Smear Review Practical

What is the formula for corrected WBC count?

(WBC x 100)/(nRBC + 100)

What does Serum Fe/TIBC assess?

Amount of iron available

What is the relationship between Serum Fe and iron stores?

directly proportional

What is the relationship between sTfR and body iron? Why is this?

1. Inversely proportional

2. The more iron other body cells absorb, the less is available for RBC’s

What is sTfR important for differentiating between?

1. IDA from ACD

2. Higher in IDA

A high percentage of IDA patients also suffer from what ailment?

GI cancers

What is CHr? What is the clinical significance?

1. HGB concentration in retics

2. Sensitive to developing IDA

What are three compensatory mechanisms in IDA?

1. Increased EPO

2. Increased transferrin

3. Increased sTfR

What are the expected smear results for IDA?

1. Poikilocytes

2. schistocytes

3. Targets

4. nRBC’s

5. Increased platelets

6. Elliptocytes

What are other expected lab results for IDA?

1. Increased ZPP

2. Increased RDW

3. Decreased Serum Fe

4. Decreased transferrin saturation

5. Decreased CHr (because decreased retics)

How does ACD develop?

Increased inflammation causes an increase in Hepcidin, which decreases iron absorption. This decreases EPO.

Why is EPO production decreased in ACD?

Because Hepcidin increases iron sequestration, the body assesses its stores and thinks it’s fine. Therefore, no EPO needs to be made.

What can suppress the BM in ACD?

Cytokines

What chemistry results correlate to ACD?

1. Low Serum Fe

2. Low TIBC

3. Normal - increased Fe

4. Normal sTfR

What do IDA and ACD have in common?

Both microcytic, hypochromic

What kind of anemia results from chronic renal failure?

Normocytic, normochromic

Why does chronic renal failure cause anemia?

The kidney can no longer produce EPO, so cells don’t divide.

What two results are expected in anemia from chronic renal failure?

1. Echinocytes

2. Creatinine > 2-3 mg/dL

Lead poisoning causes what kind of anemia?

Acquired sideroblastic w/ hemolytic component

What symptoms of lead poisoning are in children?

1. Anorexia

2. Apathy

3. Anemia

4. Mental & growth retardation

What symptoms of lead poisoning are in adults?

1. Peripheral neuropathy

2. GI problems

3. Anemia

How is heme synthesis impaired in lead poisoning?

Inhibits ALA synthase

What is the treatment for lead poisoning?

Chelation therapy

What is the screening test for lead poisoning?

Lead level

What kind of anemia is sideroblastic anemia?

Microcytic, Hypochromic

What stain is used to visualize sideroblasts in BM?

Prussian Blue stain

What inclusion signifies sideroblastic anemia in PB, and what stain is used to visualize this?

1. Pappenheimer

2. Wright’s Stain

What chemistries correspond to sideroblastic anemia? Which one is compensatory?

1. Increased serum Fe

2. Decreased TIBC (compensatory)

What are two causes of megaloblastic anemia?

1. Vitamin B12 deficiency

2. Folate deficiency

Where does the defect occur in RBC’s in megaloblastic anemia?

Nuclear maturation - impaired DNA synthesis and mitosis

What are three causes of Vitamin B12 deficiency?

1. Pernicious Anemia

2. Diet

3. GI surgery

What are three causes of folic acid deficiency?

1. Poor diet

2. Pregnancy

3. Malabsorption

In megaloblastic anemia, what part of the RBC is more mature?

Cytoplasm

What kind of anemia is megaloblastic?

Macrocytic, normochromic

How are WBCs and PLTs affected in megaloblastic anemia?

1. Leukopenia

2. Thrombocytopenia

In what nutritional deficiency are giant platelets seen?

B12 deficiency

What is the first sign of megaloblastic anemia?

Hyper segmented neutrophils

What inclusions are seen in megaloblastic anemia?

1. Howell-Jolly bodies

2. Cabot rings

What does IF do? What does transcobalamin do?

1. IF absorbs B12

2. Transcobalamin transports B12 in plasma

What causes pernicious anemia?

Autoimmune destruction of parietal cells (IF producers)

What are three symptoms of pernicious anemia?

1. Anemia

2. GI complaints

3. CNS involvement

What tests/results detect pernicious anemia?

1. Increased urine/serum homocysteine and Methylmalonic Acid (MMA)

2. Decreased B12

3. Schilling test

4. Immunoassays for Parietal Cell Ab & Intrinsic Factor Ab

Aplastic anemia is caused by a problem in what cell?

Pluripotent Stem Cell

Pure Red Cell Aplasia is caused by a problem in what cell?

Erythroid Stem Cell

In what order do WBCs, PLTs, RBCs decrease?

1. Neuts decrease first

2. PLTs decrease second

3. RBCs last to decrease

Aplastic anemia is due to what?

Overactive T-cells (autoimmune)

What chemicals cause aplastic anemia?

1. Radiation

2. Benzene

3. Alcohol

4. Chemo

5. DDT

6. Chloramphenicol

What is the cause of primary aplastic anemia?

Fanconi’s anemia (genetic)

What is the cause of secondary aplastic anemia?

Idiopathic

What is the diagnostic criteria for aplastic anemia?

