Hematopoiesis Flashcards
HIM
Full meaning?
Hematopoietic inductive environment
why can bone marrow undergo and sustain hematopoiesis. ?
HIM
HIM
It consists of 4 things
List!!
a._____
b._____
c.______
d.______
Good Blood flow
Hematopoietic tissue stoma
Extracellular stroma matrix
Specific site of precursor cell differentiation
HIM contains Hematopoietic tissue stoma that _______
contains cells on which hematopoietic cells grow and divide
HIM contains Extracellular stroma matrix that ________ by acting as a ________
provide a framework on which differentiation can occur
specific recognition and adhesion sites
TABLE
-Pluripotent gives ___ and ____
myeloid and lymphoid
Structure of the bone marrow
*____-____-____-_____ (outer - inner)
Periosteum -cortex - endosteum - bone marrow space
The space surrounded by the endosteal surfaces is known as ____, and the structure within it is known as the _____
bone cavity
bone marrow.
Blood supply to the marrow
-Arterial supply is by the ____ artery.
-The artery pierces into the ____ via the ____
nutrient
bone cortex
nutrient canal.
Blood supply to the marrow
Once the nutrient artery reaches the bone marrow space/cavity, it becomes the _____ artery.
medullary
Blood supply to the marrow
In the bone marrow space, the medullary artery often divides into the ___________ that move ____________ to reach the _____ of the ______
ascending and descending medullary branches.
across the bone marrow space
endosteal surface of the opposite side.
Blood supply to the marrow
The branches the ascending and descending medullary arteries give off while running
in the bone marrow space are known as ________ or _____ arteries.
transverse or arcuate
Blood supply to the marrow
The arcuate arteries pierce through the ___ and _____ , and then become _____ that run through the _______
endosteum and cortex
capillaries
Haversian canal
Haversian canals are _____ or _____ in ____ bone that house ____ and _____
microscopic tubes or tunnels
cortical
nerve fibers and a few capillaries
The HIM
-Haemopoiesis occurs within the bone marrow’s _______; and Within these,there is a ____________
sinusoids
Haemopoietic Inductive Environment (HIM).
The HIM
-The outside of the HIM is lined by ____ cells
endothelial
the( outer or inner?) part of the HIM is the actual site of haemopoiesis.
inner
The HIM
-The newly formed cells move from the HIM to enter the ______, from which they enter the ______,and then enter the general circulation.
medullary veins
emissary veins
THE HIM
The outer surface of the HIM, which is lined by _____ cells is known as the
_____ surface, while the inner surface is known as the _____ surface.
Endothelial
luminal
abluminal
THE HIM
The abluminal surface is lined by:
_____
_____
______
____
• Reticulum cells
• Fibroblasts
• Adipocytes
• M&s
Bone marrow cell pool
There are 3 major cell pools:
1. The ____ cell pool
2. The _____ cell pool
3. The _____ cell pool
stem
progenitor
precursor
A stem cell
-is that cell with two main properties:
-It is capable of ____ and capacity for _____
mitotic division
cell renewal
A stem cell
It is capable of cell division that results in cell _____.
differentiation
(Stem, Precursor or progenitor?) cells
These are cells in the bone marrow that can be identified morphologically.
Precursor
Progenitor cells
-They are between the ____ and ___ cells.
stem cells and precursor
Progenitor cells
They are morphologically
identifiable
T/F
F
They are not morphologically
identifiable
Progenitor cells
-do not renew themselves.
T/F
T
Erythropoiesis
-All blood cells are derivatives of the _________ cell.
pluripotential stem
Erythropoiesis
A pluripotential stem cell is capable of renewal or division and differentiation into:
•____
•_____ committed stem cell
-The length of time between maturation of the polychromatic cell to reticulocyte in the bone marrow is approximately 5 days
-In the spleen, reticulocytes take another 48-72 hours to become fully mature
erythrocytes
-In all, it takes approximately 7 days for a proerythroblast to form mature
erythrocytes.
GEMM
Lymphoid
•GEMM: ___,__,____,____
granulocyte erythroid macrophage megakaryocyte
Erythropoiesis
The length of time between maturation of the polychromatic cell to reticulocyte in the bone marrow is approximately ______
-In the ____, reticulocytes take another _____ to become fully mature
erythrocytes
-In all, it takes approximately ______ for a proerythroblast to form mature
erythrocytes.
5 days
spleen
48-72 hours
7 days
Megakaryopoiesis
-Megakaryocytopoeisis produces _______ which divide to form ________.
CFU-megakryocytes.
the megakaryoblast
Megakaryopoiesis
the megakaryoblast is a (small or large?) sized cell with a (single or double?) nucleus and the cytoplasm is ____
Small
Single
hardly visible.
note that all platelet disorders have ___eased bleeding time , _____ bleeding and _______, platelet count is usually (high or low?) but may be normal in _____ disorders
Incr
mucous membrane
microhemorrhages
Low
qualitative
Eg of microhemorrhages
??
petechiae, epistaxis
Petechiae
Are ???
Tiny round, brown-purple spots due to bleeding under the skin, may be in a small area due to minor trauma, or widespread due to blood-clotting disorder.
Myelopoiesis
-The progenitor cells for the myeloid cells (____ and _____ ) are the highly proliferating potential colony forming cell type _, which proliferates
mitotically to form HPR CFC type __.
monocytes and granulocytes
1
2
The HPP CFC type 2 is capable of differentiating into various types of cells including:
1. _____
2.______
3.______
Granulocyte/Monocyte colony forming cell (GM-CFC)
Eosinophil colony forming cell (Eo-CFC)
Basophil colony forming cell (Ba-CFC)
The GM-CFC can divide mitotically into two types of daughter cells: _____ and ____
granulocyte-CFC and Monocyte-CFC
Granulopoiesis
-Granulocyte CFU, eosinophil CFU, basophil CFU, when they divide, all differentiate into the _____.
myeloblast
The myeloblast derived from Granulocyte CFU, eosinophil CFU, basophil CFU are differentiatable from one another.
T/F
F
They are not
The myeloblast of Granulocyte CFU, eosinophil CFU, basophil CFU are usually the same in morphological characteristics.
T/F
T
This myeloblast of Granulocyte CFU, eosinophil CFU, basophil CFU is usually a (small or large?) cell with ___ nucleus, usually ___ in shape
Large
One
Oval
Lymphopoiesis
-The formation of lymphocytes also starts from the _____ cells, which are capable of differentiating into the lymphoid committed stem cells (LCSCs).
-The LSCCs are capable of diving into two types of cells:
• _-cell lineage
• _-cell lineage
pluripotential stem
B
T
B-Cell Otogeny
-The B-cell lineage (first cell) is often referred to as the ___ cell, which is capable of maturing into the B-cell in transition (BT)
-The BT is capable of dividing and maturing into the ____-cells (__)
pre-B
virgin B ; VBCs
virgin B-cells are are capable of leaving the HIM to join the circulation.
T/F
T
B-cell ontogeny
The mechanism by which different B-cells have different surface membrane
immunoglobulins is due to the phenomenon of ______
-The immunoglobulin molecule usually has ____ and _____ chains.
gene arrangement.
two heavy and two light
The gene coding for the heavy chains is on chromosome ____.
Two genes code for the light chains: The gene for K__ chain is on chromosome __, and that for ____ chain is on chromosome __.
14
Kappa; 2
Lambda; 22
T Cell Otogeny
-T-cells are derived from ____ cells often simply called ___ cells.
pre-thymic ; pre-T-
The lymphoid committed cell is capable of giving rise to the Pre-T-cell.
T/F
T
The preT-cell is a cell that is going to the ___ for its further maturation.
thymus
The thymus gland is a lymphoid aggregate that is found in the ______ and made up of two lobes, each consisting of several lobules.
Each lobule consists of a __ and a ____
anterior mediastinum
cortex
Medulla
T-cell ontogeny
-The ____ cells and the ____cells constitute 94-95% of the total T-cells.
-There are three other subtypes of T-cells that could form in small proportion in
circulation:
• T- ______ cells
• T-_____cells
• T-_____ cells
T-helper
cytotoxic T-
delay-hypersensitivity
suppressor
natural killer
____and ____ cells are the main target of HIV
CD4
helper T
Eosinophils
They Fight against ______
They are highly phagocytic for _______ complexes
They produce _____,_____, etc
helminthic infections
antigen-antibody
histaminase, MBP
Basophils
They Mediate ____ reactions;
They contain _____ and ____
They can synthesize ____ on demand
allergic
heparin and histamine
leukotriene
Basophilia is (common or uncommon?) but can be a sign of _________
Uncommon
myeloproliferative disorders
Mast cells
They Mediate ___ reactions
They contain ____ granules
They are activated by ______
They release _____,_____,_____ and ____
allergic
basophilic
tissue trauma
heparin , histamine, tryptase, eosinophil chemotactic factors
Mastocytosis is (common or rare?) and is associated with ______, increase in serum _____ and _____
Rare
c-KIT mutations
typtase and histamine
Abluminal surface is lined by?
