Peer Reviewed VETcpd - Internal Medicine

Jenny Walton BVM&S MRCVS Jenny qualified from R(D)SVS in Red cell transfusions – 1998 - she worked in mixed practice when, what and how to do it! for 4 years before moving into the Red cell transfusions are now a relatively common intervention in veterinary practice field of small in the UK and help in the treatment of many patients. This is largely due to the animal emergency availability of blood products, such as (PRBC) , from blood and critical care banks supplying directly to practices. After donation, red cells are separated from with Vets Now for 12 years. Through plasma into a concentrated packed cell form, a nutrient extender is then added to Vets Now, she ran the practical trial them. This allows the red cells to be stored for up to 42 days before being transfused researching canine blood banking in 2005-2006 – launching Pet into patients. DEA 1 blood typing prior to transfusion is essential and cross matching UK (PBB) alongside Wendy Barnett should be performed for second transfusions. Blood products are administered in 2007. She acts as the Veterinary through a filtered giving set and patients monitored closely for transfusion reactions. Supervisor for PBB, her role includes Transfusion reactions are thankfully rare but potentially life threatening. advising practitioners daily on the appropriate use of PBB blood products, Key words: Canine, Packed Red Blood Cells (PRBC), transfusion, blood typing, overseeing the practical and VMD cross matching, transfusion reactions legislative veterinary aspects of blood collection at PBB and leading research on future development opportunities. Clinical presentation Banked canine PRBC are readily available Alongside this role she works part-time in in the UK and this article primarily covers general practice. Without doubt, blood transfusions can be PRBC transfusion in the dog. However, one of the most rewarding interventions Pet Blood Bank UK the general principles of transfusion in veterinary medicine, as increasing red Units 21and 22 medicine apply to all of our companion cell numbers and the associated improved Loughborough Centre for Technology animal species and many exotic species. oxygen carriage makes an obvious and Epinal Way, Loughborough For specific species, Pet Blood Bank UK Leicestershire LE 11 3GE immediate difference to the patient. (PBB) can guide you on blood collection In many instances these transfusions and banking advice or refer you to an preserve life and many of the advances in Simon Tappin MA VetMB external advisor who has experience with veterinary medicine and surgery would CertSAM DipECVIM-CA MRCVS that species. not be possible without the ability to Simon graduated transfuse patients. from the University Red cell products of Cambridge and As with any intervention, there are mul- Red cell products available in the UK are after two years tiple considerations and with transfusions Canine Packed Red Blood Cells (PRBC), in small animal these must be carefully considered. practice undertook Fresh (collected and a residency at the Firstly blood is not ‘just another fluid’, administered within 4-6 hours) and Stored University of Bristol but a complex, physiologically balanced, Whole Blood. Fresh Whole Blood has the in Small Animal biological mixture. An understanding of advantage of containing but the Medicine and Intensive Care. He gained its content is important when considering number and function decline 4-6 hours the European Diploma in Small Animal administering transfusions. Red cells are after collection. Stored Whole Blood is Medicine. He is currently working as a uncommonly used, as numbers and consultant in internal medicine at Dick living cells and need to be carefully looked after before administration to the patient levels of Von Willebrand factor (vWF) and White Referrals where he sees cases in factors I (), V and all areas of internal medicine. which leads to practical storage and trans- requirements for these products. VIII decline quickly. Stored Whole Blood Dick White Referrals, The Six Mile Bottom has a of 21-28 days depending Veterinary Specialist Centre, Station Farm, Secondly, blood products are a very pre- on the used. If blood is to London Road, Six Mile Bottom, Suffolk, cious and limited resource. All blood avail- be stored, then separating the plasma and CB8 0UH able for transfusion is donated and so the freezing it as (FFP) health and wellbeing of the donor should (Figure 1), and then resuspension of the always be considered. It is also important that these products are used respect- fully and rationally, in patients with fair prospects of making a recovery, so that the benefit of this resource can be maximised. Used with forethought and care, the ability to give transfusions is a great addition to the veterinary therapeutic armoury and with the progression of blood banking in For Internal Medicine referrals in the UK, easily within the realms of pos- your area: vetindex.co.uk/medicine sibility for all small animal practitioners. Figure 1: PRBC and Fresh Frozen Plasma (FFP)

