Presentation is loading. Please wait.

Presentation is loading. Please wait.

Jerry A. Holmberg, MT(ASCP)SBB, Ph.D. June 6, 2013 201 Florida Association of Blood Banks Is it time to re-evaluate the gold standards in blood banking?

Similar presentations


Presentation on theme: "Jerry A. Holmberg, MT(ASCP)SBB, Ph.D. June 6, 2013 201 Florida Association of Blood Banks Is it time to re-evaluate the gold standards in blood banking?"— Presentation transcript:

1 Jerry A. Holmberg, MT(ASCP)SBB, Ph.D. June 6, Florida Association of Blood Banks Is it time to re-evaluate the gold standards in blood banking?

2 Agenda  Current status of transfusions in the U.S.  Traditional serological typing methods  Red cell genotyping as a supplemental method  Regulatory considerations  Recent Blood Product Advisory Committee discussion | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS 20132

3 Disclaimer  All blood group genotyping tests commercially available in the US and Canada are for research use only. Not for use in diagnostic procedures. | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS 20133

4 Transfusions/1,000 Population Comparison in Selected Countries USEnglandAustraliaDenmarkSweden Units of RBC per 1000 Population 48.7 (2001) 48.9 (2006) 48.8 (2008) ( ) 45.3 ( Recipient Age < % % > % < % % > % < % % > % <39 9.4% % > % <39 9.8% % > % Gender M 48.5% F 51.5% M 50.4% F 49.6 M 52.5% F 47.5% M 53.2% F 46.8% M 52.9% F 47.1% 2009 National Blood Collection and Utilization Survey Kamper-Jorgensen Transfusion 2009; 49: Cobain Transfusion Medicine 2007; 17, | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS

5 2009 HHS Blood Collection and Utilization Survey of RBC Use by Hospital Service | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS Health and Human Services’ Blood Collection and Utilization Survey 5

6 Risk Management Transfusion Risk Risk Assessment | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS

7 Challenges in Transfusion Medicine Source: FDA 2013, Notes: TRALI is transfusion related acute lung injury, which occurs within 6 hours of a transfusion. HTR is hemolytic transfusion reaction, which results in destruction of red cells and is usually caused by incompatibility. TACO is transfusion associated circulatory overload and is characterized by a sharp increase in blood pressure

8 Challenges in Transfusion Science  RBC Alloimmunization: lessons from sickle cell disease Alloimmunization in general public is % Alloimmunization in individuals receiving 3 or more units is 8.4% A review of 12 publications found a mean rate of 25% in SCD Miller ST et al. TRANSFUSION 2013;53:  RBC Alloimmunization in SCD prevalence in 2010 Editorial (TRANSFUSION 2013;53: ) Drs Treml and King advocates for genotype matching and leads to the conclusion that alloimmunization rates remain high partially to transfusions at institutions not providing extended matching | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS 20138

9 Challenges in Transfusion Science  RBC Alloimmunization in transfused patients with myelodysplastic syndrome or chronic myelomonocytic leukemia Alloimmunization occurs in 15% of MDS and CMML Alloimmunization mostly involves Rh system and Kell Antigen matching should include Kell and CcEe Sanz C et al. TRANSFUSION 2013;53:  Immunohematologic and patient safety benefit of a centralized transfusion database Puget Sound advocates for universal transfusion records since many patients bounce from hospital to hospital Delaney M TRANSFUSION 2013;53: | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS 20139

10 The Future  Are we moving towards more personalized transfusion medicine? Impact on collections? Impact on testing? Impact on data management? Impact on outcomes? | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS

11 Agenda  Current status of transfusions in the U.S.  Traditional serological typing methods  Red cell genotyping as a supplemental method  Regulatory considerations  Recent Blood Product Advisory Committee discussion | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS

