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Small animal blood transfusions

 - a practical guide

 Kindly provided by Royal Canin

 

Key PointsIntroduction

Blood and blood component transfusions play an important role in small animal medicine, especially in emergency clinical care. This article offers a practical review of the most relevant aspects to enable effective transfusions whilst minimizing risks. In many countries commercial blood banks now offer whole blood and blood components for transfusions in both dogs and cats; it is always important to select the product that will provide maximum benefits for the patient. The different blood products, their characteristics and indications are described in Tables 1 and 2 (1,2).

 

 

Transfusions in anemia

Hemoglobin is the main component involved with oxygen transport to tissues. It is hard to categorically define the hemoglobin (Hb) or hematocrit (Hct) value below which a patient needs a transfusion (the transfusion trigger), because a patient’s capacity to compensate for the anemia can vary (3). Chronic anemia is better compensated for than acute anemia, because the intraerythrocyte levels of 2,3-diphosphoglycerate (2,3-DPG) increase, facilitating oxygen transfer from the hemoglobin to the tissues. Normovolemic anemia is better tolerated than hypovolemic anemia because cardiac output (CO) can be increased efficiently. The underlying cause of the anemia and the possible presence of other disease also influence a patient’s capacity to compensate. Consequently the decision on whether to administer a transfusion (Figure 1) should not be based solely on the Hct value. The degree of tissue hypoxia caused by the anemia which can be determined by the presence of tachycardia/tachypnea, reduced level of consciousness/stupor, syncope, and increased blood levels of lactate (lactic acidosis is an indicator of tissue hypoxia; normal value is <2.5 mmol/L) - is a major factor. In general, in acute hypovolemic anemia (such as hemorrhage) the Hct should not be allowed to fall below 25-30% in dogs or 20-25% in cats. However, in chronic normovolemic anemia, patients can compensate and will not usually require a transfusion until a lower Hct value (12-15% in dogs or 10-12% in cats) (2). Suitable products that provide Hb/RBC are whole blood and packed red blood cells, as follows:

 Figure 1

1. Whole Blood (WB): this is blood that has not been separated into its various components. In dogs, one unit (1U) of WB is the volume obtained when a commercial human blood bag is filled (about 450 mL of blood and 63 mL of anticoagulant). In cats, 1U of WB is about 60 mL. It is called Fresh Whole Blood (FWB) for up to 8 hours after collection, when all the blood components remain viable; Stored Whole Blood (SWB) is WB that has been stored in a refrigerator for >8 hours after collection. After this time, the platelets are no longer viable and the most labile clotting factors (FVIII, von Willebrand Factor) gradually lose their activity.

 

2. Packed red blood cells (pRBC) in dogs: centrifugation of 1U of canine WB will give 200-250 mL of pRBC (=1U of pRBC) and 200-250 mL of supernatant (=1U of plasma) separated in a satellite bag without anti-coagulant (Figure 2). A pRBC transfusion achieves the same increase in Hb and RBC as a WB transfusion but using a much smaller volume, and so is mainly indicated for normovolemic anemia. Since pRBCs have a very high hematocrit (60-80%), 0.9% NaCl (70-100 mL) should be added to the bag before transfusion to reduce its viscosity and facilitate administration. In hemorrhagic anemia, if FWB is not available, pRBC (10 mL/kg) can be transfused together with fresh frozen plasma (FFP) (10 mL/kg).

 

3. Hemoglobin-based oxygen carriers (HBOCs): These solutions are based on polymerized/recombinant stroma-free human or bovine hemoglobin, and are capable of capturing and carrying oxygen. The advantages of HBOCs are that they do not require special storage conditions and that the risk of adverse reactions due to incompatible blood group is avoided. They are indicated in anemia and certain states of shock (2,4).

