Anemia Part II

Question 1

What are RBCs made from?

Answer 1

Iron, Folic Acid, Vitamin B12

Question 2

RBC Measures

1. Hgb, Hct, RBC: Low vs High

Answer 2

Hemoglobin: Low = anemia, High = polycythemia

Hematocrit: Low = anemia, High = polycythemia

RBC: Low = anemia, High = thalassemia

Question 3

Absolute Reticulocyte Count

Answer 3

(RBC count x % reticulocytes)/100

< 100,000/microL reticulocytosis can be excluded

Question 4

Classification of Anemia (3)

Answer 4

By onset

By pathophysiology (Hypoproliferative (RR<40,000) Proliferative (RR>100,000))

By morphology

Question 5

Anemia Classification (causes)

1. Micro
2. Macro
3. Normo

Answer 5

Micro –> almost always due to decreased hemoglobin production

Macro –> usually from a defect in the maturation of RBCs

Normo –> usually from decreased production or increased destruction of RBCs

Question 6

Microcytic Anemias

(4)

Answer 6

Iron Deficiency

Anemia of Chronic Disease

Thalassemias

Sideroblastic Anemia

Question 7

Macrocytic Anemias

1. Megaloblastic (3)

Answer 7

Megaloblastic:

1. Vitamin B12 deficiency
2. Folate Deficiency
3. Drug-related

Question 8

Macrocytic Anemias

1. Non-Megaloblastic (4)

Answer 8

1. Hypothyroidism
2. Liver Disease
3. Alcoholism
4. Myelodysplastic Syndromes

Question 9

Normocytic Anemias

1. Hemolytic (2 types; 3 subtypes)

Answer 9

Hemolytic

1. Intrinsic
   - Membrane Defects
   - Enzyme deficiencies
   - Hemoglobinopathies
2. Extrinsic
   - Autoimmune (warm and cold antbody mediated)
   - Alloimmune
   - Nonimmune (splenomegaly, physical trauma, inefctions)

Question 10

Normocytic Anemias

1. Non-Hemolytic (4)

Answer 10

1. Acute blood loss
2. Aplastic anemia
3. Anemia of chronic disease
4. Chronic renal insufficiency

Question 11

Macrocytic Anemia

1. Causes (Name the main 3 of the 14 total)

Answer 11

BIG FAT RED CELLS

B- B12 malabsorption

I- Inherited

F-Folic acid deficiency

Question 12

Anemia

1. Objective Findings

Answer 12

Tachycardia, Tachypnea, Weight Loss

Pale Skin or Mucous Membranes, Nail Changes

Systolic Murmur (may be heard)

Vibratory Sense Loss (B12 deficiency)

Jaundice

Question 13

Megaloblastic Anemia

1. 3 key findings

Answer 13

MCV > 100 fL

Macroovalocytosis

Hypersegmented neutrophils (5+ lobes)

Question 14

Vitamin B12

1. Total Body Stores
2. Daily Requirement
3. Source
4. Site of Absorption
5. Complications (if deficient)

Answer 14

Total Body Stores: 2-5 mg

Daily Requirement: 1-3 mcg

Source: Animal sources only

Site of Absorption: Terminal Ileum

Complications (if deficient): Megaloblastic anemia, Neurologic Abnormalities

Question 15

Folate (Folic Acid)

1. Total Body Stores
2. Daily Requirement
3. Source
4. Site of Absorption
5. Complications (if deficient)

Answer 15

Total Body Stores: 5-10 mg

Daily Requirements: 50-100 mcg

Source: Animal products, Leafy Vegetables, Nuts, Beans, Fruit

Site of Absorption: Proximal jejunum

Complications (if deficient): Megaloblastic Anemia, Neural Tube Defects

Question 16

How long does it take to become B12 deficient? Folate deficient?

Answer 16

B12 deficiency = 3-4 years

Folate = 3-4 months

Question 17

Vitamin B12 (Cobalamin) Deficiency

1. Causes
2. Incidence
3. Prevalence

Answer 17

1. Causes interference in DNA synthesis (via methylmalonic acid to succinyl Coa and homocystine to methionine reactions)
2. Incidence: women over 60 y/o
3. Prevalence: highest in African and Asian countries

Question 18

What is the most common cause fo Vitamin B12 deficiency?

What causes it?

Answer 18

Pernicious Anemia

-Due to autoantibodies against Intrinsic Factor or atrophy of the cells that produce it

Question 19

Other Causes of B12 deficiency (6)

Answer 19

Diet (Vegans)

Malabsorption

• Gastrectomy
• Zollinger Ellison Syndrome
• Ileal Disease (Crohn’s)
• Drugs (Meformin, Prolonged PPIs for GERD/PUD)
• Fish tapeworm

Question 20

B12 Deficiency

1. Specific Symptoms
2. PE Findings

Answer 20

1. Neurologic –> Paresthesias, Atazia, Change in Mental Status
2. PE Findings –> Decreased Position and Vibratory Sense, Disturbances of Vision, Taste, and Smell, Romberg’s Sign, Babinski’s Sign, Neuropathy

Question 21

B12 Deficiency

1. Diagnostic Labs (6)

Answer 21

1. Need CBC and Retic Count
2. Increased MCV
3. Decreased Retic Count
4. Low B12 level, High serum Methylmalonic Acid and Homocysteine levels (Normal B12 level is 160-1000 ng/L)
5. Peripheral Blood Smear –> Macrocytic RBCs, Anisocytosis, Poikilocytosis, and Hypersegmented Neutrophils
6. Bone Marrow may show megaloblasts, erythroid platelets