12 ContentsContents Preface About the Author Acknowledgments 1. Blood and the cells it contains Blood contains cells, proteins, and sugars Red blood cells transport oxygen White blood cells are part of the immune response Platelets help blood to clot Your complete blood count Hemoglobin binds oxygen Resources 2. Blood group antigens are surface markers on the red blood cell membrane Antigens stimulate an immune response Red blood cell antigens can be sugars or proteins Red blood cell antigens determine your blood group Blood groups differ around the world The classification of blood cell antigens References 3. Blood transfusions and the immune system How to launch an immune response against transfused red blood cells "Blood type and cross match" Transfusion reactions: Immune-mediated Transfusion reactions: Non-immune 4. Hemolytic disease of the newborn Maternal antibodies cross the placenta and attack fetal red blood cells Sensitization occurs during the first pregnancy HDN occurs in subsequent pregnancies The Coombs test detects Rh incompatibility between mother and fetus Preventing HDN References 5. The ABO blood group At a glance Background information Basic biochemistry Clinical significance of ABO antibodies Molecular information References 6. The Hh blood group At a glance Background information Basic biochemistry Clinical significance of H antibodies Molecular information References 7. The Rh blood group At a glance Background information Basic biochemistry Clinical significance of Rh antibodies Molecular information References 8. The Kell blood group At a glance Background information Basic biochemistry Clinical significance of Kell antibodies Molecular information References 9. The Duffy blood group At a glance Background information Basic biochemistry Clinical significance of Duffy antibodies Molecular information References 10. The Kidd blood group At a glance Background information Basic biochemistry Clinical significance of Kidd antibodies Molecular information References 11. The Diego blood group At a glance Background information Basic biochemistry Clinical significance of Diego antibodies Molecular information References 12. The MNS blood group At a glance Background information Basic biochemistry Clinical significance of MNS antibodies Molecular information References < PrevNext > Print View Bookshelf ID: NBK2264 Chapter 2Blood group antigens are surface markers on the red blood cell membrane Before the 1900s, it was thought that all blood was the same, a misunderstanding that led to frequently fatal transfusions of animal blood into humans and hazardous transfusions of blood between people. Human blood is not the same—people belong to different blood groups, depending upon the surface markers found on the red blood cell. The cells that make up the body's tissues and organs are covered with surface markers, or antigens. Red blood cells are no different. This chapter will describe the types of red blood cell antigen and explain why they are so important in medicine today. Antigens stimulate an immune response Go to: An antigen is any substance to which the immune system can respond. For example, components of the bacterial cell wall can trigger severe and immediate attacks by neutrophils. If the immune system encounters an antigen that is not found on the body's own cells, it will launch an attack against that antigen. Conversely, antigens that are found on the body's own cells are known as "self-antigens", and the immune system does not normally attack these. The membrane of each red blood cell contains millions of antigens that are ignored by the immune system. However, when patients receive blood transfusions, their immune systems will attack any donor red blood cells that contain antigens that differ from their self-antigens. Therefore, ensuring that the antigens of transfused red blood cells match those of the patient's red blood cells is essential for a safe blood transfusion. Red blood cell antigens can be sugars or proteins Go to: Blood group antigens are either sugars or proteins, and they are attached to various components in the red blood cell membrane. For example, the antigens of the ABO blood group are sugars. They are produced by a series of reactions in which enzymes catalyze the transfer of sugar units. A person's DNA determines the type of enzymes they have, and, therefore, the type of sugar antigens that end up on their red blood cells. In contrast, the antigens of the Rh blood group are proteins. A person's DNA holds the information for producing the protein antigens. The RhD gene encodes the D antigen, which is a large protein on the red blood cell membrane. Some people have a version of the gene that does not produce D antigen, and therefore the RhD protein is absent from their red blood cells.The figure below shows the red blood cell membrane and some of the blood group antigens attached to it. Aside from the sugar (glycan or carbohydrate) antigens, the red blood cell membrane contains three types of protein that carry blood group antigens: single-pass proteins, multi-pass proteins, and glycosylphosphatidylinositol (GPI)-linked proteins. Click on the blood groups to find out more about the antigens that define it. Red blood cell antigens determine your blood group Scientific Overview Blood Group Antigens Dean L. Blood Groups and Red Cell Antigens [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); Chapter 2, Blood group antigens are surface markers on the red blood cell membrane. Available from: | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS

13 Antigen Function CARBOHYDRATES ABO P1PK LE GLOB H I FORS ADHESION MOLECULES LW XG FY LU OK IN SC MER2 JMH TRANSPORTERS AND CHANNELS RH RHAG JK DI LAN CO GIL XR JR COMPLEMENT REGULATION CH/RG CROM KN H I FORS ENZYMES KEL YT STRUCTURAL OR UNKNOWN MNS GE DO | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS

14 Traditional Serological Testing Methods  Limitations of serology to detect antigens in some cases Recent transfusion (mixed field) Warm auto-antibody Antisera -Limited availability of some rare antisera -Quality  Weak expression of some RBC antigens  Impractical to screen large numbers of donors for all potential antigens Typing for rare antigens is often not performed Potential allo-immunization or reactions  Can be time consuming and costly | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS

