Hematology - Misc. Material + Broken Spreadsheets

Question 1

Common Hematology Complaints

(list 9)

Answer 1

1. Fatigue
2. Weakness
3. Lightheadedness
4. Pallor
5. Shortness of breath
6. Easy bruising
7. Bleeding problems
8. Frequent illness
9. Palpitations

Question 2

Common “Fatigue” Differentials

(list 5)

Answer 2

1. Anemia
2. Thyroid disorder
3. Insufficient sleep
4. Depression
5. Drug use

Question 3

Important Historical Questions in Eval Anemia

(6)

Answer 3

1. Onset of s/sx, duration indicates chronic disease or acute stressor
2. Nutrition, **especially vegan or vegetarian
3. Sleep patterns
4. Signs of bleeding
   
   • Gums
   • Rectal (bloody stool, assume colon cancer until proven otherwise)
5. Prevoius episodes
6. Associated symptoms

Question 4

Significant Clinical Exam Findings for General Hematologic Disorders

(8 categories, 11 findings)

Answer 4

1. General Impression
   
   • Toxic appearance
2. Skin
   
   • Petichiae
   • Purpura
3. HEENT
   
   • Conjunctiva/gums pale or spontaneously bleeding
   • Tongue c smooth surface
4. Lymphatic
   
   • lymphadopathy
5. Cardiac
   
   • tachycardia
6. Abdo
   
   • splenomegaly
   • hepatomegaly
7. MSK
   
   • bone pain, shaft > joint
8. Neuro
   
   • sensory abnormalities, stocking glove

Question 5

Reasons for total RBC mass decrease

(list 3)

Answer 5

1. Decreased production
2. Abnormal maturation
3. Increased destruction

Question 6

Decreased Hemoglobin and Hematocrit Values

(male and female, just list lower borders)

Answer 6

Males
•Hgb < 13.5 g/dl
•Hct < 41%

Females
•Hgb < 12 g/dl
•Hct < 37%

*Note: these are ranges from Current. Each lab will send you their own reference values to go off of *

Question 7

Anemia Etiology

(2 categories, place microcytic and macrotcytic anemias in each category)

Answer 7

1. Congenital
   
   • Thalasemia
   • Sickle cell disease
2. Acquired
   
   • Dietary
     
     • Iron Def anemia
     • Vit B12 deficiency anemia
     • Folic Acid deficiency

Question 8

Fill in the blanks

Answer 8

See picture below. These are just supplimentary notes

Production defect – will look different depending on cause. Normally shaped RBC but insufficient amount

•Underlying renal or hepatic disease (EPO deficiency)
•Underlying bone marrow disease (cannot actually produce)
•Blood loss in this category; the RBCs will continue to produce at high levels but it is getting lost

Maturation defect – normal amount but not forming correctly

•Thalasemia is a hemoglobinopathy
•Nuclear – RNA and ribosomes are okay. Therefore they can produce cytoplasm as sluggish nucleus growth until the age of production

Survival Defect

•Cells are produced normally but are destroyed early
•Remember, malaria is a parasite
•Drugs can cause hemolysis

Question 9

Most Common Anemia S/Sx

(5 symptoms, 6 signs)

Answer 9

Symptoms

• Fatigue
• Headache (decreased oxygen to brain)
• Exertional dyspnea
• Faintness
• Cold extremities

Common signs

• Tachycardia
• Orthostatic hypotension (less blood, less pressure)
• Pallor
• Jaundice (hemolytic origin)
• Smooth tongue (loss of papillae, nutrient deficiency origin)
• Koilonychia (spoon shaped nails, iron deficiency origin)

Question 10

Microcytic Anemia Disease Acronym

Answer 10

TICS

Thalasemias
Iron Deficiency Anemia
Anemia of Chronic Disease
Siderobastic Anemia

Question 11

Define Iron Deficiency Anemia

Answer 11

Inadequate supply of iron for synthesis of hemoglobin

Most common cause of anemia worldwide, 20% of white female Americans have it

Question 12

Etiology, Iron Deficiency Anemia

(4 general)

Answer 12

Iron absorption >1-1.5 mg/day (after absorption) due to:

1. GI tract bleeding (acute or chronic)
   
   • Often colon cancer in elderly
   • Pt will usually present late in anemia disease progression
2. Chronic asprin or NSAID use
   
   • Think geriatrics taking them for arthritis
3. Low iron intake
4. Increased Fe demands
   
   • Pregnancy/lactation
   • Heavy menstrual bleeding

Question 13

Pathophysiology, Iron Deficiency Anemia

Answer 13

Heme molecule cannot bind oxygen without sufficient iron

Question 14

S/Sx, Iron Deficiency Anemia

(6 signs, 5 symptoms)

Answer 14

Signs

1. Brittle nails
2. Koilonychia (spoon shaped nails)
3. Pale conjunctiva
4. Smooth tongue (typical of all malnutrition anemias)
5. Tachycardia
6. CHF, if untreated for prolonged period

Symptoms

1. Fatigue
2. Weakness
3. Palpitations
4. SOB
5. Pica

Note - Pica is often a board question

Question 15

Differential Diagnoses, Iron Deficiency Anemia

(3, c differntiating factors from iron deficiency)

