Pancytopenia and Bone Marrow Failure Syndromes

Question 1

does she have pancytopenia?

Answer 1

yes. deficient in more than one cell line: low RBC, and low WBC (neutrophils super low but still organised in NLMEB)

Question 2

clinical presentations of pancyotpenia

Answer 2

very broad

anemia symptoms: easy bruising, fatigue, heavy periods (cause of anemia)

platelets issues: easy bruising, mucosal bleeding, longer bleeding

WBC issues: sinopulmonary infections

Question 3

3 broad reasons for pancytopenia

Answer 3

decreased production

incresed destruction

sequestration

Question 4

why might pancytopenia arise from a production problem?

Answer 4

1. nutritional deficiency (B12/folate)
2. infiltrative marrow – hematological malignancy or nonhematological maligancy, or myelofibrosis
3. stem cell damage – chemo, toxins, aplastic anemia, myelodysplasia

Question 5

causes of normocytic anemia

Answer 5

anemia of chornic inflammatory disease

• early iron def

- bone marrow aplasia, suppression of infiltraiton

• renal failure
• myelodysplasia

- hemolysis or acute blood loss

-sequestration.

Question 6

what test best definitively diagnoses pancytopenia?

Answer 6

bone marrow biopsy

then do microscopy, stains for immunohistochemistry, flow cytometry, karyotype, and DNA analysis

Question 7

if a patient had aplastic anemia resulting in anemia and panctopenia, would retic count be high to compensate?

Answer 7

no, it would be low because there are no proliferative cells in the bone marrow to begin with.

Question 8

outline inherited and acquired causes of aplastic anemia

Answer 8

inherited: fanconis anemia, dyskaratosis congenita.

acquired; radiation and chemo, toxins (benzene), infection like HIB, EBV, parvovirus

• drug reactions like NSAIDs, Antithyroids and antiepileptics etc.
• immune disorders
• thymoma
• pregnancy.

Question 9

aplastic anemias are largely correlated by ___ ___ disorders

Answer 9

autoimmune disorders. if a patient actually has an autoimmune disorder, they can recover cellularity if they receive immune suppression (ex/ methotrexate, predisone, retuximab, cyclosporin)

Question 10

general treatment of aplastic anemia or bone marrow failure resulting in pancytopenia

Answer 10

plus immune suppression or hematopoietic cell transplantation.

immune suppression via ATG (antithrymocyte globulin), steroids, cyclosporine, sometimes growth factors like GSCF

Question 11

how do thrombopoietin receptor agonists help Aplastic anemia

Answer 11

• thrombopoietin receptors are expressed by primitive hematopoietic stem cells
• thrombopoietin potentiates stem cell expansion
• higher repsonse rates but uncertain risk of pormoting leukemia when added to immune suppression.

Question 12

risks of hematopoietic cell transplantation for SAA

Answer 12

• the only curative therapy but toxicities can be limiting
• risk of GvHD– need cyclosporin or steroids or methotrexate or something
• risk of infertility.

Question 13

Case: a 38 yo woman is short of breath and tired. She had a normal delivery of a healthy baby girl 4 months prior. She is finding it more difficult to run long distances. She experiences heavy bruising. PBS shows this:

Answer 13

auer rods present. huge cell is a blast. this is AML.

Question 14

a 58yo woman presents to ER sent in by walk-in clinic with abnomrla blood work after presenting wiht fatigue.

Hb 45, MCV 120, WBC 1.2 with neutrophils 0.8, platelets 60.

interpret her PBS and labs

Answer 14

Hb= very anemic.

Macrocytic anemia

WbC= low, but neutrophils probably are still wihtin proportion.

she’s pancytopenic for sure. platelets also low.

everything is affected- Aplastic anemia? What accounts for MCV? nutritional deficiency?

also, PBS shows hypersegmentation in neutrophil– characteristic of B12 deficiency

CASE ANSWER: B12 folate was low. showcases hematopoietic ineffectiveness.

Question 15

Case: a patient with longstanding prostate cancer is noted to have progressively increasing PSA.

• there is bone pain, on narcotics

CBC: Hb92, MCV 85, Platelets 32, neutrophils 1, with 0.1 myelocytes and 0.1 metamyelocytes seen

• nucleated red blooc cells and tear drop cells seen on PBS.

interpret results and outline Dx/what you’d you next

Answer 15

he is anemia, normocytiv anemia (chronic disease? bleeding?) low platelets, low neutorphils– pancytopenic.

• nucleated reds blood cells and tear drop cells indicate a big malignancy that is causing them to be squeezed out prematurely.
• I’d do a BM aspirate- check for infiltration/metastasis from prostate cancer?
• bone marrow aspirate shows marrow infiltrated with carcinoma cells.

Question 16

summary: