LOOD YPES AND RANSFUSIONS PART II: B C TRANSFUSION

Evelyn Maniaki DVM CertAVP PgCertVPS MRCVS, Zoetis Feline ScholarSéverine Tasker BSc BVSc DSAM PhD DipECVIM FHEA MRCVS, European Veterinary Specialist inInternal Medicine, RCVS Recognised Specialist in Feline Medicine and Honorary Professor of FelineMedicineChristina Maunder BVM&S CertSAM DipECVIM-CA MRCVS, European Veterinary Specialist inInternal Medicine, RCVS Recognised Specialist in Feline Medicine and Clinical Teaching Fellow inSmall Animal Internal Medicine, Langford Veterinary Services, School of Veterinary Sciences,University of Bristol, UK

FELINE BLOOD TYPES AND BLOOD TRANSFUSIONS

PART II: BLOOD COLLECTION AND TRANSFUSION

www.felineupdate.co.uk 1April 2020

second syringe, and this can then be givenintravenously in 0.05-0.1ml increments toprolong sedation, if necessary. Additionalsedation protocols using butorphanol andalphaxalone or tiletamine and zolazepam havealso been described (Granfone et al., 2018,Spada et al., 2015). Crystalloid fluid replacementtherapy should be administered to the donorimmediately after blood collection, with 2-3times the blood volume that was collected beinggiven over 1-2 hours.

Blood collection equipmentAll necessary equipment for blood collectionshould be ready before sedation of the donor cat(Box 1). Ideally, at least three people should bepresent: a phlebotomist, a handler and one ormore assistants.

Preparation of blood collection equipmentBefore blood collection begins, the collectionequipment needs to be prepared. Usually, up to50ml of blood is collected, necessitating, forexample, 5 x 10 ml syringes to be prepared.However, it is prudent to prepare a total of 6 x10 ml syringes in case a problem, such as theformation of a clot, occurs in one of the syringes.This allows just that syringe and its content to besyringes.

The administration of blood to feline patientscan be a lifesaving procedure. The previousarticle focused on feline blood types, themethods of blood collection and administrationas well as donor selection. This article willdiscuss the practical aspects of blood collectionand administration.

BLOOD COLLECTION

Blood collection without sedation of blooddonors has been reported and, interestingly,conscious donors were no more likely to result ininadequate blood donation volumes thansedated cats in a retrospective study (Doolin etal., 2017). Signs of donor cat anxiety ormovement during collection are more frequentlyreported during conscious donations and so, inpractice, sedation is usually administered. Thecombination of 5mg/kg ketamine and 0.25mg/kgmidazolam, mixed in the same syringe and givenintramuscularly, will last 20-30 minutes.Alternatively, 2mg/kg ketamine and 0.25mg/kgmidazolam or diazepam can be givenintravenously. An additional sedation containingthe same sedation dose should be prepared in aintravenously

discarded rather than the full donation. Somephlebotomists use 3 x 20 ml syringes instead,however this means more blood may bediscarded should a problem arise in one of thesyringes.

FELINE BLOOD TYPES AND

BLOOD TRANSFUSIONSPART II: BLOOD COLLECTION AND TRANSFUSION

April 2020www.felineupdate.co.uk 2

The first assistant draws around 1.3ml ofAnticoagulant Citrate Dextrose Solution,Solution A, U.S.P. (ACD-A) into each of the 10 mlsyringes, covering each syringe hub with aneedle immediately. Following this, the firstsyringe is attached to a 3-way tap, along witheither an extension set and needle or a butterflyneedle, depending on the phlebotomist’spreference. ACD-A is then flushed through theequipment, ready for the collection of the first10ml of blood from the donor (Image 1).

