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Jenny Helm graduated from Glasgow in 2005, after which she undertook a small animal rotating internship at the Royal Veterinary College and spent a short time in small animal practice. She subsequently returned to Glasgow to undertake a residency in oncology and internal medicine and where she is currently oncology clinician at the small animal hospital. She holds the RCVS certificate in small animal medicine and is working towards the European diploma in internal medicine.
Transfusion therapy is the mainstay of supportive treatment for dogs and cats with anaemia. The commercial availability of blood and blood products for dogs has resulted in an increase in the number of patients benefiting from transfusion therapies. This article, the first of two discussing the use of blood transfusions in dogs and cats, outlines the indications for transfusion therapy and describes the different options available. Part 2, to be published in the June issue of In Practice, will discuss the practicalities of blood collection in situations where blood products are either unavailable or inappropriate, and will describe how to administer transfusions safely.
Why transfuse?
Anaemia is the most common reason for administering a blood transfusion in veterinary practice. It can be the result of blood loss (haemorrhage or red blood cell destruction) or a lack of red blood cell production (eg, bone marrow disease) (see box below). Although blood transfusions may be life-saving, they are not a definitive treatment for disease. Hence, they are used to: Provide support; Correct deficiencies; Control disease while an underlying diagnosis is found. Patients with a debilitating non-regenerative anaemia benefit greatly from red cell transfusions (either whole blood or packed red blood cells) to provide support while underlying aetiologies are addressed. Patients with acute haemorrhage usually need volume replacement with either crystalloids or colloid fluid therapy initially, but blood transfusion can subsequently be very beneficial if haemorrhage is severe. In animals with chronic blood loss (eg, gastrointestinal
Key facts
Transfuse like with like. Blood transfusions should be carried out using the same blood group for a given species Replace what is lacking. Only replace what the patient is missing or has lost in order to reduce the risk of a transfusion reaction Blood is a biological drug. It should therefore be treated in the same way as every other prescribed medication Blood products are not a cure. In most circumstances, blood products do not provide a cure. Instead, they give support until a diagnosis is reached and/or a treatment is instigated
Clare Knottenbelt graduated from Bristol in 1994 and worked for a year in mixed practice. She subsequently undertook a residency in small animal internal medicine at Edinburgh, after which she became a lecturer at Glasgow, where she is currently a senior clinician in small animal medicine and oncology, and head of the division of companion animal sciences. She holds an MSc in feline transfusion medicine and the RCVS diploma in small animal medicine.
mucosal ulceration and bleeding), blood transfusions can stabilise the patient while diagnostics and treatment regimens are implemented. Animals with haemostatic disorders can also benefit from blood products. Plasma contains clotting factors and proteins that are useful in patients with
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When to transfuse?
The single most important factor that determines the need for transfusion is the patients clinical condition. An anaemic patient showing signs of cardiovascular compromise (eg, tachycardia, poor pulse quality, weakness, tachypnoea, collapse) will nearly always require a transfusion. In human medicine, an automatic transfusion trigger was set whenever packed cell volume (PCV) in patients dropped below 20 per cent. This figure has been widely debated in the human field and recent evidence suggests that no absolute threshold exists. Patients with chronic anaemia can have a very low PCV but will often be relatively stable at presentation, so the use of such transfusion triggers is not always appropriate. Cats tolerate anaemia well and may show only mild lethargy at a PCV of 10 to 15 per cent. Provided they remain unstressed, cats can tolerate a very low PCV for a number of days; however, the stress of examination, for example, can trigger sudden cardiovascular compromise. Transfusions carry the risk of adverse reactions, so each patient must be individually evaluated by carrying out a risk-to-benefit analysis that takes into account the clinical condition of the animal before transfusion. Transfusions are recommended if: A patient is exhibiting significant clinical signs of anaemia; An animal has a PCV of less than 10 per cent; An animals PCV has fallen rapidly to less than 20 per cent in dogs or 15 per cent in cats. In patients with a poor or absent bone marrow response, red cells are unlikely to be replenished in the short term and, hence, earlier transfusion may be indicated in order to prevent further clinical compromise. Before any blood transfusion is carried out, clinicians should consider: Is the transfusion necessary? That is, does the benefit of a transfusion outweigh the risks? What component of blood is the patient lacking? For example, an animal with immune-mediated haemolytic anaemia will often only have lost red blood cells, while a patient with a haemorrhage will have lost whole blood. Will the use of component therapy minimise the risks and maximise the benefits of a transfusion? How can the effects of a transfusion be assessed? In addition, when a patient does not require an immediate life-saving transfusion, the following sim-
Blood products
Blood is made up of several components (see diagram below) and the transfusion of specific blood products can have distinct advantages. For example, administering packed red blood cells to a normovolaemic patient will reduce the risk of volume overload. In addition, separating one unit of whole blood into two or even three separate blood products maximises the
Fresh frozen plasma or fresh plasma Cryoprecipitate or cryosupernatant platelet-rich plasma or platelet concentrate
Separate components of blood that are used to produce a variety of blood products
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The doses and dose rates provided above are a guideline only. However, the flow rate may be increased and decreased depending on an individual patient. The total dosage will also depend on the patients needs. Any blood product transfusion should be completed within four hours
benefits obtained from each individual donation (see table above). Some blood products are now commercially available in the UK, but separation of red blood cells and plasma can be performed by many commercial laboratories.
