Heme - Rbcs

Front 1

Black tarry stools

Back 1

Anemia - GI Bleed

Front 2

No leafy greens

Back 2

Anemia - low folate levels

Front 3

Paresthesias in hands and feet

Back 3

Anemia - Low B12

Front 4

Anemia in African descent?

Back 4

Sickle Cell or G6PD

Front 5

Anemia in Asian descent?

Back 5

Thalassemia

Front 6

What are the four initial labs for an anemia work-up?

Back 6

Complete Blood Count
Reticulocyte Count
Mean Cell Volume
Peripheral Blood Smear

Front 7

How is an uncorr reticulocyte count corrected?

Back 7

(uncorr retic %) x (pt HCT / nml HCT)

Front 8

Are there arbitrary good and bad values for reticulocyte counts?

Back 8

No - reticulocyte counts must be interpreted in light of a patient's condition.

Front 9

What are the causes of a high reticulocyte count?

Back 9

1) Acute blood loss (last 5-10 days)
2) Chronic blood loss
3) Hemolysis

Front 10

What are the causes of a normal MCV anemia?

Back 10

1) Renal Failure (low EPO)
2) Aplastic Anemia
3) Endocrine/Thyroid Disorders
4) Pure RBC Aplasia
5) Myelophthisic Process (CA mets to the marrow)

Front 11

In general, what causes, high MCVs?

Back 11

A high MCV indicates a problem with RBC maturation, such as DNA synthesis

Front 12

Myelodysplasia

Back 12

Myelodysplasia is a diverse collection of neoplastic disorders of hematopoietic stem cells. Formerly called "pre-leukemia"

Front 13

What are some specific causes of high MCV anemia?

Back 13

B12 & Folate Deficiency
Chemotherapy
Myelodysplasia

Front 14

In addition to the standard, what additional labs should be added for a high MCV?

Back 14

1) B12 & Folate
2) Marrow Aspirate

Front 15

Describe the work-up for normocytic, macrocytic and microcytic anemia

Back 15

Front 16

What are three ways to evaluate an Iron deficiency?

Back 16

1) Marrow macrophages won't stain with Prussian blue.
2) Serum ferritin levels fall
3) Increases in Total Iron Binding Capacity

Front 17

What heme precursor level may be evaluated to determine if iron deficiency is affecting red cell maturation?

Back 17

Protoporphyrin

Front 18

What are sideroblasts?

Back 18

Iron granules in the cytoplasm of bone marrow erythroid precursors.

Front 19

What are the two major characteristics of iron deficient anemia?

Back 19

1) Low reticulocyte index
2) Low MCV

Front 20

What work-up should all anemic adult males and anemic post-menopausal females receive?

Back 20

Fecal hemoccult to exclude a malignant GI bleed.

Front 21

What are some of the signs and symptoms of iron deficient anemia?

Back 21

* Smooth, sore tongue
* Spooning of fingernails
* "web" high in esophagus c/dysphagia
* Pica (ice eating)

Front 22

What is the usual treatment for iron deficiency?

Back 22

Ferrous sulfate tablets PO tid. Empty stomach.

Front 23

How do you measure improvement of iron stores after therapy?

Back 23

Ferritin levels will return to normal. This may take months, depending on the deficit.

Front 24

What is the major problem in Anemia of Chronic Inflammation?

Back 24

Iron sequestration. There's enough iron, but the marrow can't use it.

Front 25

What's the molecule thought to be behind ACI?

Back 25

Hepcidin production is thought to increase with inflammation, leading to iron sequestration

Front 26

What's the major issue with anemia and renal failure?

Back 26

EPO production falls of with advanced/chronic kidney disease.

Front 27

Are all blood counts affected in chronic kidney disease?

Back 27

No, platelets and WBCs are usually unaffected.

Front 28

The FDA has posted two black-box warnings for EPO. What are they?

Back 28

1) Risk of cancer progression
2) Risk of stroke

Front 29

What are the two major causes of iron overload?

Back 29

1) Hereditary hemochromatosis
2) Transfusional Iron Overload

Front 30

What screening tests are used for hemochromatosis?

Back 30

Transferrin saturation tests

Front 31

What major complication can arise from hemochromatosis?

Back 31

Hepatocellular carcinoma, especially in patients who develop a secondary cirrhosis.

Front 32

What is the therapy for hemochromatosis?

Back 32

Phlebotomy

Front 33

What patient populations are at risk for transfusion iron overload?

Back 33

Anemias associated with an underproduction of RBCs:
* Aplastic anemia
* Myelodysplasia
* Severe thalassemias

Front 34

What pharmacotherapy is available for iron overload?

Back 34

Deferoxamine

Front 35

Name exemplary cells of the Myeloid Lineage:

Back 35

Neutrophils, Eosinophils, Monocytes, Basophils

Front 36

Name exemplary cells of the Erythroid Lineage:

Back 36

Reticulocytes, Erythrocytes

Front 37

What bone marrow cells give rise to platelets?