Answer 15

1. Anemia of chronic disease
   
   • Normal ferritin levels
   • Low Serum Fe
2. Thallesemia
   
   • Sig. low MCV
   • Normal or inc. RBC
3. Sideroblastic anemia
   
   • Inc. serum Fe
   • Inc. % saturation

Question 16

Diagnostic Tests c Results, Iron Deficiency Anemia

(5 tests, listed in order in which they become abnormal in disease progression)

Answer 16

1. CBC – microcytic hypochromic RBC in late anemia progression
2. Serum ferritin – <12 mcg/dl is highly reliable (labs will provide norm. ranges)
3. Serum Fe
4. Total Iron Binding Capacity (TIBC)
5. % Saturation (of Fe in proteins)

Question 17

Medical Treatment, Iron Deficiency Anemia

(2)

Answer 17

Dependent on cause. Ultimately tx underlying reason

1. Ferrous sulfate 325 mg po tid
   
   • Expect normal hematocrit within 3 weeks
   • Expect baseline within 2 mo
   • Continue 6 mo to restore Fe stores in liver and heart
   • *If pt resistant to pills, council on dietary habits *
2. Parenteral Fe (only if oral fails)
   
   • Must be delivered in the hospital due to high risk for anaphylaxis

Question 18

Patient Education/Prevention, Iron Deficiency Anemia

Answer 18

Once levels are returned to normal, practice etiology-specific practices to prevent recurrence

Question 19

Normal Physiology of Iron Ingestion and Transport

Answer 19

Notes -

1. only 10% of the 10-20 mg of dietary iron is absorbed
2. transferrin carries all of the iron from the GI tract

Question 20

Regulation of Iron

(4 general principles)

Answer 20

• Iron absorption
• Iron recycling via marcophages
• Iron loss
• Interaction c several transport PRO
• Transferrin
  
  • Major transporter of Fe in palsma
• Ferritin
  
  • Cellular storage of iron (most important testing is for this)
• Ferroportin
• Hepicidin

Question 21

Serum Ferritin, Serum Fe, TIBC, % Saturation

(define and differentiate)

Answer 21

Serum Ferritin - Amount of stored iron bound to ferritin. This is iron from heart and liver. In iron deficiency anemia this will drop first as a compensatory mechanism

Serum Fe - Concentration of Fe bound to transferrin in plasma. This is the iron immediately availible for use in hemoglobin

TIBC, Total Iron Binding Capacity - Measurement of all proteins availible for Fe binding (empty seats on the bus)

% Saturation - Percentage of proteins saturated c Fe (full seats on the bus)

Question 22

Define Anemia of Chronic Disease

Answer 22

Anemia from inflammatory disease → impaired marrow response to EPO

Question 23

Etiology, Anemia of Chronic Disease

(4)

Answer 23

Associated c chronic diseases that chronically inflame

• Rheumatoid arthritis
• Chronic infection
• Malignancy
• Chronic renal disease (often comorbid c iron and folate deficiency anemias due to RBC loss from hemodialysis; look for ansiocytosis and polychromasia)

Question 24

Pathophysiology, Anemia of Chronic Disease

Answer 24

Disruption originating from macrophages (still in research)

• Macrophage release of cytokines (interleukins)
  
  • IL-6, IL-1β
  • Increased liver production of hepcidin
  • Hepcidin decreases iron absorption form GI epithelium
  • Hepcidin decreases recycled iron export from macrophages due to inhibited ferroportin
• TNF-α, IL-1β
  
  • Inappropriate EPO production in kidney
  • Reduced erythropoiesis in BM

Bone marrow dysfunction due to various causes

• T-cell mediated autoimmune suppression of hematopoiesis (most common)
• Radiation therapy
• Chemotherapy
• Toxins
  
  • Chronic alcohol abuse
  • Lead

Question 25

S/Sx, Anemia of Chronic Disease | (2 signs, 3 symptoms)

Answer 25

_Symptoms_ 1. Fatigue 2. Weakness 3. Symptoms consistent c underlying cause _Signs_ 1. Pallor 2. Signs consistent c underlying cause

Question 26

Differential Diagnoses, Anemia of Chronic Disease (3)

Answer 26

*Other microcytic anemias* 1. Iron deficiency anemia 2. Thallesemia 3. Sideroblastic anemia **Differentiation b/w ACD and Fe Deficiency is often on the boards**

Question 27

Diagnostic Tests, Anemia of Chronic Disease (4, order dependent on hx)

Answer 27

1. CBC – **normochromic** normocytic anemia **_or_ microcytic**, hypochromic anemia (90% of time microcytic) 2. **Serum Fe** – decreased, iron sequestered in macrophages 3. TIBC – decreased 4. **Serum ferritin** – normal or increased, adequate iron in body but hepcidin prevents uptake. _This is the key to differentiating ACD from Fe Deficiency_

Question 28

Medical Tx, Anemia of Chronic Disease | (3 c 1 general plan, cause dependent)

Answer 28

*Generally, treat underlying disease and admin **EPO injections*** 1. Chronic Renal Insufficiency – hemodialysis + EPO (usually admin. together) 2. Malignancy – chemo, radiation, EPO 3. Inflammation (RA) – NSAIDs, DMARDs, EPO

