Major Crossmatch

A “major” crossmatch is the last test used to assess the compatibility of a donor’s red blood cells with the recipient’s plasma. Note that a crossmatch is generally the last step performed in pretransfusion testing, after we have done ABO and Rh grouping, and after we have done the antibody screen and identified any significant antibodies found there.

So, you might ask, why is this crossmatch “major?” Well, it’s because protecting transfused red blood cells from hemolysis, it turns out, is of highest, or major importance. Destruction of transfused RBCs leads to hemolytic transfusion reactions, among the most deadly of transfusion complications. Don’t get hung up on remembering “major” vs. “minor,” though; frankly, almost no one still uses this term to describe a crossmatch in real life. We just say, “crossmatch” and everyone knows we mean “major crossmatch.” More on this below…

To do a crossmatch, in the simplest terms, the lab scientist in the blood bank would mix the patient/recipient’s plasma with a sample of the donor’s red blood cells (RBCs); see below for links to the three main types of crossmatches. The big idea of a crossmatch is that it serves as the final check of ABO compatibility between donor and recipient before transfusion. In other words, it is basically a way for us to check if we missed something or there was some issue with the other pretransfusion tests mentioned above, OR if we simply prepared the wrong unit in error.

For example, in a purely hypothetical scenario, if for some reason you were trying to transfuse RBCs from a blood group A donor to a blood group B recipient, blood bank personnel performing the crossmatch would mix the recipient’s plasma (which of course contains anti-A antibodies) with the donor’s group A red blood cells. Obviously, in this example, you would expect the result to be incompatible, and we would say, “Hey, wait a second!” and figure out the problem.


  1. When blood bankers use the term “crossmatch” in pretransfusion testing, they really mean “major crossmatch” in virtually all situations
  2. The major crossmatch is required for any product that contains >2 mL of red blood cells. This functionally means that whole blood, red blood cells, and granulocyte products require a crossmatch, while platelets and plasma components generally do not.

Obviously, if there is a “major” crossmatch, there must also be a “minor” crossmatch, and there is (though we really don’t use it). Also, as mentioned above, multiple types of major crossmatches exist, including immediate spin, computer (electronic), and AHG (“full”) versions.

Updated by Joe Chaffin in August 2023 and April 2024; with thanks to Vipul Prajapati for corrections!

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