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Blood Transfusions in Small Animal Medicine

Written by: Meghann R.


Introduction

Transfusion therapy has become a staple in emergency veterinary medicine, providing owners with a potentially life-saving treatment for their pet. In medicine, transfusions are defined as the process of administering blood or blood products to a patient who is deficient in that product. Deficiencies are determined by a combination of history, physical exam, and lab findings. Perhaps the most important steps to performing a  transfusion occur prior to the procedure itself: correct product(s) need to be selected, the recipient needs to be blood-typed and cross-matched, and ideally underlying causes are determined to administer co-therapies. This process is meant to decrease the risk of patients developing a transfusion reaction- both immune-mediated and non-immune-mediated. Even when this testing has been performed correctly, failure to respond to transfusion is possible and owners need to be aware of this risk.

Product Types

There are several types of products that can be used in transfusions depending on the needs of the patient. Whole blood can be administered to a patient but it contains products that may be unnecessary if they only require one component. The two most common types of products used in transfusions are packed Red Blood Cells (pRBC) and Fresh Frozen Plasma (FFP). pRBCs are pure red blood cells collected from donors that must be separated from the plasma prior to storage. FFPs are the result of removal from pRBCs which containing platelets, clotting factors, albumin, and antibodies that are stored frozen for up to a year when it is re-labeled as Frozen Plasma.1 There are other variations of these products that are available commercially or through private donation that contain combinations of the listed components. For the purpose of this article, pRBC transfusions will be discussed in depth.

pRBCs are collected in citrate anticoagulant which then must be separated from whole blood within 4 to 6 hours of collection. It is then combined with additives to promote longevity and can be stored for up to 4 weeks in a refrigerator. Individual hospitals will have preferences for unit usage for transfusions depending on age. This preference can impact the number of units discarded due to expiration.2 pRBCs can be thawed for a transfusion, re-refrigerated and thawed again for any future transfusions in the same patient if warranted.

Indications

The indicators for transfusion to be discussed were first described in humans, but have successfully translated to veterinary medicine. Patients that require a transfusion are identified based on a combination of history, physical exam and lab findings consistent with a deficiency in at least one component of a blood product. For example, most pRBC transfusions are performed based on lab work indicating severe anemia. However, some patients could have normal PCV but low oxygen carrying capacity of hemoglobin (aplastic anemia, decreased erythropoietin production, hemolysis) and also require a transfusion.3 It is therefore important for the clinician to assess the patient as a whole and not rely solely on one diagnostic result to indicate a blood transfusion.

Patients requiring pRBC to correct an anemic state can present with similar clinical symptoms. During a physical exam the anemic patient’s gums will appear pale or yellow, and act lethargic. Capillary refill time may be prolonged indicating poor perfusion. There may also be a history of hematuria or hemoglobinuria if the patient is experiencing a hemolytic disorder. On blood work, RBC count will be lower than the reference interval and hematocrit or PCV will be less than 21%.3 There are patients who may present with the above symptoms but PCV is normal. For example, an animal may have suffered acute blood loss such as trauma or splenic rupture. When PCV appears within the reference interval, it is important to assess tissue perfusion by measuring CRT, SpO2, and lactate values.

While this transfusion may correct the anemia, underlying causes must also be addressed. Many times, patients will be diagnosed with immune-mediated hemolytic anemia (patient’s own antibodies acting RBCs) and will require concurrent immunotherapy to prevent a subsequent hemolytic crisis. Other patients may be suffering from a parasitic infestation/infection and require anti-parasitics (flea preventative) to remove the inciting cause. Surgical patients may also require a transfusion if the quantified blood loss exceeds the acceptable amount based on the patient’s calculated total blood volume and pre-surgical PCV. Total blood volume in dogs = 80 ml/kg x BW (kg). Totally blood volume in cats = 70 ml/kg x BW (kg). Then, 10%, 20%, and 30% of the total volume is calculated. The allowable blood loss = ([Patient PCV- Minimum PCV]/Patient PCV) x Blood Volume. The Minimum PCV is defined as the calculated % of the total blood volume that is below the patient’s PCV. This calculation can be determined prior to surgery in order to have enough thawed blood on hand in the event that an intra-operative transfusion is indicated.