Question 29

Hepcidin | (Origin, 2 Functions)

Answer 29

_Origin_: produced in liver _Functions_: 1. Decrease iron absorption from GI tract after diffusion thru epithelial cells 2. Decrease iron release from marcophages via pheroportin protein blockage *Plays important role in anemia of chronic disease*

Question 30

DMARD (what it stands for, function, 3 examples)

Answer 30

**D**isease **M**odifying **A**ntirheumatic **D**rugs * Function - *Used in combo c EPO to treat RA * Examples* 1. Methotrexate 2. Etanercept (embrel) 3. Infliximab (remicade)

Question 31

Define Thalasemia

Answer 31

Group of hereditary disorders characterized by reduction in synthesis of globin chains (α or β)

Question 32

Etiology, Thalasemias | (2)

Answer 32

* α thal – HBA1 and HBA 2 gene **deletion** causing reduced α-globin chain synthesis. Severity depends on how many present alleles out of 4 * β thal – gene **mutation** terminating DNA chain responsible for β-globin prdctn. May be homozygous (major) or homozygous (minor)

Question 33

Pathopysiology, Thalasemias | (3 steps)

Answer 33

1. Reduced globin chain synthesis 2. Reduced hemoglobin synthesis 3. Hypochromatic mircocytic anemia

Question 34

S/Sx, Thalasemias (1 symptom, 5 alpha signs, 2 beta categories c 4 specifics)

Answer 34

**Symptoms** Typical anemia symptoms c varying severity depending on etiology **Signs** * α Thalasemia, severity depends on number of missing alleles * 4 alleles – normal hbg * 3 alleles – silent carrier, asymptomatic * 2 alleles – “trait” exhibits mild microcytic anemia symptoms * 1 allele – “**Hbg H Disease**” variable severity splenomegaly and pallor * 0 alleles – “**hydrops fetalis**” stillborn fetus * β Thalasemia * Major – symptom development upon unsuccessful Hbg F → Hbg A conversion * Growth failure * Bone deformities * Hepatosplenomegaly * Jaundice * Minor –clinically insignificant microcytic anemia (often discovered in routine physical

Question 35

Differential Dx, Thalasemias | (1, c differentiating factors)

Answer 35

Iron deficient anemia, due to microcytic hypochromatic cells * Higher MCV * Abnormal Fe studies

Question 36

Diagnostic Tests, Thalasemias

Answer 36

1. CBC – * **_Microcytosis out of proportion to degree of anemia_**, RBCs also hypochromatic * MCV 55-70 fl * Poikilocytosis – abnml RBC shape * Target cells * Hgb between 3 and 6 gm/dL 2. **Serum Fe** – normal 3. **Hemoglobin electrophoresis** – definitive dx ![]()

Question 37

Medical Tx, Thalasemias | (severity dependent, 3 txs)

Answer 37

* Mild (α thal trait or β thal minor) – no tx * Hgb H disease – folic acid supplementation * β Thalasemia major * Chelation therapy * Transfusions * Folate supplementation ## Footnote *Note - iron supplimentation is contraindicated and dangerous for β Thal patients!*

Question 38

Surgical Tx, Thalasemias | (1)

Answer 38

Stem cell/bone marrow transplantation for β Thalasemia major

Question 39

Pt Education/Prevention, Thalasemias | (3)

Answer 39

* Highly inheritable, take a thorough hx * Patients usually live to 30's until overcome c heart failure * **Avg patient populations** * α thal – SE Asian * β thal – Mediterranean (Greek, Sicilian)

Question 40

Define Sideroblastic Anemia

Answer 40

Genetic or acquired defective heme synthesis

Question 41

Etiology, Sideroblastic Anemia | (3 causes)

Answer 41

1. Lead 2. EtOH abuse 3. Myelodysplasia (umbrella term)

Question 42

Pathophysiology, Sideroblastic Anemia

Answer 42

Reduced Hgb synthesis due to inability to incorporate heme into protoporhyn. Results in iron accumulation in mitochondria.

Question 43

S/Sx, Sideroblastic Anemia | (1 symptom, 1 sign)

Answer 43

Both consistent c general anemia, no identifying s/sx

Question 44

Differential Dx, Sideroblastic Anemia | (3)

Answer 44

Other microcytic anemias 1. Iron deficiency anemia 2. Thallesemia 3. Anemia of chronic disease

Question 45

Diagnostic Tests, Sideroblastic Anemia | (4 c results)

Answer 45

1. CBC * Normochromatic, micro AND macrocytic anemia * **Basophilic stippling of RBC** – rRNA remnants from impaired hgb synth 2. Serum Fe – increased 3. Lead test - positive in the presence of lead poisoning 4. **Bone marrow biopsy** – diagnostic * Erythroid hyperplasia * Ringed sideroblasts (iron ring within nucleated RBC)

Question 46

Medical Tx, Sideroblastic Anemia | (1)

Answer 46

Manage offending agent

Question 47

Basophilic Stippling

Answer 47

Iron accumulations in mitochondria of RBC as a result of siderblastic anemia ![](). Indicates sufficient iron levels but insufficient distribution to hemoglobin molecules *Note - Basophilic stippling occurs in conditions other than sideroblastic anemia. That is why a bone marrow biopsy is necessary for dx*

