What are the main 2 diseases that cause stem cell failure?
- Congenital (Fanconi's)
What causes stem cell failure (or aplasia)? What does BM look like?
Aplastic anemia - Empty marrow
What is the condition where the stem cell differentiates but is ineffective? What does BM look like?
MDS - Cellular marrow but cytopenic pt - Dyspoietic cells
What is the condition where the stem cells differentiate but proliferators are out of control? What does BM look like?
MPD (neoplasms) - Marrow is hypercellular - High Hct, WBC, or platelets - Abnl megakaryoctyes---fibrosis, big spleen
What is the condition where the stem cells proliferate out of control but do not fully differentiate? What does BM look like?
Acute myelogenous leukemia (AML) - Cellular marrow with primitive cells (blasts) replace marrow and circulate
What can cause pure red blood cell aplasia?
- Congenital (Diamond-Blackfan) - Parvovirus - Thymoma (autoimmune) - MDS (5q minus syndrome)
T/F: Anemia of CRD involves platelet dysfunction? Why/why not?
True! Bleeding in uremic pts
What may cause reticulocytosis (4)?
- Treatment/resolution of hypo-proliferative anemia (recovery after aplastic crisis, from relative hypoproliferative state like moving from Houston to Denver, or with treatment of iron, folate, or B12 deficiency) - Bleeding (in iron replete pt) - Myelophthisis (marrow w/ fibrosis or tumor) - Hemolytic anemia
What are the main microcytic anemias (4)?
- Iron deficiency anemia - Sideroblastic anemia - Thalassemias - Anemia of chronic disease
What are hepcidin levels/characteristics in the following states: - Anemia of chronic inflammation - Hemochromatosis - Renal failure
- Anemia of chronic inflammation: increased - Hemochromatosis: mutate or downregulated - Renal failure: not cleared; higher levels
What are the key characteristics of Beta thal minor. Hb allotype specifics?
- Decreased beta chain production - Damage to RBCs from excess alpha - Increased A2 on electrophoresis!
What are the key characteristics of Alpha thal minor. Hb allotype specifics?
- Decreased alpha chain production due to gene deletions - Common in Black Americans - Damage due to beta tetramer (hemoglobin H) - Normal hemoglobin electrophoresis
What is a common cause of congenital sideroblastic anemia?
dALA synthase deficiency - Pyridoxine may be effective
What is the inheritance of sideroblastic anemia?
X-linked (some AR)
What is the most important cause of cobalamin (B12) deficiency from an impaired absorption standpoint?
- Gastric bypass - (Also pernicious anemia)
What substances will be elevated in folate deficiency? B12 deficiency?
Folate - Increased homocysteine B12 - Increased homocysteine - Increased MMA
What are some RBC characteristics you will see with liver disease (histo)?
- Target RBCs - Acanthocytes/spur cells
What symptoms/signs are seen with macrocytosis?
- Megaloblastic anemia - Liver disease (target RBCs, acanthocytes/spur cells) - Extreme reticulocytosis - Hypothyroidism - Artifactual: cold agglutinin disease
How do you treat hypoproliferative anemias?
- Iron - B12 - Folate - EPO
What organs are affected in hemochromatosis? How?
- Liver: cirrhosis, hepatoma - Heart: congestive CM, conduction blocks/arrhythmias - Endocrine: diabetes, pituitary (hypogonadism, etc.) - Joints - Skin
What gene commonly is affected in hemochromatosis?
- HFE gene near HLA-A on chrom 6 - Also TfR-2 (ferroportin) can cause the phenotype as well
What could this be? (Pic 1)
- HUS - DIC
When do we commonly see cold agglutination?
- Mycoplasmic infections - Indolent lymphomas
What do EPO levels look like in secondary erythrocytosis vs. primary?
Secondary: EPO high Primary (polycythemia vera): EPO low
What are common translocations in AML?
- t(8;21)- good prognosis - t(15;17)- AML type 3, acute promyelocytic leukemia (response to ATRA, presents with DIC) - inv(16)- AML type 4
What translocation is commonly seen in Burkitt's lymphoma? Gene expressed?
t(8;14) - Bcl-2
What translocation is commonly seen in follicular lymphoma? Gene expressed?
t(14;18) - C-myc BCL6
What are some tie ins/closely related lymphomas and leukemias?
What is Richter's transformation?
CLL transforming into malignant lymphoma
What do they following translocations correspond to? - t(14;18) - t(11;14) - t(8;14) - t(2;8) - t(8;22)
- t(14;18): Follicular lymphomas (NHL), BCl-2 - t(11;14): Mantle cell lymphomas, Cyclin D1 - t(8;14): Burkitt lymphomas, IgH/K/n and c-myc - t(2;8): Burkitt lymphomas, IgH/K/n and c-myc - t(8;22): Burkitt lymphomas, IgH/K/n and c-myc