There are many reasons that a transfusion may be necessary. These triggers to initiate a transfusion are all related to a patient’s ability to adequately deliver oxygen to its tissues. This is why it is important to assess the patient has a whole and not rely only on one trigger to determine the need for a transfusion.

Blood Typing and Cross Matching

Like humans, veterinary species carry specific blood types that are important to identify in order to prevent an immune-mediated hemolytic reaction. However, there are species-related differences that exist that allow for more or less flexibility when deciding if a product is appropriate for that patient.

There are 8 major blood groups identified in dogs- Dog Erythrocyte Antigen (DEA) 1-8. These blood groups are further classified as positive or negative to signify presence of that antigen in an individual canine’s blood. The major antigens of clinical significance are DEA 1.1 and 1.2. If a dog is negative for both of these antigens, they are considered a universal donor. However, they are only required to be negative for one of these in order to be eligible to donate. A unique aspect with regards to blood typing prior to a transfusion is that a dog typed as DEA 1.1 negative can be transfused once with DEA 1.1 positive blood without developing a severe immune reaction as seen in mismatched human transfusions. This would allow veterinarians to forego typing in an emergent situation. The result, however will sensitize the negative patient to DEA 1.1 antigens and will cause an acute hemolytic transfusion reaction if transfused with positive blood in the future.4 Some veterinarians will opt to always blood type prior to any transfusion to avoid a possible reaction if transfusion history is unknown. Aside from the major blood groups, a newly identified antigen has been characterized. This antigen called Dal, was found to be absent in Dalmatians when a patient with a transfusion reaction had developed allo-antibodies against this antigen.5 The frequency at which this occurs is still unknown but is predicted to occur in other dog breeds besides Dalmatians.

Feline blood transfusions carry much stricter requirements in order to be successful. First, there are 3 blood antigen groups: A, B, and AB. Type A is seen most commonly in domestic felines, with an incidence of >95% in domestic short and long hair cats. Type B is less frequent but specific in exotic breeds such as British Shorthairs, Devon Rex and Cornish Rex. Both Type A and B blood carry natural antibodies and will exhibit acute hemolytic transfusion reactions if a mismatch occurs. A common phenomenon demonstrating this mismatch is Feline Neonatal Isoerythrolysis (NI). This occurs when a Type B queen gives birth to kittens with Type A blood. When the kittens suckle the first few days, they receive colostrum containing maternal antibodies. These antibodies include anti-A blood group antibodies which will attack the Type A blood of the kitten who will suffer from an immune-mediated hemolytic crisis.6 Type AB is extremely rare but considered a universal donor as these cats lack natural antibodies to these antigens.7

The process of blood typing and cross-matching is fairly simple. For blood typing, species specific typing cards are commercially available. A small sample of blood is collected from the intended recipient and mixed with a reagent and allowed to sit for a few minutes with a test strip. The test strip will include a control indicator and indicators for DEA 1.1 positive or negative (canines) or indicators for A or B (felines).8 Once the test result is in, the correct donor unit of blood can be selected for the recipient.

Cross-matching is a more complete diagnostic that tests compatibility of blood and plasma via a major or minor crossmatch.4 The major crossmatch tests the compatibility of donor blood with recipient plasma. If the test is incompatible, a visible hemagglutination reaction will occur and therefore the donor blood should not be used in the transfusion. Absence of hemagglutination indicates compatibility and the blood can be utilized in the transfusion. The minor cross-match tests compatibility of donor plasma and the recipient. This diagnostic is typically utilized in transfusion of whole blood where the donor unit will contain plasma products in addition to RBCs. Typically, transfusion of whole blood is not utilized as most patients require on RBCs, and therefore, this test is less commonly performed.

Blood Donors

Acquiring blood products for veterinary patients is quite different for animal patients. The number of qualified animals that can donate blood is much less than the number of human patients and typically breed-specific. Emergency clinics and university hospitals will enroll animals in private donor programs but can order certain products if they have a demand for that specific product. The requirements for donation will be hospital-specific with policies that best fit their needs.

