AUTOLOGOUS (pre-operative), DIRECTED & DESIGNATED DONATIONS Blood Centre Perspective Transfusion Medicine Resident Topic Teaching October 11, 2011 D.K. Towns, MD, FRCPC (Anesthesia) Medical Director - Calgary Canadian Blood Services dale.towns@blood.ca

Autologous Donation Autologous donor: an individual who donates blood for the purpose of transfusion back to him/herself at a later time. At Canadian Blood Services, autologous donors must meet Donor Selection Acceptance Criteria, modified from the Whole Blood Programme for allogeneic donors. This is most commonly requested in preparation for upcoming, scheduled elective surgery Consent is required No age limits Must be requested by a physician (usually the surgeon, or, the family physician) If outside of CBS criteria, may consider collection at the hospital

Autologous Donation (con’t) Minimum weight of 55 lb - If less than 110 lb, a formula-driven reduced collection is performed Minimum hemoglobin/hematocrit at first donation: 110 g/l/.33 - Subsequent donations: 105/.32 Red cell shelf life is 42 days - Therefore, usually a maximum of 4 units, 1 week apart, and no more than 72 hours prior to surgery Consider oral iron replacement - ?erythropoietin Collected in CPD with added SAGM - Red blood cells and plasma produced - Plasma discarded unless specifically requested - then issued as FP Whole blood no longer available

Indications Consider only if the chance of requiring a transfusion is > 10% How many and when to collect? The same number as would be ordered for an allogeneic crossmatch using M-BOS (or a case-by-case assessment) Common surgical indications: major vascular surgery, including cardiac radical prostatectomy major orthopedic, including hip and knee (particularly re-do), scoliosis liver resection “at risk” obstetrics

Many Canadian hospitals have autologous donation programs Patients deemed high risk at Canadian Blood Services may be considered for in-hospital donation PAD programs are available at most Canadian Blood Services permanent donor clinics

Acceptance criteria differs from allogeneic donation (hemoglobin, hematocrit, collection intervals) The donor questionnaire is significantly abbreviated, focusing primarily on risks of the donation process to the donor or risks of bacterial contamination Other areas differing from allogeneic donation: Can donate if: received blood/blood products recently cancer some cardiac conditions recent invasive procedures (example, tattoos, piercings) medication use (which does not increase risk to the donation process) pregnancy syphilis positive

Contraindications Evidence of infection/risk of bacteremia IHSS (idiopathic hypertrophic subaortic stenosis) Aortic stenosis Left main coronary artery disease Unstable angina Cardiac failure MI in previous 6 weeks A-V block Uncontrolled hypertension Cyanotic heart disease Active seizure disorder

Each unit in every series is tested for the same infectious disease markers as for allogeneic donations TD positive units (except for syphilis) must be discarded TD markers repeat reactive for infectious diseases but confirmatory negative or indeterminate can be released but have a biohazard label Anti-HBcore positive units with or without a positive anti-HBs can be similarly released Note: Hospital-collected autologous units "should be" tested for transmissible diseases, but if positive - do not have to be discarded; a policy shall simply be in place as to how to deal with them

Advantages Major impetus - particularly in the past - was patient and physician desire to eliminate the risk of transfusion-transmitted viral diseases (particularly HIV and Hepatitis) Autologous transfusion minimizes exposure to allogeneic red cells and leukocyte antigens which could lead to future transfusion compatibility difficulties There is some evidence that allogeneic transfusion can lead to modulation of the recipients immune system Autologous donation theoretically can enhance the available allogeneic supply Provides compatible blood for patients with alloantibodies/rare blood Decreases risk of some adverse transfusion reactions (febrile reactions, TRALI reactions, allergic reactions, delayed hemolytic reactions)

Disadvantages Higher costs High wastage (approximately 50%) Logistic issues - The blood must be at the right place in the right condition at the right time - Must be specially labelled - Must be a system in place at both the hospital and blood centre - The hospital blood bank must know the blood is available, and how many units are available, so that autologous blood is used before allogeneic High wastage (approximately 50%) Surgical delay may result in outdating and discard of units Units cannot be crossed over into the allogeneic pool (differing acceptance criteria) Subjects patients to perioperative anemia, in general.

Risks which are NOT decreased Bacterial contamination Risk of driving to and from donation Clerical error leading to wrong unit being transfused (1:50,000) Receiving allogeneic blood before, or instead of autologous blood Autologous donors have approximately 12x higher risk of reaction than allogeneic donors at the time of donation. (Usually in young patients, underweight, previous reaction, or first time donation.) **Never transfuse autologous blood simply because it’s there

Krever Recommendations – Interim Report Using The Patient’s Own Blood (articles 18-25) The programs for autologous blood be made available throughout Canada to patients who are scheduled for elective surgery That Departments of Public Health determine in which public hospitals it would be feasible to create autologous programs That programs be ‘inclusive’ That hospitals, surgeons, physicians inform patients of the existence of autologous programs That written information be provided well in advance of elective surgery

Krever Recommendations – Interim Report Recommendations to the Blood Service The blood service should: Examine ways in which it can extend its PAD to a greater number of patients over a wider geographic area Ensure that its PAD Program is available to patients about to undergo surgery outside their province of residence Take active measures to publicize its PAD service

The Cochrane database of Systematic Reviews Volume 2, 2002 Pre-operative autologous donation reduced the risk of receiving allogeneic blood transfusion by a relative 63% The risk of receiving any blood transfusion was 43.8%. Billote, et al. J Bone Joint Surg 2002 prospective randomized controlled trial: patients undergoing total hip arthroplasty - hemoglobin ≥ 120 g/L half donated autologous blood, half did not *pre-determined transfusion trigger was defined neither received allogeneic blood of the autologous donors, 69% received an autologous transfusion 41% of the autologous units were wasted