Back 37

Megakaryocytes

Front 38

What's the lifespan of a mature RBC? What about a myeloid cell?

Back 38

RBCs = 120 days
Myeloids last less than 24 hours

Front 39

What are the major growth factors of the bone marrow?

Back 39

1) Erythropoietin
2) Thrombopoietin
3) GM-CSF
4) Stem Cell Factor

Front 40

Where is DPG made? What biochemical pathway?

Back 40

2,3-DPG is made in the RBC through the Luebering-Rapaport Pathway.

Front 41

What are some of the major causes of sideroblastic anemia?

Back 41

1) Myelodysplastic syndrome
2) Drugs (Isoniazid et al.)
3) Toxins (lead, EtOH)
4) Hereditary

Front 42

What is the fundamental problem in sideroblastic anemia?

Back 42

Inhibition of heme synthesis.

Front 43

Name the globin constituents of the following:
1) Hg-A
2) Hg-A2
3) Hg-F
4) Hg-H

Back 43

1) Hg-A alpha2-beta2
2) Hg-A2 alpha2-delta2
3) Hg-F alpha2-gamma2
4) Hg-H beta4 (only in alpha thal syndrome)

Front 44

What are some of the symptoms of sideroblastic anemia?

Back 44

Microcytic, anisocytic RBCs. Normal WBCs and PLTs.

Front 45

What's the function of transferrin?

Back 45

Binds extracellular iron. Transferrin/Iron complex is then endocytosed by cells with a Transferrin receptor

Front 46

Proteins modulating intestinal iron importation include:

Back 46

* Iron Regulatory Proteins - block translation of ferritin, ferroportin when iron is low
* Hepcidin - decreases intestinal absorption of iron. Produced by liver in response to inflammation

Front 47

What is the hematocrit cutoff for anemia (female and male)?

Back 47

Female < 36%, Male < 38%

Front 48

What are the two major questions to ask about an anemia?

Back 48

1) Are red cells being produced appropriately?
2) Do the red cells mature normally?

Front 49

What are the three major causes of low reticulocyte counts?

Back 49

1) Marrow is missing something it needs
2) Something's keeping the marrow from doing what it's supposed to do
3) Primary stem cell defect

Front 50

What are the two big cases were we see anemias with high reticulocyte counts?

Back 50

1) Blood Loss
2) Hemolysis (intrinsic, extrinsic)

Front 51

What are the three major types of intrinsic hemolytic anemias?

Back 51

1) Membrane abnormalities (hereditary spherocytosis)
2) Enzyme abnormalities (G6PD...)
3) Hb abnormalities (thal, HbS, HbC...)

Front 52

What are the extrinsic causes of hemolytic anemia?

Back 52

1) Fragmentation hemolysis (DIC, TTP, HUS)
2) Mechanical heart valve
3) Toxins
4) Immunohemolytic anemia

Front 53

What are the three RBC membrane disorders causing hemolytic anemia?

Back 53

1) Paroxysmal Nocturnal Hemoglobinuria
2) Hereditary Spherocytosis
3) Hereditary Elliptocytosis

Front 54

PNH

Back 54

Paroxysmal Nocturnal Hemoglobinurea: membrane disorder with PI membrane anchor. Sensitive to complement and hemolysis. Dx by flow cytometry.

Front 55

Hereditary Spherocytosis

Back 55

Defect in membrane proteins akyrin, spectrin, et al. Cells "sphere up" to minimize surface area.

Front 56

How is Hereditary Spherocytosis diagnosed?

Back 56

Morphology and osmotic fragility test.

Front 57

What does the Direct Coombs Test measure?

Back 57

Complement or antibody bound to RBCs

Front 58

What does the Indirect Coombs Test measure?

Back 58

Circulating antibodies specific to RBCs.

Front 59

Warm reactive antibodies do what?

Back 59

Warm antibodies (IgG) cause extravascular hemolysis. Cells in the spleen or liver pick out the tagged RBCs and destroy them.

Front 60

Autoimmune Hemolytic Anemia (AIHA)

Back 60

Destruction of RBCs caused by antibodies binding to the RBC surface.

Front 61

What are the causes of Warm Reactive AIHA?

Back 61

1) Idiopathic
2) Drug-induced
3) Chronic Lymphocytic Leukemia or Lymphoma
4) SLE

Front 62

What are the three mechanisms of Drug-Induced AIHA?

Back 62

1) Hapten formation (i.e., PCN binding to RBC)
2) Immune Complex Formation (Quinine + AB)
3) Apparent Cross-Specificity (Methyldopa)

Front 63

How is Warm-Reactive AIHA treated?

Back 63

1) Steroid therapy
2) Splenectomy

Front 64

What are the causes of Cold-Reactive AIHA?

