Dec 29, 2012
247
3
Thompson
Status
Medical Student
Hi guys
I'm having difficulties differentiating between febrile nonhemolytic transfusion rxn and extravascular hemolysis in acute hemolytic transfusion rxns. they're both type II hypersensitivity rxns and both involve the pt having prior exposure to some foreign antigen (and making antibodies against it). is it just a difference of symptomology?
Tried goljan, wasn't helpful this time :(
Thanks
 

Old Style Nanny

Mrs. Doubtfire ¯\_(ツ)_/¯
Dec 1, 2010
215
2
Status
Isn't the cause also different? One is ABO / RBC incompatibility while the other is HLA / WBC incompatibility.
 
Oct 20, 2012
101
1
Status
Non-Student
Yep
And add to acute hemolytic transfusion reaction-jaundice when its extracellular
 

Old Style Nanny

Mrs. Doubtfire ¯\_(ツ)_/¯
Dec 1, 2010
215
2
Status
Yep
And add to acute hemolytic transfusion reaction-jaundice when its extracellular
You mean extravascular don't you? Although intravascular jaundice can still cause increased UCB and jaundice when there is a haptocidin imbalance, like a massive hemolysis.
 
OP
Zuhal
Dec 29, 2012
247
3
Thompson
Status
Medical Student
ok so please correct me if my understanding is wrong:

In nonhemolytic, you have antibodies from the host against the donor's MHC I located on WBCs? (I don't even know why wbc are involved here but it wouldn't make sense if we say against RBC because they don't even have an MHC). and the symptoms are minor

in hemolytic intravascular: you're a type A and we transfuse you with a type B so you naturally have antibodies against B and the hemolysis of those RBC happens intravascullarly.
in extravascular, i'm totally confused...is it just that it happens in the spleen where macrophages digest the cells? or is there more to it?

Thanks for your replies btw!
 
Oct 20, 2012
101
1
Status
Non-Student
You mean extravascular don't you? Although intravascular jaundice can still cause increased UCB and jaundice when there is a haptocidin imbalance, like a massive hemolysis.
Yes Extravascular
agree on fact that massive intravascular hemolysis can cause jaundice
 
Oct 20, 2012
101
1
Status
Non-Student
ok so please correct me if my understanding is wrong:

In nonhemolytic, you have antibodies from the host against the donor's MHC I located on WBCs? (I don't even know why wbc are involved here but it wouldn't make sense if we say against RBC because they don't even have an MHC). and the symptoms are minor

in hemolytic intravascular: you're a type A and we transfuse you with a type B so you naturally have antibodies against B and the hemolysis of those RBC happens intravascullarly.
in extravascular, i'm totally confused...is it just that it happens in the spleen where macrophages digest the cells? or is there more to it?

Thanks for your replies btw!
In non hemolytic as the name denotes there is no hemolysis (rbc s lack HLA antigens and therefore are not involved) Other elements which come with transfused blood such as lymphocytes, platelets etc having HLA on surface can induce type 2 hypersensitivity in host and thats the reason for this

Extravascular hemolysis occurs in spleen where defective or opsonized rbc are phagocytosed by macrophages, degraded and remaining heme transformed into bilirubin which is released into circulation and transported to live for glucuronidation
 
OP
Zuhal
Dec 29, 2012
247
3
Thompson
Status
Medical Student
In non hemolytic as the name denotes there is no hemolysis (rbc s lack HLA antigens and therefore are not involved) Other elements which come with transfused blood such as lymphocytes, platelets etc having HLA on surface can induce type 2 hypersensitivity in host and thats the reason for this

Extravascular hemolysis occurs in spleen where defective or opsonized rbc are phagocytosed by macrophages, degraded and remaining heme transformed into bilirubin which is released into circulation and transported to live for glucuronidation
Great! Thank you so much, that clears up a lot of things! I have one more question: in a chronic transplant rejection the MOA in FA is a little confusing. So the grafted CD8 cells are recognized as self by recipient's CD8 cells. so no problem there. But the grafted tissue presents an antigen on their MHCI that the recipient's CD8 cells recognize as foreign. Is that the general idea?

Also, according to goljan, someone with DiGeorge will have a danger of GVH reaction...Is that because they've never "seen" or been exposed to T cells before? Would you expect the same thing in someone with AIDS/SCID?
Sorry those are just a few questions bothering me lately! I appreciate your help!
 
Oct 20, 2012
101
1
Status
Non-Student
Great! Thank you so much, that clears up a lot of things! I have one more question: in a chronic transplant rejection the MOA in FA is a little confusing. So the grafted CD8 cells are recognized as self by recipient's CD8 cells. so no problem there. But the grafted tissue presents an antigen on their MHCI that the recipient's CD8 cells recognize as foreign. Is that the general idea?

Also, according to goljan, someone with DiGeorge will have a danger of GVH reaction...Is that because they've never "seen" or been exposed to T cells before? Would you expect the same thing in someone with AIDS/SCID?
Sorry those are just a few questions bothering me lately! I appreciate your help!
In chronic graft rejection self CD8 cells recognize foreign MHC1 molecules as self+antigen and attack together with antibodies-this process is irreversible and not controlled anymore by immunosuppressives
In contrast acute graft rejection is recognition of foreign MHC1 as non self and proliferation of CD8 cells against those nonself MHC1 molecules which is controlled by immunosuppression (not allowing reactive clones to proliferate, but eventually the whole immune system recognize the foreign MHC1 molecules as self + antigen and thats the transition from acute to chronic irreversible rejection)

In digeorge syndrome u got no T cells and due to this there is possibility for foreign T cells(CD8+CD4) in transplanted tissue to proliferate
immunity can not efficiently clear them

I think whatever decreases Tcell response can predispose to graft vs host disease (when sufficient amounts of immunocompetent cells are transplanted)
 
OP
Zuhal
Dec 29, 2012
247
3
Thompson
Status
Medical Student
I think whatever decreases Tcell response can predispose to graft vs host disease (when sufficient amounts of immunocompetent cells are transplanted)
Thanks for your answer! About your last statement,if someone gets a bone marrow transplant i can understand how the new donor cells start attacking the body because they don't recognize it but what I don't get is why is it that thats specifically true for those who are IC? These ppl don't even have any T/B cells to fight off in the first place? Am I missing something here?
 
Oct 20, 2012
101
1
Status
Non-Student
Thanks for your answer! About your last statement,if someone gets a bone marrow transplant i can understand how the new donor cells start attacking the body because they don't recognize it but what I don't get is why is it that thats specifically true for those who are IC? These ppl don't even have any T/B cells to fight off in the first place? Am I missing something here?

Yep immunocompromised individuals are at risk
If person has weak Immunity he is more prone to develop grafts immune response when transplanted tissues have high numbers of Tcells (bone marrow or liver)
 

yankees527

5+ Year Member
Aug 5, 2013
676
466
Status
Medical Student
BUMP

So First Aid seems to be behind on this:Febrile nonhemolytic reactions are supposedly from accumulated cytokines in the donor product

Uptodate says alot about this mechanism being best supported:

"FNHTRs are commonly caused by cytokines that are generated and accumulate during the storage of blood components. Implicated cytokines include interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor-alpha (TNFα)."

This is in contrast to FA which states it is from antibodies against donor HLA and WBCs (although this is given one line as an"alternate mechanism proposed" on uptodate)

Just thought us test takers would want to be aware of this!