Hematologic Disorders Flashcards
Blood Cell Formation Process: Contribution to changes in RBC, WBC, platelets
Infection (abnormalities) may affect WBC, Hgb, platelet along with malignancy and chronic diseases
Physiology: ALL blood cells come from Hemocytoblasts
–> Proerythroblast –> Polychromatic erythroblast –> RBC
–> Myeloblast –> Progranulocyte –> Granulocytes (Basophil, Eosinophil, Neutrophil)
–> Lymphoblasts –> Lymphocytes (A granulocytes)
–> Monoblast –> Monocyte (Agranulocytes)
–> Megakaryoblast –> Megakaryocyte –> platelets
- Granulocytes & Agranulocytes are leukocytes
Anemia
- Definition
- What is the first step in treating anemia?
- a complex of signs and symptoms characterized by decreases in numbers of red blood cells (RBCs) or hemoglobin (Hb) or hematocrit (hct) content caused by a variety of sources
- Determining the anemia’s etiology is the first step in treatment
- Look at RBC, hb/hgb, or hct. If any are decreased –> Anemia
- Figure out WHY. It is not normal to be anemic.
Anemia Common Causes
- Acute blood loss
-Chronic low-volume blood loss (small amount of blood loss every day) - Reduced RBC production (deficient production; not making enough RBCs)
- Premature destruction
Anemia - Acute blood loss
1. Mechanism
2. Common clinical presentation
- In adult, >/= 1L acute blood loss before clinically significant drop in hemoglobin (sudden)
This is UNCOMMON in primary care
- In patient with anemia caused by acute blood loss (hemorrhage), clinical presentation usually includes:
- dizziness
- tachycardia
- lowered BP
Anemia - Chronic low-volume blood loss
1. Mechanism
2. What happens to iron in this situation? Why is this disorder significant?
- Chronic low-volume blood loss from erosive gastritis, menorrhagia, GI malignancy, others
- Iron from RBC wasted via blood loss cannot be recycled. Clinically significant blood loss can be as little as a few mL/day.
Note: 85% iron is stored in RBC. Iron deficiency anemia lost iron with RBC
Anemia - Reduced RBC production
Mechanism and Possible etiologies.
- *Nutritional deficit
- vitamin B12
- folic acid
- iron deficiency
- Anemia of chronic disease (ACD); HIV, RA
- Bone marrow suppression
- reduced erythropoietin production (chronic renal failure)
- Also associated with the use of select medications that prevent micronutrient absorption including chronic PPI use (vitamin B12 and iron malabsorption), metformin (vitamin B12 malabsorption)
- If on PPI, you can check vitamin B12 and ferritin
Anemia - Premature destruction
1. Mechanism
2. What is the RBC lifespan?
3. What is hemolysis? Is it common in primary care?
- Hemolysis, shortened RBC lifespan
- Normal RBC lifespan: 90-120 days
Shortened RBC lifespan = part of mechanism in anemia of chronic disease
- Hemolysis is the destruction of red blood cells (erythrocytes). Hemolysis is UNCOMMON anemia etiology in primary care.
What is the red blood cell size?
RBC size is measured by the Mean Corpuscular volume (MCV).
RBC size remains unchanged during TBC’s 90-120 day lifespan.
Wintrobe’s classification of anemia by evaluation of mean corpuscle volume (MCV)
Range: 80-100 fL
Suffix: -cytic
*Microcytic - Small cell: MCV <80 fL
*Normocytic - Normal size cell: MCV 80-100 fL
*Macrocytic - abnormally large cell: MCV >100 fL
Microcytic –> most likely hypochromic
Normocytic –> with normochromic
Macrocytic –> with normochromic
*RBC size remains unchanged during TBC’s 90-120 day lifespan.
What is the red blood cells’ hemoglobin content?
Reflected by mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC)
Hemoglobin: RBC’s color source (-chromic_
Suffix: -chromic
RBC = 90% hemoglobin
*Normochromic = normal color = MCHC 31-37 g/dL (310-370 g/L)
*Hypochromic = pale = MCHC <31 g/dL (<310 g/L)
*Hyperchromic = over color = MCHC >37 (>370 g/L); but some evidence question that RBCs can get any redder
*RBC color remains unchanged during RBC’s 90-120 day lifespan
What is the RDW (RBC distribution width)?
The cells are all the same size, so an increase in RDW = bigger variation in RBC sizes –> evolving micro- or macro- anemia
An index of variation in RBC size
NL = 11.5 - 15%; 0.115 - 0.15 proportion)
Abnormal value = >15% (>0.15 proportion), indicating that new cells differ in size (larger or smaller) when compared with older cells.