Back 64

1) Idiopathic
2) Mycoplasma pneumonia (resolves with infection)
3) Infectious mononucleosis (resolves with infection)
4) Chronic Lymphocytic Leukemia/Lymphoma
5) Drug-induced

Front 65

What are the symptoms of Cold-Reactive AIHA?

Back 65

Acrocyanosis - plugging of the vasculature of the extremities by agglutinated RBCs.

Front 66

What are the three microangiopathic hemolytic anemias?

Back 66

1) Disseminated Intravascular Coagulation
2) Thrombotic Thrombocytopenic Purpura
3) Hemolytic Uremic Syndrome

Front 67

DIC

Back 67

Disseminated Intravascular Coagulopathy: loss of fibrinolysis and consequent hypercoagulation state consumes clotting factors and infarcts small vessels. Therapy is supportive (organ support, transfusions.)

Front 68

What are the general principles of managing hemolytic anemia?

Back 68

1) Folic acid supplements
2) Transfusion
3) Splenectomy = Infection, so ABs if febrile
4) Aplastic Crisis (e.g. parvo on SCA) will require short-term transfusion
5) Monitor reticulocyte counts for improvement

Front 69

What are the compositions for the following hemoglobins: A, A2, F, H, Barts

Back 69

Front 70

A SCA patient suddenly drops her hematocrit to 12% What's the differential dx?

Back 70

1) Sequestration Crisis - sudden, massive splenomegaly due to trapping of RBCs by splenic REs
2) Aplastic Crisis: temporary cessation of erythropoiesis (parvo or bacterial)

Front 71

What neurotransmitter is depleted during a sickle cell crisis? How might this be treated?

Back 71

Nitric oxide is depleted from the vascular endothelium. Sildenafil is a possible treatment.

Front 72

What are the vaso-occlusive complications of SCA?

Back 72

1) Acute pain crisis
2) Dactylitis
3) Splenic sequestration
4) Osteonecrosis

Front 73

What are the hemolytic complications of SCA?

Back 73

1) Pulmonary arterial hypertension
2) Priapism
3) Leg ulcers
4) Bile calculi

Front 74

What are the systemic/long-term complications of SCA?

Back 74

1) Stroke
2) Acute Chest Syndrome
3) Renal Concentrating Problems
4) Retinopathy
5) Sickle Hepatopathy
6) Infection (asplenia, encapsulated organisms)
7) Iron Overload

Front 75

What are the causes of RBC Macrocytosis?

Back 75

1) B-12 / Folate deficiency
2) Drugs (anti-metabolite)
3) Myelodysplasia
4) Liver disease
5) Brisk reticulcytosis

Front 76

Hypersegmented Neutrophils

Back 76

Pathognomonic of megaloblastic anemia. Think B12/Folate, etc.

Front 77

What lab test helps differentiate Folate from B12 deficiency?

Back 77

Serum Methylmalonic Acid
* MMA is high in B12 deficiency
* MMA is normal in Folate deficiency

Front 78

Why would a Thalassemia Major (B0) patient show significant amounts of Hb-A on her Hb electrophoresis?

Back 78

The transfused blood contains a normal complement of Hb-A. Whole blood electrophoresis can't distinguish the two.

Front 79

Do Alpha Thalassemias come in major and minor?

Back 79

No, only Beta Thalassemias are rated major, intermedia, and minor. Alpha Thalassemia pts have either trait or disease.

Front 80

What is the differential diagnosis of pancytopenia?

Back 80

* Acute leukemia
* Aplastic anemia
* marrow replacement with tumor, fibrosis, or granuloma
* Drug side effect
* Myelodysplasia
* Occasionally deficiency of vitamin B12 or folate

Front 81

How do you diagnose pancytopenia?

Back 81

Marrow aspirate and stain.

Front 82

What is the treatment of choice for aplastic anemia?

Back 82

Allogenic bone marrow transplant if a matched donor can be found.

Front 83

What is a shift cell?

Back 83

A young reticulocyte released early from the bone marrow which retains much of its RNA.

Front 84

What two disease classes would give a positive result to an osmotic fragility test?

Back 84

Hereditary Spherocytosis
Autoimmune Hemolytic Anemia

Front 85

What is the cause of pernicious anemia?

Back 85

The majority of cases involve autoimmunity against gastric parietal cells, or antibodies to Intrinsic Factor iteself (or both.)

Front 86

How is Pernicious Anemia diagnosed?

Back 86

Shilling Test: Radio-labelled B-12 is given and absorption tested.

Front 87

What procedures/diseases are commonly associated with Pernicious Anemia?

Back 87

1) Auto-immune disorders (Graves, etc.)
2) Gastric bypass surgery
3) Crohn's

Front 88

What are the causes of a warm autoimmune hemolytic anemia?

Back 88

* Idiopathic
* Drug-induced
* CLL
* Lymphoma
* SLE