extramedullary hematopoiesis vs erythroid hyperplasia

[johndoe3344]

Do these two always occur together? For example, in beta thal major, you have both extramedullary hematopoiesis and erythroid hyperplasia.

Why do they happen? If it's just a condition of "i need to make more RBCs" why doesn't it happen in alpha thal? Or maybe an iron deficiency anemia? Could someone just explain a little bit of background?

Or is this one of those things that you just memorize that it's just associated with specific diseases?

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[iCY]

Do these two always occur together? For example, in beta thal major, you have both extramedullary hematopoiesis and erythroid hyperplasia.

Why do they happen? If it's just a condition of "i need to make more RBCs" why doesn't it happen in alpha thal? Or maybe an iron deficiency anemia? Could someone just explain a little bit of background?

Or is this one of those things that you just memorize that it's just associated with specific diseases?

My understanding is that extramedullary hematopoiesis is considered an "expansion" of hematopoiesis outside of the bone marrow, i.e., the bone marrow can't keep up RBC production with RBC destruction.

Also note that there is "ineffective erythropoiesis" occuring in beta-thal, where the alpha chains form inclusions --> causing RBCs to undergo apoptosis in the bone marrow as they are being produced. Perhaps the ineffective erythropoiesis + the extravascular hemolysis that occurs in beta-thal causes severe hemolytic anemia --> triggering expansion of hematopoiesis outside of the bone marrow b/c the bone marrow can't keep up with the hemolytic anemia.

I don't see this happening in iron deficiency anemia, b/c the bone marrow should be able to keep up w/ the RBC production.

edit* as for alpha thal, 1 & 2 gene deletions in alpha thal produce no symptoms/mild anemia respectively. 4 gene deletions is lethal in utero (hydrops fetalis), so the only one that can really cause severe hemolytic anemia is 3 gene deltion (HbH disease). As for why it doesn't lead to expansion of hematopoiesis, i have written in my notes (annotated from pathoma I believe) that beta chain aggregates are not as damaging to RBCs as alpha chain aggregates (in beta-thal major) are, so there is no ineffective hematopoiesis (apoptosis during RBC production). So alpha thal w/ 3 gene deletions is not as severe as beta-thal major??

again, thats just from my understanding, feel free to correct me on anything!

 

[Phloston]

Do these two always occur together? For example, in beta thal major, you have both extramedullary hematopoiesis and erythroid hyperplasia.

Why do they happen? If it's just a condition of "i need to make more RBCs" why doesn't it happen in alpha thal? Or maybe an iron deficiency anemia? Could someone just explain a little bit of background?

Or is this one of those things that you just memorize that it's just associated with specific diseases?

In beta-thalassaemia, since the beta-chains are defective, there is a compensatory increase in HbA2 (alpha2-delta2) and HbF (alpha2-gamma2) production. This induces erythroid hyperplasia because of the attempt to meet metabolic demands for oxygen. HbA2 and HbF demonstrate left-shifted Hb-O2 curves, so in order to maintain similar oxygen unloading in tissues, despite increasing 2,3-BPG, etc., their production would be increased much greater than just simply one-to-one. In other words, many HbA2 or HbF would replace one HbA1 because the former don't unload oxygen as well. Metabolic demands are not met despite the intra-marrow hyperplasia ("crew-cut" skull), so production continues in the liver and spleen.

In alpha-thalassaemia, however, since the alpha-chains are defective, HbA2 and HbF could not be produced to compensate for deficient HbA1 because they themselves contain alpha-chains. This means that as long as only one or two alpha-mutations are present, minor erythroid hyperplasia in an attempt to increase HbA1, with a concomitant increase in 2,3-BPG, would be sufficient to only produce Sx similar to a minor iron-deficiency anaemia. The extramedullary erythropoiesis, as seen with beta-thalassaemia, isn't necessary to the same extent because there is no capacity to produce excess HbA2 or HbF. Splenomegaly would still occur due to increased RBC turnover.

Iron-deficiency anaemia would produce Sx similar to alpha-thalassaemia trait (2 alpha-mutations) because the net result is the same: deficient production of HbA1.

 

[johndoe3344]

Okay, let me see if I'm understanding you correctly. Basically any process where hematopoiesis needs to be increased (hemolysis, thalassemia, whatever) will have some degree of erythroid hyperplasia, but only in a few specific cases (where this hematopoiesis needs to be dramatically increased) will it happen to the extent of showing up as crewcut/chipmunk. When even that is not enough (e.g. beta major and HbS) then erythropoiesis will continue in extramedullary sites. Is that accurate?

Another thing -- besides HbS and beta major, is there anything else that will cause crewcut/chipmunk + extramedullary hematopoiesis?

Thanks a lot, both of you

 

[iCY]

Okay, let me see if I'm understanding you correctly. Basically any process where hematopoiesis needs to be increased (hemolysis, thalassemia, whatever) will have some degree of erythroid hyperplasia, but only in a few specific cases (where this hematopoiesis needs to be dramatically increased) will it happen to the extent of showing up as crewcut/chipmunk. When even that is not enough (e.g. beta major and HbS) then erythropoiesis will continue in extramedullary sites. Is that accurate?

Another thing -- besides HbS and beta major, is there anything else that will cause crewcut/chipmunk + extramedullary hematopoiesis?

Thanks a lot, both of you

That sounds good to me lol. I wouldn't stress crew cut too much, out of the 130 or so questions i've done for RBC/WBC disorders, "crew cut" wasn't really all that useful in figuring out what the disease process was.

Other things that I can think of w/ extramedullary hematopoiesis is myelofibrosis or myelophthisic processes (metastatic cancer, osteopetrosis, myeloproliferative disorders, etc...)

 

[Pills Of Soap]

I think you can see it in sickle cell too, but I wouldnt worry about that too much.