VETcpd - Vol 4 - Issue 4 - Page 29 VETcpd - Internal Medicine red cells in a nutrient solution (SAG-M) allows the most efficient use of the whole Table 1: The indications for using whole blood and packed red blood cells unit of blood. This extends PRBC shelf Process Whole Blood Packed Red Blood Cells life to 42 days and plasma products have a frozen shelf life of up to five years. Regenerative anaemia ◆ ★ Table 1 illustrates the utility of the PRBC versus whole blood, and Table 2, specific Non regenerative anaemia ◆ ★ differences in their content. If plasma is frozen within 24 hours of collection Fresh of the whole blood unit, Fresh Frozen Plasma (FFP) is produced, the use of Anaemia with hypoproteinaemia ◆ ★ which is outside the scope of this article but is discussed in more detail in Kit Anaemia with hypovolemia ◆ ★ Sturgess’s article on fresh frozen plasma (Sturgess 2014). Anaemia with coagulopathy ◆ ★ Indications for DIC ◆ ◆ red cell transfusions Liver disease with anaemia ◆ ◆ Patients with a wide variety of conditions causing symptomatic anaemia will benefit Thrombocytopenia Fresh from red cell transfusions alongside treat- ment of their underlying condition. Thrombocytopathia Fresh If a diagnosis has not been reached, transfusion can enable further diagnostic Neonatal isoerythrolysis ★ tests to be performed safely. Put simply, red cell transfusions are indicated for any ◆ Indicates suitable blood products that can be utilised in treating the disease process. patient developing clinical signs of low ★ Designates the superior product choice when more than one suitable product can be utilized. tissue oxygenation due to anaemia, which (Courtesy of Dr Anne Hale). usually manifests as weakness and lethargy, their clinical presentation and diagnosis has The purpose of a red cell transfusion in pale mucous membranes, tachycardia and to be considered before making a decision companion animals would be to alleviate tachypnoea on examination. The speed whether to transfuse or not. clinical signs but not to remove stimulus at which the anaemia develops will also for the patient’s own red cell production impact on the need for transfusion. If In human medicine, detectable changes in (if this capacity still exists in the recipient). red cell numbers fall slowly, for example tissues at the cellular level start to occur As a rough guide, in canines capable of a chronic anaemia secondary to bone secondary to reduced oxygenation at a regeneration, transfusion to a stable end marrow disease, then adaptive mechanisms PCV of 30% or less and the same is likely point of 25-30% PCV would be suggested. such as increased 2,3-diphosphoglycerate true in our patients. On a clinical level in In those incapable of regeneration, aiming improve the efficiency of oxygen carriage animals (especially with chronic anaemias), for mid-range of normal PCV (35%-55%) leading to a delay in the development clinical signs are not often seen until PCV may be beneficial. of clinical signs. Conversely if red cell drops to a much lower value. Sympto- The average lifespan of a canine red cell numbers fall quickly, for example blood matic anaemias typically present as a weak, is usually stated as 120 days. Cellular life loss secondary to a road traffic accident, tachypnoeic, tachycardic patient with expectancy may be reduced due to the there is no time for adaptation and the altered mucous membrane colour. Pale collection and storage process, although a clinical need for transfusion may occur mucous membranes are consistent with consensus as to what degree this impact with relatively modest blood loss. anaemia, but can also be seen in severe is has not been reached. The red cells in The causes of anaemia are wide ranging . Icteric mucous membranes can be each unit of transfused blood will be of but can be broadly defined into three seen in animals with pre-hepatic jaundice variable age and as a result the effect of a aetiological groups: secondary to red cell destruction. transfusion will wane over time. Response • Loss of red cells (e.g. haemorrhage) In acute instances, transfusion should be to transfusion is also dependant on the host response to the red cells and the • Destruction of red cells (e.g. immune considered where whole blood loss is underlying disease process. mediated disease) demonstrated to be the cause of clinical • Failure of production of red cells symptoms. This should be regardless of (e.g. bone marrow disease) the red cell numbers as the PCV recorded Diagnostic tests may reflect total blood loss without an Diagnostic tests useful for the evaluation When to transfuse adjustment in blood volume to allow the of anaemic patients include: PCV to drop. Chronic anaemias in canines A precise trigger point or ‘magic number’ Packed Cell Volume (PCV) in terms of red cell number, haemoglobin are usually relatively well compensated content or Packed Cell Volume (PCV) for and tend only to cause significant and Total Solids (TS) when to transfuse a specific patient cannot symptoms once PCV drops to less than PCV should be measured using a percent- be given. Each and every individual patient, 20% and occasionally much lower values. age reader and TS should be measured