Likely earliest laboratory indicators of an evolving microcytic or macrocytic anemia
- Quantification of anisocytosis or abnormal variation in RBC size
In an evolving microcytic anemia, what happens to the MCV and RDW?
The MCV decreases and RDW increases.
In an evolving macrocytic anemia, what happens to the MCV and RDW?
The MCV increases and RDW increases.
What is the reticulocyte percentage?
The body’s normal response to anemia is the attempt correction via increasing the number of young RBCs (reticulocytes).
In a healthy person, reticulocyte (immature RBC) percentage is 1-2%
NL response to anemia = Reticulocytosis (>2%), increase in number, percentage of circulating reticulocytes
If anemic, kidney detected decrease in perfusion –> erythropoietin –> triggers bone marrow to release –> increase reticulocyte
If no reticulocyte –> Bone marrow suppression
Anemia type:
Normocytic normochromic anemia with NL RDW
- Common etiologies
- Description/lab
- Next-step test
- “MR B CALM”
Marrow failure
Renal failure (chronic)
Blood loss (acute)
Chronic disease* (most common etiology)
Aplastic anemia
Leukemia
Metastasis (cancer)
3 Most common:
- Anemia of chronic diseases (RA, kidney, SLE, HIV, etc)
- Acute blood loss/hemorrhage
- Early iron deficiency (normocytic, normochromic, but RDW will be ↑)
- Cells made with sufficient iron, vitamin B12, folate, other micronutrients
- Hgb ↓
- Hct ↓
- RBC ↓
- MCV = NL
- MCHC = NL
- RDW = NL
*If NL MCV, MCHC, RDW, then iron, vitamin B12, folate deficiency is essentially ruled out
Next-step test: Dictated by suspected underlying cause. Again, if NL MCV, MCHC, RDW, then iron, vitamin B12, folate deficiency is essentially ruled out
Anemia type:
Microcytic hypochromic anemia with elevated RDW
- Common etiologies
- Description/lab
- Next-step test
- “LID”
Lead toxicity
Iron Deficiency* (most common; #1 cause)
Ex: Erosive gastritis (IDA) –> iron ↓
Menorrhagia (IDA) –> iron ↓
Plumbism –> lead toxicity
Small cell (microcytic) due to insufficient hemoglobin (hemo = iron, globin = protein) (hypochromic), with new cells smaller than old cells (elevated RDW)
Hgb ↓
Hct ↓
RBC ↓
MCV ↓
MCHC ↓
RDW ↑
Next-step test: Ferritin for estimate or iron stores, lead testing in younger children or if suspected industrial exposure in adult
Anemia type:
Microcytic hypochromic anemia with NL RDW
- Common etiologies
- Description/lab
- Next-step test
Most common etiology: Alpha or beta thalassemia minor (aka thalassemia trait)
Thalassemia (genetic mutation, ↑ RBC count = hemoconcentration)
- Alpha –> Asian/African
- Beta –> Mediterranean/Middle Eastern
Note: At-risk ethnic groups for alpha thalassemia minor: Asian, African ancestry, (A, A, A)
At-risk ethnic groups for beta thalassemia minor: African, Mediterranean, Middle Eastern ancestry (B, A, M, M, E)
Through inherited genetic variation, small (microcytic), pale (hypochromic) cells that are all around the same size (NL RDW)
Hgb ↓
Hct ↓
RBC ↑*
MCV ↓
MCHC ↓
RDW = NL*
Next-step test: Hemoglobin electrophoresis for evaluation of hemoglobin variants
Anemia type:
Macrocytic, normochromic anemia with elevated RDW
- Common etiologies
- Description/Labs
- Next-step test
- FAT RBC
Fetus (pregnancy, rare)
Alcohol excess
Thyroid (hypo)
Reticulocytosis
B12 and folate deficiency* (most common)
Cirrhosis and chronic liver disease
Vit B12 deficiency = pernicious anemia
*#1 and #2 B12 & folate deficiency; get levels, often go hand in hand
Abnormally large (macrocytic) cells due to altered RNA:DNA ratio, hemoglobin content WNL (normochromic)< new cells larger than old cells (elevated RDW)
Hgb ↓
Hct ↓
RBC ↓
MCV ↑
MCHC = NL
RDW ↑
Next-step test: Serum vitamin B12 and RBC folate
Anemia type:
Drug-induced macrocytosis usually without anemia
- Common etiologies
- Description/Labs
- Next-step test
Big cells but no anemia
#1 cause = Excessive alcohol (men >5 drinks/day, women >3 drinks/day)
Alcohol (excess)
Antiepileptic drugs (AED including carbamazepine [Tegretol], phenytoin [Dilantin], methotrexate)
Hgb = NL
Hct = NL
RBC = NL
MCV ↑
MCHC = NL
RDW = NL
Next-step test: Usually not needed. Reversible when use of offending medication is discontinued but usually not a reason to curtail the drug’s use, except for excessive alcohol intake
Tx: Quit drinking
If r/t drug –> do nothing, monitor
1 drink = beer? wine? 80-proof liquor?
