Dr. Dale Towns, MD, FRCPC, Anes. Medical Director, Canadian Blood Services Calgary

1. TOPIC TEACHING: DEDICATED (Directed and Designated) & (Pre-operative) AUTOLOGOUS DONATIONS Dr. Dale Towns, MD, FRCPC, Anes. Medical Director, Canadian Blood Services Calgary Friday September 12, 2008

2. 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.

3. AUTOLOGOUS DONATIONS: • Donation of blood by a patient for his/her own future use, most commonly prior to scheduled elective surgery.

4. DIRECTED DONATIONS: Donated by relatives or friends who are specifically chosen by the recipient (or parents) Advantages: • may decrease total donor exposure if appropriately indicated and planned • may decrease anxiety in the recipient or parents who have fears about the safety of the blood supply Disadvantages: • contravenes the normal principles of voluntary blood donations • loss of donor anonymity • donor may be less than candid to sensitive donor questions • fails to increase safety

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

12. 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?

13. 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.

14. 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?

15. AUTOLOGOUS DONATIONS

16. PAD programs are available at most CBS permanent donor clinics for elective surgery in otherwise health donors • criteria not as stringent as for allogeneic donations • ensure that it is safe for donor to participate in the donation process • contraindications: • evidence of infection and risk of bacteremia • heart disease or atherosclerotic disease including • aortic stenosis • unstable angina • MI within 6 months of donation • high grade left main CAD • cyanotic heart disease • uncontrolled hypertension • active seizure disorder • significant cardiac or pulmonary disease not yet cleared for surgery

17. many hospitals in Canada have autologous donation programs • patients deemed high risk at CBS may be considered for in-hospital donation

18. at CBS autologous donations are collected into "B-2's" (RBC + FP) • Hemoglobin 110 g/L Htc .33 (subsequent 105/.32) • RBC's have 42 day shelf life • FP issued only if requested by transfusing physician • indicated only if 10% or greater change of receiving a transfusion

19. Advantages • prevents transfusion-transmitted disease • prevents red cell alloimmunization • supplements the blood supply • provides compatible blood for patients with alloantibodies • prevents some adverse transfusion reactions (febrile reactions, TRALI reactions, allergic reactions, delayed hemolytic Tx reactions)

20. Disadvantages • autologous donors have increased risk of reactions at donation (1 in 16,000 or about 12x higher than allogeneic donors) • usually in young patients, underweight, previous reaction, or first time donation • not as likely in the elderly over 75, or on medications • risk of driving to and from the donation • does not affect the risk of bacterial contamination • does not affect the risk of receiving the "wrong unit" (1 in 50,000) • risk of receiving allogeneic blood before, or instead of autolgous blood • more costly than allogeneic

21. Disadvantages (con’t) • risk of surgery date postponement • blood is wasted if not transfused • subjects patients to perioperative anemia • in general physiological erythropoiesis is not effective in the time frame that we provide • (for optimal benefit should collect between 21 and 34 days prior to surgery; not within 2 weeks prior to surgery) • increases the likelihood of perioperative transfusion • induced anemia • know the "blood is there" • doesn't decrease the risk of TACO

22. CSA standards: • must test for: • anti-HIV 1/2 • anti-HCV • HBsAg • anti-HTLV I/II • NAT, HIV-1 p24 Ag, and syphilis are not required ** must have written policy on disposition of blood that is repeat reactive to any of these tests

23. Autologous donations are collected at most CBS permanent donor clinics for elective surgery in otherwise healthy donors • CBS has collection data since its • inception in 1998

24. Autologous Donations 1999 to 2007, Canadian Blood Services 14,000 12,000 2000 10,000 2001 2002 8,000 2003 2004 6,000 2005 Number of Donations 2006 1999 4,000 2007 2,000 0 5,739 12,037 10,565 9,026 9, All Regions / Centres / Clinics 8,758 8,7 7,865 7, 6,579 5,878 4,531 All Regions/Centres/Clinics Year

28. CBS Calgary autologous collections: • 2001/02 - 259 • 2002/03 - 193 • 2003/04 - 855 • 2004/05 - 731 • 2005/06 - 564 • 2006/07 - 323 • 2007/08 year to date - 278 Simply looking at collection statistics at CBS can be misleading.

29. Summary • Autologous collections are decreasing. • Utilization is about 50% or less. We have incomplete information pertaining to: • hospital collection statistics • utilization data • appropriateness of the request for autologous donation 4) appropriateness of the transfusion 5) surgical subspecialty use • additional requirements for allogeneic transfusion

30. Krever Recommendations – Interim ReportUsing 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

31. Krever Recommendations – Interim ReportRecommendations 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

32. 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% (or an absolute decrease of 43.8%) • 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

33. 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

34. 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

35. 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

36. 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

37. Case Study #3 • 63 year old female undergoing bilateral mandibular osteotomy • oral surgeon orders 2 units RBC • donation takes place at CBS • negative past history • first unit anti-HCV positive • *surgeon cancels surgery altogether

38. Case Study #4 • 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?

39. Most successful autologous programs have a dedicated perioperative program that includes: 1) cooperation and communication between all physicians involved • appropriately indicated surgical procedures warranting autologous donation 3) appropriately selected patients 4) have policies for managing TD positive or indeterminate units 5) donor/patient consent to proceed, and to release positive results 6) proper labelling (may include "biohazard" or "untested") 7) appropriate selection of volume of blood drawn 8) appropriate donation intervals, including timing before surgery 9) iron and/or erythropoietin therapy as appropriate 10) transfusion of autologous blood only if indicated, and at same transfusion trigger as allogeneic 11) quality review and audit of the program, including utilization, physician education

40. Acute normovolemic hemodilution andCell Salvage • CSA standards state that the blood centre or transfusion service should be involved in the development of the policies and procedures used in the management of the perioperative blood recovery program.

41. Questions?