Hematopoiesis Flashcards
When does hematopoiesis begin and where?
Blood cell formation begins in the embryo yolk sac –> liver –> bone marrow (5th month)
What kind of marrow produces the blood cells?
‘Red marrow’ is hematopoietic: In long bones, marrow becomes yellow (fatty) by age 20 and in flat bones, red marrow persists for life.
All marrow cells derive from a multipotent master stem cell.
What are the three general types?
hematopoietic stem cells (HSCs)
endothelial cells (ECs)
mesenchymal stem cells (MSCs)
What two cell lineages come from HSCs?
myeloid and lymphoid
What two cell types are lymphoid?
B and T cells
What four cell types are myeloid?
erythroid, granulocyte, monocyte and megakaryocytes
Which cells are used in BM transplantation?
HSCs
What are clusters of differentiation?
~250 cell surface markers on bone marrow cells integral cell membrane proteins that enable “typing” of bone marrow cells
What is the definition of myeloid?
Myeloid includes: granulocytes monocytes basophils eosinophils eythroids megakaryocytes
Each cell type arises from a Colony-Forming Unit (CFU) which are induced by growth factors/cytokines termed what?
CSFs (Colony-Stimulating Factors)
What is the Multipotent CSF we have to know?
Stem Cell Factor (SCF) binds c-Kit -> all myeloid & lymphoid CFUs
What are four unipotent CSFs?
- Erythropoietin -> CFU-E (erythropoiesis)
- Thrombopoietin -> CFU-meg (thrombopoiesis)
- G-CSF = Granulocyte-Colony Stimulating Factor -> CFU-G (neutrophils)
- M-CSF -> monocyte -> macrophage
25 year old male with hypocellular (high fat) bone marrow core biopsy would you expect cytoses or cytopenia?
cytopenia due to low cellularity of the marrow
If a pt has hypocellular BM what are the clinical consequences?
marrow being wiped out = no capacity to make RBCs (cause SOB), granulocytes (infection) or platelets (bleeding)
What types of cells should you transplant in a pt with hypocellular marrow?
progenitor cells
60 year old male core BM biopsy is hypercellular dominated by one type of immature cell. How would this pt present clinically?
marrow being one type of immature cell = no capacity to make mature RBCs (cause SOB), granulocytes (infection) or platelets (bleeding)
If erythroids dominate an aspirate smear, what growth factor could cause this?
Erythropoietin
What is the difference between automated and manual WBC differentials?
Automated: done by analyzer counts thousands of cells in less than 5 minutes but cannot categorize abnormal cells
Manual: done by tech counts about 100 cells in 20 minutes potentially less accurate
How do you do a manual WBC?
pick a good spread of cells where they don’t overlap much and use a scanning pattern counting and categorizing all WBCs until you reach 100
Erythropoietin is produced by the ______ in the setting of _______ and stimulates red blood cell production
kidney & hypoxia
Thrombopoietin increases ____________ production and platelet formation
megakaryocyte
______ plays a central role in increasing neutrophil production
Granulocyte colony-stimulating factor (G-CSF)
What decreases EPO production?
normoxia and polycythemia
What is the transcription factor for EPO?
Hypoxia-inducible factor is bound during normoxia and released during hypoxia
What are some recombinant forms of EPO?
epoetin alfa & darbopoietin
When would you use recombinant EPO?
Anemia induced by CKD, chemo, myelodysplastic syndrome, HIV, infants with low birth weights and people who refuse blood transfusions.
What are the side effects of recombinant erythropoeitin
?
HYPERTENSION, HEADACHE, venous thrombosis, CVD and pure red cell aplasia
Thrombopoietin (TPO) is constitutively produced where?
LIVER plus some kidney and spleen
In the setting of thrombocytopenia, TPO levels ____ from the absence of platelets, leading to _______ megakaryocyte binding
rise & increased
Elevated platelet counts (thrombocytosis) ________ circulating TPO, thereby ______ megakaryocyte activity
decrease for both
What are the thrombopoietin receptor agonists?
eltrombopag & romiplostim
What are thrombopoietin receptor agonists used for?
Treatment of thrombocytopenia, most commonly immune thrombocytopenia (ITP) and is associated with decreased need for platelet transfusions
What are the side effects of thrombopoietin receptor agonists?
Side effects include headache, venous thrombosis and myelofibrosis
What is the myeloid growth factor produced by monocytes, macrophages, fibroblasts, and endothelial cells?
Granulocyte Colony Stimulating Factor (G-CSF)
When is Granulocyte Colony Stimulating Factor (G-CSF) increased?
G-CSF levels increase in the setting of pro-inflammatory mediators including IL-1 and TNF
What is the recombinant G-CSF ?
filgrastim
When is filgrastim used?
- Prevention of infection in patients with chemotherapy-induced neutropenia (most commonly in acute leukemia and breast cancertherapy)
- Treatment of fevers, infections in patients with neutropenia
- HIV associated neutropenia
- Chronic neutropenia syndromes (eg autoimmune neutropenia)
- Mobilization of stem cells prior to autologous bone marrow
What are the side effects of filgrastim?
fever, bone pain and rare fluid retention/pulmonary edema
