There has been an ongoing debate over the importance of ABO matching for platelet transfusions for well over 50 years. A survey from 2007 showed that 17% of North American institutions did not have a formal ABO policy and 50% of the institutions with a policy gave ABO incompatible platelets if a compatible unit was not available.1 Today, in 2018, there is still no consensus on how blood banks handle the question of ABO compatibility for platelet transfusions.

This is a two-part blog post to help unpack the debate on ABO matching for platelets. Part 1 provides an overview of the ABO system as it applies to platelets, definitions of ABO platelet matching terminology, and common endpoints for studies looking at the impact of ABO matching on platelet transfusion.

Part 2 is a literature review that details the results of an extensive review of the evidence surrounding the impact of ABO incompatibility for prophylactic transfusions to hematology-oncology patients. Ultimately, the conclusion from the literature review in Part 2 may come as a surprise to many, because we found that the evidence suggests there is a relatively small impact on clinical outcomes from platelet ABO incompatibility (major mismatch), when compared to other product factors impacting transfusion success.

If you would like to jump straight to the literature review you can do so by clicking on this link: Understanding the Impact of Platelet ABO Matching – Part 2: Literature Review

ABO and Platelets

It is well known that the appropriate matching of compatible ABO blood groups is critical for safe red blood cell transfusion. The source of this requirement is the interaction of antigens on the surface of the red blood cell and antibodies in the plasma. Table 1 below gives an overview of the distribution of antigens and antibodies in the four primary blood groups, A, B, AB, and O (The extremely rare hh phenotype will not be considered for this blog post.).

Table 1 Antigens and Antibodies on Red Cells by blood group
[image available for use via wiki commons]



However, unlike red blood cells, the platelets of most individuals in the A, B, or AB blood groups express a low level of A and/or B antigens.2,3 One notable exception is individuals with the A2 subtype: they do not express A antigens making them effectively the same as O platelets.2,4 In addition to variability in the level of antigen expression between individuals, there is also significant variability among the platelets of a single individual.2,3,5

In contrast with the near complete removal of transfused platelets, as is the case in platelet refractoriness, studies have shown that in ABO-mediated removal of platelets only a small subset of platelets are removed rapidly while the remaining platelets exhibit near-normal survival in vivo.6,7 It has been suggested that the variability of antigen expression among platelets explains this phenomenon—platelets with high antigen expression are cleared rapidly and those with low expression remain in circulation.8

Defining ABO compatibility or “matching” status

Before diving into the literature on ABO compatibility for platelet transfusions an important clarification must be made. What exactly does it mean when we say a platelet transfusion is ABO compatible or incompatible? Reviewing the literature of the past 50 years does not reveal consistent and well-defined terminology for describing the different types of ABO incompatibility.

A key reason for confusion is the important difference between a major ABO mismatch (platelet incompatibility) and a minor ABO mismatch (plasma incompatibility). This important distinction has often not been made or not been discussed. Publications typically refer to transfusions as “matched” or “unmatched” without differentiating between major or minor mismatch. However, this distinction is important. In this blog we will use the following three terms and borrow the definitions used in the PLADO study and the recent publication by Seigeot et al:9,10

ABO identical—Donor and recipient have the same ABO RBC/Platelet antigens and plasma antibodies

Minor mismatch—Donor’s plasma antibodies are incompatible with the antigens of the recipient’s RBC/platelets (e.g. O donor anti-A given to an A recipient with A antigens). This is sometimes called a plasma incompatibility.

Major mismatch—Donor’s RBC/platelet antigens are incompatible with the recipient’s plasma antibodies (e.g. A donor A antigen given to an O recipient with anti-A). This sometimes called a platelet incompatibility.

Defining Endpoints

Another important clarification is defining which study endpoints matter and what clinical outcome measures are used to reach these endpoints. The goal of a prophylactic transfusion is to raise the platelet count in order to reduce the risk of bleeding and thus lower the risk of mortality. Patients with hematologic malignancies are the main recipients of prophylactic platelet transfusions. Due to the low rates of bleeding and the high variability among hematology-oncology patients, it is quite difficult to execute studies powered to show a significant difference in rates of bleeding. However, as discussed in Part 2, the PLADO study was able to accomplish this.

In routine clinical practice, platelet effectiveness is determined by the platelet increment or the difference between the platelet count before and after the transfusion. Consequently, studies of transfusion effectiveness usually assess platelet increments. This serves as a clear and objective surrogate metric for transfusion effectiveness in most cases. However, there is a lack of evidence showing a correlation between platelet increment and reduction of bleeding risk once patients have surpassed a minimal platelet count of 6000/µL (6).11,12

Continuing the discussion

Now that the basics have been covered it is time to look at what evidence there is in the literature of an impact from ABO matching for platelet transfusion. Click on this link: Understanding the Impact of Platelet ABO Matching – Part 2: Literature Review

 

References

  1. Fung MK, Downes KA, Shulman IA. Transfusion of platelets containing ABO-incompatible plasma: a survey of 3156 North American laboratories. Arch Pathol Lab Med 2007;131:909-16.
  2. Curtis BR, Edwards JT, Hessner MJ, Klein JP, Aster RH. Blood group A and B antigens are strongly expressed on platelets of some individuals. Blood 2000;96:1574-81.
  3. Ogasawara K, Ueki J, Takenaka M, Furihata K. Study on the expression of ABH antigens on platelets. Blood 1993;82:993-9.
  4. Skogen B, Rossebo Hansen B, Husebekk A, Havnes T, Hannestad K. Minimal expression of blood group A antigen on thrombocytes from A2 individuals. Transfusion 1988;28:456-9.
  5. Dunstan RA. Use of fluorescence flow cytometry to study the binding of various ligands to platelets. J Histochem Cytochem 1985;33:1176-9.
  6. Aster RH. Effect of anticoagulant and ABO incompatibility on recovery of transfused human platelets. Blood 1965;26:732-43.
  7. Pfisterer H, Thierfelder S, Stich W. ABO Rh blood groups and platelet transfusion. Blut 1968;17:1-5.
  8. Curtis BR, McFarland JG. Human platelet antigens – 2013. Vox Sang 2014;106:93-102.
  9. Seigeot A, Desmarets M, Rumpler A, et al. Factors related to the outcome of prophylactic platelet transfusions in patients with hematologic malignancies: an observational study. Transfusion 2018.
  10. Triulzi DJ, Assmann SF, Strauss RG, et al. The impact of platelet transfusion characteristics on posttransfusion platelet increments and clinical bleeding in patients with hypoproliferative thrombocytopenia. Blood 2012;119:5553-62.
  11. Slichter SJ. Relationship between platelet count and bleeding risk in thrombocytopenic patients. Transfus Med Rev 2004;18:153-67.
  12. Heddle NM, Cook RJ, Sigouin C, et al. A descriptive analysis of international transfusion practice and bleeding outcomes in patients with acute leukemia. Transfusion 2006;46:903-11.