Bone Marrow Failure Syndromes

Question 1

Aplastic anemia: definition

Answer 1

The bone marrow fails to produce blood cells -> hypocellular bone marrow, pancytopenia

Question 2

Aplastic anemia: severity

Answer 2

Very Severe: ANC < 200/mcL (0.2 x 10^9/L)

Severe: Two or more of the following:

• ANC 200-500/mcL (0.2-0.5 x 10^9/L)
• platelet count <20,000/mcL (20 x 10^9/L)
• abs reticulocyte count < 40,000/mcL (40 x 10^9/L)

Moderate: ANC 500-1000/mcL (0.5-1.0 x 10^9/L)

Question 3

What percentage of aplastic anemia is inherited?

Answer 3

15-20% of pts

Question 4

In acquired cases of aplastic anemia, rule out the following causes:

Answer 4

• drugs
• infection
• toxins
• radiation exposure

Question 5

MC form of congenital aplastic anemia:

Answer 5

Fanconi’s Anemia

Question 6

Characteristics of Fanconi’s Anemia:

Answer 6

• MC form of congenital aplastic anemia
• Autosomal recessive (X-linked)
• skin defects
• short stature
• hypogonadism
• microcephaly
• urogenital abnormalities

Question 7

Pathophysiology of acquired aplastic anemia:

Answer 7

• Immune dysfunction is thought to be central to pathophysiology
• abnormal expression of suppressor T cells is often present

Question 8

Typical symptoms of aplastic anemia:

Typical lab findings:

Answer 8

• fatigue, exertional dyspnea, worsening angina
• bleeding due to thrombocytopenia, infection due to neutropenia
• CBC shows pancytopneia or more isolated anemia, neutropenia, thrombocytopenia
• peripheral blood smear may show morphologic changes of other disorders ex: myelodysplasia
• ** essential to diagnosis: bone marrow aspirate and biopsy; shows hypocellular marrow with increased fat space and decrease in hematopoeitic elements

Question 9

What does this show?

What disease is this associated with?

Answer 9

• hypocellular marrow with increased fat space, decreased hematopoeitic elements
• seen on bone marrow aspirate and biopsy in aplastic anemia

Question 10

What other tests should you do to work up aplastic anemia?

Answer 10

• cytogenetic analysis to r/o chromosome mutations seen in hypocellular myelodysplastic syndrome
• serum B12, folate, LFTs, HIV, hepatitis, PNH screening (including absence of CD55 and CD59 via flow cytometry)
• chromosomal breakpoint analysis in pts <50 yo to r/o Fanconi’s anemia

Question 11

Treatment of severe aplastic anemia in pts <40 yo:

Answer 11

• if pt has minimal comorbidities and a HLA-compatible sibling, offer allogeneic HSCT as initial therapy (cure rate 75-90%)
• for pts who are not HSCT, immunosuppressive therapy = antithymocyte globulin and cyclosporine, long-term survival in 65-80% of pts

* however relapses can occur in 1/3 of pts, esp as cyclosporine is tapered

Question 12

To minimize risk with transfusions in aplastic anemia:

Answer 12

• Leukodepletion of transfused erythrocytes and platelets
• CMV-negative products should be transfused
• Irradiated blood products to prevent GVHD after transplantation

Question 13

Platelet transfusion goals:

Answer 13

• prophylactic: > 10
• febrile or hypothermic: > 20
• undergoing procedure or spontaneous bleeding: >50
• undergoing intracranial bleeding or intervention: > 100