Reticulum/adventitia cells
Adipose cells
Fibroblasts
Marrow/stromal cells
Macrophages
The HIM reticulum cells are responsible for production of ________ that are secreted into the ______ into the space of the HIM
Reticulin fibers
Matrix tissue
The ______ and _______ cells produce collagen fibers
be specific about the collagen fibers
fibroblasts and stromal
Collagen 1,3,4
The cement tissue of the HIM space is often referred to as ________ and include
____
______
_____
____
Aminoglycans
Hyaluronic acid
Heparin sulfate
Chondroitin (4) sulfate
Dermatan
Besides aminoglycans, the cells of the abluminal surface also synthesize and secrete _______ into the HIM space
Hematopoietic growth factors
Hematopoietic growth factors include:
Granulocyte colony stimulating factor
Granulocyte macrophages colony stimulating factor
List proteins that ensure that immature cells do not leave the HIM
Fibronectin
Hemonectin
Vitrectin
Requirement for platelet adhesion
VWF
enough platelets
Glp 1b receptor
Requirement for platelet aggregation
Glp2b/3a receptor
Fibrinogen
Glanzmann’s disease- deficiency of ______
Bernard soulier’s disease- deficiency of ______
Glp 2b/3a receptor
Glp1b receptor
Platelet-platelet =_____
Platelet-sub endothelial structures=_____
Aggregation
Adhesion
MCV=_____
Pcv/ rbc count
MCH=_____
Hb/rbc count
MCHC=_______
Hb/pcv
In megaloblastic anaemia, issue is with ______ and not _____
In microcytic anaemia, issue is with ______ and not _____
Replication; transcription
Transcription; replication
WHERE blood is formed
First 3-4 months of IUL
4th week
4th week-4th month of IUL
End of 4th month
6th month of IUL
7th month of IUL to 24months after birth
Yolk sac
Liver
Liver and spleen
Liver and spleen reduces
Liver and spleen ends
All bones in the body
By the ______ month of IUL, the liver and spleen no longer form blood
Sixth to seventh
When do long bones reduce or stop producing blood
18years of age
Which bones produce forever
Bones at the base of the skull
Pelvic girdle
Shoulder girdle
Vertebral column
Rib cage
By the _____ month, the human bones have been well formed, and cavitations appear to show in the bones. These cavities are usually occupied by the bone marrow. As early as the ______ of intra-uterine life, some haemopoiesis has begun to occur in these cavities.
However, in this early stage, only _______ and _______ occur in the foetal bone marrow.
5th
5th month
granulopoiesis and megakaryopoiesis
sources of oxygen delivery to bone cells?
Haversian capillaries
Haversian capillaries turn back to re-enter the bone marrow space and then
balloon out to become the _____, which drain into the ______ that leave the bone marrow as ______
bone marrow sinusoids
medullary veins
emissary veins.
Separating the luminal from the abluminal surface is a very (thin or thick ?) subendothelial structure made of _____ and ______
Thin
laminin and elastin.
Erythropoiesis occurs within HIM at the level that is closest to the ______
surfaces of the HIM.
Megakaryopoiesis occurs at __________ within the HIM.
abluminal
the same level as erythropoiesis
Inner to the erythropoietic and megakaryopoietic islands within HIM are the ___________
granulopoietic islands.
Lymphopoietic islands are found at the ________ of the HIM.
very core
Progenitor cells renew themselves
T/F
F
A pluripotential stem cell
is capable of renewal or division and differentiation into:
• ____
•______
GEMM
Lymphoid committed stem cell
GEMM:_____
granulocyte erythroid macrophage megakaryocyte
The GEMM can renew itself or divide and differentiate into:
1.____________
2.____________
3. ________________
BFU-E: burst forming unit—erythroid
BFU-MK: burst forming unt—megakaryocyte
HPP-CFC: highly proliferative potential colony forming cells
the first morphologically identifiable erythroid cell in the bone marrow is
the ________ (the first precursor cell).
proerythroblast
The most important morphological identity of a proerythroblast, like other red cell precursors, is the __________
coin circularity of the nucleus.
