Hypoproliferative Anemias

Question 1

Definition and common causes of megaloblastic anemias

Answer 1

defect in DNA synthesis leading to characteristic morphology of bone marrow cells

b12 and folate cause

Question 2

hematologic smear features of megaloblastic anemia

Answer 2

MCV elevated as is RDW, have hypersegmented PMNs

Question 3

What reaction does folate help with in DNA synthesis?

Answer 3

homocysteine to methionine

Question 4

what reactions does B12 help with?

Answer 4

homocysteine to methionine
AND
methylmalonic acid to succinic acid

Question 5

What is important about succinic acid and B12 deficiency?

Answer 5

b12 helps make succinic acid which helps myelin synthesis…why B12 deficiency has neurological issues

Question 6

salivary R protein role in B12 absorption

Answer 6

made in salivary glands and binds B12, travels through stomach attached to B12

Question 7

pancreatic enzymes role in B12 absorption

Answer 7

these clip off the salivary R from the B12

Question 8

parietal cells role in B12 absorption

Answer 8

produce intrinsic factor

Question 9

intrinsic factor role in B12 absorption

Answer 9

binds with B12 and this complex is absorbed by cells

Question 10

where is B12 actually absorbed?

Answer 10

in the distal/terminal ileum

Question 11

How does pernicious anemia cause B12 deficiency?

Answer 11

autoimmune response against parietal cells so no IF to attach and help absorb B12

Question 12

How does gastric bypass cause B12 deficiency?

Answer 12

bypassing the parietal cells so not getting IF on the B12

Question 13

what drug decreased B12 absorption in the ileum?

Answer 13

metformin

Question 14

What two GI disorders can inhibit B12 absorption?

Answer 14

celiac and crohns

Question 15

3 other ways leading to B12 deficiency?

Answer 15

pancreatic insufficiency, competition for B12 by tapeworms or bacteria, inactivation of cobalamin by nitrous oxide

Question 16

What are the neurological changes seen in B12 deficiency?

Answer 16

loss of proprioception (falling at night), and loss of vibrational sense

can lead to dementia

Question 17

in addition to hypersegmented PMNs and macrocytosis, what else can you have in lab findings for B12 deficiency?

Answer 17

elevated LDH and bilirubin because of intramedullary hemolysis

Question 18

what are the 3 core lab values that signal B12 deficiency?

Answer 18

low B12
high homocysteine
high methylmalonic acid

Question 19

how long does it take B12 deficiency to develop?

Answer 19

5-10 years…liver has big time stores

Question 20

how to treat pernicious anemia?

Answer 20

intramuscular injection of B12 for life

Question 21

where is folate absorbed? and where do we get folate from?

Answer 21

it is absorbed throughout the small intestine and is found in leafy veggies and bread and cereal products

Question 22

what happens if you have a biliary drain?

Answer 22

enterohepatic circulation is important for folate…leads to folate deficiency within minutes

Question 23

what is the most common form of folate deficiency?

Answer 23

malnutrition

Question 24

when to give extra folate?

Answer 24

pregnancy, hemolytic anemia patients

Question 25

Definition of aplastic anemia

Answer 25

pancytopenia caused by hypocellularity in bone marrow due to deficiency in hematopoietic stem cells

Question 26

5 common secondary causes of Aplastic Anemia?

Answer 26

``` ionizing radiation chemotherapy benzene exposure (dry cleaners) viruses (parvovirus, EBV, hepatitis) paroxysmal nocturnal hemoglobinuria ```

Question 27

clinical presentation of aplastic anemia

Answer 27

anemia leads to weakness and fatigue low platelets cause bruising and oozing low neutrophils cause infections NO SPLENOMEGALY or ADENOPATHY

Question 28

to make a diagnosis of aplastic anemia what 4 things must you rule out?

Answer 28

B12folate deficiency splenomegaly other marrow toxins autoimmune conditions like lupus

Question 29

what test do you run for aplastic anemia?

Answer 29

test for PNH, viruses and drug exposures BONE MARROW BIOPSY

Question 30

what is included in supportive care of aplastic anemia?

Answer 30

transfusions, antibiotics and growth factors

Question 31

what is the definitive therapy for aplastic anemia?

Answer 31

stem cell transplant...

Question 32

if you cannot give stem cell therapy for aplastic anemia, what is the other drug therapy you should give to patients?

Answer 32

T cell directed therapy with cyclosporine and antithymocyte globulin

Question 33

paroxysmal nocturnal hemoglobinemia information

Answer 33

clonal disorder of hematopoietic stem cells that are acquired

Question 34

what is the missing gene for in PNH?

Answer 34

PIG-A enzyme for making glycosyl phosphophatidyl inositol

Question 35

PIG-A makes GPI and GPI is lacking in PNH..what is GPI important for??

Answer 35

anchoring proteins that inhibit complement on RBCs

Question 36

what is the most common clinical manifestation of PNH?

Answer 36

hemolysis of blood cells at night leading to iron loss and hemoglobin lost in urine

Question 37

what is a vascular risk of PNH?

Answer 37

thrombosis in arterial and venous circulation

Question 38

what is the common type of thrombosis in PNH called and what does it affect?

Answer 38

Budd Chiari sydrome leading to thrombosis of hepatic veins and liver failure

Question 39

how to treat PNH?

Answer 39

replenish iron and treat thrombosis treat hemolysis with eculizumab

Question 40

eculizumab treatment for PNH

Answer 40

targets C5 and blocks complement...need to be careful with neisseria infection

Question 41

Fanconi anemia cause and inheritance pattern

Answer 41

mutation in one of many genes dealing with DNA repair it is X linked or autosomal recessive

Question 42

what are clinical signs of fanconi anemia?

Answer 42

``` pancytopenia short stature cafe au lait spots hypo pigmented spots thumb abnormalities microcephaly hypogonadism DD ```

Question 43

what test to use to diagnose fanconi anemia?

Answer 43

the Diepoxybutane (DEB) test that looks for abnormal chromosome breakage in lymphocytes

Question 44

treatment for fanconi anemia?

Answer 44

allogeneic transplant with reduced intensity conditioning

Question 45

dyskeratosis congenita classic triad and other findings

Answer 45

hyperpigmentation of neck, arms shoulders abnormal nails and fingers/toes mucosal leukoplakia it is inherited, and causes bone marrow failure premature grey hair, liver cirrhosis, pulmonary fibrosis

Question 46

dyskeratosis congenita predispositions

Answer 46

acute leukemia and solid tumors

Question 47

dyskeratosis congenita cause

Answer 47

telomere shortening involving one of 9 genes

Question 48

treatment for dyskeratosis congenita

Answer 48

allogeneic transplant with reduced intensity conditioning since have sensitive chromosomes