15 European Perspective British Committee for Standards in Haematology  Where there is a discrepancy in reaction strength between different anti-D reagents, or where the reagent fails to give a clear-cut strong positive reaction, 1 a decision to investigate further needs to be made based on whether the development of anti-D is likely to cause clinical problems.  7.9. Females of child-bearing potential Females of child-bearing potential should receive K negative red cells unless they are unavailable in an emergency (Lee & de Silva, 2004; BCSH, 2006a).  Foetal transfusions D negative, K negative (and further antigen negative where appropriate) units should be crossmatched against the maternal plasma by IAT if the maternal plasma contains red cell antibodies of likely clinical significance. | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS Guidelines for the Blood Transfusion Services in the UK Guidelines for pre-transfusion compatibility procedures in blood transfusion laboratories, British Committee for Standards in Haematology Transfusion Medicine doi: /j x 15

16 European Perspective British Committee for Standards in Haematology  Interpretation of D grouping has become more complex, with the increase in variety of monoclonal reagents, and molecular testing. The historical distinction between weak and partial D, based on whether the individual is able to make anti-D, has become blurred and a new algorithm is included in Fig. 1. | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS 2013 Guidelines for pre-transfusion compatibility procedures in blood transfusion laboratories, British Committee for Standards in Haematology Transfusion Medicine doi: /j x Guidelines for the Blood Transfusion Services in the UK 2012) 16

17 European Perspective British Committee for Standards in Haematology | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS 2013 Guidelines for pre-transfusion compatibility procedures in blood transfusion laboratories, British Committee for Standards in Haematology Transfusion Medicine doi: /j x Guidelines for the Blood Transfusion Services in the UK 2012) 17

18 Agenda  Current status of transfusions in the U.S.  Traditional serological typing methods  Red cell genotyping as a supplemental method  Regulatory considerations  Recent Blood Product Advisory Committee discussion | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS

19 Bloodgen Consortium | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS Courtesy of Dr. Nuria Nogues, Barcelona

20 Genotyping for RBC Antigens  Case for genotyping Basis for predicting phenotypes from genotyping results 324 blood group antigens recognized 33 blood group systems / 40 unassigned antigens Most blood group polymorphisms are now understood  Potential clinical application Determination of blood type in transfused patients Patients with “allo” or “auto” antibodies warm autoantibodies positive direct antiglobulin test Resolution of phenotype discrepancies | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS

21 Potential Clinical Application of RBC Molecular  Detection of rare but significant antigens  Typing for antigens when antisera are not available  Identification of a fetus at risk for HDFN Determination of parental zygosity Typing of fetal blood  Mass screening of donors for antigen-negative blood  Identification of null and novel alleles | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS Courtesy of Dr. Nuria Nogues, Barcelona

22 German Consensus on Blood Group Genotyping  In 2000 a German consensus statement was developed on the use of blood group genotyping and its potential application in clinical situations (Legler et al. Infusioinsther Transfusionmed 2000; 27: )  In fetus from amniotic fluid or trophoblastic cells (chorionic villi)  In multiply transfused patients, if standard serology fails  In case of auto and allo-immunohemolytic anemia, if standard serology fails  For weak D types and other variant RH alleles, if serology is inconclusive | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS

23  Prior to 2001 the usual source of fetal DNA was a sample of amniotic fluid or chorionic villi.  Cell-free fetal DNA is detectable in the blood of pregnant women  amount increasing throughout gestation. 23 Fetal Blood Group Typing in Europe  Fetal RhD type can be predicted reliably from the fetal DNA in the plasma of D neg pregnant women from beginning of 2nd trimester. | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS Courtesy of Dr. Nuria Nogues, Barcelona

24  Non-invasive fetal blood group typing from maternal plasma cell-free fetal DNA is now a clinical reality.  Offered by many laboratories in Europe, to identify the fetus not at risk of HDFN.  Different assays are currently used for reliable genotyping of D, C, c, E and K by quantitative real-time PCR techniques. Fetal Blood Group Typing in sensitized pregnant women European Experience | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS Courtesy of Dr. Nuria Nogues, Barcelona

