Anemia: Diminished Erythropoiesis - Aplastic Anemia

Question 1

MCC of anemia among hospitalized patients in the US?

Answer 1

Anemia of chronic disease → systemic inflammation

Question 2

In general, what is anemia of chronic disease?

Answer 2

1. systemic inflammation
2. reduced proliferation of erythroid progenitors
3. impaired iron utilization (it is there, just can’t be used)

Question 3

3 categories of chronic illnesses that cause anemia

Answer 3

1. chronic microbial infection
2. chronic immune disorders
3. neoplasms

Question 4

3 examples of chronic microbial infections that may → anemia

Answer 4

1. osteomyelitis
2. bacterial endocarditis
3. lung abscess

Question 5

Which neoplasms may lead to anemia?

Answer 5

1. lung/breast carcinoma
2. Hodgkin’s

Question 6

Which chronic immune disorders may lead to anemia?

Answer 6

1. RA
2. regional enteritis

Question 7

Anemia resulting from chronic disease is similar to which type of anemia?

Answer 7

iron deficiency anemia

Question 8

lab findings for anemia of chronic disease

Answer 8

1. ⇡ stored Fe
2. ⇣ Fe
3. ⇡serum ferritin
4. ⇣ total iron-binding capacity

(do NOT give oral Fe, but EPO can help)

Question 9

Anemia of chronic disease pathogenesis: due to persistent systemic inflammation →

Answer 9

iron sequestration → IL-6 = increased hepatic hepcidin synthesis

(results in decreased absorption & hematopoiesis; progenitors can’t use the iron)

Question 10

How does iron sequestration help the body fight infection?

Answer 10

keeps it from microbes that might also need it to survive (ex: H. flu)

(hepcidin = structurally similar to defensins)

Question 11

Anemia of chronic disease: tx

Answer 11

1. underlying causes
2. EPO

Question 12

Define aplastic anemia

Answer 12

Chronic primary hematopoietic failure and pancytopenia (no RBC, WBC, or platelets)

Question 13

4 Causes of aplastic anemia

Answer 13

1. Autoimmune
2. Chemical / drug exposure
3. Viral infection
4. Whole body radiation

Question 14

Define fanconi anemia

Answer 14

Rare AR disorder caused by inherited defects in DNA repair complex → hypofunctioning marrow early in life

(also have other congenital anomalies)

Question 15

Congenital anomalies seen with fanconi anemia

Answer 15

1. Hyperplasia of kidney and spleen
2. Bone anomalies → thumbs of radii

Question 16

10-15% of adult-onset aplastic anemia is due to _____

Answer 16

inherited telomerase defects or abnormally short telomerases

Question 17

Inherited telomerase defects → ______(2)

Answer 17

1. premature hematopoietic stem cell exhaustion
2. marrow aplasia

Question 18

Answer 18

Question 19

2 major etiologies of aplastic anemia (pathogenesis)

Answer 19

1. T-cell suppression of hematopoietic stem cells
2. fundamental stem cell abnormality

Question 20

T-cell suppression of hematopoietic stem cells that leads to aplastic anemia is caused by _______.

Answer 20

Stem cell antigenically altered by drug exposure, infection, etc → killing of progenitors

(apoptotic pathways upregulated by IFN-g)

Question 21

Karyotypic abnormalities may transform aplastic anemia into _____ or _____.

Answer 21

• myeloid neoplasms
• AML

Question 22

If ______ is present, it is NOT aplastic anemia

Answer 22

splenomegaly

Question 23

Aplastic anemia has an insidious onset and initial findings depend on ______.

Answer 23

which cell line is affected first

(eventually → pancytopenia)

Question 24

Signs of thrombocytopenia (2)

Answer 24

1. petechiae
2. ecchymoses

Question 25

Anema: s/sx (3)

Answer 25

1. progressive weakness 2. pallor 3. dyspnea

Question 26

Neutropenia s/sx (2)

Answer 26

1. persistent minor infections 2. sudden onset or chills/fever/prostration

Question 27

Bone marrow biopsy of a patient with aplastic anemia will show \_\_\_\_\_; whereas myeloid neoplasms will show \_\_\_\_\_.

Answer 27

* very hypocellular marrow * hypercellular marrow

Question 28

Viral causes of aplastic anemia (3)

Answer 28

1. CMV 2. EBV 3. Herpes Zoster (Varicella)

Question 29

Chemical agents that may cause aplastic anemia (5)

Answer 29

1. Alkylating agents 2. Antimetabolites 3. Benzene 4. Chloramphenicol 5. Inorganic arsenicals

Question 30

5 Idiosyncratic causes of aplastic anemia

Answer 30

1. Carbamazepine 2. Gold salts 3. Mesantoin 4. Phenylbutazone 5. Penicillamine

Question 31

“Dry tap”

Answer 31

marrow aspirates w/little material | (better to do a marrow biopsy)

Question 32

In addition to hypocellular bone marrow, aplastic anemia may show _____ (morphological findings)

Answer 32

1. granulocytopenia 2. thrombocytopenia → mucocutaneous bacterial infections, abnormal bleeding

Question 33

If aplastic anemia patients need multiple transfusions, this could lead to \_\_\_\_\_.

Answer 33

hemosiderosis

Question 34

aplastic anemia tx : _____ or \_\_\_\_\_.

Answer 34

* bone marrow transplant * immunosuppressive tx (if no donor or they are too old) (Blood transfusion if progressing)

Question 35

Morphology unique to myelophthisic anemia (2)

Answer 35

1. Teardrop red cells (aka Dacrocytes) : due to tortuous escape from fibrotic marrow 2. Leukoerythroblastosis: abnormal release of RBC precursors and immature granulocytes

Question 36

Myelophthisic anemia is a form of bone marrow failure where _____ replace normal marrow.

Answer 36

space-occupying lesions

Question 37

In myelophthisic anemia space-occupying lesions replace normal bone marrow leading to

Answer 37

1. Distortion 2. Fibrosis 3. Disturbed the egress of WBC/RBC

Question 38

Most common cause of myelophthisic anemia

Answer 38

metastatic cancer (usually breast, lung or prostate; can be any marrow infiltrative process i.e. granulomatous disease)

Question 39

How does chronic renal failure lead to anemia (3)?

Answer 39

1. Decreased renal EPO synthesis → decreased RBC production 2. Extracorpuscular defect reduces RBC lifespan 3. Platelet dysfunction → Iron deficiency

Question 40

Treatment of anemia in chronic renal failure

Answer 40

EPO + iron

Question 41

Hepatocellular liver disease can be associated with macrocytic anemia due to \_\_\_\_\_\_

Answer 41

decreased marrow function | (toxic, infectious or cirrhotic)

Question 42

Liver failure causes lipid abnormalities → RBC membrane to acquire _____ in the blood.

Answer 42

phospholipids/cholesterol

Question 43

Hypothyroidism can cause a mild _____ anemia

Answer 43

normochromic, normocytic