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