Page 30 - VETcpd - Vol 4 - Issue 4 Table 2: The different makeVET up of wholecpd blood- Internal and packed Medicine red cell products, indications for use and rates of administration using a refractometer (this is using the Component Whole Blood (Fresh) Packed Red Blood Cells (PRBC) serum protein {SP} gauge which meas- ures in g/L rather than the urine specific Storage • Collected in CPD or CPDA 1 • In SAG-M nutrient solution gravity scale). At the time of spinning instructions • Must be transfused within 4-6 • 2-6°C. 42 days in SAG-M PCV tubes, gross assessment of the serum and shelf life hours to have any viable platelets • 1 unit average volume = 250ml for hyperbilirubinaemia (yellow) or hae- and all coagulation factors moglobinaemia (pink/red) is also helpful. • Average PCV 62% unless measured • 1 unit average volume = 450ml Blood Smears • Average PCV 45% unless measured In practice, these can be stained with a Indications • Symptomatic anaemia (blood loss) • Symptomatic anaemia in presence Romanowsky stain, such as Diffquick®, for use • Platelet deficiency: Fresh Whole of normovolaemia without clotting and are used to assess red cell morphol- factor deficits ogy, number and regeneration, platelet Blood is unlikely to have a number, white cell morphology and for significant effect on platelet numbers in a severely the presence of red cell parasites, such as thrombocytopaenic patient canis. • GUIDELINE: 10ml/kg of fresh Slide Agglutination Tests whole blood raises the PLT count 9 A drop of blood on a slide and a drop of by 10 x 10 /l 0.9% mixed together, can be used Action • Restores O2 carrying capacity and • Restores O2 carrying capacity to visually assess for auto-agglutination in blood volume, if used promptly suspected Immune Mediated Haemolytic post collection Anaemia (IMHA). Examination under a • Supplies all coagulation factors microscope will help differentiate: and some viable platelets • Agglutination – red cells attached to each other due to the presence of Not • Pharmaceutically treatable • Pharmaceutically treatable on the cell surface (Figure 2) indicated for anaemias (i.e. those that will anaemias (i.e. those that will respond to specific non- respond to specific non- • Rouleaux – which is the normal transfusion therapy) because of transfusion therapy) because of physiological stacking of red cells risks associated with transfusions risks associated with transfusions (Figure 3) • Clotting factor and platelet deficits The presence of rouleaux will disperse if additional saline is added, whereas Hazards • Infectious disease transmission • Infectious disease transmission agglutination will not. Note: This MUST • Immunologic transfusion • Immunologic transfusion reactions be performed with equipment and samples reactions (e.g. incompatibility and (e.g. incompatibility and allergic) at room or body temperature. allergic) • Non-immunologic transfusion • Non-immunologic transfusion reactions e.g septic, toxic and Coagulation Times reactions (e.g septic, toxic and circulatory overload In emergency situations, a rough circulatory overload) • Ammonia levels can increase in assessment of global coagulation can be stored red cell products. These performed by assessing the whole blood should be used with caution in clotting time (WBCT). Blood is collected dogs with known liver disease into a plain glass tube and gently rocked within the closed hand of the investigator Rate of • To calculated dose, to complete • To calculated dose to complete and regularly assessed for the formation of infusion transfusion in < 4 hours transfusion < 4 hours a clot. Although a relatively crude test, a Use an in line • According to patients’ fluid status. • According to patients’ fluid status. clot should form within six minutes. blood filter with If hypovolaemic at rates up to If hypovolaemic at rates up to An activated clotting time (ACT) tube all products shock doses (as fast as blood shock doses (as fast as blood uses diatomaceous earth within the tube (170-260 is being lost), if normovolaemic is being lost), if normovolaemic as an activator, which speeds up the microns) 5-10ml/kg/hr 5-10ml/kg/hr process, with times of 60-110 seconds • If compromised circulation • As PRBC are a lower total volume, being normal for canines. Both WBCT (cardiovascular compromise/renal they can be given at slightly higher and ACT will be prolonged in animals failure) 1-2ml/kg/hr rates if indicated with marked thrombocytopenia (platelet counts <10x109/l or <1 platelet per high power field on smear analysis). Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) are now available as patient side tests. These are more accurate and specifically evaluate secondary coagulation. If in house analysis is not available, freezing separated plasma Figure 2: Red cell agglutination, which confirms an Figure 3: Rouleaux formation which is normal collected into a citrate tube will allow incompatible crossmatch (Courtesy of Paola Monti, physiologically and will disperse with the addition analysis at a later stage. DWR diagnostics). of further saline and gentle agitation of the slide (Courtesy of Paola Monti, DWR diagnostics). VETcpd - Vol 4 - Issue 4 - Page 31 VETcpd - Internal Medicine

Buccal mucosal bleeding time This is a simple test used to assess primary haemostasis (platelet function) where platelet numbers are adequate on a smear and clotting times (when measurement is possible) are normal. It should NOT be performed in a confirmed thrombocy- topaenia or when coagulation times are prolonged. The time for the bleeding to stop should be 2-4 minutes but may be slightly longer in sedated animals. 4a 4b A prolonged buccal mucosal bleeding time (BMBT) in this circumstance suggests a thrombocytopathia or Von Willebrand factor deficiency (Von Willebrand factor analysis can be submitted at this stage for confirmation).