The long extension tubing of the plain blood bagshould be tied off and clamped to prevent bloodrunning down its length. This tube is designedfor direct blood collection into the bag, but thelength and diameter make it difficult to achievea satisfactory flow of blood. In the FelineCentre, we prefer not to use this and collect viasyringes instead. Blood is later injected directlyinto the bag via the port using 19 G needles toprevent damage to the red blood cells (RBCs).Alternatively, small (50-150mls) dry bloodcollection bags are available (Jorgensen,distributed in the UK by Kruuse Ltd), enablingcollection of blood from the donor directly intothe collection bag, rather than into a syringe.apple

Box 1: Necessary equipment for open blood collection

• Clippers to remove fur from jugular area (not pictured)

• Swabs with surgical scrub• Spirit• A bag of ACD-A• 6 x 10 ml syringes• 12 x 21 G ⅝-inch needles, used to draw

ACD-A from the bag, then to cover each syringe hub before and after blood collection

• A 3-way tap• A 21 G ⅝-inch butterfly needle• A plain 150 ml blood collection bag• 6 x 19 G 1.5-inch needles, used to transfer

the blood slowly from each syringe to the collection bag

• Blood giving set with filter, used to administer the blood. If not available, the blood can be administered in a syringe on a syringe driver, using a syringe filter.

• Artery forceps

Image 1: Preparation of blood collection equipment bydrawing 1.3ml ACD-A into a 10ml syringe, then attachinga 3-way tap, along with a butterfly needle, and flushingit through the equipment.

Anticoagulant must be added to these bags andthe collection system must be flushed throughwith anticoagulant before use.

Preparation of the donor catBefore blood collection begins, an intravenouscatheter (22 G), T-connector, tape, bandagematerial and heparinised saline for flushingshould be prepared. An intravenous catheter isplaced in the cephalic vein of the donor ideallybefore or immediately after sedation (Image 2).An ophthalmic lubricant should be applied to theeyes during sedation to help prevent cornealulceration.

The donor is positioned according to thepreference of the phlebotomist; blood collectioncan be achieved in dorsal (Image 3), sternal orlateral recumbency. After positioning the donor,the handler holds both front legs back, allowingthe neck to extend for optimal visualisation of thejugular veins, and the area is clipped of hair onthe preferred side to be used. A blanket or thicktowel placed under the donor cat’s neck can helpwith visualisation of the jugular vein. The area isthen prepared aseptically first with surgical scrubthen spirit.


Blood collection techniqueSurgical gloves should be worn by thephlebotomist to maintain sterility and reduceinfection risk (Image 4).

The phlebotomist holds the prepared butterflyneedle in one hand and the cat’s head in theother hand. The handler raises the jugular veinby applying pressure at the thoracic inlet, awayfrom the sterile area, and the first assistantholds the attached syringe. The phlebotomistinserts the butterfly needle into the jugular veinto its hub and holds the needle steady inposition (Image 5).

Image 2: Placement of intravenous cephalic catheterbefore or after donor sedation will allow for additionalsedation to be administered, if necessary, during bloodcollection. It is also used to administer crystalloid fluidsimmediately after blood collection.

Image 3: Donor cat positioned in dorsal recumbency,with the handler holding both front legs back and theneck extended for optimal visualisation. Carefulpreparation of the jugular area ensures optimalvisualisation and minimises infection risk.

Image 4: Placement of sterile gloves should always beundertaken before blood collection begins.



The first assistant then begins to withdraw theblood slowly by applying suction to the syringe.Blood should flow easily, without too muchpressure on the syringe. If this is not the case, thephlebotomist will need to readjust the needlebefore the first assistant starts applying gentlesuction again, collecting blood into the syringe(Image 6).

When the first syringe is filled to 10ml, the firstassistant carefully closes the 3-way tap to thedonor cat, disconnects the full syringe from the3-way tap and hands it to the second assistantwho immediately places a needle or a bung on itsend. The second assistant then passes the nextprepared syringe containing ACD-A followingremoval


removal of the needle or bung, ready to beattached to the 3-way tap. The process isrepeated until all five syringes are filled withblood. Following withdrawal of the needle, thehandler should place pressure onto the jugularvein.