Legal limit?
12 oz (0.35 L) of beer
5 oz (0.15 L) of wine
1.3 oz (0.04 L) of 80-proof liquor
Legal limit: 0.08 g/dL blood alcohol concentration (BAC) for operating motor vehicles
General interventions in Anemia
- Treat underlying cause.
Etiology MUST be accurately determined. In severe and/or chronic anemia, consider multiple causes. - Replace needed micronutrients when deficient, such as iron, vitamin B12, and folate.
Micronutrient requirements increase in reticulocytosis. - Epoetin alfa (EPO, Procrit) is indicated. Biologically identical to endogenous erythropoietin, induces erythropoiesis.
Helpful in severe anemia, particularly presence of advancing renal failure. Erythropoietin supply is diminished in CKD, usually beginning when GFR <49 (CKD 3).
Normal GFR: 90-120 mL/min/1.73 m2
Most common type of anemia in the following age group:
1. Childhood
2. During pregnancy
3. Women during reproductive years?
4. Elderly?
- Iron deficiency
- Iron deficiency
- Iron deficiency
- Anemia of chronic disease; 2. Iron deficiency; 3. B12 deficiency (Pernicious anemia)
Anemia:
1. With a person who follows a vegan diet, what would you supplement them with?
- What advice would you give a patient who is taking oral iron therapy to maximize the medication’s effectiveness?
- Vitamin B12, which comes from animal-based products
- Take the medication on an empty stomach
Note: Orange juice –> with folic acid * vitamin D
Which of the following nutritional supplements is potentially associated with increased bleeding risk and should be discontinued at least 7-10 days prior to elective surgical procedure and used with caution with drugs such as aspirin, direct oral anticoagulants (DOAC; rivaroxaban/Xarelto, apixaban/Eliquis) and warfarin/Coumadin?
a. Ginsing
b. Gingko
c. Fish oil
d. Vitamin D
A, B, and C
Discontinue 7-10 days due to ↑ risk of bleeding, careful with coumadin
Beta Thalassemia → Reflects risk with each pregnancy
Father → Beta thalassemia minor/trait with mild microcytic hypochromic anemia + Mother → Beta thalassemia minor/trait with mild microcytic hypochromic anemia
Possible Children:
→ Does NOT have anemia, no genes affected
→ Beta thalassemia minor/trait with mild microcytic, hypochromic anemia
→ Beta thalassemia minor/trait with mild microcytic, hypochromic anemia
→ Beta thalassemia major, severe microcytic anemia; will require transfusion at birth for life
Alpha thalassemia major: clinical presentation
Will not survive outside of utero
Sickle Cell → Reflects risk with each pregnancy
Father → Has sickle cell train, on copy of sickle cell gene + Mother → Has sickle cell train, one copy of sickle cell gene
Possible Children:
→ Does NOT have sickle cell anemia, two copies of unaffected gene
→ Has sickle cell train, one copy of sickle cell gene
→ Has sickle cell train, one copy of sickle cell gene
→ Has sickle cell anemia, two copies of sickle cell gene
White blood count (WBC)
1. Normal range
2. What is leukocytosis? Leukopenia?
3. What can you anticipate in response to infection? Cancer? Viral? Leukemia?
4. What should you always order when ordering WBC?
- 6,000 - 10,000/mm3
- Leukocytosis >10,000; leukopenia <6,000
- Anticipate leukocytosis response in significant bacterial infection such as appendicitis, pyelonephritis, bacterial pneumonia, pelvic inflammatory diseases, cancer, etc.
For viral and leukemia, you may see leukopenia instead.
- Always order WBC with differential!
WBC Cell line (types of WBC)
1. What is the mnemonic to help recall cell lines and order of reporting?
- Nobody Likes My Educational Background
Neutrophils (aka poly or segs) = ~60%
- Bands (0-4%) - Young neutrophil form (if increase, called “left shift”)
- Point of action: Bacteria; increases with bacterial infection
- When cell line elevated → Neutrophilia
Lymphocyte = ~30%
- Point of action: Virus (increases with viral infection)
- When cell line elevated → Lymphocytosis
Monocyte = ~6%
- Point of action: Debris (recovery from bacterial infection)
- When cell line elevated → Monocytosis
Eosinophil = ~3%
- Point of action: Allergens, parasites (worms, wheezes, weird diseases)
- When cell line elevated → Eosinophilia
Basophil = ~1%
- Point of action: Anaphylaxis, not fully understood; allergic, inflammation
- When cell line elevated → Basophilia
Acute hemorrhage
1. Definition. Keep in mind what when considering labs with acute hemorrhage?
2. Classes + presentation
- Bleeding. Initial hgb and hct during active bleeding may be in the normal range if checked immediately. May take up to several hours for the blood loss to show up on the CBC/platelet count.