Question 48

Cooley's Anemia

Answer 48

Just another name for Beta Thal Major

Question 49

MCV Parameters | (3 categories, numeric parameters)

Answer 49

1. Microcytic \< 80 fl 2. Normocytic 80-100 fl 3. Macrocytic \> 100 fl

Question 50

Fill in the Chart

Answer 50

Question 51

Macrocytic Anemias (list 2, alternate name - kind of-, and general MOA)

Answer 51

_Name_: Megaloblastic Anemias _Included Conditions_: 1. Vitamin B12 deficiency 2. Folic acid deficiency _MOA_: Both B12 and folic acid contribute to DNA synthesis. Without these "ingredients" it takes much longer for erythroblasts to reach nuclear maturity. Meanwhile, RNA responsible for cytoplasmic proliferation is functional. While nuclear progression is retarded, cytoplasmic is not. This creates cells with excess cytoplasm, disturbing erythrocytic strength and oxygen carrying capacity.

Question 52

# Define Vitamin B12 (Cobalamine) Deficiency Anemia

Answer 52

Anemia due to inadequate supply of vitamin B12 for erythrocyte DNA synthesis

Question 53

Etiology, Vitamin B12 (Cobalamine) Deficiency Anemia (4 causes)

Answer 53

1. **Pernicious anemia** (autoimmunity directed at parietal cells) 2. Strict vegan diet (decreased B12 intake) 3. Gastric surgery (bypass parietal cells) 4. Crohn’s Disease

Question 54

Pathophysiology, Vitamin B12 (Cobalamine) Deficiency (2 steps, 3 causes of step 1)

Answer 54

1. Inadequate B12 absorption due to * Lack/dysfunction/bypass of terminal ilium parietal cells responsible for B12 absorption * Lack of intrinsic factor (IF) in parietal cells * Lack of B12 intake 2. Leads to **impaired erythroblast DNA assembly, despite normal cytoplasm proliferation**. Results in fragile macrocytic cells c poor oxygen carrying capacity.

Question 55

S/Sx, Vitamin B12 (Cobalamine) Deficiency Anemia (1 symptom, 4 signs)

Answer 55

**Symptoms** * Typical anemia symptoms **Signs** * **Glossitis c burning sensation** * Neuro dysfunction * **Stocking glove parathesia** * Loss of sensation in position, fine touch, vibration * Clumsiness and ataxia

Question 56

Differential Dx, Vitamin B12 (Cobalamine) Deficiency

Answer 56

Folic Acid Deficiency Anemia ## Footnote *Difference - B12 presence of neurological symptoms*

Question 57

Diagnostic Tests, Vitamin B12 (Cobalamine) Deficiency (4 tests)

Answer 57

1. CBC * Severe anemia * MCV \>100 (macrocytic) * **Hypersegmented neutrophils** * Anisocytosis * Poikilocytosis * **Howell Jolly bodies** 2. **Vitamin B12 assay = decreased** 3. Folate assay = normal 4. Shilling test – antiquated

Question 58

Medical Tx, Vitamin B12 Deficiency Anemia (4)

Answer 58

* Vitamin B12 supplimentation * First month = weekly IM injections * Remainder of life = monthly IM injections, 1000 mcg * *Overwhelming the system c B12 will work even in pts lacking IF. This is due to passive diffusion against the B12 concentration gradient in the event of excess B12 * * Oral cobalamin, 0.5-2 mg/day * Only if pt is lacking B12 intake due to necessity of functional parietal cells to absorb * OTC SQ tablet, not as effective * Nightly nasal spray, not as effective and expensive

Question 59

Pt Education/Prevention, Vitamin B12 (Cobalamine) Deficiency Anemia (2)

Answer 59

1. Hemostalogic correction usually occurs within 6 weeks 2. Neurologic improvement may take up to 18 months, if at all * *Reactivity to tx depends on how long neuro symptoms have been present. Usually, \< 6 mo has positive prognosis*

Question 60

Provider Pearls, Vitamin B12 (Cobalamine) Deficiency Anemia (2)

Answer 60

1. Patients may try to self-treat the glossitis c oral rinses. Since this is a neuro sign the rinces will not work but the bacteria in the mouth will be eliminated, often resulting in Candida 2. Cells may never appear macrocytic. In suspicion of B12 anemia, the most reliable test is the B12 assay

Question 61

Define Folic Acid Deficiency Anemia

Answer 61

Inadequate supply of vitamin B12 for erythrocyte DNA synthesis

Question 62

Etiology, Folic Acid Deficiency Anemia | (4 causes)

Answer 62

1. Poor dietary intake * **Alcoholics** * Anorexia (psychological or secondary to comorbidity like cancer) * Diet low in citrus fruits and dark leafy greens 2. Malabsorption (celiac, Crohn’s) 3. Pregnancy 4. Hemolytic anemia

Question 63

Pathophysiology, Folic Acid Deficiency Anemia

Answer 63

Inadequate folic acid absorption leads to **impaired erythroblast DNA assembly, despite normal cytoplasm proliferation**. Results in fragile macrocytic cells c poor oxygen carrying capacity.

