A patient was tested positive for HLA antibody in platelet refractory panel. We were recommended to transfuse irradiated crossmatched platelet units. Irradiated to prevent graft vs host reaction. But we were informed that transfusion of leuko-reduced pRBC did not have to irradiated unless doctor specified. Can anyone explain the logic? Reference lab screened 9 units of platelets to find 1 compatible unit.

If the patient is given HLA-matched platelet, the unit of platelet needs to be irradiated to prevent graft vs. host disease as irradiation inactivates T-cells in the donor unit. For PRBCs, it's not necessary to be irradiated. Using leuko-reduced PRBCs can reduce the risk of exposure of CMV, cannot inactivate T-cells.

My confusion is, for simplicity 1 in 9 random pRBC units will have HLA matching leukocytes with a patient. If we are trying to prevent graft vs host disease, shouldn't we irradiate pRBC? Or is the leukocytes count in pRBC insignificant?

If PRBC unit and HLA-matched platelet unit are leuko-reduced, the residual leuckocytes should be similar in both of them (<5x10^6/unit - AABB technical manual). According to the theory of graft vs. host disease, I guess giving HLA-matched platelet has much, much higher possibility to cause graft vs. host disease than 1 in 9?

Irradiated Blood Products

All pediatric cancer patients will receive irradiated blood products in order to prevent

transfusion related graft-versus-host disease.

Filtered Blood Products

All pediatric cancer and sickle cell patients will receive filtered blood products. Filtration

is an effective way to eliminate the risk of CMV infection in patients with cancer, and

prevents alloimmunization.

CMV Negative Blood Products

CMV negative blood products will be reserved for cancer patients who are documented

to be CMV seronegative and are scheduled to undergo a bone marrow transplant. At the

time of transplant, these patients are more immunocompromised, and the low level of

CMV that may remain in a filtered product can still pose a risk.

Platelet refractoriness will be defined as inadequate rise in platelet counts as measured

within 1 hour of platelet transfusion.

Approaches to platelet refractoriness:

1. Make sure platelets are ABO compatible.

2. Ask for fresh units.

3. Test for HLA antibodies and platelet specific allo-antibodies.

4. Consider IVIG (0.5 gm/kg) and Amicar in patients with significant bleeding.

 

REMEMBER always THE ONLY WAY one can prevent graft-versus-host disease

is through IRRADIATION.

I hope this will help.

REMEMBER always THE ONLY WAY one can prevent graft-versus-host disease

is through IRRADIATION.

Edited August 24, 201410 yr by Abdulhameed Al-Attas

You say that the reference lab screened 9 donors to find 1 compatible.  Are you sure that you are talking about HLA antibodies?  HLA matched products are not screened on the shelf. You identify a donor and collect them specifically for the recipient.  You may luck out and have a product from a matching donor available but you don't go screening units.  What you describe sounds like a platelet crossmatch because your patient has platelet antibodies.

 

As for HLA:  TAGVHD is caused by having transfused lymphocytes that are a very close HLA match to the recipient mount an immune response against host tissue and the host immune system not being able to successfully recognize the transfused lymphocytes as non-self.  Unless you are living in a relatively homogenous community (I recall case reports coming out of Israel and Japan years ago when irradiation was first being employed) this should not be a problem for RBC transfusion with a regular volunteer donor unit.  The odds of finding an HLA A,B match in the general US population is far less than 1 in 9.

 

Also WBC's don't fare well in the refrigerator.  After about 72 hours at 2-4 degrees they are mostly dead.  Most TAGVHD cases from RBC transfusion that you see in the literature are from fresh blood.

I'm trying to follow this post but it's confusing. If the thought is to irradiate (PLTs) to prevent GVHD by inactivating the T-cells then why not irradiate the RBCs? (especially if the residual leukocytes are about the same in both components).  It's leuko-reduced RBCs not leukocyte-free RBCs. Sorry if it was clear to the rest but it seems like every other post says yes you should then no not necessary. I want to learn about this because we are presently having discussions about guidelines on when to or not to irradiate and or give CMV neg blood products. Also, does refrigeration inactivate cytokines that may be released from WBC's too?

The reason that you irradiate HLA matched platelets is because the risk of TAGVHD is greater when you have the likelihood of a close HLA match between donor and recipient.  Such a match is unlikely with an RBC from the shelf.  As for cytokines, my thinking would be that refrigeration would lead to a greater amount of them being released since WBC's do not fare well in the fridge.

I understand some of your confusion.  When dealing with non-immunocompromised patients, the main thing to think about is:  "Is the donor of the blood product an unusually close HLA-match to the patient?"

 

When we are transfusing random Packed Red Cells or Platelets to the patients, it is very unlikely that they are a close HLA-match.  (Think about how difficult it is for most transplant candidates to find a close HLA-matched organ donor.)

 

If we are giving HLA-matched platelets to the patient there is an increased risk of Transfusion Associated Graft Versus Host (as JEMarti explained) because they are HLA similar.  If we are giving Packed Red Cells or Platelets from a close relative (ie: a "first degree relative"), it is also likely that they may be HLA similar to the patient (at least significantly similar to the patient than donor blood that comes from a random stranger.)

 

Now, if we are dealing with very young or immunocompromised patients, their weak immune systems increase the risk that transfused T-cells in the donor blood might engraft and result in TAGVHD, so those patient might need all donor Packed Red Cells and Platelets to be irradiated before transfusion.

Thank you all for the explanations!!! I get it now

The risk explained to me in HLA-matched platelets is that the donor would be homozygous for an HLA antigen shared with the recipient.  The T-cells in the unit would survive and could engraft because the recipient does not see them as foreign.  However, the recipient may be heterozygous for that shared antigen and so have an HLA antigen that the donor lacks.  Because the recipient can't destroy the T-cells with the homozygous expression but the donor's engrafted T-cells can make HLA antibodies directed at the recipient and cause GVHD the platelets must be irradiated so the donor's T-cells don't survive to engraft.  This is also why countries with more closely related populations may require that all blood products be irradiated because even a RBC unit could carry one of these stealthy homozygous T-cells.