Reticulocytosis will increase within a few days.
- Classes + % of blood loss + presentation
- I → up to 15% → minimal increase in HR, no change in BP and RR
- II → 15-30% → tachycardia (HR 100-120), tachypnea (RR 20-24), and ↓ pulse pressure
- severe hemorrhage → 30-40% → HR >120, weaker pulse, ↑ RR, ↓ UOP, and AMS; look for s/s shock
Neutropenia
* Lab
1. Most common cause
2. Normal range for ANC
3. Initial evaluation
4. When to have a sense of urgency?
- ANC <1,500/mm3
- Benign ethnic neutropenia (African Americans have a slightly lower ANC) and drug-induced neutropenia
Drugs:
- psychotrophics
- antivirals
- antibiotics
- NSAIDs
- antithyroids
- ACEi
- propranolol
- ANC > 1,000
- CBC with diff
- Blood smear
- health history
- medication, +OTCs, herbs, supplements
- physical exam
- CBC with diff
- If patient is febrile and yo u suspect bacterial infection → urgent eval is important! HIGH risk of bacteremia or sepsis
Vitamin B12 Deficiency
- Clinical presentation
- Lab findings
- Gradual onset of symmetric peripheral neuropathy starting in feet and/or arms;
- numbness
- ataxia (+ Romberg test)
- loss of vibration and positive sense
- impaired memory
- dementia (severe cases)
- Macrocytic anemia, MCV >100 fL
Peripheral smear: - macro-ovalocytes
- some megaloblasts
- multisegmented neutrophils (>5-6 lobes)
Hodgkin’s Lymphoma
1. Definition
2. Clinical Presentation
3. Incidence
4. Hallmark characteristic
- Cancer of the beta lymphocytes (B cells); cancer of the lymph nodes (lemon)
- Night sweats
- Fevers
- Pain with ingestion of alcoholic drinks
- Generalized pruritus with painless enlarged lymph nodes (neck)
- Anorexia
- Weight loss
- Night sweats
- Higher among young adults (20-40 years) or older adults (>60 years); MALES; Whites
- Presence of Reed-Sternberg cells
Non-Hodgkin’s Lymphoma
1. Definition
2. Clinical Presentation
3. Incidence
4. Hallmark characteristic
- Cancer o f the lymphocytes (usually B cells) and killer cells; cancer of the lymph nodes (lemon)
- Night sweats
- Fever
- Weight loss
- Generalized lymphadenopathy (painless)
- Night sweats
- Usually in older adults (>65 years)
- Prognosis is poor.
Multiple Myeloma
1. Definition
2. Clinical Presentation
3. Incidence
4. Hallmark characteristic
- Cancer of the plasma cells
2/4. - Fatigue
- Weakness
- Bone pain that is usually located in the back or chest
- Proteinuria with Bence-Jones proteins
- Hypercalcemia
- Normocytic anemia
- More common in adults >/= 70 years
Thrombocytopenia
1. Definition
2. Normal lab
3. Clinical Presentation
- Platelet count <150,000/uL
- 150,000 - 450,000/uL
- Symptoms usually do not show until platelet count is <100,000/uL.
- easy bruising (ecchymosis, petechiae)
- bleeding gums
- spontaneous nosebleeds
- hematuria
Hemophilia A
1. Definition
2. Incidence/Prevalence
3. Causes
4. Signs & Symptoms
5. Labs
6. Avoid what?
- An X-linked recessive disease that predominately affects males who have only one X chromosome.
- Males with one X chromosome
- Factor VIII deficiency
- Easy bruising
- excessive bruising
- bleeding into joints (hemarthrosis)
- bleeding for several hours to days (circumcision, dental extractions)
- severe bleeding with trauma, heavy menses, and hematuria
- Easy bruising
- aPTT → prolonged
PT = WNL
Fibrinogen = WNL
platelets = WNL - Medicines that increase bleeding (anticoagulants, aspirin, and NSAIDs) should be avoided
hemarthrosis
bleeding into joints
Hemoglobin (Hgb)
Males: 14-18
Females: 12-16
Hematocrit
The proportion of RBCs in 1 mL of plasma
Males: 42-52%
Females: 37-47%
Mean Corpuscular Volume (MCV)
The measure of the average size of the RBCs in a sample of blood
Normal: 80 - 100 fL (femtoliter)
MCV < 80 → microcytic anemia
MCV 80-100 → normocytic anemia
MCV > 100 → macrocytic anemia
Mean Corpuscular Hgb Concentration (MCHC
A measure of the average color of the RBCs in a sample of blood.