Question 22

B12 Deficiency

1. Treatments
2. Responses

Answer 22

1. FIND THE CAUSE
   - B12 1000 mcg SC or IM weekly x1 month, then monthly
   - Sublingual or oral B12 1-2 mg PO if not due to malabsorption
   - Intranasal gel
2. ***Hypokalemia*** (watch for this)

Response: Bone marrow becomes normoblastic in 12 hours, Reticulocytosis in 3-5 days, Hgb normalizes in 2 months

Question 23

B12 Deficiency

1. Implications (3)

Answer 23

1. Demyelination of the posterior spinal cord can occur, causing spastic ataxia and dementia
2. Can lead to infertility in both men and women
3. Can cause cervical smear abnormalities

Question 24

***Post Gastrectomy Patients***

Answer 24

ALL total gastrectomy patients need B12 supplementation

10-15% of partial gastrectomy patients will develop deficiency

Question 25

**Pernicious Anemia** 1. What is it? 2. Results 3. Most common 4. Highly associated with 5. Increased incidence of 6. Average age of onset

Answer 25

1. What is it? --\> **Hereditary Autoimmune disorder-immune-mediated atrophy of gastric parietal cells** 2. Results --\> **Absent gastric acid/intrinsic factor** 3. Most common --\> among **Northern Europeans/African Americans** 4. Highly associated with --\> **Autoimmune Disorders** 5. Increased incidence of --\> **Intestinal Type Gastric Cancer/Gastric Carcinoid Tumors** 6. Average age of onset --\> **60** years old

Question 26

**Pernicious Anemia** 1. Diagnostic Labs

Answer 26

Parietal cell and Intrinsic Factor **antibody positive** (90% and 70%) Serum Gastrin level is **high**; Serum Pepsinogen 1 level is **low** (90%) Gastric biopsy shows **atrpohy of all layers of the body and fundus** with **absence of parietal and chief cells** and _replacement by mucous cells_

Question 27

**Subclinical B12 Deficiency** 1. What is it? 2. Elevated? 3. Treatment

Answer 27

1. Borderline Serum B12 level 2. **Elevated** homocysteine or methylmalonic acid levels 3. No clear guidelines for treatment - MVI with B12 is **not sufficient** - 500-1000 mcg daily is **lowest dose sufficient to correct** \*\*\*Basically treated as if they have B12 deficiency\*\*\*

Question 28

**Folate Deficiency Anemia** 1. Main Causes (5)

Answer 28

1. **Inadequate Dietary Intake --\> Alcoholism, Elderly** 2. Increased needs --\> pregnancy, lactation, prematurity, hemolytic anemia, exfoliative dermiatitis, RA, Crohn's, Dialysis patients 3. Malabsorption --\> Celiac disease, IBS 4. Drugs --\> Methotrexate, Trimethoprim, Dilantin, OCPs 5. Liver Disease

Question 29

**Folace Deficiency Anemia** 1. Signs/Symptoms 2. Objective Findings

Answer 29

1. Similar to B12 deficiency, **but no neurologic abnormalities** - Fatigue, weight loss, lightheadedness, abdominal pain - **Neural Tube Defects** (pregnant women) 2. Objective Findings --\> **Pallor, Glossitis, Jaundice**

Question 30

**Folate Deficiency** 1. Diagnostic Labs

Answer 30

1. Low Hgb with macrocytosis 2. **Low serum (2-15 mcg/L) and RBC folate level** 3. Peripheral smear --\> Hypersegmented neutrophils 4. High homocysteine levels 5. Normal or low B12 level 6. **Normal methylmalonic acid**

Question 31

**Folate Deficiency** 1. Treatment

Answer 31

1. Consume foods rich in folate 2. **Supplement Folate (1-5 mg/day) orally** 3. Correction may take up to 8 weeks, common to continue longer

Question 32

**Aplastic Anemia** 1. Causes 2. Results

Answer 32

1. Bone marrow failure caused by **suppression or injury to _stem cells_** - Bone marrow fails to produce **mature blood cells** 2. **Pancytopenia** results

Question 33

**Aplastic Anemia** 1. Causes (most common)

Answer 33

1. Autoimmune: **Idopathic, SLE** Congenital Chemotherapy, Radiotherapy Toxins Drugs Posti-viral Hepatitis Pregnancy Paroxysmal Nocturnal Hemoglobinuria

Question 34

**Aplastic Anemia** 1. Symptoms (3) 2. PE Findings (3)

Answer 34

**Symptoms:** 1. Weakness/Fatigue (Anemia) 2. Bacterial/Fungal Infections (Neutropenia) 3. Mucosal/Skin Bleeding/**Petechiae** (Thrombocytoepnia) **PE Findings:** 1. Pallor, Petechiae, Purpura 2. HSM (in advanced disease) **Hepatosplenomegaly** 3. \*\*\*Lymphadenopathy and bone pain should **NOT BE PRESENT**\*\*\* (This is actually suggestive of CANCER)

Question 35

**Aplastic Anemia** 1. Diagnostic Labs

Answer 35

**Pancytopenia** (more severe = worse prognosis) **Bone Marrow Biopsy --\>** Will appear **hypocellular** (hardly any cells present)

Question 36

**Aplastic Anemia** 1. Treatment (Mild vs Severe)

Answer 36

**Mild** --\> Supportive Care (Not too many transfusions to avoid sensitizing potential transplant candidates) **Severe** --\> Bone Marrow Transplant

Question 37

What lab findings help you differentiate between **Vitamin B12 Deficiency** and **Folate Deficiency**?

Answer 37

Serum Folate: **B12 Deficiency** --\> Normal **Folate Deficiency** --\> **_Low_** Methylmalonic Acid: **B12 Deficiency** --\> **_High_** **Folate Deficiency** --\> Normal