Specific tests prior to transfusion Canine blood typing and Dog Erythrocyte 1 (DEA 1) It is no longer appropriate to assume that 4c 4d a patient is likely to only receive one transfusion in their lifetime, or to believe what has previously been quoted that Figure 4: (4a) A buccal mucosal bleeding time is performed using a spring loaded mechanical cutting device such as the Simplate or Surgicutt devices. (4b) the upper lip is folded up and tied to create mild congestion of in canines “the first transfusion is free”. the oral mucosa. (4c) the device is used to make a standard cut and the wound allowed to bleed. (4d) The wound Incompatibility reactions in canines to first must not be disturbed but can be blotted from around a 1cm away using the blotting paper and the time for time transfusion are rare, however, if DEA bleeding to stop is recorded. Images courtesy: Amanda Boag Vets Now Emergency Ltd. 1 is not known and recorded at the time of the first transfusion, and Historically DEA 1 was considered to (4-7 days) and this recipient will remain a subsequent transfusion occurs later on have 3 subgroups and the terminology permanently sensitised to the DEA 1 anti- in the animals life - severe and avoidable DEA 1.1, 1.2 and 1.3 was used. With the gen. If a subsequent transfusion is given at reactions can occur. development of monoclonal antibody and a later date containing DEA 1 positive red Blood typing is recommended for all testing, it has been cells, an acute reaction will occur. This donors and recipients as best practice and found that DEA 1.2 and 1.3 are actually will involve the production of antigen helps to make the most of the transfusion red cell populations with a lower density antibody complexes that shows as an acute products available to us. The only blood of the DEA 1 antigen on their surface. type II hypersensitivity reaction, involving typing test currently widely available for Testing allows for detection of low level agglutination and haemolysis of the donor canines is the test for Dog Erythrocyte DEA 1 which means an individual canine red cells in the recipient’s circulation. This Antigen (DEA) 1. patient is now only either DEA 1 postive can be a fatal reaction and will, at the very or negative (Acierno et al. 2014). least, negate any benefit of the red cells Benchtop methods for DEA 1 typing administered in an already compromised include agglutination cards and mono- Tests for DEA 1 antigen were developed patient. Alloimmunisation is considered clonal antibody impregnated quick tests. as DEA 1 was identified as a significant to be lifelong in the canine species - so These tests are simple to use and allow us factor involved in causing severe reactions these reactions occur at any time in that to make decisions about which products to to second transfusions. patient’s life in the case of subsequent use [www.alvedia.com/assets/procedure- DEA 1 is absent in 30-60% of the incompatible blood administration. quick-test.pdf]. UK canine population (Barnett et al. Conversely 40-70% of the canine popula- The important concept to note is that a 2013). Transfusion with untyped blood tion are DEA 1 positive. It is completely universal canine donation type does not leads to a reasonable risk of transfusing appropriate to transfuse them with DEA 1 exist. DEA 1 negative donors have been a DEA 1 negative canine with DEA 1 positive PRBC. Knowing the blood type incorrectly termed as "universal donor" positive blood and sensitising it to future of a canine patient helps reduce the risk in the past and this is a misconception. transfusions. of transfusion reactions, but also optimises There have been over 13 canine red cell the use of blood bank resources. surface proposed internationally Sensitisation (alloimmunisation) is when a and some identified (Hale 1995). Amongst DEA 1 negative patient is transfused with In an acute instance for a first time red these red cell antigens, there are some that DEA 1 positive blood. In this scenario cell transfusion when recipient typing is are also capable of causing reactions and the recipient will produce anti-DEA 1 not available for a genuine reason; DEA 1 this needs to be considered. within a few days of transfusion negative product should be used.

Page 32 - VETcpd - Vol 4 - Issue 4 VETcpd - Internal Medicine

Other canine blood types take to receive results. The basis of the test Sensitisation can occur to some of the is that the gel matrix will not allow the other red cell antigen types also (e.g. passage of agglutinated (clumped) red cells DEA 4,7, Kai and Dal ) but the reactions during light centrifugation in a normal lab associated are either very rare due to centrifuge. Hence, in a positive cross match low incidence of canines negative for where an agglutination reaction occurs, common antigen (DEA 4 and Dal) or red cells will remain at the top of, or in the can be less acute or severe than those seen top part of the gel column. In a negative with DEA 1 incompatibility (Euler et al. cross match, non-agglutinated red cells 2016). However they may be significant pass straight through the gel and rest at the to the overall transfusion picture both bottom of the tube. around the time of the transfusion and in the weeks following. As canine transfusion Consent for develops, more extensive typing When dealing with a patient requiring a may become available, which will, in turn, transfusion, it must be remembered that expand our understanding and help reduce these are complex biological products the incidence of incompatibility reactions. with many components and no absolute guarantee can be made about their safety. Cross matching As a result, consent for their administra- Two common misconceptions that arise Figure 5: Heat sealed aliquots of blood and of red tion should be obtained, where possible, are that if both donor and recipient are cells allowing crossmatches to be performed without in writing. typed for DEA 1, cross matching is not broaching bags of stored packed red cells. Suggested wording that could be included required, or that typing is the same as cross compatible red cell unit is supplied for on a consent form for transfusion product matching. The lack of comprehensive transfusion by the blood bank. Recipient administration would be: knowledge of canine blood types and samples required would normally be 1ml the inability to type beyond DEA 1 of whole blood in EDTA and 2ml sepa- I consent to the administration of whole blood/ means that cross matching is necessary rated serum (4 serum gel tubes) if multiple blood components to my pet. I accept that there to detect other serious antibody led cross matches are to be run. is a risk of reactions to blood/blood components incompatibilities. and that rarely these can be life threatening. Finding a compatible unit requires Cross matching is an in vitro test mixing multiple cross matches as 30% cross match WARNING. In spite of serological testing, donor and recipient components (blood incompatibility has been reported in the risk of transmitting infectious agents to the or plasma) to look for potential reactions. canines receiving subsequent transfusions patient is present. Careful donor selection, care, Cross matching test result assessment even if DEA 1 type matched transfusions and available laboratory tests do not eliminate involves looking for agglutination or have been administered previously the hazard. Also, septic and toxic reactions can haemolysis reactions. This test looks for (Ferreira et al. 2014). result from transfusion of bacterially contami- those reactions that could cause severe nated blood and components. Such reactions are Cross matching should be performed complications. It is best practice to both rare, but may be life threatening. without breaching any stored blood type and cross match for any transfusion. product. With fresh whole blood, donors In addition, blood components may contain However, for second and subsequent samples can be collected and submitted immunizing substances that can cause reactions transfusion in canines, it is mandatory at before the unit is taken. With stored even in typed and cross matched transfusions. any time greater than 4-7 days post the products blood banks normally supply heat initial transfusion. This is the time it takes sealed citrated aliquots that are attached Dose calculations for a recipient to produce alloantibody, i.e. to the blood units and can be torn off to antibody against foreign red cell antigens. for red cell transfusion submit for cross match (Figure 5). Packed Initial doses of red cells are usually Major and minor cross matching is the cell or whole blood aliquots can be used calculated to an amount in mls, but then terminology used depending on whether by laboratories for the purpose of a major adjusted on the basis of whether a full recipient red cells or plasma are being cross match. Plasma aliquots can be used whole or half unit of PRBC should be tested for incompatibility against the donor for the minor cross match. administered. The aim is to maximise the red cells or plasma. Major cross match tests Traditional in-house or benchtop cross benefit of the transfusion and make best donor red cells against recipient plasma. matching using slides is a time consum- use of the resource (Short et al. 2012). The Minor cross match tests recipient red cells ing procedure, although simple enough following equation is used to calculate dose against donor plasma. Choice of which to perform. Assessing the results can be of red cells but the patient’s individual to run depends on the component being difficult if it is not a procedure commonly response should be monitored closely and administered and the individual case. In performed by the practitioner. There therapy adjusted according to response: red cell transfusions, the major cross match are now gel tests that act as an in-house is the most important to assess. Blood volume to be transfused (mls) = test and these are a lot simpler to both k x Weight (Kg) x (required PCV-Recipient PCV) Blood banks will normally offer a perform and read. These tests assess for PCV of red cell product cross match service via an external or agglutination and are extremely useful for internal laboratory to allow assessment emergency cross matching in critical cases k is a constant = 70 for canines and 60 for felines for compatibility against multiple donors. when external lab cross matching is simply Average PCV of packed cells in nutrient On reading the cross match – a suitable not an option due to the time it would solution (SAG-M) unless measured is 62%