 Table 1

Table 2 

Transfusions in clotting factor deficienciesFigure 2

The following coagulation disorders require transfusion most frequently in small animals: disseminated intravascular coagulation (DIC, deficiency of all clotting factors), rodenticide intoxication (deficiency/inactivity of vitamin K-dependent factors II, VII, IX, X), liver failure (deficiency of all factors except FVIII), von Willebrand disease (vWF deficiency), hemophilia A (FVIII deficiency) and hemophilia B (FIX deficiency). A transfusion is indicated when the clotting factor deficiency causes significant hemorrhage or if the patient is to undergo a surgical procedure that entails a bleeding risk. Plasma is the most indicated blood product for coagulation disorders (5,6). If plasma is not frozen it gradually loses the clotting factor functions after 8-12 hours. If it is frozen at -30 °C within 6 hours of blood collection, it is known as Fresh Frozen Plasma (FFP) and will retain viable clotting factors and other plasma proteins for at least one year. If frozen after 6 hours, it is called Frozen Plasma (FP); this name is also given to plasma that has been thawed and refrozen, to FFP that was collected/ frozen more than a year previously, and to plasma collected from the supernatant of a cryoprecipitate. FP retains the viability of albumin, globulins and all but the most labile clotting factors. Blood typing is not strictly necessary for plasma transfusions in dogs, but is required in cats.

 

The initial dose for plasma is 8-12 mL/kg/6-12 h until bleeding is controlled or clotting times return to normal values. It is always preferable to transfuse fresh plasma or FFP, because both products provide active clotting factors. FP is also acceptable for coagulation disorders induced by Vitamin K antagonists (e.g. rodenticides) and in coagulation disorders associated with liver failure. In the case of DIC, which also involves thrombocytopenia, FWB is also indicated (because it supplies clotting factors and platelets). In the case of haemophilia A or von Willebrand disease, the most indicated product is cryoprecipitate (CRYO) - where available - at a dose of 1U/10 kg (7). If plasma is not available, FWB can be transfused (10-20 mL/kg/24h).

 

 

Transfusions in other plasma protein deficiencies

Plasma protein deficiencies can result from conditions such as hypoalbuminemia, pancreatitis and parvovirus. Hypoalbuminemia causes a reduction in plasma oncotic pressure, leading to edema. It can also cause hypercoagulability, delay wound healing, and alter the transport or action of certain drugs, and is associated with a significant increase in morbidity/mortality in severely ill/critical patients (8). It is well recognized that transfusions of albumin solutions alone do not fully guarantee a good clinical outcome for hypoalbuminemia; the correct approach is to treat the primary cause (and in particular to resolve any inflammatory processes), and it is also extremely important to ensure that enteral nutrition provides adequate protein intake. A blood transfusion should be considered if the hypoalbuminemia causes edema or if there is a high risk of edema developing (plasma albumin <1.5-2 g/dL). Plasma is indicated in this situation, and it is calculated that 45 mL/ kg is needed to increase plasma albumin by 1 g/dL. Due to its high cost, many authors recommend administering plasma until albumin values of ≥1.5 g/dL are attained, and then combine it or replace it with synthetic colloids (20 mL/kg/day) to maintain oncotic pressure (9).

 

Another option is to administer a highly concentrated (20-25%) human albumin solution. Its oncotic pressure is >100 mmHg, and therefore a small amount increases the oncotic pressure and circulating volume very efficiently. However in dogs its use causes antibody production that can trigger severe immediate or delayed anaphylactic reactions, especially with a second infusion (10,11). Canine albumin solutions are now commercially available (7), but due to their marked oncotic effect they should not be used in patients with heart failure, renal failure or chronic normovolemic hypoalbuminemia.

 

The usual transfusion regimen for human albumin is 0.5 g/kg over 2-4 hours, followed by an infusion rate of 0.05-0.1 g/kg/h (maximum 2 g/kg/day) until serum albumin levels of ≥1.5 g/dL are achieved (9,12). It is recommended that a small test dose of 0.25 mL/kg/h should be given for 15 minutes, discontinuing the transfusion if any sign of anaphylaxis is detected. The transfusion should not take longer than 72 hours and (in order to reduce the risk of reaction from antibody formation) should not be repeated. Very little data are available regarding albumin transfusions in cats.

