeutic plan for CPV infection include appropriate fluid therapy and early enteral nutrition (which is too often overlooked). Currently recommended indications of plasma product transfusions include coagulation factor and fibrinogen supplementation in patients with deficiencies that are actively bleeding or have a planned invasive procedure.

#9 Blood Can be Stored for 42 Days
Current practices in blood banking involve the usage of anticoagulant preservative and additive nutrient solutions which are labeled for 28-42 days of storage.

The Truth: Evidence points to stored red blood cells having impaired survival, reduced efficacy as an oxygen carrier, and inciting adverse effects in the recipient increasing mortality and morbidity (Kisielewicz 2014). Biochemical changes to stored RBCs, or “storage lesions”, are responsible for these effects, and adverse effects such as arrhythmias, thrombosis, systemic inflammation, transfusion-related acute lung injury (TRALI), acute respiratory distress syndrome (ARDS), hypotension, and multiple organ dysfunctions are seen. These changes become significant around 14 days into storage, making supplying our patients with safe and beneficial transfusion products a realistic challenge. Storage lesions and their clinical impact is a topic of ongoing investigation while blood banks strive to balance provision of fresher products and minimizing wasting of blood.
Were any of these surprising? What other questions do you have on transfusion medicine?

References
1) Bragg RE, Duffy AL, DeCecco FA, et al. Clinical evaluation of a single dose of immune plasma for treatment of canine parvovirus infection. J Amer Vet Med Assoc 2012;240(6):700-704.
2) Chiang V, Hopper K, Mellema MS. In vitro evaluation of the efficacy of a veterinary dry heat fluid warmer. J Vet Emerg Crit Care 2011;21(6):639-647.
3) Heikes BW, Ruaux CG. Effect of syringe and aggregate filter administration on survival of transfused autologous fresh feline red blood cells. J Vet Emerg Crit Care 2014;24(2):162-167.
4) Kisielewicz C, Self IA. Canine and feline blood transfusions: controversies and recent advances in administration practices. Vet Anaesth Analg 2014;41(3):233-42.
5) Marti-Carvaial AJ, Sola I, Gonzalez LE, et al. Pharmacological interventions for the prevention of allergic and febrile non-haemolytic transfusion reactions. Cochrane Database Syst Rev 2010 (6): CD007539.
6) McDevitt RI, Ruaux CG, Baltzer WI. Influence of transfusion technique on survival of autologous red blood cells in the dog. J Vet Emerg Crit Care 2011; 21(3):209-216.