VETcpd - Vol 4 - Issue 4 - Page 33 VETcpd - Internal Medicine

Alternative dose calculations in a more are permeable to allow gaseous exchange red cell units remain between 2-6oC. The urgent situation can be used in order for optimum red cell storage. Red cells thermometer should be checked daily to to decide a baseline volume in units to should be stored only in the labelled blood ensure product is maintained at an appro- transfuse. These are: collection bag they are supplied in and any priate temperature. Red cell units should additional packaging or protection should be inspected and agitated gently every few To raise the PCV by 1% takes 1 ml/kg of be removed prior to storage to allow air to days to ensure an even mix of the red cells packed red cells or 2ml/kg whole blood. circulate around the bag. with the nutrient solution in which they This also equates to a general dose rate of are stored. 10ml/kg of PRBC’s being expected to The temperature within the storage fridge raise the PCV by around 10% (5% using should be monitored with a maximum/ What about platelets? whole blood) in an anaemic but normo- minimum thermometer to ensure that Primary haemostasis involves the activa- volaemic patient. tion of platelets and their adhesion to an These guidelines can be utilised as a start- initial site of injury. Clinically - primary ing dose rate and then adjusted according coagulopathies arise when this process to required response. does not happen, this leads to petechial haemorrhage, ecchymosis and overt In practice storage bleeding. Problems with primary haemo- stasis occur due to inadequate platelet Practices that have a high transfusion numbers (thrombocytopenia), a lack of caseload (more than one case every six platelet activation (thrombocytopathia) weeks) can order and store PRBC on their – this can be genetic or secondary to premises. A separate blood fridge should be drug therapy such as aspirin), or due to used for PRBC to ensure no regular traffic Von Willebrand Factor (vWF) deficiency in and out of the fridge causing fluctua- (vWF deficiency leads to to an inability of tions in temperature. A domestic fridge is platelets to adhere to the site of injury). a reasonable option; however a specially designed laboratory or blood fridge will The only available product in the UK (at allow more accurate temperature regula- this time) that provides any level of viable tion. Although tempting, the blood fridge platelets is Fresh Whole Blood (transfused should not be used to store other things within 4-6 hours of collection). Each such as drugs, food (for staff or patients) unit only provides the normal amount of and laboratory samples as the storage bags Figure 6: A unit of packed red cells alongside the platelets in 450ml of the donor canine’s fridge's temperature probe to ensure correct storage.

VetIndex Business Directory – 2018

Whatever you are looking for, check FREE out VetIndex Business Directory first! to practices! • VetIndex contains 260 pages of useful practice information! • Over 105 sections, covering everything from Accountancy Services to X-ray Equipment. • VetIndex Business Directory is an indispensable source of information and the only classified directory of its kind in theUK. • Plus, with over 30 referral sections – it’s a great way to market your own referral service to all UK practices! • On-line guide available at www.vetindex.co.uk • Book your 2018 ads in December 2017 and benefit from ongoing year round marketing with VetIndex Directory and VetCPD Journal. • FREE: Press Releases worth £99 + VAT each in VetCPD Journal 2018! • FREE: Your logo on VetCPD websites (~300,000 page views p/a)

VetIndex BUSINESS Directory is supplied FREE of charge to ALL UK practices Contact us for more information T: 01225 445561 E: [email protected] vetindex.co.uk