 

The administration of FP or FFP in patients with acute pancreatitis has been proposed as a source of albumin, antithrombin, alpha-2-macroglobulin and alpha-1- antitrypsin, and clotting factors. There are no conclusive results in human or veterinary medicine on the potential benefits; one retrospective study in dogs concluded that there were no significant differences in mortality/ outcome of patients who received plasma compared with those who did not (13). It has also been suggested that FFP/FP transfusions in dogs with parvovirus infection may be beneficial (due to a possible passive transfer of antibodies and albumin), but there have been no controlled studies to support this assertion.

 

 

Transfusion in thrombocytopenia and thrombocytopathies

Platelet transfusion may be necessary to stop/prevent hemorrhage (14,15); this is known as therapeutic transfusion if there is active bleeding due to thrombocytopenia or thrombocytopathy (generally, there is no serious risk of bleeding until the platelet count is <10,000-20,000/ μL), and prophylactic transfusion (recommended when the platelet count is <10,000/μL in the absence of factors that increase platelet requirements, such as surgery, or <20,000/μL in the presence of such factors). Indicated products are platelet concentrates (PC) and platelet-rich plasma (PRP). These products can be obtained by apheresis or by slow centrifugation of FWB, so that the platelets remain in the supernatant (PRP). To obtain the PC, the PRP is centrifuged again, and the platelets (sediment, PC) is separated from the plasma (supernatant, FFP) and transferred to another satellite bag. One unit of PC contains approximately 60x109 platelets in 40-60 mL of plasma. PC has very limited use in veterinary medicine because it is hard to obtain a sufficient volume to be therapeutic, and because of storage challenges. An alternative is the PRP resulting from slow centrifugation of the FWB, which should be transfused within 24 hours of collection. 1U of PC or PRP increases the platelet count by 10,000/μL in a 30 kg dog. Lyophilized or cryopreserved canine platelets are now available in some markets, and they have the advantage of being readily available and easy to store, although more research is needed on their effectiveness (15). 10 mL/kg of FWB can increase the platelet count by about 10 x 103/μL.

 Figure 3

 

Blood collectionFigure 4

Blood donors should be young adults weighing at least 25 kg (dogs) or 4 kg (cats). They must be healthy, up to date with vaccinations/deworming, not have received transfusions, and free of blood-borne disease (which varies by geographical area) (16). Sedation is not usually necessary in dogs although it is generally required in cats (ketamine 5-10 mg/kg and diazepam 0.5 mg/kg IV is recommended); drugs that cause hypotension/bradycardia should be avoided. The blood can be collected in single commercial bags (whole blood), in double bags (main bag with anticoagulant and another satellite bag without anticoagulant for separation of plasma or platelet-rich plasma) or triple bags (main bag with two satellite bags for separation of cryoprecipitate and/or platelet concentrate) (2,6).

 

In dogs: the jugular vein is the best site for collecting blood from a donor. Place the animal in lateral recumbency, shave the neck, clean the area aseptically and perform venipuncture with a needle attached to thebag collection system (Figure 3a). Place the bag below the patient so that blood flow is aided by gravity, and continuously move the bag manually or mechanically. Check the bag weight regularly until the desired volume (approximately 450 mL) has been collected.

 

In cats: specific feline collection bags can be used, or a butterfly needle attached to a 20 mL syringe previously filled with CPDA1, sodium citrate 3.8% (1 mL per 9 mL of blood) or sodium heparin (5-10 IU/mL of blood) can be used (Figure 3b). Blood collected by syringe can be directly administered by attaching a neonatal transfusion filter (Figure 4), or transferred to a human collection bag that has had the anticoagulant removed. Blood collected using this open collection method should not be stored for more than 24 hours due to risk of bacterial growth; it should not be stored for more than 12 hours if sodium citrate or heparin is used.