↓ in IDA and thalassemia (hypochromic)
Normal in macrocytic and normocytic anemias
Normal: 31-37 g/dL
Mean Corpuscular Hemoglobin (MCH)
Indirect measure of the color of RBCs. Decreased values mean pale or hypochromic RBCs.
↓ in IDA and thalassemia
Normal with macrocytic anemias
Normal: 25 - 35 pg/cell
Total Iron-Binding Capacity (TIBC)
A measure of available transferrin that is left unbound (to iron); used to transport iron in the body.
↑ if not enough iron to transport (IDA)
Normal with thalassemia, vit B12 deficiency and folate deficiency (because iron levels are normal)
Normal: 250 - 410 mcg/dL
Serum Ferritin
The stored form of iron; produced in the intestines and stored in body tissue such as the spleen, liver, and bone marrow. Correlates with iron storage status in a healthy adult.
- Most sensitive test for IDA
↓ in IDA (may be high if patient was misdiagnosed with IDA and erroneously given iron supplementation. AVOID iron supplements before testing serum ferritin level)
Normal or high → thalassemia
Normal: 20 - 400 ng/mL
Serum Iron
Not as sensitive as ferritin; affected by recent blood transfusions
↓ in IDA
Normal to high in thalassemia and macrocytic anemias.
Red Cell Distribution Width (RDW)
A measure of the variability of the size of RBCs in a given sample.
↑ in IDA and thalassemia
Reticulocytes
Immature RBCs that still have their nuclei; slightly larger than RBCs. After 24 hours in circulation, reticulocytes lose their nuclei and mature into RBCs (no nuclei). The bone marrow will normally release small amounts to replace damaged RBCs.
RBCs survive for 120 days before being sequestered by the spleen and broken down by the liver into iron and globulin (recycled) and bilirubin (bile)
Normal: 0.5 - 2.5% (of total RBC count)
Reticulocytosis
> 2.5% of Total RBC Count
An elevation of reticulocytes is seen when the bone marrow is stimulated into producing RBCs; elevated within a few days with supplementation of iron, folate, or vitamin B12 (after deficiency) and after acute bleeding episodes, hemolysis, and leukemia, and with erythropoietin (EPO) treatment.
Chronic bleeding does not cause ↑ of reticulocytes d/t compensation
If no reticulocytosis after an acute bleeding episode (3-4 days), after appropriate supplementation of deficient mineral (iron, folate, or vit B12), or with EPO, rule out bone marrow failure (i.e., aplastic anemia; diagnosed with bone marrow biopsy)
Poikilocytosis
Definition: variable shapes of RBCs
Obtained from peripheral smear
Seem with severe IDA
May be accompanied by anisocytosis
Anisocytosis
Variable sizes of RBCs in peripheral smear; may be accompanied by poikilocytosis
Serum Folate and Vitamin B12
Low values if deficiency occurs → macrocytic anemia aka megaloblastic anemia
Normal folate: 3.1 - 17.5 ng/mL
Normal Vit B12: >250 pg/mL
Hemoglobin Electrophoresis
The GOLD-STANDARD (definitive) test to diagnose hemoglobinopathies such as sickle cell anemia, thalassemias, and many others.
- Normal hemoglobin contains two alpha and two beta chains
Adult norms
Hemoglobin A (HbA): 97%
HbA2: 2.5%
An extremely small amount of <1% of total hemoglobin is fetal hemoglobin (HbF), which is a normal finding
Secondary Polycythemia
Polycythemia:
Hct in adults – F > 48%, M > 52%
Hgb in adults – F >16.5; M >18.5
Chronic smokers and individuals with long-term COPD, long-time residents in high altitudes, or who had EPO treatment – higher incidence of secondary polycythemia (as opposed to primary polycythemia vera)
Primary polycythemia vera
a type of blood cancer. It causes your bone marrow to make too many red blood cells. These excess cells thicken your blood, slowing its flow, which may cause serious problems, such as blood clots.
Glossitis
sore and shiny red tongue; “beefy” tongue
in folate, Vit B12, and iron deficiency
Pica
cravings for nonfoods such as ice or dirt, see in IDA
angular cheilitis
irritated skin or fissures at the corners of the mouth
seen in IDA
koilonychia
spoon-shaped nails
Iron-rich foods
red meat
some beans (black beans)
green leafy vegetables
Treatment of IDA
Ferrous sulfate 325 mg PO TID
How should ferrous sulfate be taken?