Page 34 - VETcpd - Vol 4 - Issue 4 VETcpd - Internal Medicine circulation and is dependant on skilled when passing down a giving set at room as no problems are identified, the rest of collection technique. In a deficient canine temperature. If warming is necessary, the unit should be delivered over 4 hours. patient, this number is not likely to make this can be achieved by placing the red The easiest way to calculate this rate is to any significant impact in platelet number cell unit in a waterproof zip lock bag to estimate the remaining volume left in the in the recipient. However it may provide prevent contamination of the ports, and bag and divide that by 4 for the hourly enough platelets to stop bleeding at a criti- placing this in a commercial water bath of rate. In an emergency (e.g. severe acute cal site (for example in the central nervous <37°C. A max/min thermometer should haemorrhage), red cells can be given as system) limiting the progression of symp- be used to monitor the water temperature fast as necessary. toms. As a rough guide it is considered that of warm water in a bowl/sterile litter Due to the nature of the recipient’s 10ml/kg whole blood, which is expected tray if a water bath is unavailable. Gentle problems, the calculated dose of product to raise the PCV by 5%, will raise the and slow warming of products is sensible may need to be given more slowly e.g. in platelet count by 10x109/l. if time allows, as red cell viability can be an animal with compromised circulation, reduced if they are exposed to sudden In the USA canine blood banking such as heart failure. However, meticulous changes in temperature. industry, they have the market for, and sterility and hygiene must be maintained are able to produce, concentrated forms when handling the products. In most of platelet products similar to those avail- Routes for transfusion instances, it is perfectly possible to admin- able in human medicine. Platelet Rich The recipient should be prepared with a ister transfusions within the optimum Plasma (PRP) is a concentrated version central or peripheral intravenous catheter timescale. In a normovolaemic animal, a of platelets from one unit of blood. Even using aseptic technique. The largest gauge maximum transfusion rate of 20ml/kg/hr more concentrated PRP containing higher catheter suitable for the patient’s size and is suggested. levels of platelets can be harvested using vasculature should be placed. In very the process . These sensi- moribund patients if intravenous access is Monitoring tive products can only be stored at room not possible, then the intra osseous route Monitoring of transfusion patients should temperature, under constant agitation can also be utilised as an effective and be given thought and attention. Constant and are known to have a high incidence rapid method of administration. monitoring is advisable over the initial of potential for bacterial contamination 30 minutes of a transfusion. After that, if The catheter should be flushed with due to their special storage requirements. no concerns have arisen and continuous normal 0.9% saline and a T-port or sterile These could be processed in the UK but monitoring is not possible, regular checks cap placed. All blood products should demand is currently not high enough to (i.e. every 15-30 minutes) are appropri- be administered via a filtered giving set support them as a commercial product. ate. A monitoring chart is essential as to reduce the risk of microthrombi and trends are important - an example can Veterinary surgeons in the USA have given to a calculated dose. Pre, during be found on PBB’s website (https:// access to frozen and Dimeythylsulfoxide and post transfusion the patient should be www.petbloodbankuk.org/media/1184/ (DMSO) preserved platelet concentrates monitored closely. frmsis0502-transfusion-record.pdf). In and experimental work to produce a Transfusions should not be administered anaemic patients heart and respiratory lyophilised (freeze dried) product is through the same intravenous catheter as rate will slow during the transfusion as ongoing. For specific cases, such as any solutions containing calcium (such as oxygen carriage improves; any sudden or patients with thrombo- lactated Ringers or Hartmann’s solution) unexpected increase in temperature, heart cytopenias or severely affected immune due to the risk of calcium chelation and or respiratory rate should prompt that a mediated thrombocytopenias, these the formation of particulate matter, or transfusion reaction is imminent. A multi- products could theoretically be obtained administered alongside glucose due to the parameter monitor recording ECG, blood from the USA via a Veterinary Medicines potential for osmotic damage to the red pressure and temperature can be very Directorate Special Treatment Certificate cells. Normal 0.9% saline can be used to useful to aid the member of staff who is in the absence of any more suitable UK flush giving sets or bags of remaining red monitoring the recipient. However, hands licenced product. However, canine studies cells or to administer concurrent crystal- on monitoring of temperature, heart rate into their efficacy are currently limited loid requirement. and respiratory rate is perfectly adequate in (Callan et al. 2009). the absence of this equipment. In the past, PRBC’s required resuspension Preparation of product with 0.9%NaCl as their PCV was so high that they could not be infused alone. Infusion pumps for administration However, PRBC products today typically and syringe drivers Blood products need to be prepared have a red cell extender (the SAG-M It is recommended that red cell products carefully for use and once breached have nutrient solution) added so this is less of are transfused by gravity alone to both a very limited lifespan due to the risk a problem and resuspension with saline is canine and feline patients as a recent of bacterial contamination. The recom- rarely necessary. publication raised a concern that the mendation from human medicine is red longevity of red cells transfused by both cells should be transfused within 4 hours Rate of transfusion syringe driver and may be of breach. In stable patients, an initial infusion rate reduced compared to transfusion using Recipients are often critically ill, and of 0.5-1.0 ml/kg/hr should be used for gravity alone (McDevitt et al. 2011). therefore administering products at room the first 15-30 minutes. During this time, In human medicine however, validated temperature is recommended. In most the patient should be monitored for any peristaltic type infusion pumps and syringe instances, refrigerated red cells will warm evidence of a transfusion reaction. As long drivers are used to administer transfusions.