 

Dogs can donate up to 20 mL/kg every 4 weeks; fluid replacement is not required to replace the blood taken. In cats, 10 mL/kg can be collected every 4 weeks, or up to 60 mL/cat if donation is not a regular occurrence, but it is advisable to replace the withdrawn volume with an isotonic crystalloid. When blood collection has been completed, the bag must be hermetically sealed (by heat or tight knots) and then centrifuged if blood components are to be separated.


 

Blood groups and compatibility testing

Canine blood groups are classified using the DEA (Dog Erythrocyte Antigen) system: DEA-1.1, DEA-1.2, DEA- 3 to DEA-8. The ideal donor is DEA-1.1 negative, because the DEA 1.1 group has the highest antigenic potential. A new dog erythrocyte antigen, the Dal antigen, has been described, but its clinical significance is unknown. Dogs do not have significant levels of alloantibodies against other blood groups unless the patient has received a transfusion and has developed antibodies against the donor’s blood group. Severe adverse reactions in the first transfusion are therefore highly unlikely, but the recipient will produce significant numbers of antibodies against other blood groups 3-4 days after receiving the transfusion, which means that compatibility testing should always be carried out after that period (2,17,18).

 Figure 5

Cats have three blood groups: A, B and AB. A is dominant over B. Prevalence of these groups varies greatly by breed and geographic region, but A is the most common and AB is the least common. The newly-discovered Mik blood group can also cause incompatibility reactions. Cats have naturally-occurring alloantibodies against other blood groups; tests must therefore be performed even for the first transfusion to check for compatibility. The most severe reaction (which is often fatal) occurs when group A blood is transfused to a group B recipient. Cats with type AB blood can receive group A blood. The alloantibodies present in cats can cause neonatal isoerythrolysis if a group B female is mated with a group A (dominant) or AB male; group A (or AB) kittens ingest maternal anti-A antibodies in the colostrum, which can cause severe hemolysis, weakness, tail necrosis, hemoglobinuria, jaundice, severe anemia and sudden death. If an affected kitten requires a transfusion, this can be given using maternal washed red blood cells (or another B-group cat) at a dose of 5-10 mL/kitten administered over several hours.

 

There are several commercial tests available to determine if a dog is DEA-1.1 antigen positive or negative, and if a cat has group A or B blood (Figure 5).

 

 

Compatibility testingTable 3

Blood typing detects the presence of antigens of a certain blood group in the red blood cell membrane, while cross-matching determines the presence of antibodies in the plasma of the donor and recipient which may cause incompatibility reactions (17,18). Cross-matching must always be performed if the blood type cannot be determined, or in any dog or cat that has already received a transfusion. Major cross-matching verifies if the recipient’s plasma has antibodies to the donor’s red blood cell antigens, while minor cross-matching checks if the donor’s plasma contains antibodies to the recipient’s red blood cell antigens. A control should also be performed (using the recipient’s red blood cells and plasma). If hemolysis and/or agglutination occurs with major cross-matching, the transfusion cannot be performed (because the recipient has antibodies against the donor’s red blood cells). If hemolysis and/or agglutination occurs with minor cross-matching, the transfusion may be performed whilst closely monitoring the patient (because the donor has antibodies to the recipient’s antigens, but the quantity present in the transfused blood does not confer serious risk). If there is underlying auto-agglutination and/or hemoglobinemia in the recipient, such tests will be inconclusive. The correct procedure for cross-matching involves washing the donor and recipient red blood cells several times (by centrifugation with 0.9% NaCl).

 

In emergencies, simplified (but less reliable) compatibility test can be performed: centrifuge the donor and recipient blood, dilute the RBC to 5% (1 drop RBC + 20 drops normal saline) and perform the three tests (major, minor and control) on three slides, mixing each one with one drop of plasma and one drop of RBC. Incubate for 2-5 minutes, and check for agglutination under the microscope. There are also commercial kits for performing cross-matching quickly and reliably.

