1 / 33

Ammar Alsughayir TM Fellow Ottawa

Ammar Alsughayir TM Fellow Ottawa. Background. Platelet supply –inventory Management Platelet Antigen expression. Background. the effects of 393 transfusions of pooled PLT products in pediatric cancer patients between 1973 and 1974 ABO matching had no effect on the success of

laken
Download Presentation

Ammar Alsughayir TM Fellow Ottawa

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Ammar Alsughayir TM Fellow Ottawa

  2. Background • Platelet supply –inventory Management • Platelet Antigen expression

  3. Background • the effects of 393 transfusions of pooled PLT products in pediatric cancer patients between 1973 and 1974 • ABO matching had no effect on the success of a transfusion van Eys J, Thomas D, Olivos B. Platelet use in pediatric oncology: a review of 393 transfusions. Transfusion 1978; 18:169-73.

  4. The TRAP trial • higher PLT increments after transfusion of ABO-compatible PLTs. • In lymphoma patients undergoing autologous marrow transplantation, leukoreduced ABO identical PLT transfusions were associated with reduced morbidity ABO-mismatched PLT transfusions may be associated with a poor outcome

  5. Factors affecting Response to platelets TX • Platelet production factors • Whole blood derived vs. APC • storage conditions, • storage time, • PLT yield per apheresis procedure • increasing BW of the recipient favoured successful transfusions

  6. Study objective • The present prospective study was designed to investigate the impact of providing either ABO-identical or out-of-group APCs to children with thrombocytopenia suffering from hematologic malignancies, solid tumors, or aplastic anemia.

  7. PATIENTS AND METHODSStudy design and objectives • Differences in transfusion efficacy,measured by the 1-hour percentage of PLT recovery (PPR1hr) • ABO-identical vs major ABO- mismatched PLT • Secondary objectives were • to compare the efficacy of ABO-identical PLT transfusions with major mismatched transfusions of group A subtypes A1 and A2 as well as with minor-mismatched transfusions • side effects of PLT transfusions and data on the production process of APCs were recorded prospectively

  8. 2004-2006 all consecutive patients with hematologic malignancies, solid tumors, or aplastic anemia requiring at least one PLT transfusion Exclusion criteria were refusal of study fever of 38.5°C or greater before transfusion, clinically enlarged spleen, thrombosis, Adverse events requiring interruption of transfusion, Hemorrhage of WHO Grade 3 or greater Patients

  9. Preparation and delivery of PLTs • PLTs were obtained from healthy volunteer donors, either by single- or by double-needle thrombocytapheresis using a cell separator (Amicus Crescendo) • single-needle procedures using one of two different cell separators (Trima Accel or COBE Spectra) • Depending on the yield, the apheresis product was split into units containing at least 2.0 x10 11 PLTs, corresponding to the minimum content required by the standards of the Swiss Red Cross at the time

  10. Inventory management guidelines • Older products were delivered first . • ABO-identical products were provided first; • otherwise minor- or major-mismatched PLTs were delivered at the discretion of the staff. • Wherever applicable no D+ PLTs were given to D– female recipients. • Group O PLT donors were screened for the presence of anti-A and anti-B hemolysins. If a titer of more than 4 was present, the product was labelled accordingly and released for group O recipients only

  11. PLT transfusions • Most patients received prophylactic PLT transfusions, with only a few receiving PLT transfusions for therapeutic purposes. • Children less than 2 years old received half an APC product, and patients aged 2 years or more received a full APC product independent of their BW.

  12. Efficacy measures: PPR1hr and 1-hour CCI (CCI1hr) • The CCI1hr allows to assess the efficacy of PLT transfusion accounting for the body surface area (BSA) and the number of transfused PLTs • PPR1hr [%] = (posttransfusion count [109/L] - pretransfusion count [109/L]) x blood volume [L]/PLT dose [1011/L]

  13. Determination of A antigen expression and A1/A2subgroup typing • For major-mismatched transfusions from group A donors, A antigen expression on PLT surfaces was measured by flow cytometry both in the APC and in the recipient before and 1 hour after transfusion. • Fluorescent microscopy • to identify glycoprotein IIIa on PLTs • Isohemagglutinin titer testing • For patients and APCs

  14. RESULTSPatient characteristics, PLT transfusions, andindications

  15. Constellations of ABO blood group matching ofdonors and recipients

  16. Interim analyses of the primarystudy variable • The three planned interim analyses did not result in a proposal to stop the study early because of proven difference or proven futility