At Iowa State University, canine patients are required to weigh more than 50 lbs (most common breeds are Greyhounds and Labrador Retrievers), between the ages of 1-6 years with no history of severe disease, must be on monthly heartworm preventative, not currently on certain medications, be overall healthy and are preferred to be neutered. If initial blood screening indicates the potential donor is DEA 1.1 negative (strong candidate to donate), further tests are performed for various infectious diseases. ACVIM currently recommends testing for diseases that are documented to cause infection in blood donor recipients, diseases that can be asymptomatic and passed to recipients, can be cultured from blood, or disease is difficult to treat.9 Examples of these diseases that are tested for prior to donation are Babesiosis, Leishmaniosis, Ehrlichiosis, Anaplasmosis, Mycoplasmosis, Bartonellosis, and Brucellosis. Methods of testing for these diseases includes light microscopy, culture, serum antigen tests (SNAP testing), and PCR testing. Careful interpretation of these tests is critical as each has its own limitations. Once tests have come back negative, the patient is added to the donor list and is brought in monthly for at least 2 years to donate.10

For potential feline donors at Iowa State University, they must be 1-6 years of age lacking a history of severe disease, not be on certain medications, weigh at least 10 lbs, test negative on feline leukemia/FIV, be current on vaccinations, and also test negative for other infectious diseases such as Mycoplasmosis, Bartonellosis, and Hemoplasmosis.9 There are no restrictions on eligible blood types (A or B) however Type B blood is rarely kept on hand due to few donors and less demand for Type B blood. Because there is no distinction between positive and negative blood antigens in cats, there is no universal donor. Once screening has been successful, donations take place one every other month for two years.

When patients donate blood, bloodwork is ran to make sure the animal is healthy prior to the transfusion. If the patient is asymptomatically sick with increased white blood cell count or is anemic, the donation will not take place. Once the blood work is completed, the patient is taken to a quiet, calm room where they will be lightly sedated. A larger gauge needle is placed in the jugular vein that will be connected to an empty unit bag that acting as a vacuum and easily draws enough blood to fill at least one bag. Once the desired unit is collected. The needle is removed and a bandage is placed around the neck. As the sedation wears off, the donor will receive fluids to replace the volume lost during the transfusion. The new unit of blood is spun down to separate plasma from the RBCs and is labeled with the date, donor name, blood type, and blood product and then is stored in a designated fridge. Overall this process is about 15-20 minutes and strives to be as low stress as possible for the donor.

The Transfusion Process

Once the transfusion recipient has been blood-typed/cross-matched and a unit has been selected, the transfusion can begin. The amount transfused is calculated based on body weight and desired PCV. Administering pRBCs is done very carefully by monitoring the patient for the duration of the transfusion and post-transfusion for any adverse reactions.

The unit of blood is removed from the fridge and warmed to room temperature. This should be done slowly and not in a microwave to prevent damage to the red blood cells. The IV catheter (ideally > 22 gauge) should be as large as possible for the patient so that the RBCs are delivered undamaged.3 When setting up the pump, there should be a bag of non-heparinized saline (to prime the line) and the unit of blood on a hook. A primary line is connect to each bag and runs to the fluid pump. There should be a blood filter placed between the unit of blood to remove clots that may have formed during the collection and storage process. From the fluid pump, extension lines are placed to comfortably reach the patient and are attached to the T-port on the IV catheter.

The most common method to calculate total volume to transfuse is the formula: 1 ml x % PCV rise x kg BW. According to Short et al, this formula was found to under transfuse a patient by over-predicting PCV rise. Two different formulas were found to be more accurate- 1: 90 ml x kg BW x ([desired PCV- patient PCV]/ PCV of donor blood) or 2: 1.5 ml x % PCV rise x kg BW.11 There is no consensus in regards which to use in veterinary medicine. Usually the fluid rate is started at 1 ml/kg/hr for the first 15-30 minutes and then bumped up to 2 ml/kg/hr for the duration of the transfusion (no more than 4 hours to prevent bacterial growth in the blood sample).