Question 64

S/Sx, Folic Acid Deficiency Anemia (1 symptom, 3 main signs - 1 has 4 aspects)

Answer 64

​_Signs_ 1. Glossitis 2. Vague GI complaints * Anorexia * Nausea * Abd Pn * Constipation/diarrhea 3. **No neurologic s/sx** _Symptoms_ Typical to general anemia

Question 65

Differential Dx, Folic Acid Deficiency Anemia (1)

Answer 65

B12 (Cobalamine) deficiency anemia ## Footnote *It is likely folic acid if there are no neuro s/sx and the pt is an alcoholic *

Question 66

Diagnositc Tests, Folic Acid Deficiency Anemia (3)

Answer 66

* CBC * Severe anemia * MCV \>100 (macrocytic) * Macro-ovalocytes * **Hypersegmented neutrophils** * **Howell Jolly bodies** * Vitamin B12 assay = normal * **Folate assay = decreased**

Question 67

Medical Tx, Folic Acid Deficiency Anemia (3)

Answer 67

1. Folic acid 1 mg po daily 2. Avoid alcohol 3. Avoid folic acid antagonists, or prophylactically supplement if avoidance is unreasonable * Methotrexate * Trimethoprim sulfate (antibiotic) * Phenytoin (dilantin)

Question 68

Pt Education/Prevention, Folic Acid Deficiency Anemia

Answer 68

Pregnant women c folic acid anemia may lead to fetuses c neural tube defects. Recommendation: start folic acid tx 3 mo before conceiving

Question 69

Vitamin B12 (Cobalamine) Sources

Answer 69

**Animal products** 1. Red meat 2. Poultry 3. Dairy *The body also produces some B12 and stores amounts to last for months (2-6) before s/sx of B12 deficiency anemia present*

Question 70

Define Pernicious Anemia

Answer 70

Anemia resulting from lack of intrinsic factor production in the stomach. This decreases Vitamin B12 (cobalamine) absorption in the ilium, eventually causing Vitamin B12 Deficiency Anemia

Question 71

Stocking Glove Deformity | (define, 2 associated conditions)

Answer 71

Neurologic condition demonstrated by parasthesia on the hands and feet in the shape of a glove or stocking. *Associated Conditions* 1. Vitamin B12 (Cobalamine) Deficiency 2. Diabetic Neuropathy

Question 72

Hypersegmented Neutrophil

Answer 72

Neutrophil c \> 8 nuclear lobuoles, present in megaloblastic anemias. Exact MOA for this finding is up for debate but it is the landmark for this group of anemias.

Question 73

Howell Jolly Bodies | (define, significance in hemotology)

Answer 73

**Definition**: RBC inclusion bodies representing DNA fragments of dysfunctional nucleus. Cells with Howell Jolly Bodies in the presence of megaloblastic anemia may also be macrocytic **Signif**: Identifying factor for megaloblastic anemias

Question 74

Dietary Folic Acid Sources | (2)

Answer 74

1. Dark, leafy greens 2. Citrus fruits

Question 75

Hemolytic Anemia Classifications | (2, 3 disorders per category)

Answer 75

1. Intrinsic * Cell membrane disorders (spirocytosis) * Enzyme system disorders (for cell membrane formation) * Hgb disorders 2. Extrinsic * Autoimmune disorders (commonly RA, lupus) * Microangiopathic hemolytic disorders (shows RBC fragments) * Malaria

Question 76

What do greasy stools indicate?

Answer 76

Folic Acid Deficiency Anemia, when in conjunction c other anemia s/sx

Question 77

Common Dx Tests and Results for Hemolytic Anemias (4)

Answer 77

*Note - these results are often encountered after obtaining a fairly normal CBC* 1. Decreased haptoglobin, usually * Hemoglobin carrier. If you have RBC destruction then more of these are full so the levels are low 2. Increased indirect bilirubin * Bliiverdin is precursor for blilrubin. This is free bilirubin in the blood, unbound 3. Increased total bilirubin * Includes indirect bilirubin and direct bilirubin – bound bilirubin 4. Increased LDH * Lactate dehydradinase – released from broken RBC

Question 78

Intrinsic Hemolytic Anemias | (define, list 3)

Answer 78

**Definition**: RBC destruction is due to decrease in the RBC itself **Intrinsic Hemolytic Anemias**: 1. Hereditary Spherocytosis 2. G6PD Deficiency 3. Sickle Cell Disease

Question 79

Define Hereditary Spherocytosis

Answer 79

Genetic hemolytic anemia due to fragile spherical erythrocytes

Question 80

Etiology, Hereditary Spherocytosis

Answer 80

Autosomal dominant disorder

Question 81

Pathophysiology, Hereditary Spherocytosis (3 steps)

Answer 81

1. RBCs produce deficient number of membrane PRO 2. RBC form c decreased surface:volume ratio and fragile spherical shape (spherocytes) 3. Decreased flexibility causes hemolysis when passing through spleen

Question 82

S/Sx, Hereditary Spherocytosis | (2 symptoms, 3 signs)

Answer 82

**Symptoms** * RUQ Pain * Family history **Signs** * Jaundice noted by scleral icterus * Gallstones c predominating bilirubin crystal composition * Palpable spleen

Question 83

Differential Dx, Hereditary Spherocytosis (5)