Between meals, better absorbed on empty stomach (but usually taken with meals d/t lower GI distress)
Take with vit C or orange juice for better absorption
Increase fiber and fluids; consider fiber supplements for constipation (psyllium, guar gum)
Use cast iron cookware can increase iron source for vegans and vegetarians
Side effects of ferrous sulfate
- constipation
-black-colored stools - stomach upset
Take docusate sodium (colace), a stool softerner (not a laxative); take daily to soften stool
Interactions with ferrous sulfate
Avoid taking iron supplements at the same time as antacids (wait 4 hours before taking iron med to minimize binding), dairy products, quinolones, or tetracyclines (iron binds with these substances and is inactivated; take 2 hours before or after)
When to recheck labs for IDA after treatment with ferrous sulfate?
Hgb and Hct will normalize in 2 months but continue therapy until ferritin level increases to normal levels, which can take 3-6 months
Check reticulocyte count 2 weeks after starting supplementation to check for treatment response (elevated reticulocytes indicates normal bone marrow)
Vitamin B12 sources
All foods of animal origin
meat, poultry, eggs, milk, and cheese
Pernicious Anemia
- Definition
- Etiologies
Exam tip: Just remember, pernicious anemia results in (think labs)
An autoimmune disorder caused by the destruction of parietal cells in the fundus (by antiparietal antibodies) → cessation of intrinsic factor production
- Intrinsic factor is necessary to absorb vitamin B12 from the small intestine
Etiologies
- Dietary insufficiency
- Stomach, small bowel, and pancreatic disorders (e.g., bariatric surgery, gastrectomy, alcoholics, small bowel diseases, strict vegans)
- Infections
- Severe dietary deficiencies of meats and milk (strict vegetarians)
Exam tips:
- Vitamin B12-deficiency anemia
- Macrocytic/megaloblastic normochromic anemia
- neurologic symptoms
Cobalamin
Vitamin B12
Pernicious anemia (Vit B12 deficiency)
Objective findings
- Tingling/numbness of hands and feet
- Neuropathy starts in peripheral nerves and migrates centrally
- Difficulty in walking (gross motor)
- Difficulty in performing fine motor skills (hands)
- Decrease reflexes in affected extremity
- Motor tests: weak hand grip, decreased vibration sense, abnormal Romberg
- 0 none, +1 sluggish, +2 normal reflex
- Inflamed tongue and glossitis (not a specific finding because it is found in other disorders)
- Pallor
- Pale conjunctivae
- glossitis
- other signs of anemia
Pernicious anemia (Vit B12 deficiency)
Treatment Plan
Check for both Vit B12 and folate level (*Both levels must always be checked together)
- Decreased vitamin B12 <150 pg/mL
- Antibody tests: ↑ Antiparietal and anti-intrinsic factor (IF) antibody
- 24-hour urine test for methylmalonic acid (MMA): elevated
- Homocysteine level: Elevated in vitamin B12 and folate deficiency
- Schilling test: Not commonly used now
→ Positive if vitamin B12 (radioactive) excretion is normal after administration of intrinsic factor (but has poor excretion when given vitamin B12 alone)
- Peripheral blood smear: Macrocytosis, hypersegmented neutrophils (>5 or 6 lobes), evidence of defective erythropoiesis
- Check reticulocyte count and CBC ~2 weeks after starting supplementation to check fo treatment response (elevated reticulocytes, hemoglobin/hematocrit will increase)
Pernicious anemia (Vit B12 deficiency)
Medications
- B12 injections 1,000 mcg (1mg) per week for 4 weeks
- Then, monthly B12 injections for lifetime
OR
- Very high oral doses of B12 (1,000-2,000 mcg) by mouth daily
Consider parental replacement for patients with neurologic changes and/or concerns regarding gastric absorption of vitamin B12
Aplastic Anemia
Definition
Caused by destruction of the pluripotent stem cells inside bone marrow and has multiple causes (e.g., radiation, adverse effects of a drug, viral infection). Bone marrow production slows or stops–call cell lines are affected → pancytopenia (leukopenia, anemia, thrombocytopenia)
Aplastic Anemia
Signs and symptoms
Severe case of anemia
- fatigue
- weakness
- skin and mucosa are pale color
- Tachycardia
- systolic flow murmur
- Neutropenia (due to bacterial and fungal infection)
- Thrombocytopenia (large bruising from trauma and bleeding)
**Signs and symptoms depend on severity of aplastic anemia
Aplastic Anemia
Labs
Treatment
Labs
- CBC with diff
- Platelet count
- GOLD STANDARD: Bone marrow biopsy
Treatment
- Refer to hematologist ASAP. If septic → ED
Hemochromatosis
1. Definition
2. Etiology
3. Clinical Presentation
4. Labs
5. Treatment
- Hereditary hemochromatosis – a genetic disorder; the intestinal absorption of iron ↑ → total-body iron overload. Takes decades for significant iron deposition to occur
- Genetic
- Chronic fatigue
- skin hyperpigmentation (bronze)
- swelling of the second and third metacarpal phalangeal joints (fingers)
- generalized joint stiffness
Iron overload → damages organs
- liver: fibrosis, cirrhosis, liver cancer
- heart: cardiomyopathy, heart failure, arrhythmias, death
- Chronic fatigue
- ↑ aspartate aminotransferase (AST)
- ↑ alanine aminotransferase (ALT)
- ↑ high serum ferritin > 500 ng/dL
- ↑ high transferrin saturation
- ↑ aspartate aminotransferase (AST)
- Therapeutic phlebotomy
Sickle Cell Anemia Gold Standard diagnostics
- In the US and territories + District of Columbia require what for every newborn in terms of sickle cell?