The cytoplasm of the proerythroblast is completely _____ in colour.
Traces of haemoglobin can be
detected by ______ test.
dark bluish
Feugen
The proerythroblast undergoes division and matures into the __________, which undergoes mitotic division and matures into ________, which in turn divides mitotically into the _________,
which in turn divides into the ________.
basophilic erythroblast type 1
basophilic erythroblast
type 2
polychromatophilic erythroblast
orthochromatophilic erythroblast
The orthochromatophilic eryrthroblast is capable of further mitotic division
T/F
F
The reticulocyte is capable of moving out of the HIM
T/F
T
The reticulocyte travels out of the HIM through the blood to the _____, where it becomes a mature red blood cells.
spleen
The orthochromatophilic erythroblast has (minimal or maximal?) amount of Hb RNA .
Minimal
1 proerythroblast gives rise to ____ reticulocytes.
16
erythroid maturation implies cytoplasmic ______ and _____ of
the nucleus.
haemoglobinization
pyknosis
Howell-Jolly bodies: fragments of _____
Heinz bodies: are usually precipitates of ______
Pappeinheimer bodies: ion-laden _______
Cabot-ring inclusion bodies:_____
red blood cell nucleus
haemoglobin
mitochondria
Telophase strings
Megakaryocytopoeisis produces __________ that divide to
form the ________.
CFU-megakryocytes.
megakaryoblast
the megakaryoblast is a (small or large ?) sized cell with a single nucleus and the cytoplasm is ______
The megakaryoblast is often commonly confused or misidentified as a ______\in the bone marrow. But because it can easily be stained for ______, it can easily be differentiated
Small
hardly visible.
matured lymphocyte
platelet derived growth factor
The _______ is the first morphologically identifiable megakaryocytic cell in the bone marrow.
megakaryoblast
The megakaryoblast undergoes mitotic division, resulting in the single nucleus
becoming ______. But there is usually a failure of _______, such that the
daughter would remain a _______ single cell.
This cell is called the ___-stage
megakaryocyte which also undergoes mitotic division, to form the ____-stage megakaryocytes. Nuclear
differentiation can continue to the
____-N stage megakaryocytes.
binucleated; telophase; binucleated
2-N
4-N
128
The phenomenon of mitosis with failure of telophase is referred to as ________.
endonuclear reduplication
The progenitor cells for the myeloid cells (monocytes and granulocytes) are the
__________, which proliferates
mitotically to form ________.
highly proliferating potential colony forming cell type 1
HPP CFC type 2
The HPR CFC type 2 is capable of differentiating into various types of cells including:
1. _______
2._______
3.________
Granulocyte/Monocyte colony forming cell (GM-CFC)
Eosinophil colony forming cell (Eo-CFC)
Basophil colony forming cell (Ba-CFC)
The macrophage CFC, on mitotic division, becomes a ______ , which is the first morphologically recognisable monocytic cell in the bone marrow.
Which gives rise to ______, which gives rise to the ______.
monoblast
pro-monocyte
monocyte
The monocyte is capable of leaving the HIM environment to join the circulation.
T/F
T
Monocytes
Those that migrate to the liver become ______
• Those that migrate to the spleen are called _______
• Those that migrate to the lungs become the _________
• Those that migrate to the brain become the _____
• Those that move to the lymphatics become the ____.
• Those in the kidneys are known as the _______
• Those that move back to the bone marrow itself are known as the _____ or _____
• Those in the skin are the _______
Kupffer cells.
follicular dendritic cells.
pulmonary alveolar macrophages.
glial cells.
veil cells
mesangial cells.
histiocytes or bone marrow macrophages.
Langerhans cells.
major function of monocyte-macrophage mononuclear system is to mediate:
1. ______
2. ___________
Opsonization
Phagocytosis of damaged cells or foreign cells
The most important characteristic of monocytes is that they express on their
__________________ and are as such able to identify any other cell that have ________ deposited on them.
The _______ on bacterial or microbial surface is recognized as opsonin by the monocyte or monocyte-derived cell.