 

 

Conclusion

The actual administration of blood and blood products is summarized in Table 3. Adverse reactions to transfusion can occur and may be immunological or non-immunological in origin, and either acute (occurring during the transfusion or within 24 hours) or delayed (occurring >24 hours after the start of the transfusion) (3,19). However risks may be minimized by carefully selecting the donor and blood product, and applying the most appropriate techniques in terms of collection, storage, handling and administration. Performed properly, blood transfusions can be a fundamental factor in treating various critical care cases, and a good knowledge of the different options is a key requisite for the emergency veterinarian.

 

 

 

This article was kindly provided by Royal Canin.  If you would like printed copies of this material or other Focus publications please contact your Veterinary Business Manager:

 

 

 

References

1. Haldane S, Roberts J, Marks S, et al. Transfusion Medicine. Comp Cont Educ Pract Vet 2004;26(7):503-518.

2. BSAVA Manual of canine and feline haematology and transfusion medicine, 2nd edition. Day M, Kohn B. eds. Gloucester, BSAVA 2012.

3. Prittie, JE. Controversies related to red blood cell transfusion in critically ill patients. J Vet Emerg Crit Care 2010;20 (2):167-176.

4. Day TK. Current development and use of hemoglobin-based oxygen-carrying (HBOC) solutions. J Vet Emerg Crit Care 2003;13(2):77-93.

5. Logan JC, Callan MB, Drew K, et al. Clinical indications for use of fresh frozen plasma in dogs: 74 dogs (October through December 1999). J Am Vet Med Assoc. 2001;218(9):1449-55.

6. Tocci LJ. Transfusion medicine in small animal practice. Vet Clin North Am Small Anim Pract 2010;40(3):485-494.

7. Animal Blood Resources International, www.abrint.net

8. Kerl ME, Cohn LA. Albumin in health and disease: causes and treatment of hypoalbuminemia. Comp Cont Educ Pract Vet 2004;26(12):940-948.

9. Mazzaferro EM, Rudloff E, Kirby R. The role of albumin replacement in the critically ill veterinary patient. J Vet Emerg Crit Care 2002;12(2):113-124.

10. Martin LG, Luther TY, Alperin DC, et al. Serum antibodies against human albumin in critically ill and healthy dogs. J Am Vet Med Assoc 2008;232(7): 1004-9.

11. Francis AH, Martin LG, Haldorson GJ, et al. Adverse reactions suggestive of type III hypersensitivity in six healthy dogs given human albumin. J Am Vet Med Assoc 2007;230(6): 873-879.

12. Mathews K, Barry M, The use of 25% human serum albumin: outcome and efficacy in raising serum albumin and systemic blood pressure in critically ill dogs and cats. J Vet Emerg Crit Care 2005;15(2):110-118.

13. Weatherton LK, Streeter EM. Evaluation of fresh frozen plasma administration in dogs with pancreatitis: 777 cases (1995-2005). J Vet Emerg Crit Care 2009;19(6):617-622.

14. Callan MB, Appleman EH, Sachais BS. Canine Platelet Transfusions. J Vet Emerg Crit Care 2009;19(5):401-415.

15. Hux BD, Martin LG. Platelet transfusions: treatment options for haemorrhage secondary to thrombocytopenia. J Vet Emerg Crit Care 2012;22(1):73-80.

16. Wardrop KJ, Reine N, Birkenheuer A, et al. Canine and feline blood donor screening for infectious disease. J Vet Intern Med 2005;19:135-142.

17. Giger U. Blood typing and crossmatching. In: Bonagura JD, Twedt DC, eds. Kirk’s Current Veterinary Therapy, vol. XIV, St. Louis: Saunders Elsevier 2009:260-265.

18. Tocci LJ. Increasing patient safety in veterinary transfusion medicine: an overview of pre-transfusion testing. J Vet Emerg Crit Care 2009;19(1):66-73.

19. Fragío C. Transfusiones de sangre y hemoderivados. En: Fragío C, ed. Manual de urgencias en pequeños animales. España, Multimedica Ediciones 2011;201-224.


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