During the transfusion, a monitoring sheet is utilized to record vitals and any additional treatments that are performed. Reactions are commonly observed in the first 15-30 minutes which is why fluids are started at a slower rate. Types of reactions to look for in a recipient early in the transfusion is a transient apnea, hypotension, bradycardia or arrhythmia, seizures, vocalization, urination or defections, and death. Less immediate reactions to monitor for is tachypnea, tachycardia, increased temperature, vomiting, restlessness, mentation changes, hemoglobinuria/emia, and death. Allergic reactions such as wheals, urticaria, erythema, and pruritis can also be observed.12 It is also important to not only observe for reactions but to assess the patient as a whole. For example, a patient receiving a transfusion may have a starting heart rate of 160 bpm but as the transfusion is taking place, it may drop to 110. This could be a reaction, or it could be normal response to increased blood volume if the patient was hypovolemic prior to the transfusion.

After completion, a post-transfusion PCV is performed to assess the patient. If PCV has increased to the desired amount (to the calculated predicted PCV), the transfusion is considered complete. Even if the PCV is increased initially after the transfusion, close monitoring of the patient during hospitalization is critical since PCV can still plummet to pre-transfusion levels. Even after multiple transfusions, there is no 100% guarantee that they are curative.

Prognosis

Sometimes after a successful transfusion, patients do not respond and quickly become anemic again. Many times an underlying disease such as IMHA can impact the overall prognosis. However, patients with these diseases can respond well to transfusions and only need one or two before placement on lifelong medications. Depending on the patient as a whole, prognosis can be good based on the severity of the anemia and the underlying cause. The more serious patients presenting for a transfusion carry a more guarded prognosis.

Conclusion

Blood and blood product transfusions have become a staple treatment in emergency medicine. Through the process of carefully selecting qualified blood donors and testing recipients prior to transfusion, risk of adverse reactions are minimized. Recipients are carefully assessed before the transfusion to determine the course of treatment, co-therapies, and establish baselines for monitoring purposes. Post-transfusion monitoring has helped determine whether future transfusions are necessary and determine long-term prognosis of the patient. With a cooperative veterinary team, transfusions can often be successful and lifesaving to animal patients.


Bibliography:

  1. Cornell University College of Veterinary Medicine. Blood Components. eclinpath.com (2013). Available at: http://www.eclinpath.com/hemostasis/transfusion-medicine/components/. (Accessed: 10th July 2017)
  2. Holowaychuk, M. K. & Musulin, S. E. The effect of blood usage protocol on the age of packed red blood cell transfusions administered at 2 veterinary teaching hospitals. 25, 679–683 (2015).
  3. Davidow, B. Tra n s f u s i o n M e d i c i n e i n Sm a l l Animals Transfusion medicine Red blood cells Plasma Platelets Albumin TRALI. Vet. Clin. NA Small Anim. Pract. 43, 735–756 (2013).
  4. Tocci, L. J., Sbb, M. T. A. & Ewing, P. J. Increasing patient safety in veterinary transfusion medicine : an overview of pretransfusion testing. J. Vet. Emerg. Crit. Care 19, 66–73 (2009).
  5. Blais, M., Berman, L., Oakley, D. A. & Giger, U. Canine Dal Blood Type: A Red Cell Antigen Lacking in Some Dalmatians. 281–286 (2007).
  6. Silvestre-ferreira, A. C. & Pastor, J. Feline Neonatal Isoerythrolysis and the Importance of Feline Blood Types. SAGE-Hindawi Access to Res. 2010, (2010).
  7. University of California Davis Veterinary Genetics Lab. AB Blood Group in Felines. Available at: https://www.vgl.ucdavis.edu/services/abblood.php. (Accessed: 8th July 2017)
  8. Alvedia- Alice Veterinary Diagnostic. No Title. (2013). Available at: http://www.alvedia.com/quick-test-blood-typing.html. (Accessed: 8th July 2017)
  9. Wardrop, K. J. et al. ACVIM Consensus Statement. 135–142 (2005).
  10. Iowa State University College of Veterinary Medicine. Blood Donor Program. Available at: https://vetmed.iastate.edu/vmc/services/blood-donor-program. (Accessed: 10th July 2017)
  11. Short, J. L., Diehl, S. & Seshadri, R. Accuracy of formulas used to predict post-transfusion packed cell volume rise in anemic dogs. 22, 428–434 (2012).
  12. Bracker, Kiko DVM, Drellich, S. D. Transfusion Reactions. VetFolio, Emerg. Med. 27, (2005).

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