The monocyte also has, in addition to Fc fragment receptor, the _____ receptor.
membrane FC-fragment receptors
altered immunoglobulins
immunoglobulin
C3b
When a microbial agent is opsonized, the altered Fc fragment, depending on the type of immunoglobulin, is also capable of activating ______, which generate
______, which is deposited on the membrane of the microbial agent.
Thus, the monocyte can identify the microbial agent either by identifying the immunoglobulin with _______ or by ______
complement proteins
C3b
Fc
fragment receptor, or by C3b.
myeloblast is usually a (small or large?) cell with ____ nucleus, usually ____ or ____ in shape but never _______
Large
one
oval or round
point circular
The cytoplasm of the myeloblast is filled with ohh granules .
T/F
F
usually empty of granules
myeloblasts also undergo mitotic division and become or differentiate into a cell known as _______.
promyelocyte
The promyelocyte is also a (small or big?) cell with a (small or big?) , round nucleus
Big
Big
The promyelocyte is usually like the myeloblast.
T/F
T
The major characteristic of
a promyelocyte is that it ________
has large numbers of primary granules.
The promyelocyte undergoes mitotic division and differentiate into a cell called ______.
myelocyte
The myelocyte are usually (smaller or larger?) than the promyelocyte
Smaller
The major characteristic of the myelocyte is that it is at this stage of development that _______.
the secondary granules appear
Difference between the secondary and primary granules
Secondary is more but smaller
Primary is less but larger
Light microscopy is capable
of resolving the size of secondary granules.
T/F
F
The myelocyte has a ____ nucleus and a _____ which many not be visible or prominent
Single round
Nucleoli
myelocyte divides and differentiates into a cell referred to as _______.
metamyelocyte
The morphological characteristic of metamyelocyte is that _________, and the____________. —
the round nucleus of the myelocyte has become indented
The metamyelocyte is incapable of cell division
T/F
With reason
T
Doesn’t have nucleoli
The metamyelocyte only further matures by ________ and when this covers more than 1/3 of the cytoplasm is usually
referred to as ___________
further deepening of its nuclear indentation.
band granulocyte.
myelocytes of granulocytes, eosinophils, and basophils are (same or different?)
from one another
Different
The promyelocytes of neutrophils, eosinophils and basophils are (same or different ?) from one another.
Same
The myeloblasts of neutrophils, eosinophils and basophils are (same or different?) from one another.
Same
For erythropoesis
Myeloid stem cells to ——- to ——- to ———- to ——— to ——— to ———- to ——— to ——- to ———
CFU GEMM
BFU E
CFU E
Proerythroblast
basophilic erythroblast 1
basophilic erythroblast 2
Polychromatic erythroblast
Orthochromatic erythroblast
Erythrocyte
For megakarycytopoesis
From myeloid stem cells to —— to —— to ——— to ———— to ————
CFU GEMM
CFU MEG
megakaryoblast
Megakaryocyte
Platelets
For Granulocytopoesis
From myeloid stem cells to —— to ——- to ——— to ——- to ——— to ——- to ——- to ——- to ——- to ———-
CFU GEMM
HPP-CFC type 1
HPP CFC type 2
CFU GM
CFU G
Myeloblast
Promyelocyte
Myelocyte(N,E,B)
Metamyelocyte(N,E,B)
Band (N,E,B)
N, E, B
For monocytopoesis
From myeloid stem cells to —— to ——- to ______ to _______ to _______ to ______ to _____ to ______ to _______
CFU GEMM
HPP CFC 1
HPP CFC2
CFU GM
CFU M
monoblast
Promonocyte
Monocyte
Macrophages
An average functional platelet has the lifespan of _____
RBC_____
5-7 days
120days
What percentage of the adult marrow is occupied by hematopoetic tissue?
