Hematopoiesis

Question 1

When does hematopoiesis begin and where?

Answer 1

Blood cell formation begins in the embryo yolk sac –> liver –> bone marrow (5th month)

Question 2

What kind of marrow produces the blood cells?

Answer 2

‘Red marrow’ is hematopoietic: In long bones, marrow becomes yellow (fatty) by age 20 and in flat bones, red marrow persists for life.

Question 3

All marrow cells derive from a multipotent master stem cell.

What are the three general types?

Answer 3

hematopoietic stem cells (HSCs)
endothelial cells (ECs)
mesenchymal stem cells (MSCs)

Question 4

What two cell lineages come from HSCs?

Answer 4

myeloid and lymphoid

Question 5

What two cell types are lymphoid?

Answer 5

B and T cells

Question 6

What four cell types are myeloid?

Answer 6

erythroid, granulocyte, monocyte and megakaryocytes

Question 7

Which cells are used in BM transplantation?

Answer 7

HSCs

Question 8

What are clusters of differentiation?

Answer 8

~250 cell surface markers on bone marrow cells integral cell membrane proteins that enable “typing” of bone marrow cells

Question 9

What is the definition of myeloid?

Answer 9

Myeloid includes:
granulocytes
monocytes
basophils
eosinophils
eythroids
megakaryocytes

Question 10

Each cell type arises from a Colony-Forming Unit (CFU) which are induced by growth factors/cytokines termed what?

Answer 10

CSFs (Colony-Stimulating Factors)

Question 11

What is the Multipotent CSF we have to know?

Answer 11

Stem Cell Factor (SCF) binds c-Kit -> all myeloid & lymphoid CFUs

Question 12

What are four unipotent CSFs?

Answer 12

• Erythropoietin -> CFU-E (erythropoiesis)
• Thrombopoietin -> CFU-meg (thrombopoiesis)
• G-CSF = Granulocyte-Colony Stimulating Factor -> CFU-G (neutrophils)
• M-CSF -> monocyte -> macrophage

Question 13

25 year old male with hypocellular (high fat) bone marrow core biopsy would you expect cytoses or cytopenia?

Answer 13

cytopenia due to low cellularity of the marrow

Question 14

If a pt has hypocellular BM what are the clinical consequences?

Answer 14

marrow being wiped out = no capacity to make RBCs (cause SOB), granulocytes (infection) or platelets (bleeding)

Question 15

What types of cells should you transplant in a pt with hypocellular marrow?

Answer 15

progenitor cells

Question 16

60 year old male core BM biopsy is hypercellular dominated by one type of immature cell. How would this pt present clinically?

Answer 16

marrow being one type of immature cell = no capacity to make mature RBCs (cause SOB), granulocytes (infection) or platelets (bleeding)

Question 17

If erythroids dominate an aspirate smear, what growth factor could cause this?

Answer 17

Erythropoietin

Question 18

What is the difference between automated and manual WBC differentials?

Answer 18

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

Question 19

How do you do a manual WBC?

Answer 19

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

Question 20

Erythropoietin is produced by the ______ in the setting of _______ and stimulates red blood cell production

Answer 20

kidney & hypoxia

Question 21

Thrombopoietin increases ____________ production and platelet formation

Answer 21

megakaryocyte

Question 22

______ plays a central role in increasing neutrophil production

Answer 22

Granulocyte colony-stimulating factor (G-CSF)

Question 23

What decreases EPO production?

Answer 23

normoxia and polycythemia

Question 24

What is the transcription factor for EPO?

Answer 24

Hypoxia-inducible factor is bound during normoxia and released during hypoxia

Question 25

What are some recombinant forms of EPO?

Answer 25

epoetin alfa & darbopoietin

Question 26

When would you use recombinant EPO?

Answer 26

Anemia induced by CKD, chemo, myelodysplastic syndrome, HIV, infants with low birth weights and people who refuse blood transfusions.

Question 27

What are the side effects of recombinant erythropoeitin

?

Answer 27

HYPERTENSION, HEADACHE, venous thrombosis, CVD and pure red cell aplasia

Question 28

Thrombopoietin (TPO) is constitutively produced where?

Answer 28

LIVER plus some kidney and spleen

Question 29

In the setting of thrombocytopenia, TPO levels ____ from the absence of platelets, leading to _______ megakaryocyte binding

Answer 29

rise & increased

Question 30

Elevated platelet counts (thrombocytosis) ________ circulating TPO, thereby ______ megakaryocyte activity

Answer 30

decrease for both

Question 31

What are the thrombopoietin receptor agonists?

Answer 31

eltrombopag & romiplostim

Question 32

What are thrombopoietin receptor agonists used for?

Answer 32

Treatment of thrombocytopenia, most commonly immune thrombocytopenia (ITP) and is associated with decreased need for platelet transfusions

Question 33

What are the side effects of thrombopoietin receptor agonists?

Answer 33

Side effects include headache, venous thrombosis and myelofibrosis

Question 34

What is the myeloid growth factor produced by monocytes, macrophages, fibroblasts, and endothelial cells?

Answer 34

Granulocyte Colony Stimulating Factor (G-CSF)

Question 35

When is Granulocyte Colony Stimulating Factor (G-CSF) increased?

Answer 35

G-CSF levels increase in the setting of pro-inflammatory mediators including IL-1 and TNF

Question 36

What is the recombinant G-CSF ?

Answer 36

filgrastim

Question 37

When is filgrastim used?

Answer 37

• 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

Question 38

What are the side effects of filgrastim?

Answer 38

fever, bone pain and rare fluid retention/pulmonary edema