Answer 83

Other hemolytic anemias 1. G6PD deficiency 2. Sickle cell disease 3. Autoimmune hemolytic anemia 4. Microangiopathic hemolytic anemia 5. Aplastic anemia

Question 84

Diagnostic Tests, Hereditary Spherocytosis (4 tests)

Answer 84

* CBC * Variable anemia c aplastic crises concurrent c BM stress * Dimorphic population including spherocytes * **Microcytosis c increased MCHC (\>36 g/dl)** * Reticulocyte count increased * Indirect bilirubin increased * **Osmotic fragility test – positive **

Question 85

Medical Tx, Hereditary Spherocytosis

Answer 85

Folic acid x 1 mg/d *Explaination - * * *Folic acid helps inc RBC count by quickening nuclear maturation* * *Usually these pts live c a dimorphic cell population. Folic acid helps to push dimorphism to favor normal RBCs*

Question 86

Surgical Tx, Hereditary Spherocytosis

Answer 86

Splenomegaly

Question 87

Spherocyte (definition, conditions creating spherocytes)

Answer 87

Fragile, extra round RBC that is formed due to a decreased SA; lacking cell membrane to make bionclave disk. These cells are very fragile and often lyse with very little physical stress (ex - entering the spleen). Due to the decrease in SA, spherocytes posess deficient oxygen carrying capacity **Present in**: 1. Hereditary spherocytosis 2. Following a blood transfusion

Question 88

Bilirubin and Hemolytic Anemias | (2 signs, their MOAs)

Answer 88

1. Scleral icterus (jaundice seen in the eyes) * Excess hemolysis * Increased bilirubin secretion to aid in RBC byproduct excretion * Excessive bilirubin circulation in bloodstream * Jaundice * Scleral icterus 2. Cholelithiasis * Excess hemolysis * Increased bilirubin secretion to aid in RBC byproduct excretion * Excessive bilirubin traveling from bile duct * Occlusion of bile ducts * Gallstones

Question 89

Osmotic Fragility Test | (Indication, Procedure)

Answer 89

**Indication**: suspected presence of spherocytes **Procedure**: Place RBC in hypotonic soln •Normally, cell membranes can withstand this and swell •Spherocytes cannot stand the swelling and they burst

Question 90

Splenectomy in Hemolytic Anemia | (explain this tx)

Answer 90

The spleen is usually the site of hemolysis of fragile cells associated c hemolytic anemia. Splenic elimination allows for these cells to persist and carry O₂, even if their carrying capacity is less than healthy RBCs Liver can compensate and filter blood in the absence of the spleen

Question 91

Define G6PD Deficiency

Answer 91

Episodic hemolytic anemia due to glucose 6 phosphate dehydrogenase deficiency

Question 92

Etiology, G6PD Deficiency (1 cause, 3 stressors - 1 c 4 specifics)

Answer 92

Y-linked disorder, common among 10-15% of African black men who encounter an oxidative stress: * Infection (viral or bacterial) * Hypoxia (often from pneumonia) * Drugs * **Quinidine** * **Sulfa drugs (trimethoprim sulfa)** * **Nitofurantoin (macrodantin)** * **Asprin** * *Many other drugs, but you will usually have the ability to look these up in clinic. These are just the most commonly used ones* **Board Question - sulfa drugs and G6PD crisis**

Question 93

Pathophysiology, G6PD Deficiency | (5 steps)

Answer 93

1. RBC lose G6PD as they age 2. Lack of G6PD decreases RBC’s ability to deal c oxidative stress (crisis) 3. Oxidized hgb denatures to form **Heinz bodies** 4. Heinz bodies formation damages the membrane 5. Damaged RBCs removed by spleen

Question 94

S/Sx, G6PD Deficiency | (2 symptoms, 3 signs)

Answer 94

**Symptoms** *Asymptomatic until oxidative stress. Stress induces* 1. SOB 2. Organ specific hypoxia complaints **Signs** *Without signs until oxidative stress. Stress induces* 1. Hypoxia * SOB * Cyanosis 2. Jaundice noted by scleral icterus 3. Organ specific s/sx related to hypoxia

Question 95

Differential Dx, G6PD Deficiency | (5)

Answer 95

Other hemolytic anemias 1. Hereditary spherocytosis 2. Sickle cell disease 3. Autoimmune hemolytic anemia 4. Microangiopathic hemolytic anemia 5. Aplastic anemia

Question 96

Diagnostic Tests, G6PD Deficiency | (4)

Answer 96

* CBC and blood smear * **Heinz bodies **abnl RBC shape from hemoglobin denaturation in crisis/age * **Bite cells **Heinz bodies with the inefficient proteins removed (by the spleen) * Reticulocyte count increased * Indirect bilirubin increased * G6PD assay * **During crisis – non revealing **(crisis stimulates RBC production. When first formed, cells have greater [G6PD]) * Weeks after crisis – deficient (this is when the cells age and rapidly lose G6PD)

Question 97

Medical Tx, G6PD Deficiency

Answer 97

Remove source of hypoxia ## Footnote *This could be emergent depending on crisis serverity *