Blood collected in an open system should ideallybe used immediately (within 4 hours), althoughstudies have described storing bloodsuccessfully in the fridge for up to 21 days(Hourani et al., 2017). ACD-A acts as apreservative to enable storage of the bloodshould the transfusion not go ahead or if the fullvolume of collected blood is not required.Citrate phosphate dextrose adenine (CPDA) isan alternative anticoagulant which is availableand can be used at the same concentration asACD-A. CPDA may allow longer storage of bloodbefore use (see below). Heparin anticoagulanthas also been used (625units per 50mls ofblood), but blood collected into heparin must beused immediately. Additionally, heparin mayincrease microthrombi formation by stimulatingplatelet aggregation.

BLOOD TRANSFUSION

Blood collection without sedation of blooddonors has been reported and, interestingly,conscious donors were no more likely to resultin inadequate blood donation

Amount to be transfusedThe amount of blood that the recipient needscan be estimated using various formulae but arecent study (Reed et al., 2014) found that thefollowing simple formula was the most reliable:

Volume of blood to be transfused (ml) = 2 x weight of patient (kg) x (desired PCV %

increase)

This equates to 2 ml/kg of whole bloodincreasing a patient’s PCV by 1%.

Image 5: Insertion of butterfly needle into the leftjugular vein of the donor cat.

Image 6: Withdrawal of blood from the jugular veinof the donor by the first assistant applying gentlesuction to the syringe.



The target PCV does not have to be within thereference interval for PCV as this is often too higha target. As 50-60 ml of blood is usually collectedfrom a donor, the desired PCV of, for example,20% may still not be reached in the recipient.However, even a modest increase in PCV canmake a huge clinical difference to the anaemicrecipient.

The total blood volume in cats is approximately66ml/kg, so a 4.5kg cat has around 297ml ofblood. Collection of 20% of blood volume shouldnot result in clinically significant anaemia and canbe done safely, ensuring crystalloid intravenousfluids are administered to guard againsthypovolaemia which could develop with rapidblood collection. Collection of less than 10%blood volume from a donor does not requirecrystalloid replacement therapy. A 4.5kg cat cantherefore safely donate around 60ml of blood,equivalent to 20% of its blood volume.

Other formulae include the blood donor PCV incalculations to determine how much blood tocollect (Reed et al., 2014). Unfortunately, in catsthe expected PCV increase following whole bloodtransfusion is not often realised. This may bebecause significant decreases in haematologicalparameters (such as haemoglobin, RBCs) arefound in donated whole blood units compared tothe corresponding blood sample collected fromthe donor before blood is collected for thetransfusion (Spada et al., 2017). This can be partlydue to the dilution of the RBCs in the unit as aresult of the anticoagulant used or if intravenousfluid therapy is given partway through bloodcollection.

Blood transfusion techniqueAs previously mentioned, in the Feline Centre weprefer to collect blood via syringes and inject itdirectly into a plain blood bag. This allows theinsertion of a blood filter giving set into theinsertion


blood collection bag to enable safe and easyintravenous transfusion of the blood to thepatient (Image 7).

If blood has been collected directly into a bloodcollection bag, the bag can be connected to ablood filter giving set for administration. Filtersare required to reduce the risk of microthrombientering the circulation. Microthrombi can formsecondary to infusion pump damage of RBCs. Asyringe driver may be used instead if blood wascollected into a 20ml syringes, adding a bloodfilter onto the syringe to prevent microthrombi(Image 8).

Blood is typically administrated via the cephalicvein. Intraosseous administration via theproximal femur is also effective if peripheralveins are not available. The blood should begently warmed to 37oC before administrationnot only to prevent hypothermia andvasoconstriction in the recipient, but also toincrease blood viscosity. This can be done byvasoconstriction



Image 7: Prepping of blood filter giving set beforethe start of blood transfusion.

Image 8: A blood filterneeds to be used ifadministering blood using asyringe driver.

immersion in a warm water bath within a sealedbag. Take care to avoid overzealous heating asthis can result in haemolysis and clotting.

Blood must not be given through a catheter thatcontains, or has contained without salineflushing, calcium-containing fluids (e.g.Hartmann’s / Lactated Ringer’s, some colloids).Care must be taken to ensure that the catheterhas been flushed with 5 ml of saline before bloodadministration. It is prudent to connect the bloodfilter giving set onto a T-connector instead ofdirectly on the intravenous catheter to decreasethe likelihood of catheter dislodgement duringthe blood transfusion (Image 9).