__%
50
______ and _____ expresses immaturity receptors
Collagen
Recticulin
List 2 other Hemopoetic growth factors besides Granulocytes Colony Stimulating Growth Factor and Granulocyte Macrophage Colony Stimulating Growth Factor
Eythropoetic Growth Factor
Thrombopoetic Growth Factor
The homing factors help to _______
attract stem cells to the HIM
List 6 homing factors for stem cells
Laminin
Vimentin
Fibronectin
Haemonectin
Tenascin
Endoglin
The biochemical identification of an erythroid progenitor cell is the appearance of (small or large?) quantity of ________ on the membrane of these cells
Small
ABO blood group antigens
Xterics of proerythroblast
______ nucleus
(Small or large?) cell
_______ cytoplasm
Large
Large
Thin rim of
The most important morphological characteristic of the basophilic erythroblast 1 is ______
Coin circularity of nucleus
Who has bigger cytoplasm
Who has deeper blue color
Proerythroblast or basophilic erythroblast1
basophilic erythroblast1
Proerythroblast
Polychromatic erythroblast has a coin circular nucleus
T/F
T
Orthocromatic erythroblast
_____ sized cell
Cytoplasm is ______ in size and ____ in color
Nucleus is ______ placed
Small
Large; reddish
Eccentrically
Reticulocute leaves the HIM as _______ cell
Anucelated
The basophils are referred to as the ___ cells of the body
Alarm
Mention 2 opsonins
Immunoglobulin and C3b
Stem cell pools are CD ___
34+
Erythroid progenitor cells
Cannot be differentiated
Has morphologic characteristics
Divides to yield both progenitor and precursor cells
Can not be identified under a light microscope
T/F
F
F
F
T
Polychromatic erythroblast
Increased cytoplasm
Stains both blue and red
Stains for both Hb and DNA
T/F
T
T
F(RNA)
Pappeinheimer bodies are seen in ________ anemia
Sideroblastic
Diameter of a discocyte
What is a discocyte
8 microns
Normal erythrocyte
Blood cells are of_______ origin
mesodermal
The blood cells are produced intra vascularly in the liver and yolk sac
T/F
F
extra
Primitive hematopoietic stem cells are found first in the ____,_____,_____
aorta, gonad, and mesonephros
Kidneys also produce blood in the IUL
T/F
F
Kidney doesn’t do shit
Stem cell isn’t resistant to radiation
T/F
T
The nucleus:cytoplasmic ration for proerythroblast is ______
80:1
You shouldn’t be able to see proerythroblast to orthochromatic erythroblast in a peripheral smear.
T/F
If you do, it’s a ______
T
pathology
During Bcell maturation, there is accompanying immunoglobulin production
T/F
T
Bcell-numbers are (low or high?)
Tcell-numbers are (low or high?)
High
Low
Answer with does or does not contain iron
Howell jolly bodies
Basophilic stippling
Heinz
Pappeinheimer
does not contain iron
does not contain iron
Does contain iron
Does contain iron
Heinz is as a result of ______ deficiency
G6PD
In megaloblastic anaemia,
Level of MCV, MCH, and MCHC
large/high
Large /high
Normal or high
In microcytic anaemia,
Level of MCV, MCH, and MCHC
Low
Low
Low
Which of the following is the primary site of hematopoiesis in a fetus at 20 weeks of gestation?
a. Spleen
b. Liver
c. Bone marrow
d. Yolk sac
B
Which of the following interleukin is implicated in early hemato poiesis?
a. IL–1 b. IL–2 c. IL–3 d. IL–4
C
Very high reticulocyte count is seen in:
a. Acute hemorrhage
b. PRCA
c. b-thalassemia
d. Hb E disease
A
in b-thalassemia, there is ineffective erythropoiesis
T/F
T
When there is ineffective erythropoiesis, reticulocyte count increases
T/F
F
does not increase
CD34 is a marker of:
a. Angiogenesis b. T-lymphocytes c. B-Lymphocytes d. Myeloblasts
A
Hematopoiesis in the fetus starts in the:
a. Liver at 12 weeks
b. Liver at 6 weeks
c. Bone marrow at 8 weeks
d. Yolk sac at 4 weeks
B
Which of the following growth factors/cytokines are not of potential clinical value to stimulate hematopoiesis?
a. Thrombopoieitn
b. Erythropoietin
c. GM-CSF
d. Interleukins e. IFN-γ
E
Earliest hemoglobin to appear is ??
Division occurs in orthochromatic erythroblast?
Erythropoietin therapy is most effective in??
Stem cell constitute 1% of bone marrow cells?
Portland
No
Anemia of renal failure
No
Which of the following statements is not true regarding extra medullary hematopoiesis?
a. Occurs in severe hemolytic anemia
b. May rarely be seen in megaloblastic anemia
c. Occurs in fetus
d. Occurs in secondary polycythemia
D