Question 98

Define Sickle Cell Disease

Answer 98

Chronic illness resulting in anemia from abnormal hemoglobin

Question 99

Etiology, Sickle Cell Disease

Answer 99

Autosomal recessive genetic disorder where **v****aline substitutes for glutamine on beta chain**. Most common in Africans (1/400 are homozygous) Hemoglobinopathy Variations: * Hgb SS – sickle cell disease * Hgb AS – sickle cell trait

Question 100

Pathophysiology, Sickle Cell Disease | (4 steps)

Answer 100

1. Infants are born normally c predominating Hgb F levels 2. S/sx appear as Hgb f is replaced by abnormal Hgb S 3. Underlying anemia due to splenic attempt to clear abnormal cells 4. Crises – Upon oxidative stress Hgb S crystallizes and sickles RBC shape. These get caught throughout system causing pain and potential organ swelling, dysfunction, and infarction

Question 101

Symptoms, Sickle Cell Disease | (3, 3 common sites)

Answer 101

Asymptomatic unless in crisis. Crisis symptoms may occur in varying frequency/duration and are characterized as acute pain due to vaso-occlusive episodes: * Hypoxia * Infarction * Dehydration (manifested in stomach pn) Common pain sites * Spine * Long bones (esp distal portions c smaller BV) * Chest

Question 102

Signs, Sickle Cell Disease (include 6 signs c 8 consequence)

Answer 102

Asymptomatic unless in crisis. Crisis signs may occur in varying frequency/duration and are characterized as * Jaundice * Pigment gallstones * Splenohepatomegaly (esp in peds) * Blood pooling in extremities – edema/ecchymosis/ulcer * +/- low grade fever * Vaso-occlusive crisis may lead to * CVA * Priapism * MI * PE * Ischemic necrosis * Liver * Bone – Staph related osteomyelitis Permanent anatomic changes due to repeated crises * Poorly healing ulcers overlying distal tibia * Scull “towering” and “bosses” Associated Mortality * Infections * Pulmonary emboli * Occlusion of vital vessel * Renal failure *Crisis stimulation for sickle cell trait is much more extreme – ie rigorous exercise at high altitude *

Question 103

Differential Dx, Sicle Cell Disease | (5)

Answer 103

Other hemolytic anemias 1. Hereditary spherocytosis 2. G6PD deficiency 3. Autoimmune hemolytic anemia 4. Microangiopathic hemolytic anemia 5. Aplastic anemia

Question 104

Diagnostic Tests, Sickle Cell Disease | (5 tests)

Answer 104

1. CBC * Hct increased * **WBC count increased – 12,000-15,000/mcl** * **​**Due to inc physiologic or pathologic stress 2. Peripheral blood smear * **5-50% RBC are sickled** * **Nucleated RBC’s **(polychromasia) * Howell Jolly bodies (export immature RBC to compensate for hemolysis) * Target cells (underlying hypochromic anemia) 3. Reticulocyte count increased 4. **Bilirubin assays – both total and indirect increased** 5. Hbg electrophoresis –**confirmatory test** * Sickle Cell Disease * Hgb S 85-98% * Hgb F 5-15% * Hgb A2 1-3% * Hgb A 0% * Sickle Cell Trait * Hgb A 60% * Hgb S 40%

Question 105

Medical Tx, Sickle Cell Disease | (4)

Answer 105

* Folic acid supplementation * Pneumococcal vaccine (prevent strep pneumo, a common cause for crisis) * Transfusions as needed * Hydroxyurea to inc. Hgb F levels

Question 106

Surgical Tx, Sickle Cell Disease

Answer 106

Allogenic hematopoietic stem cell transplant from sibling donor

Question 107

Emergency Tx, Sicke Cell Diseaes | (5)

Answer 107

Crisis Tx 1. Vigorous oral or IV hydration 2. Analgesics (morphine) 3. Narcotics 4. Treat precipitating factor – Oxygenate for hypoxia 5. Blood transfusions * If Hgb \< 5mg/dl * Cardiac failure

Question 108

Pt Education/Prevention, Sickle Cell Disease (2)

Answer 108

Life expectancy for disease = 40-50 years Behavior change to avoid crises if possible

Question 109

Prevelence, Sickle Cell Disease

Answer 109

1/400 African black people

Question 110

Age of Presentaion - Sickle Cell Disease (5 ages, % of diagnosed pts)

Answer 110

* Six months of age — 6 percent * Twelve months of age — 32 percent * Two years of age — 61 percent * Six years of age — 92 percent * Eight years of age — 96 percent

Question 111

Extrinsic Hemolytic Anemias | (Define, List 4)

Answer 111

**Definition**: Hemolytic anemia characterized by destruction of normal RBC by another source (it isn't the RBC's problem, it is the body's problem) **Extrinsic Anemias**: 1. Autoimmune Hemolytic Anemia 2. Microangiopathic Hemolytic Anemia 3. Malaria 4. Drugs * Nitrofurantoin (uti antibiotic) * Sulfonamide (uti antibiotic) * Chloramphenicol (anticancer) * Primaquine (anti-malarial)

Question 112

Define Autoimmune Hemolytic Anemia

Answer 112

Aquired anemia caused by IgG autoantibody attack on normal RBC

Question 113

Etiology, Autoimmune Hemolytic Anemia

Answer 113

* 50% are idiopathic * Other cases associated c * SLE (lupus) * CLL * Lymphomas

Question 114

Pathophysiology, Autoimmune Hemolytic Anemia (5 steps)