VETcpd - Vol 4 - Issue 4 - Page 35 VETcpd - Internal Medicine

Transfusion reactions Table 3: Possible transfusionVET reactions,cpd - Internalcauses and clinicalMedicine Types of transfusion reaction are presentations. Comparative human information is also included summarised in Table 3. Clinically, they present as an increase in temperature, a Transfusion reaction Clinical presentation change in the respiratory and heart rate, change in mucous membrane colour, Transfusion associated Rapid or excess volume Within 6 hours of end of visible oedema or as gastro-intestinal signs circulatory overload delivery in a susceptible patient transfusion such as vomiting. If any reaction occurs (e.g.small patient, cardiac Cough then the transfusion should be stopped abnormality, delicate haemo- Tachypnoea to allow assessment of the patient. If the dynamic status, renal failure) Tachycardia reaction is mild, then slowing the rate of Signs of volume overload: transfusion may be enough to reduce the - jugular venous distension signs. If reactions are severe, the transfusion - nasal fluid should be stopped until the reaction is - Pulmonary oedema categorised and a decision made whether drug treatment is necessary or whether Acute haemolytic Known DEA incompatibility Fever restart is appropriate. If not, the transfusion transfusion reaction Unknown DEA incompatibility Hypotension may need to be abandoned. If a severe Other RBC antigen Haemoglobinaemia/uria anaphylactic hypersensitivity (type I) reac- incompatibilities (for eg Kai, Dal) tion is suspected intravenous antihistamine and/or corticosteroids may be appropriate. Bacterial contamination in Fever enters recipient Vomiting Older red cells have in some studies been Result in bacteraemia and Tachycardia, tachypnoea associated with an increase in incidence immune reaction of transfusion reactions and morbidity in canine patients – so the age of the red cells Delayed haemolytic Allo-immunization to other Fever should also be taken into account when transfusion reaction unknown antigens. Lethargy administering transfusions. Unexpected anaemia, usually within first two weeks after Summary transfusion Blood transfusions can be lifesaving in Febrile non-haemolytic Humoral and cellular-mediated Onset 1-2 hours after a number of clinical situations. Used transfusion reaction inflammatory reaction transfusion prudently, with forethought and adequate Fever preparation, the risks associated can be Nausea/ vomiting minimized. The availability of Pet Blood Increase in BP Bank products in the UK has opened up many therapeutic options that have Allergic transfusion Inflammatory reaction Urticarial rash enabled many disease processes, trauma reaction resulting in release of Pruritus cases, anaesthetics and surgical procedures histamine by mast cells Nausea, vomiting to be carried out with far more positive Diarrhoea, abdominal pain outcomes. Hypotension (less common) Dyspnoea (less common)

Anaphylactic Severe allergic reaction against Immediate respiratory distress transfusion reaction transfused blood (seconds to minutes) Upper airway oedema→obstruction Lower airway signs and symptoms – tachypnoea, increased chest noise Depressed mentation Vomiting Hypotension, weak pulses and Pet Blood Bank UK, ultimately circulatory collapse Units 21 and 22 Transfusion related IN HUMANS : Within 2 to 6 hours of start Loughborough Centre for Acute lung injury Leukocyte antibodies in the of transfusion Technology (N.B This has yet to donor blood react with recipient Coughing Epinal Way, Loughborough be formally recognised leucocytes, primarily causing Tachypnoea, hypoxaemia Leicestershire LE11 3GE in veterinary patients lung injury Tachycardia www.petbloodbankuk.org – it is NOT known as Associated with higher Fever yet if it occurs) concentrations of plasma, e.g: fresh frozen plasma Page 36 - VETcpd - Vol 4 - Issue 4 VETcpd - Internal Medicine

Step by Step - Administration of Red Cell Products

Equipment Required: • Unit of red cells • Zip lock bag • Clean bowl/tray to act as a water bath to warm the product • Thermometer • Filtered giving set • IV catheter – largest gauge possible for the patient Figure 7: Red cells are placed in a protective water- Figure 8: PRBC’s should be removed from the protective proof zip lock bag and are warmed to room or body bag and one of the administration ports on the red cell temperature in a water bath of no more than 370C. bag should be accessed by tearing the protective cover.

Figure 9a Figure 9b Figure 9c

Figure 9a, b and c: A filtered giving set is removed from its outer packaging and prepared for use by closing off the in-line C clamp and the drip wheel. Note the chamber drip rate at this time (a standard filtered giving set will usually be 20 drops/ml).

Figure 10: The insertion spike is unsheathed in an Figure 11: Firmly push the insertion spike into the Figure 12: The insertion spike has now breached into aseptic manner. bag of red cells via the port. the bag of red cells, this bag of red cells must be used within 4 hours.

Figure 14: The in-line clamp should be released and the drip wheel slowly released to allow the blood to flow into the administration set.

