Phen X Curative Therapies WG Complications Iron overload

Phen. X Curative Therapies WG Complications: Iron overload Stella Chou, MD January 15, 2021

Pre-transfusion evaluation ● Definition: laboratory studies required (ABO/Rh. D type, antibody screen) and recommended (extended red cell antigen profile) prior to transfusion ● Rationale: degree of antigen matching is an important consideration of therapy outcome ● Considerations o ABO/Rh. D matched red cells lacking antigens for which patient has already been alloimmunized to is the minimum level of matching required o Rh (C, E or C/c, E/e) and K matching is recommended for patients with SCD 1, 2 o Additional antigen matching for other blood group systems is occasionally implemented 2

Existing measurement protocols in Phen. X Toolkit? ● No, there are no blood bank assays in Phen. X Toolkit 3

Recommendations to the WG: Pre-transfusion evaluation ●Recommendation to add 4 measurement protocols o Antibody Screen o Determines presence or absence of red cell antibody o Antibody Identification o Determines antigen specificity of red cell antibody o Involves testing patient plasma against a panel of donor red cells with known antigen phenotypes o Direct antiglobulin test o Determines whether red blood cells are coated with immunoglobulin, complement, or both o Aka direct Coombs test 4

Recommendations to the WG: Pre-transfusion evaluation ●Recommendation to add 4 measurement protocols, continued o Red cell antigen profile, include o Obtained via serologic vs genotype method o Antigen phenotype: (positive or negative) o o 5 Rh (D, C, c, E, e), K/k Jka/Jkb, Fya/Fyb, M/N, S/s Additional red cell antigens 1 RH variants (presence/absence of partial, weak antigens)2, 3

Transfusion history ● Definition: laboratory studies required (ABO/Rh. D type, antibody screen) and recommended (extended red cell antigen profile) prior to transfusion ● Rationale: degree of antigen matching, transfusion burden, and alloimmunization are important consideration of therapy outcome ● Considerations o ABO/Rh. D matched red cells lacking antigens for which patient has already been alloimmunized to is the minimum level of matching required o Rh (C, E or C/c, E/e) and K matching is recommended for patients with SCD 1, 2 6

Existing measurement protocols in Phen. X Toolkit? ● Yes, one covering aspects of transfusion history ●Protocol – History of transfusion ● Includes three self-administered questions from Duke-UNC-Emory Outcome Modifying Genes Study ● Estimate the number of units (pints) of blood that you have ever received (none, 1 -10, … >50) ● Are you on chronic transfusion therapy at this time? (yes/no, don’t know) ● Are you on iron chelation treatment? (yes/no, don’t know) 7

Description of measurement protocols in the Phen. X Toolkit ● Coverage of Curative Therapies Research/Scope Element? o Insufficient for transfusion history in SCD ● Pros/Cons of the measurement protocols in the Toolkit o Pros: self-administered o Cons: alloimmunization history lacking, degree of antigen matching lacking, frequency choices may only be relevant to episodically transfused ● Can the measurement protocol be annotated for use in SCD Curative Therapies? o No, need a tool meant for providers to annotate rather than self-administered 8

Recommendations to the WG: transfusion history ●Recommendation to add measurement protocols o Chronic transfusion, currently or in past (Y/N) o Number of donor exposures (exact number or none, 1 -10, 11 -50, over 200, over 1000) o Red cell antigen matching for units transfused: o ABO/Rh. D only o Prophylactic Rh (C, E or C/c, E/e), and K matching o Prophylactic or Responsive extended matched (Jka/Jkb, Fya/Fyb, S/s) o Specific antigen matching 9

Recommendations to the WG: transfusion history ●Recommendation to add measurement protocols, continued o Red cell alloimmunization o (Y/N) o Antibodies identified o Delayed hemolytic transfusion reaction o Number of DHTR events o With antibody specificity identified (Y/N) o Treated with: 1 o o 10 Steroids IVIg Rituximab Eculizumab

Transfusion complications: alloimmunization ● Definition: antibodies formed against foreign red blood cell antigens ● Rationale: patients with SCD have the highest prevalence of alloimmunization among transfused patient populations, and may lead to poor outcomes following transfusion ● Considerations o The degree of prophylactic antigen matching is a key factor o Rh (C, E or C/c, E/e) and K matching is recommended for patients with SCD 1, 2 11

Existing measurement protocols in Phen. X Toolkit? ● No, there are no measurement protocols in Phen. X Toolkit pertaining to red cell alloimmunization 12

Recommendations to the WG: alloimmunization ●Recommendation to add measurement protocol o Antigens alloimmunized against o Consider listing antigens o If Rh antibody, was patient on Rh-matched transfusion protocol o D, C, E or D, C, c, E, e o Was there an associated delayed hemolytic transfusion reaction at time of antibody identification? o Defined by 13

Recommendations to the WG: alloimmunization ●Recommendation to add measurement protocol, continued o Was there an associated delayed hemolytic transfusion reaction at time of antibody identification? o Defined as a significant drop in hemoglobin within 21 days posttransfusion associated with 1 or more of the following: new red cell alloantibody, hemoglobinuria, accelerated increase in Hb. S% with concomitant fall in Hb. A%, relative reticulocytosis or reticulocytopenia from baseline, significant lactate dehydrogenase rise from baseline, and exclusion of an alternative cause 1 14

Transfusion complications: transfusion reactions ●Definitions: An allergic transfusion reaction can be associated with fever, chills, pruritis or hives. In severe reactions, respiratory distress or hypotension can occur. A febrile transfusion reaction typically involves fever, +/- chills. ●Rationale: transfusion reactions are relatively common ●Considerations: multiple allergic transfusion reactions may lead to a requirement for washed or saline suspended red cell products 15

Existing measurement protocols in Phen. X Toolkit? ● No, there are no measurement protocols in Phen. X Toolkit pertaining to allergic or febrile transfusion reactions ●Protocols do exist for ● Body temperature – tympanic thermometers ● Normal range defined as 96. 1 to 99. 3 Farenheit or 35. 637. 4 Celcius 1 ● Body temperature – oral thermometers ● Normal range defined as 96. 8 to 99. 7 Farenheit or 36. 037. 6 Celcius 1 16

Recommendations to the WG: transfusion reactions ●Recommendation to add measurement protocol o Allergic transfusion reaction (Y/N, don't know) o Consider listing symptoms experienced o If had allergic transfusion reaction o Was treatment required? (Y/N, don’t know) o Benadryl, steroids, epinephrine? (Y/N, don’t know) o Pre-medication required for future transfusions (Y/N, don’t know) 17