25 Fetal RHD typing: Application to all D neg pregnant women European Experience  Trials of high-throughput methods have demonstrated that accurate fetal D testing in all D- pregnant women is feasible.  Fetal RHD typing to target antenatal anti-D prophylaxis already introduced in Denmark (2010) and the Netherlands (2011). TRANSFUSION Volume 52, April 2012 | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS

26 26 Blood Donors Molecular Typing Barcelona Blood Center Experience Focused on specific groups of donors:  Extensive genotyping of blood donors from immigrant populations  Aim: Identify blood donors expressing low-incidence antigens (Di a, Js a, Mi a, Co b, Kp a ) or donors with rare phenotypes: Di(a+b), Co(a-b+), Fy(a-b-), HPA-1(a-b+)  Utility: - For transfusion (rare phenotype blood units) - RBC panel units (Antibody identification) - Diagnostic (reagent cells) | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS Courtesy of Dr. Nuria Nogues, Barcelona

27  Utility: - Quality control of D negative units - Estimate the real incidence of Del units  RHD Genotyping of D negative blood donors with RhC and/or RhE positive  Used the BLOODchip Reference platform  Total of blood donors extensively genotyped  1.6% Blood Donors Molecular Typing Barcelona Blood Center Experience | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS Courtesy of Dr. Nuria Nogues, Barcelona

28 28  Finnish Red Cross Blood Service experience Routine genotyping of blood donors with ID-Core+ since September 2012 Criteria – blood group A or O, K neg – previous donation within a year – rare donors, ethnic minorities Blood Donors Molecular Typing Finnish Red Cross Blood Service Experience | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS Courtesy of Dr. Nuria Nogues, Barcelona

29 Agenda  Current status of transfusions in the U.S.  Traditional serological typing methods  Red cell genotyping as a supplemental method  Regulatory considerations  Recent Blood Product Advisory Committee discussion | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS

30 Traditional Serological Testing Methods  Regulatory Process for Serology Biologics License Application (BLA) Applicable regulations 21 CFR CFR Part (Labeling) 21 CFR Part 820 (Quality System Regulations)  Definitions: Biological Product – 21 CFR Part (h) Blood Grouping Reagent - 21 CFR Part 660, Subpart C Reagent Red Blood Cells – 21 CFR Part 660, Subpart D Anti-Human Globulin – 21 CFR Part 660, Subpart F | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS

31 Traditional Serological Testing Methods  Hemagglutination assays (HA) defined immunohematology Over 300 blood group antigens recognized  Reagent Approvals - FDA Polyclonal antisera Monoclonal antisera Anti-Human Globulin (AHG) Panel or screening cells with known antigens | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS

32 Regulatory Consideration  High degree of accuracy has been reported  FDA established molecular testing laboratory to created DNA reference panels  No licensed or approved molecular device for RBC genotyping  Pathway Investigational device exemption (IDE) Premarket approval (PMA) -Assurance of safety and effectiveness -Scientific evidence -180-day review clock | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS

33 Regulatory Consideration RBC Genotyping Workshop, NIH  RBC genotyping promises significant technical and clinical benefits for transfusion medicine  Assay systems for RBC genotyping will be reviewed under the PMA pathway  FDA currently considers that: In-house validation of RBC genotyping systems will require panels of specimens pedigreed by gene sequencing of the donor Candidate technology should be defined within review process to permit appropriate labeling, limitations, and comparison to serology  Guidance and policy will be needed Dr. Epstein, Director of CBRR, Sept 14, 2012 | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS

34 Agenda  Current status of transfusions in the U.S.  Traditional serological typing methods  Red cell genotyping as a supplemental method  Regulatory considerations  Recent Blood Product Advisory Committee discussion | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS

35 Blood Product Advisory Committee Supports integral labeling with historic antigen type results  December 2012, BPAC asked to comment on Reporting based on historical RBC typing results from two donations Validated process to confirm donor identification and accurate linkage to historical data Confirmation of relevant negative results on the current unit prior to transfusion, when feasible to mitigate risk form historical data Would BPAC’s response to the first questions vary if serology or molecular testing, or both were performed.  Committee supported historical data as part of the label and their responses would not vary whether the test was serologic or molecular | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS

36 Thank you The secret to complex serology is in the genes | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS

37 | Re-evaluating the Gold Standards| Holmberg | 24April2013 | CBBS


Download ppt "Jerry A. Holmberg, MT(ASCP)SBB, Ph.D. June 6, 2013 201 Florida Association of Blood Banks Is it time to re-evaluate the gold standards in blood banking?"

Similar presentations


Ads by Google