The blood should be given at an initial rate of0.25-0.5ml/kg/hour over the first 30 minuteswith the recipient observed for adversereactions. The rate can then be increased to1ml/kg/hour for a further 30 minutes, thencontinued at the required rate (Image 10). Innormovolaemic patients, care should be takennot to administer the remaining blood tooquickly. In hypovolaemic patients, the rate ofadministration can be increased more quickly;maximum rate is 22ml/kg/hour for emergencies,but it is prudent not to exceed a rate ofadministration


10ml/kg/hour. In patients with chronic severeanaemia as a result of renal disease or patientswith cardiac disease there is a higher risk ofvolume overload, therefore a rate of2ml/kg/hour should be maintained. Indeed, catswith a PCV ≤ 18% were shown to have evidenceof volume overload on echocardiography(Wilson et al., 2010). These cats are susceptibleto the development of congestive heart failuredue to increased intravascular volume; thisoccurs as a result of the haemodynamiccompensatory responses that occur withchronic severe anaemia. In all cases, bloodtransfusion should be completed within 6 hoursof start of administration to minimise the risk ofbacteraemia.

Anaemia is the most common indication forblood transfusion in cats. Whole blood is usuallyadministered as described above. However, ifpacked RBCs are available, these are thetreatment of choice for normovolaemicanaemic cats. Packed RBCs can be obtained byremoving plasma from collected blood. Bloodbank centrifuges are not commonly available inveterinary practices, so removal of plasma canbe achieved by letting the RBCs sediment inrefrigerated whole blood for 6 hours and thenbank

vasoconstriction



Image 10: Initial rate should be 0.25-0.5ml/kg/hourover the first 30 minutes, 1ml/kg/hour for a further30 minutes, then continued at the required rate toensure the entire volume is administered within 4-6hours from the start of the blood transfusion.

Image 9: Connecting the blood filter giving set onto aT-connector instead of directly on the intravenouscatheter will make catheter dislodgement less likelyduring the blood transfusion.

removing the supernatant plasma. Packed RBCscan be resuspending in saline (or another non-calcium containing crystalloid) beforeadministration. The plasma can be stored frozenfor several months for future use. To enable easyaseptic preparation and separation of packedRBCs and plasma, transfer blood bags areavailable from Kruuse Ltd to allow collection ofblood components from whole blood collectionbags. More recently, feline blood products havebecome available from the Animal Blood Bankthat is based in Portugal (http://bsanimal.co.uk).

Blood transfusion reactionsAll cats receiving blood should be monitoredclosely and continuously for signs of transfusionreactions. Vital signs and demeanour should berecorded. Plasma and urine can also be evaluatedfor the presence of haemoglobin. Vomiting mayoccur as a non-specific finding but has also beenreported when blood is administered too rapidlyand in association with haemolysis. Clinical signsof a transfusion reaction generally depend on theamount of blood transfused, the type andamount of antibody involved in the reaction, andwhether the recipient has had previoussensitisation. The incidence of transfusionreactions varies in different studies and has beenreported to occur in 1% of cats by Weingart et al(2004) and in 23% of cats by Sylvane et al (2018).In this study, almost all the reactions were febrilenon-haemolytic transfusion reactions, which areless serious than haemolytic reactions.

Types of transfusion reactions and signs are listedin Table 1. Acute reactions typically occur withinminutes to hours of starting the transfusion butcan also occur up to 48 hours after the end of theblood transfusion. Immunological acutehaemolytic anaemia arises when alloantibodies inthe recipient’s plasma destroy transfusederythrocytes, particularly in type B cats giventype A blood. Further information on this can behaemolytic


found in the first part of the Blood Transfusionseries.

Acute hypersensitivity reactions are mediatedby IgE antibodies and arise due to recipientantibodies to foreign proteins given in thetransfusion. Severe intravascular haemolyticreactions may occur within minutes of the startof the transfusion, causing haemoglobinaemia,haemoglobinuria, disseminated intravascularcoagulation and clinical signs of shock.Extravascular haemolytic reactions usually occurlater and will result in hyperbilirubinaemia andbilirubinuria. Signs of transfusion reactions arelisted in Table 2.