Vamvakas in 2002 and 2007 (Vox Sang) critical reappraisal of clinical trials on the immunomodulatory effect of allogeneic blood transfusion did not unequivocally identify an association between allogeneic erythrocyte concentrate transfusion and postoperative infection, or short term mortality

Utilization CBS data Calgary-specific data Gail Rock (Transfusion Medicine, 2006; A review of nearly two decades in an autologous blood programme...) other ... All show < 50% utilization rates of autologous blood

PAD not recommended unless the clinical circumstances are exceptional Guidelines for policies on alternatives to allogeneic blood transfusion. 1. PAD and transfusion. Transfusion Medicine, 2007 PAD not recommended unless the clinical circumstances are exceptional rare blood groups children with scoliosis patients at serious psychiatric risk patients who refuse to consent to allogeneic transfusion

Caspari - letter to the editor (Transfusion Medicine 2007) autologous donation may be indicated for patients with rare blood groups and/or blood group antibodies for patients in highly developed countries - where safety and supply is not an issue it is difficult to demonstrate a net benefit of autologous over allogeneic blood transfusion

Case Study #1 63 year old female undergoing bilateral mandibular osteotomy family physician takes responsibility for ordering 2 units RBC donation takes place at CBS negative past history first unit anti-HCV positive *surgeon cancels surgery altogether

Case Study #2 45 year old male undergoing total hip arthroplasty 2 units RBC ordered 1st unit anti-HIV positive a) donation takes place at CBS - what do you do with the unit? b) donation takes place at hospital ... and now? what are the issues?

Dedicated Donations: 1) Directed Donations an allogeneic donation where the patient who requires a blood transfusion selects an individual or individuals (usually friends or relatives) to provide the necessary blood products (usually RBCs). For patients who are not yet of legal age, the selection of the donor(s) is done by the parents. 2) Designated donations selected from a specific donor for a specific recipient, for medically indicated reasons.

Directed Donations have been available in the U. S Directed Donations have been available in the U.S. (and Europe, Australia . . .) for many years Until 1996, not permitted by the CRCS - BTS (unless medically indicated, now termed "designated") In January 1996, Dr. Francine Décary convened an advisory group of experts: concluded that DD should be made available but not actively promoted At the same time, a court order obliged the CRCS in Montreal to provide DD to a child undergoing heart surgery from his two parents

The CRCS program started soon after Héma-Québec - which now became the blood operator in Quebec, also started a DD program CRCS (and now CBS) provided DD from parent (biological or adoptive) to a minor aged child, as does CBS currently Héma-Québec's program is open to any compatible donor/recipient pair irrespective of recipient age or donor and recipient relationship

Dr. Goldman's 1998 article in the CSTM Bulletin summarizes the first 2 years of Héma-Québec's experience: it was a small program the utilization rates were poor it decreased donor exposure in only 20% of recipients

CBS procedure: The transfusing physician must fill out a requisition after determining the selected donor's blood is compatible with the recipient. If CMV seronegativity is required, this must be determined and ensured by the physician prior to the request. The donor must fulfill the same criteria as an allogeneic donor (a few exceptions) Bled into a "B-2" pack (capability to make RBC and FP) shelf life 42 days BUT will likely be irradiated, therefore 28 days * Note, FP is only issued if specifically requested * Note also, RBC may be compatible but FP might not last donation must be at least 72 hours prior to transfusion

What about safety? possibility of graft vs. host disease (risk mitigated by appropriate gamma irradiation) transmissible disease risk: Dr. Nadine Shehata analyzed CBS TD data: Directed Donors in Canada had slightly higher rates of positivity for Hepatitis B, C, and syphilis than regular allogeneic doors

Other risks: Same as allogeneic transfusion, but in addition: In newborn - maternal antibodies against paternally inherited antigens (therefore don't use plasma; TRALI risk reduction measures have since prevented maternal plasma transfusion) In newborn - father's red cells may be incompatible with maternally derived antibodies still present If any adverse event related to the blood transfusion were to occur - ? guilt/blame

Case Presentation #1 8 year old child undergoing craniotomy and tumor removal Mom is a family physician Dad is selected as compatible RBC donor 2 units requested First unit successfully donated 24 hours later, dad called with post donation information . . . What are the issues? What would you do with this unit? What about the next planned donation?

Designated Donations: Some of the medically indicated reasons for designated donations include: patients with rare blood groups and antibodies infants with NAIT or HDN children with major blood loss surgery where designated donors may decrease donor exposure children with anticipated lifelong transfusion requirements (thalassemia, sickle cell anemia) patients with leukemia in relapse after bone marrow transplantation (donor leukocytes are used as adoptive immunotherapy to induce graft versus leukemia) HLA – matched apheresis platelets Designated Donors may, or may not be known or selected by their recipient They may be selected by the Blood Centre Crossover is acceptable if the donor has met all criteria for allogeneic donation.

Case Presentation #2 48 year old male post bone marrow transplant for CML Bone marrow donor is identical twin (therefore identical match) (*but has never donated blood) Post transplant: patient bleeding, first mucosal and bladder, finally GI tract platelet count 5 random platelet transfusions from hospital blood bank fail to produce increment Oncologist wants plateletpheresis product(s) from twin Wants to transfuse “urgently" prior to completion of testing What are the issues to consider?