Figure 15a Figure 15b

Figure 15 a and b: The filtered drip chamber should be filled to above the filter but not so full that the drip Figure 13: Hang the bag of red cells from a drip stand rate cannot be seen. in order to prime it ready for use. VETcpd - Vol 4 - Issue 4 - Page 37 Figure 16a Figure 16b

Now claim your CPD Hours! Take the online exam 0.5 1.0 and turn your ad hoc HOURS HOURS reading into ONE HOUR of DOCUMENTED DOCUMENTED Documented CPD CPD CPD with a certificate

1) A Jack Russell Terrier weighing 10kg has a chronic anaemia associated with renal failure – he has a Packed cell volume (PCV) of 10%. You would like to raise his PCV to 30%. What would you Figure 16 a and b: The tubing is fully primed with no air remaining and at this point the end of the giving set can order from Pet Blood Bank UK? be uncapped and attached to the patient’s catheter in a sterile manner. The transfusion can be initiated. A) Half a unit of packed red cells B) One unit of packed red cells Figure 17a Figure 17b C) Two units of packed red cells D) One unit of fresh whole blood

2) Which of the following statements is false? A) Red cells should be stored in a refrigerator at 2-6 oC B) Red cells can be stored in the middle shelf of the practice lab fridge used for insulin and vaccines

Figure 17 a and b: All blood products should be administered through a microaggregate filter (normally 170-260 C) Red cells should be gently inverted every micron) to facilitate removal of any small clots and other debris that may be present These filters may be present few days to mix them with the nutrient within the lines of blood giving sets as in Figure 18 (a) or may be attached separately as an in line filter (such solution they are stored in as Hemo-Nate filters) Fig 17 (b), if using a syringe for the transfusion. This is more common in cats and small D) Packed red cell units do not contain canine patients. viable platelets References 3) Which of the following statements Acierno, M.M., Raj, K., Giger, U. (2014) DEA Hann, L., Brown, D.C., King, L.G., and Callan, M.B. is true? 1 expression on dog erythrocytes analyzed by (2014) Effect of Duration of Packed Red Blood A) First transfusions in dogs are “free” Cell Storage on Morbidity and Mortality in Dogs immunochromatographic and flow cytometric B) DEA 1 –ve donors are universal techniques. J Vet Intern Med 28(2),592-8 After Transfusion: 3,095 cases (2001–2010). J Vet Intern Med 28, 1830–183 C) Blood typing is the same as cross matching Barnett, W., Walton, J., Dean, R. (2013) The Preva- so if you know the blood type of the dog lence of Dog Erythrocyte Antigen 1.1 in the Do- Iazbik, M.C., O’Donnell, M., Marin, L., Zaldivar, S., you do not need to cross match nor Population of the First Canine Voluntary Blood Hudson, D., et al. (2010) Prevalence of dog erythro- Bank in the . Proceedings of the cyte antigens in retired racing Greyhounds. Vet Clin D) Cross matching is necessary before a BSAVA congress. 4-7th April, Birmingham UK Pathol 39(4), 433-5 further transfusion in an anaemic 12 year Blais, M.C., Berman, L., Oakley, D.A., Giger, U. McDevitt, R.I., Ruaux, C.G., and Baltzer,W.I. old dog that received a DEA 1 type matched (2007) Canine Dal blood type: A red cell anti- (2011) Influence of transfusion technique on sur- transfusion when he was six weeks old gen lacking in some Dalmatians. J Vet Intern Med. vival of autologous red blood cells in the dog. 21(2),281-6 J Vet Emerg Crit Care 21(3), 209–216 4) Which of the following statements Callan, M.B., Appleman, E.H., Sachais, B.S. (2009) Short, J.L., Diehl, S., Seshadri, R., and Serrano, S. are true? Canine platelet transfusions. Journal of Veterinary (2012) Accuracy of formulas used to predict post- A) In saline agglutination tests should be run Emergency and Critical Care, 19, 401–415 transfusion packed cell volume rise in anemic dogs. using refrigerated EDTA blood samples Day, M., and Kohn, B. (2012) In: BSAVA Manual of Journal of Veterinary Emergency and Critical Care 22, B) Total protein can be estimated using a small animal haematology and transfusion medicine. 428–434 refractometer and the serum out of a 2nd edn. Eds M. Day, and B. Kohn. Sturgess, K. (2014) Fresh frozen plasma – why every Heamatocrit tube Euler, C.C., Lee, J.H., Kim, H.Y., Raj, K., Mi- practice should keep a bag in their freezer. C) Blood smears can be stained for in practice zukami, K., et al. (2016) Survey of Two New (Kai VetCPD Journal 1 (1), 32-38 1 and Kai 2) and Other Blood Groups in Dogs of red cell examination using diff quick North America. J Vet Intern Med 30(5), 1642–1647 D) Buccal mucosal bleeding time should be Feldman, B.F,. Zinkl, J.G., Jain, N.C. (eds) In: used to diagnose thrombocytopenia Schalm’s Veterinary Haematology. 5th edn. Ferreira, M., Thomas, E., Walton, J. (2014) Frequency of cross match incompatibility between canine Visit vetcpd.co.uk blood donors and recipients. Proceedings of the to answer all the CPD questions! BSAVA congress. 3-6th April, Birmingham UK Hale, A. S.(1995) Canine Blood Groups and their GOLD Take this exam using our Importance in Veterinary Transfusion Medicine Vet- Gold or Silver Subscriptions erinary Clinics. In: Small Animal Practice, Volume £99 25, Issue 6. pp 1323 - 1332 + VAT www.vetcpd.co.uk/subscribe For Internal Medicine referrals in Page 38 - VETcpd - Vol 4 - Issue 4 your area: vetindex.co.uk/medicine