Table 1: Classification of Transfusion Reactions

ImmunologicalAcute• Haemolysis• Acute hypersensitivity• Platelet sensitivity• White blood cell sensitivityDelayed• Haemolysis• Immunosuppression• Neonatal isoerythrolysis

Non-immunologicalAcute• Pretransfusion haemolysis of donor RBCs• Circulatory volume overload• Bacterial contamination of blood• Others e.g. citrate toxicity,

hyperammonaemia, acidosis, hypothermia, pulmonary embolism

Delayed• Transmission of infectious agents• Haemosiderosis

http://bsanimal.co.uk/

https://www.langfordvets.co.uk/media/2321/final-feline-update-zoetis-2803.pdf

Non-immunological transfusion reactions canarise due to abnormal handling or storage ofblood before transfusion leading to RBChaemolysis or bacterial contamination. Sepsis caninduce non-immunological haemolysis in thepatient. Over aggressive or rapid transfusion ofblood can lead to circulatory overload,particularly in cats with renal or cardiacinsufficiency. Signs include dyspnoea andtachypnoea and can progress to pulmonaryoedema. Management involves cessation of thetransfusion, diuretic treatment and oxygensupport. Citrate in blood products chelatescalcium and following transfusion the citrateusually undergoes rapid hepatic metabolism.However, in patients with hepatic disease,hypocalcaemia can develop due to citrateoverload with rapid administration of blood.Muscle tremors and cardiac abnormalities maybe seen, and calcium treatment is required. Theadministration of cold blood products can lead tohypothermia, particularly in young cats, and isavoided by prewarming the blood beforetransfusion.

Termination of the transfusion, glucocorticoids,antihistamines and/or adrenalin may be requiredas treatment (Table 3). anti


Recipient antibody against donor platelet orwhite blood cells can result in self-limitingfebrile non-haemolytic reactions. Antipyreticsmay be required in these cases. Pyrexia can alsobe seen with haemolysis or sepsis; hence thesecon



Table 2: Signs of Transfusion Reactions

• Urticaria• Pyrexia• Restlessness• Vocalisation• Vomiting• Diarrhoea• Change in respiratory rate with/without

dyspnoea• Change in heart rate with/without change

in rhythm• Weak pulses• Hypotension

Table 3: Procedures in cases of suspected transfusion reaction

• Stop the transfusion immediately; record volume infused and rate of infusion (do not discard the blood, line or fluids)

• Start cardiopulmonary resuscitation if necessary

• Examine the donor blood for haemolysis by spinning a microhaematocrit tube and looking for haemoglobinaemia

• Examine the recipient for haemolysis by spinning a microhaematocrit tube and looking for haemoglobinaemia

• Consider starting intravenous fluid therapy, especially in cases of severe intravascular haemolysis in order to avoid renal damage

• Consider treatment with glucocorticoids (e.g. hydrocortisone 2-4 mg/kg IV or IM), antihistamines (e.g. diphenhydramine 1 mg/kg IV or IM), and/or adrenaline (20 mcg/kg of a 1:10,000 solution (100 mcg (0.1mg) per ml) IV)

• Consider diuretic treatment and oxygen support in cases of pulmonary oedema due to volume overload; thoracic imaging and/or echocardiography may be indicated

• Bacterial culture of a sample of the donor blood unit may be required if infection or contamination is suspected

• Antipyretics (e.g. meloxicam) may be indicated in some cases. Assess renal function prior to administration.

conditions should be ruled out cats in developingpyrexia during or after a transfusion.