can therefore be used in many conditions, including acute or severe haemorrhage, haemolytic anaemia, chronic blood loss or non-regenerative anaemia, and coagulopathies if other blood products are not available. Whole blood must be used within four to six hours of collection to maximise its full range of benefits.
Whole blood
Historically, whole blood was the only canine blood product available to veterinary practitioners and, at present, remains the only blood product available for cats.
Haggis weighs 15 kg and has a packed cell volume (PCV) of 10 per cent. His target PCV has been set at 25 per cent. Therefore, as determined by the calculation below, he requires at least 500 ml of whole blood (with a donor PCV of 40 per cent) to achieve this
Blood volume* Weight (Required PCV Recipient PCV) = k x x to be transfused (kg) PCV of donated blood where k is a constant, which is 90 in dogs and 66 in cats The blood volume required for Haggis is therefore: 50625 ml of = whole blood 40 If packed red blood cells were to be used from a donor with a PCV of 62 per cent, then Haggis would require: 90 x15 x 32661 ml of packed = red blood cells 62 Since the volume of blood required by a recipient depends heavily on a donors PCV, it is important to choose donors with a PCV within the top half of the normal range whenever possible. Note a unit of commercial packed red blood cells will have a series of straws attached to the bag. These straws are full of blood from the individual bag and can be used for cross-matches or determining a donors PCV, without opening the bag and breaching sterility. 90 x15 x *Equation from Pichler and Turnwald (1985) (25 10) (25 10)
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Cryosupernatant
Cryosupernatant is the plasma that remains following separation of the cryoprecipitate as described above. It is a source of all coagulation and plasma proteins, except for clotting factors VII, VIIIc and XIII, fibrinogen and vWF. When stored at 18C, it is stable for one year. Cryosupernatant can be used for the treatment of most clotting factor deficiencies, except haemophilia A and von Willebrands disease, and can also be used for plasma protein deficiencies.
Frozen plasma
Frozen plasma has lost the action of many clotting factors (V, VIII, von Willebrand factor [vWF]) and plasma proteins, but it still contains vitamin K-dependent factors (II, VII, IX, X). Frozen plasma has either been frozen more than six hours after collection, has been thawed and refrozen, or has been frozen beyond the recommended maximum storage time (see above). This product can be used in patients with deficiencies of the non-labile clotting factors (eg, anticoagulant rodenticide toxicity and some plasma protein deficiencies).
Platelet transfusions
Platelet-containing products, such as platelet concentrate or platelet-rich plasma, are made from fresh whole blood by centrifugation at a slower rate than is used for the production of packed red blood cells and plasma. Such products must be used within 48 hours of collection and are the only ones available that contain enough platelets to be clinically useful in thrombocytopenic patients. In addition, platelet concentrate needs to be stored on a rotating or rocking surface to prevent activation and aggregation, which usually makes storage impractical outside of a blood bank laboratory. There is some experimental veterinary interest in the use of cryopreserved platelets (Appleman and others 2009), but these are not available in the UK. In a patient that is actively bleeding, whole blood may provide enough platelets to stop haemorrhage, but this does not usually raise the circulating platelet count.
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Cryoprecipitate
Cryoprecipitate is made up of approximately 20 per cent fibrinogen, 50 per cent clotting factor VII and 30 per cent clotting factors VIIIc, XIII and vWF. It is separated from the plasma fraction of blood using a process of controlled thawing and centrifugation. Cryoprecipitate must be stored frozen at 18C and is stable at this temperature for up to one year. It can be used in patients with inherited clotting factor deficiencies such as haemophilia A and von Willebrands disease.
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Since then, eight different blood groups have been recognised in the dog, with the major and most immunogenic being DEA 1.1 for which dogs can be either positive or negative. The others include DEA 1.2, DEA 3, DEA 4, DEA 5, DEA 7 and a new antigen in dalmatians called DAL. DEA 1.1 is the most common blood type in dogs and, although naturally occurring antibodies to DEA 1.1 are rare, the determination of DEA
Cross-matching
Cross-matching assesses the effect that recipient serum antibodies have on donor cells (major cross-match) and the effect that donor serum has on recipient cells (minor cross-match). As the main aim of a transfusion is to provide the recipient with red blood cells, it is vital that the recipients serum antibodies do not destroy these cells and, in doing so, evoke a transfusion reaction. The minor cross-match assesses the risk of recipient cell destruction by the donor serum, which poses a much smaller risk because the volume of transfused serum will comprise only a small volume of the recipients total serum. To perform both major and minor cross-matches, blood collected in both heparin and EDTA anticoagulants must be obtained from both the donor and recipient. Cross-matching can be performed by mixing the washed cells and plasma either on slides, or in test tubes or well plates. The use of slides, while more rapid, is less reliable as only serum with high titred antierythrocyte antibody will show agglutination. Although mixing whole blood from a recipient and donor may give a crude indication of compatibility, this method is unreliable and is not recommended.