- Why are we concern about sickle cell in African Americans (incidence)?
GOLD Standard: Hemoglobin Electrophoresis
- Every newborn be tested for sickle cell disease as part of the newborn screening tests after birth
- Almost 1 out of every 500 African Americans in the US has sickle cell anemia.
Clinical Pearl:
In a person with normal bone marrow, supplementing the deficient substance (iron, B12, folate), when will you expect to see an increase in hemoglobin/hematocrit? When will it be back to normal?
- Expect to see increase starting at 1-2 weeks
- back to normal within 4-8 weeks
Clinical Pearl:
Regarding vitamin B12 levels, what should you keep in mind when collecting levels? What can happen if you miss a vitamin B12 deficiency diagnosis? If so, when should you always check a vitamin B12 level?
Serum vitamin B12 levels may be normal in up to 5% of patients with vitamin B12 deficiency. Do not rely on vitamin B12 alone. Also check antibodies, urine MMA, and etc.
Missing a vitamin B12 deficiency diagnosis can result in irreversible neurologic damage. Any patient complaining of neuropathy or who has dementia should have a vitamin B12 level check.
Folic Acid Deficiency Anemia
- Definition
- Etiologies
- Folate deficiency can result in damage to the DNA of RBCs → macrocytosis (MCV > 100 fl). Body’s supply lasts 2-3 months. Does NOT cause neurologic damage.
- Most common cause: inadequate dietary intake (elderly, infants, alcoholics, overcooking vegetables, low citrus intake)
- Chronic alcoholism
- Poor nutrition
- Pregnancy (physiologic need)
- Gluten enteropathy (malabsorption)
- Drugs (long term) interfering with folate absorption: Phenytoin (Dilantin), trimethoprim-sulfa, metformin, methotrexate, sulfasalazine, zidovudine (Retrovir, azidothymidine)
Folic Acid Deficiency Anemia
1. Clinical Presentation
2. Labs
3. Food sources
- Anemia sign/symptom s(tiredness, fatigue, pallor, reddened/sore tongue, or glossitis).
- NO neuro signs
- If severe anemia → tachycardia, palpitations, angina, or HF - CBC: ↓ Hgb, Hct, ↑ MCV
Peripheral smear: macro-ovalocytes, hypersegmented neutrophils (>5-6 lobes)
Folate level: ↓ low (>4 ng/mL, rules out folate deficiency) - Food sources: leafy green vegetables (kale, collard greens), grains, beans, liver
Folic Acid Deficiency Anemia
Medications
- Childbearing age women considerations
Correct primary cause.
Improve diet.
Stop overcooking vegetables.
- Folic acid PO 1 - 5 mg/day. Treat until RBC indicators and anemia are normal.
Women or childbearing age: it is recommended that all women who may become pregnant take a folic acid supplement, 400 mcg daily, at least 1 month (or longer) prior to conception to enhance normal fetal development and ↓ incidence of neural tube defects. Women who had a previous child with a neural tube defect require higher doses of folic acid, 4 mg daily.
Hemolytic Anemias
- Definitions
A group genetic diseases that decrease red blood cell life span with increased lysis. Acute hemolysis of RBCs causes a drop in hemoglobin and hematocrit, reticulocytosis, and ↑ of indirect bilirubin (causes jaundice)
Two types (for this exam)
- Glucose-6-Phosphate Dehydrogenase Deficiency Anemia (G6PD)
- Sickle Cell Anemia
Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD) Anemia
1. Definition
2. Etiology/Incidence/Prevalence
3. Clinical Presentation
4. Labs/Diagnostics
5. Treatment
- An x-linked recessive genetic disease; M >F (XY chromosome, only one x chromosome; usually asymptomatic unless hemolysis occurs. G6PD protects RBCs against oxidative damage.