  17. PLT transfusion efficacy • The median PPR1hr of all transfusions was 31 percent. • Univariate analysis showed PPR1hr for 76 major mismatched transfusions to be significantly inferior to that for 282 ABO-identical transfusions (median, 21% vs. 32%; p = 0.034) • major-mismatched transfusions were significantly more often unsuccessful than ABO-identical transfusions (p = 0.033), especially many major-mismatched transfusions from subgroup A1 donors failed (p = 0.002). • Major-mismatched A2 PLTs were as successful as ABO-identical ones (p = 1.00

  18. PLT transfusion efficacy

  19. Multivariate analysis • Major-mismatched transfusions were significantly more often unsuccessful than ABO-identical transfusions (p = 0.005).

  20. subgroup analysis revealed that PLTs from donors with ABO subgroup A2 given to group O or B recipients, although major mismatched transfusions, by definition, were just as successful as ABO-identical PLTs (p = 0.90). • the failure rate of major-mismatched transfusions was even more striking (p = 0.002).

  21. Fate of transfused A antigen-positive PLTs • in the majority of group O and B recipients, no A antigen-positive PLTs were detectable in the circulation 1 hour after transfusion. • after ABO-identical PLT transfusions from group A1 donors to group A2 Recipients, whose RBCs but not PLTs express A antigen, the majority of transfused A antigen positive PLTs remained detectable in the circulation

  22. Fluorescent microscopy of A antigen-positive PLTs • using the MoAb anti-CD61 for identification of PLTs and anti-A BRIC-145 for expression of A antigen, depletion of transfused A antigen-positive PLTs from the circulation of a blood group O recipient is visualized at a single-cell level by dual-color fluorescent microscopy

  23. Regression analysis showed that for group A major-mismatched transfusions, there was a significant negative correlation (p = 0.002) between the percentage of A antigen-positive PLTs in the APC and the PPR1hr; that is, the more PLTs expressed A antigen, the lower the PPR1hr

  24. Safety review and isohemagglutinin titers • no clinically detectable hemolytic transfusion reaction was observed. • no association between transfusion efficacy and the recipient’s isohemagglutinin titers were detected (data not shown)

  25. DISCUSSION • ABO-incompatible PLTs may be associated with decreased PLT increments after transfusion. • The majority of studies have been performed in adult patients, and PLT transfusion in children is poorly investigated • A randomized study design would have increased the power of the study. However, in view of the preceding studies in adults it is considered such a design incompatible with good clinical practice in this vulnerable pediatric population.

  26. DISCUSSION • statistical endpoints is based on CCI1hr and PPR1hr as surrogate parameters for PLT transfusion efficacy • CCI1hr accounts for BSA and is well established in adults, whereas PPR1hr accounts for BW and is reported to be more appropriate in children, particularly in infants and toddlers. • The final analysis was based on PPR1hr.

  27. DISCUSSION • The results demonstrate that transfusion efficacy and transfusion success, the latter defined as PPR1hr of more than 30 percent, of major-mismatched PLTs are significantly inferior to those of ABO-identical PLTs, whereas efficacy and success of minor-mismatched transfusions are not different from those of identical transfusions.

  28. DISCUSSION • diversity in the percentages of PLTs expressing A antigen among A1 donors (median, 40%; range, 3%-80%). • the percentage of A antigen-expressing PLTs and PPR1hr were inversely related; that is, the higher the percentage of A antigen-expressing PLTs, the lower the PPR1hr. • Median anti-A titers in the plasma of blood group O recipients was higher than in plasma of group B recipients , this may explain the slightly better survival of transfused A1 PLTs in group B recipients • A2 PLTs can be considered group O compatible

  29. Critical Appraisal • Prospective observational study . • Were all patients who entered the trial properly accounted for at its conclusion? • Will the results help me in caring for my patients? • Can the results be applied to my patient care? • Were all clinically important outcomes considered?

  30. Conclusion • major-mismatched PLT transfusions were significantly less successful than ABO-identical transfusions. • In children requiring regular and continued PLT support, an ABO-compatible transfusion strategy should be the first choice. • PLT concentrate suppliers would have to provide A1/A2 subgroup typing of group A PLT donors

  31. Conclusion • In this study, transfusion of plasma-incompatible PLTs was as successful as that of identical PLTs, although an inherent risk for hemolytic transfusion reactions will remain • To volume reduce or not? • Will blood supplier or hospital test donor for high titer Anti A once and for all ?

More Related