1. BM cellularity < 25%

2. Grans < 0.5 × 10³/uL

3. PLTs < 20 × 10³/uL

4. Anemia

Three features of Fanconi’s anemia

1. Congenital anomalies

2. Aplastic anemia

3. Malignancy risk

What test is used to screen for Fanconi’s anemia?

DEB for chromosomal breaks

What condition is associated with Pure Red Cell Aplasia?

Diamond-Blackfan Syndrome (multiple anomalies, progressive)

HB F is comprised of what two chains?

alpha and gamma

Hemoglobin A is comprised of what two chains?

alpha and beta

hemoglobin A2 is comprised of what two chains?

alpha and delta

How many genes code for HGB? What chromosomes code for HGB?

1. 6 genes

2. Chromosome 11 & 16

What kind of defect is associated with hemoglobinopathies? What about thalassemias?

1. Hemoglobinopathies: qualitative

2. Thalassemias: quantitative

Why does hemolysis occur in hemoglobinopathies?

1. Altered solubility due to crystal formation

2. Instability causes Heinz body formation

The spleen removes what kind of sickle cells?

Irreversible

What causes the anemia in Sickle Cell?

Extravascular hemolysis

What are Sickle Cell crisis symptoms?

1. Pain

2. Low-grade fever

3. Tissue necrosis

4. Infarctions throughout body

5. Aplastic crisis following viral infection

6. Iron overload from transfusions

What are conditions associated with untreated sickle cell?

1. Gallstones

2. Folate deficiency

3. Increased cardiac complications

4. Hyperplastic BM

5. Hair on end X-ray

6. Splenomegaly

7. Dactylitis

8. Hand-foot syndrome

9. Bacterial infections

What lab results correspond to sickle cell?

1. Increased retics

2. Decreased H & H

3. Neutrophilia w/ left shift

4. Thrombocytosis

5. Increased iron stores

What smear results correspond to sickle cell?

1. Sickle and target

2. NRBC’s

3. Spherocytes

4. Basophilic stippling

5. H-J bodies

6. Siderocytes

7. Retics

What are two screening tests for sickle cell?

1. HGB electrophoresis

2. Solubility test

What are three confirmatory tests for Sickle Cell?

1. Capillary electrophoresis

2. Isoelectric focusing

3. High Performance Liquid Chromatography

What lab chemistries correspond to Sickle Cell?

1. Increased indirect bilirubin

2. Decreased haptoglobin

3. Increased uric acid and LDH

4. Increased Ferritin

5. Increased Inflammatory markers

What is the treatment for sickle cell?

Hydroxyurea

HGB C disease causes what kind of anemia?

Hemolytic

Smear findings of HGB C disease

1. HGB C crystals

2. Target cells

3. Retics

Beta Thalassemia causes excess of what HGB chains? How are these chains visible?

1. Alpha

2. Heinz bodies

Thalassemia is what kind of anemia?

Microcytic, Hypochromic

What results would you expect to see in babies?

Normal until beta/gamma switch at 1 year old

Untreated thalassemia causes what?

1. Extramedullary hematopoiesis

2. Bone deformities

3. Retardation

Smear results for beta thalassemia

1. Aniso and poikilocytosis

2. Targets, teardrops, basophilic stippling

3. Increased retics & nRBCs

4. Leukopenia & thrombocytopenia

5. Heinz bodies

What lab result corresponds with thalassemia?

Increased unconjugated bilirubin

Alpha thalassemia causes an excess of what chains?

Beta and gamma

What is the treatment for alpha thalassemia?

1. Transfusion independent but may have hemolytic crisis

2. Splenectomy

Smear result for Alpha thal?

Hb H inclusions (green-blue rasberry golf-ball shape)

What can you visualize with a supravital stain? Wright stain?

1. Supravital: Heinz body

2. Wright: Pappenheimer body

Can hemolysis alone cause anemia?

No

Trisomy 8 causes what two conditions?

1. AML M1

2. MDS

What gene causes M2?

t(8;21)

What gene causes M3?

t(15;17)

What gene causes M4, what is the name of this condition, and what cell is often increased?

1. inv 16

2. AMMoL

3. Eosinophils

What gene causes M5, and what is the name?

1. 11q23

2. AMoL

What gene causes CML? Karyotype?

1. t(9;22)

2. BCR/ABL1

What is the cell breakdown for CML?

Absolute basophilia, < 3% monos, < 3% blasts

What is the treatment for CML?

Gleevec

What is the diagnostic test for CML?

FISH

What gene causes PV, ET?

JAK2V617F

What is the treatment for PV, ET?

Therapeutic phlebotomy or hydroxyurea

What is the treatment for Primary myelofibrosis?

Steroids

What are three causes of Primary myelobfibrosis?

1. Lead poisoning

2. Benzene

3. Radiation

Primary myelofibrosis causes what?

Fibrotic marrow

What lab results accompany Primary Myelofibrosis?

1. Prolonged PT

2. PLT strands/dysfunction

3. Immature WBC’s, especially myelocytes

4. Teardrops, aniso, poikilocytosis

What specific morphology is found in Primary Myelofibrosis?

Giant platelets

Dysplasia is caused by what two genes?

1. 5q-

2. Trisomy 8

What is the most common cytopenia in MDS?

Anemia