Cross-matching using feline blood. (above) Results of a conventional in-house crossmatching test. (below) Example of a gel crossmatch kit (RapidVet-H; DMS Laboratories) that indicates a cross-match type A donor to type B cat. The negative control is on the far left and the positive control on the right. The cross-match sample in the middle indicates absolute haemolysis of the sample. (Pictures, Jenny Walton)
Method Centrifuge donor blood in EDTA anticoagulant at 3000 rpm for 10 minutes Remove the supernatant (plasma and buffy coat layer) and wash the erythrocytes by resuspending them in saline Recentrifuge the cells and remove the supernatant Resuspend the erythrocytes in saline to make a 3 to 5 per cent solution Place two drops of cell suspension in contact with heparinised plasma from the recipient (one to two drops) either on a slide or preferably in test tubes or well plates Assess the cell/plasma mixture for haemolysis (diffuse reddening of solution that fails to settle out) or agglutination (granular appearance) Perform a minor cross-match in the same way using recipient cells and donor plasma
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DEA 7
so the collection and administration of blood in-house remains the only alternative for cats. In addition, veterinary surgeons should be able to perform blood collection in emergency situations and to administer blood and blood products safely.
References and further reading
ADAMANTOS, S., BOAG, A. & HUGHES, D. (2005) Clinical use of a haemoglobin-based oxygen-carrying solution in dogs and cats. In Practice 27, 399-405 APPLEMAN, E. H., SACHAIS, B. S., PATEL, R., DROBATZ, K. J., GROMAN, R. P., KENNEDY, D. R., ODONNELL, P. A., BRYAN, C. & CALLAN, M. B. (2009) Cryopreservation of canine platelets. Journal of Veterinary Internal Medicine Volume 23, 138-145 BLAIS, M. C., BERMAN, L., OAKLEY, D. A. & GIGER, U. (2007) Canine Dal blood type: a red cell antigen lacking in some dalmatians. Journal of Veterinary Internal Medicine 21, 281-286 CALLAN, M. B. & GIGER, U. (1994) Transfusion medicine. In Consultations in Feline Internal Medicine. Ed J. R. August. Philadelphia, W. B. Saunders. pp 525-532 GABRIO, B. W. & FINCH, C. A. (1954) Erythrocyte preservation. I. The relation of the storage lesion to in vivo erythrocyte senescence. Journal of Clinical Investigation 33, 242-246 GIGER, U., STIERGER, K. & PALOS, H. (2005) Comparison of various canine blood-typing methods. American Journal of Veterinary Research 66, 1386-1392 KLEIN, H. G., SPAHN, D. R. & CARSON, J. L. (2007) Red blood cell transfusion in clinical practice. Lancet 370, 415-426 KNOTTENBELT, C. & MACKIN, A. (1998) Blood transfusions in the dog and cat 1. Blood collection techniques. In Practice 20, 110-114 KNOTTENBELT, C. & MACKIN, A. (1998) Blood transfusions in the dog and cat 2. Indications and safe administration. In Practice 20, 191-199 KNOTTENBELT, C. M., ADDIE, D. D., DAY, M. J. & MAKIN, A. J.(1999) Determination of the prevalence of feline blood types in the UK. Journal of Small Animal Practice 40, 115-118 MATTHEWS, K. A. & BARRY, M. (2005) The use of 25 per cent human serum albumin: outcome and efficacy in raising serum albumin and systemic blood pressure in critically ill dogs and cats. Journal of Veterinary Emergency and Critical Care 15, 110-118 PICHLER, M. E. & TURNWALD, G. H. (1985) Blood transfusion in dogs and cats. Part I. Physiology, collection, storage and indications for whole blood therapy. Compendium on Continuing Education for the Practicing Veterinarian 7, 64-71 SOHMER, P. R., MOORE, G. L., BEUTLER, E. L. & PECK, C. C. (2003) In vivo viability of red blood cells stored in CPDA-2. Transfusion 22, 479-484
Summary
Blood and blood products may be used for a number of applications in veterinary medicine. Understanding the benefits of each product will ensure that maximum benefit is gained from an individual donation. Commercial blood products are available for dogs, but there is currently no feline blood banking system
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These include:
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Notes