Father (+G6PD) + Mother (Unaffected) = daughters 100% carriers, sons 100% not affected
Father (unaffected) + Mother (carrier) = daughters 50% unaffected; 50% carrier, sons 50% unaffected; 50% will have +G6PD
- 5 variants; most common enzymatic RBC disorder in humans.
Males > females in African or Mediterranean descent, some are Asians
Most females are unaffected carriers
Infants are at higher risk of neonatal jaundice
Hemolysis can be triggered by:
- some drugs (primaquine, hydroxychloroquine, sulfa drugs, acetazolamide, dapsone) fava beans, red Egyptian and black henna, fever, acute infections, stress, etc.
- 2-4 days after drug ingestion → hemolytic episode
- acute onset of jaundice
- yellow sclerae
- pallor
- fatigue
- shortness of breath
- tachycardia
- dark urine
- abrupt fall of hgb 3-4 g/dL - CBC, peripheral blood smear (can be mild and self-limiting or severe and life-threatening)
Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD) Anemia
1. Definition
2. Etiology/Incidence/Prevalence
3. Clinical Presentation
4. Labs/Diagnostics
5. Treatment
- An x-linked recessive genetic disease; M >F (XY chromosome, only one x chromosome; usually asymptomatic unless hemolysis occurs. G6PD protects RBCs against oxidative damage.
Father (+G6PD) + Mother (Unaffected) = daughters 100% carriers, sons 100% not affected
Father (unaffected) + Mother (carrier) = daughters 50% unaffected; 50% carrier, sons 50% unaffected; 50% will have +G6PD
- 5 variants; most common enzymatic RBC disorder in humans.
Males > females in African or Mediterranean descent, some are Asians
Most females are unaffected carriers
Infants are at higher risk of neonatal jaundice
Hemolysis can be triggered by:
- some drugs (primaquine, hydroxychloroquine, sulfa drugs, acetazolamide, dapsone) fava beans, red Egyptian and black henna, fever, acute infections, stress, etc.
- 2-4 days after drug ingestion → hemolytic episode
- acute onset of jaundice
- yellow sclerae
- pallor
- fatigue
- shortness of breath
- tachycardia
- dark urine
- abrupt fall of hgb 3-4 g/dL - CBC, peripheral blood smear (can be mild and self-limiting or severe and life-threatening)
Sickle Cell Anemia
1. Definition
2. Etiologies/Incidence/Prevalence
3. Clinical Presentation
4. Labs/Diagnostic
5. Treatment
- A genetic hemolytic anemia (autosomal recessive); takes many forms ranging from sickle cell trait to various forms of full-blown disease. Have an increased resistance to malarial infection; higher risk of death from infection with encapsulated bacteria due to hyposplenia; patients with splenectomy (for other causes) are also at higher risk of death)
- Life expectancy: Males 42 years; Females 48 years
- In US, most commonly found in African Americans (1 in 500 have disease and >2 mil carry trait)
- Higher prevalence in Africa, the Mediterranean, the Middle EAst, and some areas of India
- Mean hgb: 8
- Shortened RBC lifespan: 17 vs 120 days
- Hgb Electrophoresis: 80-100% HbS, ↑ HbF (no HbA) - Most as asymptomatic
If full-blown sickle cell disease (SCD) →
- extremely anemia
- Frequent sickling episodes
- Painful crises (of affected organ systems)
- Necrosis of bones/skin (aseptic necrosis of femoral head, unexplained bone pain)
- Renal/liver dysfunction
- Priapism
- Hemolytic episodes
- Hyposplenism
- Frequent infections - CBC (screening test)
- GOLD STANDARD: Hgb Electrophoresis (HbS) - Genetic counseling if both partners are at risk. If each parent has the train, 1/4 (25%) will have disease. Prenatal screening is available as early as 8-10 weeks gestation via chorionic villus sampling or amniocentesis
- Black patients with normocytic anemia should be screened with peripheral smear, hemoglobin (Hb) solubility testing, and Hgb electrophoresis
- Management by hematologists
- Genetic counseling if both partners are at risk. If each parent has the train, 1/4 (25%) will have disease. Prenatal screening is available as early as 8-10 weeks gestation via chorionic villus sampling or amniocentesis
How can RBC size be described as in exam:
1. MCV <80
2. MCV >100
- microcytic and hypochromic RBCs, small and pale RBCs
- macrocytes or macro-ovalocytes, larger than normal RBCs, or RBCs with enlarged cytoplasms
