NEW HARMONISED DEFINITIONS FOR COMPLICATIONS OF BLOOD DONATION

NEW HARMONISED DEFINITIONS FOR COMPLICATIONS OF BLOOD DONATION: INTERNATIONAL VALIDATION (5 A-S 29 -02) Kevin Land MD Chair, ISBT Haemovigilance Working Party Member, AABB Hemovigilance Steering Committee Blood Systems Inc. , USA University of Texas Health Science Center

Aim Validate harmonized donor haemovigilance definitions using potential users and subject matter experts around the world.

Background: Globally harmonized definitions…~23 years in the making ~1993: Countries begin aggregating AE data ~1994: Medical event reporting system work begins (MERS) 1998: European Haemovigilance Network formed (now IHN) 2002: EU Blood Directive mandates HV systems 2006: Formal efforts in US begin 2008: ISBT standard for surveillance of complications related to donation: i. STARE database started 2009: AABB publishes terms, built on ISBT terms and recent research. Donor. HART database started 2014: ISBT and AABB surveillance terms harmonized and jointly published 2016: Global validation of surveillance terms (NOW)

Methods: 30 real world cases selected some contained multiple diagnoses Type of Adverse Event # of Cases A 1 Blood outside vessel 6 A 2 Arm pain 7 A 3 Localized infection/ inflammation of vein/soft tissues 2 A 4 Other major vessel injury 6 B Vasovagal reactions 6 C Related to apheresis 2 D Allergic reactions 2 E Other serious complications 2 F Other (give diagnosis) 1 • Minimally edited • Often lack complete information • Few created from case reports • Reside on HV WP website SUBMIT

Methods: Survey went out • Sent to ISBT, AABB, ABC members • Cover letter with examples, definitions, cases, answer sheet • Asked to provide at least one diagnosis and grade for severity and imputability for each • Asked to consider all optional criteria in their answer • Given one month to respond (July 2016) • Results compiled in Excel database

Results: 54 Respondees 12 self reported were group responses 17(12) 21(3) 11 (6) 1 2 (2) 1 Thank you all for your time, answers, & comments! It is because of your dedication to Haemovigilance this project is even possible

Results • 52/54 respondees provided at least one diagnosis, severity, and imputability result for each case. • Multiple and alternated diagnoses were given • Median # single responses 52 (range 18 -54) • Median total responses 57 (range 54 -106) • 18/30 Questions utilized optional responses • ~1/2 respondees provided optional information • Duration of nerve injury, length of LOC/presence of complications, presence of injury, on/off site most often left empty or incomplete • Other arm pain (A 2. 2) not used often (except tendon injury) • ~400 total comments • 7/respondee (range 0 - 30), 13/question (range 8 - 26) • # correlates with complexity of case

Initial Results Diagnosis - fairly consistent except • Haematoma v Arm pain • Presence of significant potential donor factors • Rare AE or non-standard presentation • Incomplete donor information or followup Severity - most varability • Optional • Lack of objective criteria • More consistent when using a range (mild-moderate) Imputability – most consistent • Exceptions likely the same reasons seen with Diagnosis

Questions to consider • How should we manage multiple diagnoses? Use one or multiple? • If using one, do you report dx associated with first symptom, worst symptom, or the probable cause of the case? • When would you choose haematoma over arm pain? • Should there be a modifier for haematoma leading to arm pain? • Severity • Is “not working for 3 days” enough to classify a reaction as “moderate”? • Should all cases seeking outside medical care be considered > moderate? • Should some diagnoses (e. g. arterial puncture) always be moderate or severe? • Should “delayed bleeding” remain an optional category? • Should it be a modifier to describe haematoma or arterial puncture?

Dubai Working Party Thoughts & Recommendations • Free text important especially in complicated cases • Remember that real utility of the terms is to increase our focus on donor safety • Increases communication and stimulates questions for future research • Keep classification simple to help staff use appropriately • Users should use a single diagnosis as much as possible, but use multiple diagnoses when necessary • Please clarify how blood outside vessel with arm pain should be reported (First? Last? Worst? ) • In A 4 Other major vessel injury: drop “deep” from A 4. 1 Deep venous thrombosis • “unresponsivenenss” should be added to LOC definition

Dubai Working Party Thoughts & Recommendations • “fall” should be added to VV complications list • Unsure if >60 sec or <60 sec or w/o complications is best • In D. Allergic Reactions: drop “anaphylaxis” from D 2 term • But make sure there is a way to identify anaphylaxis to indicate severity • F Other category is good, but make sure to supply a diagnosis and clarify when to use it • Continue to explore ways to classify severity more objectively • Clarify how “donor factors” should affect reporting

Overall impression when information is relatively complete • Terms provide adequate coverage of donor reactions, including optional terms • Some terms and definitions need clarification • Severity grading is currently optional and the terms mild, moderate, and severe are not well defined • Imputability while optional is fairly consistently interpreted

Next Steps • Finalize full report • Waiting for a few more responses • Send final complete slide deck to all respondees • Publish on ISBT HV WP Website • Provide link to submit more cases • Include cases, answers, and discussion as resources • Organize small group to address working party recommendations • Edit standardized definition document as needed • Publish manuscript

Special Thank you! • • • All 54 respondees ISBT & AABB working groups Judith Chapman Mindy Goldman Hany Kamel Lou Katz Philippe Renaudier Mary Townsend Barbee Whitaker Jo Wiersum