Should I give canine blood to a cat?Xenotransfusion is the act of transfusing bloodfrom one species into another species, in thiscase from a dog to a cat. There are publishedreports of canine blood administration to cats inemergency situations where a rapidimprovement in clinical signs was seen (Bovensand Gruffydd-Jones, 2013, Oron et al., 2017). Theeffect of the xenotransfusion is short-lived as thetransfused canine RBCs only survive for anaverage of 4 days (Clark and Kiesel, 1963). This ismost likely as the result of haemolysis, with morerecent studies suggesting that antibodies areproduced quicker than the usually quoted 4 days(Hourani et al., 2017). A fatal haemolytictransfusion reaction can occur if canine blood isgiven to a cat that has received canine bloodwithin four days or less. It had been previouslysuggested that first transfusions were relativelysafe (Bovens and Gruffydd-Jones, 2013), howevera recent report described acute haemolytictransfusion reactions in two cats given canineblood for the first time (Euler et al., 2016),thereby disputing this.

Xenotransfusions should generally be avoidedand only be performed as a potential life-savingmeasure when it is not possible to obtaincompatible feline blood, either from a local donoror a blood bank. The risks from this short-termbenefit need to be justified by a potentially goodlong-term outcome (e.g. whilst therapy takeseffect), and only considered in a cat that hasnever received canine blood before. The ownermust also fully understand the risks involved.long

On occasion, reference may be made to drugs which are not licensed for use in animals. The Editor does not take any responsibility forthe safety and efficacy of such products. Any persons using these products do so entirely at their own risk.www.felineupdate.co.uk 9



ReferencesBovens, C. & Gruffydd-Jones, T. 2013. Xenotransfusionwith canine blood in the feline species: review of theliterature. J Feline Med Surg, 15, 62-7.Clark, C. H. & Kiesel, G. K. 1963. Longevity of Red BloodCells in Interspecies Transfusion. J Am Vet Med Assoc,143, 400-1.Doolin, K. S., Chan, D. L., Adamantos, S. & Humm, K.2017. Retrospective evaluation of unexpected eventsduring collection of blood donations performed withand without sedation in cats (2010-2013). J Vet EmergCrit Care (San Antonio), 27, 555-560.Euler, C. C., Raj, K., Mizukami, K., Murray, L., Chen, C. Y.,Mackin, A. & Giger, U. 2016. Xenotransfusion of anemiccats with blood compatibility issues: pre- andposttransfusion laboratory diagnostic andcrossmatching studies. Vet Clin Pathol, 45, 244-53.Granfone, M. C., Walker, J. M. & Smith, L. J. 2018.Evaluation of an intramuscular butorphanol andalfaxalone protocol for feline blood donation: a pilotstudy. J Feline Med Surg, 20, 793-798.Hourani, L., Weingart, C. & Kohn, B. 2017.Alloimmunisation in transfused patients: serial cross-matching in a population of hospitalised cats. J FelineMed Surg, 19, 1231-1237.Oron, L., Bruchim, Y., Klainbart, S. & Kelmer, E. 2017.Ultrasound-guided intracardiac xenotransfusion ofcanine packed red blood cells and epinephrine to theleft ventricle of a severely anemic cat duringcardiopulmonary resuscitation. J Vet Emerg Crit Care(San Antonio), 27, 218-223.Reed, N., Espadas, I., Lalor, S. M. & Kisielewicz, C. 2014.Assessment of five formulae to predict post-transfusionpacked cell volume in cats. J Feline Med Surg, 16, 651-6.Spada, E., Proverbio, D., Baggiani, L., Bagnagatti DeGiorgi, G., Ferro, E. & Perego, R. 2017. Change inhaematological and selected biochemical parametersmeasured in feline blood donors and feline whole blooddonated units. J Feline Med Surg, 19, 375-381.Spada, E., Proverbio, D., Bagnagatti De Giorgi, G.,Perego, R., Valena, E., Della Pepa, A. & Baggiani, L. 2015.Clinical and haematological responses of feline blooddonors anaesthetised with a tiletamine and zolazepamcombination. J Feline Med Surg, 17, 338-41.Wilson, H. E., Jasani, S., Wagner, T. B., Benigni, L., Milne,J. R., Stokes, A. L. & Luis-Fuentes, V. 2010. Signs of leftheart volume overload in severely anaemic cats. J FelineMed Surg, 12, 904-9.

LOOD YPES AND RANSFUSIONS PART II: B C TRANSFUSION

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