Answer 114

1. IgG binds to RBC 2. Antigen/antibody complex interacts c splenic macrophages 3. Macrophages remove only that portion of the RBC membraine 4. RBC leaves spleen as spherocyte 5. Spherocyte fragile either spontaneously lyse or are removed by spleen

Question 115

S/Sx, Autoimmune Hemolytic Anemia | (2 symptoms, 4 signs)

Answer 115

**Symptoms** * **Acute onset** * Fatigue **Signs** * Jaundice * Pallor * Gallstones * Splenomegaly

Question 116

Diagnostic Tests, Autoimmune Hemolytic Anemia (4)

Answer 116

1. CBC * Variable anemia * Spherocytes 2. Reticulocyte count increased 3. Indirect bilirubin increased 4. **Coombs test (direct antiglobulin) positive** * Indirect Coombs is + or -

Question 117

Medical Tx, Autoimmune Hemolytic Anemia | (3, in order of progression)

Answer 117

Do not move on until tx fails 1. **Prednisone (divided doses totaling 1-2 mg/kg/day)** * **​​***Retards immune response* 2. **Blood transfusion if Hct \<30%** 3. Immunosuppressive agents * Rituxamib - *antibody againt B cell antigen* * Cyclosporine - *suppress cell mediated immune response * **Common PANCE question - Prednisone is drug of choice**

Question 118

Surgical Tx, Autoimmune Hemolytic Anemia (2)

Answer 118

1. Splenectomy if pt is refractory to prednisone 2. Plasmapheresis in pts c rapid hemolysis

Question 119

Direct and Indirect Coombs Tests | (definitions, use)

Answer 119

**Defintions:** * _Coombs Test_ - mix RBC c Coombs reagent (IgG) to test for agglutination * _Indirect Coombs_ - evaluate plasma or serum for abnormal antibodies **Uses****:** * _Coombs Test_ - diagnose autoimmune hemolytic anemia * _Indirect Coombs_ - not for diagnosing autoimmune hemolytic anemia

Question 120

Plasmapheresis | (def, function)

Answer 120

_Definition_: Replace all of the plasma in a person’s body. Requires a special machine, reserved for highly severe cases _Use_: Tx autoimmune hemolytic anemia for pts c rapid hemolysis

Question 121

Define Microangiopathic Hemolytic Anemia

Answer 121

Group of disorders characterized by RBC fragmentation

Question 122

Etiology, Microangiopathic Hemolytic Anemia (6)

Answer 122

1. Disseminated intravascular coagulopathy 2. Thrombotic thrombocytic purpura 3. Hemolytic uremic syndrome 4. **Malfunctioning cardiac valve prosthesis** 5. **Malaria** 6. **Drugs** * Nitrofurantoin * Sulfonamide * Chloramphenicol * Primaquine

Question 123

Pathophysiology, Microangiopathic Hemolytic Anemia

Answer 123

Variable source of fragmentation; most popular is RBC interaction c abnormal intravascular fibrin strands. RBC fragments are not useful and are disposed of in spleen. Paired c coagulopathy and thrombocytopenia.

Question 124

S/Sx, Microangipathic Hemolytic Anemia | (1 sign, 1 symptom)

Answer 124

Both signs and symptoms depend on underlying cause. Heart-valve related cases may resemble iron deficiency

Question 125

Differential Dx, Microangioplastic Hemolytic Anemia (6)

Answer 125

* Iron deficiency anemia * Other hemolytic anemias * Hereditary spherocytosis * G6PD deficiency * Sickle cell disease * Autoimmune hemolytic anemia * Aplastic anemia

Question 126

Diagnostic Tests, Microangioplastic Hemolytic Anemia (2)

Answer 126

1. **Peripheral Smear indicates fragmented RBCs** 2. CBC may reveal decreased Hct and Hgb

Question 127

Medical Tx, Microangioplastic Hemolytic Anemia (1)

Answer 127

Treat the underlying disorder

Question 128

Define Aplastic Anemia

Answer 128

Pancytopenia due to bone marrow failure

Question 129

Etiology, Aplastic Anemia | (7)

Answer 129

1. Idiopathic 2. **SLE (lupus) or any autoimmune disease** 3. **Chemotherapy** 4. **Radiation therapy** 5. **Toxins** * Benzenes (organic) * Toluenes (organic) * Insecticides (inorganic) 6. Drugs * Chloramphenicol * Sulfonamides * Phenytoin * Carbamazepine 7. Pregnancy (uncommon)

Question 130

Pathophysiology, Aplastic Anemia

Answer 130

Hematopoeitic stem cell injury/abnormal expression causes defects in all blood cell lines

Question 131

S/Sx, Aplastic Anemia | (2 symptoms, 5 signs in 3 categories)

Answer 131

**Symptoms** Anemia effects * Fatigue * Weakness **Signs** * Anemia effects * Pallor * Leukopenia effects * Increased infections * Thrombocytopenia effects * Mucosal/skin bleeding * Purpura * Petechiae

Question 132

Differential Dx, Aplastic Anemia | (3, 1 has 3 specifics)

Answer 132

1. Increased Blasts - Acute Leukemia 2. Sepsis 3. Normomarrow pancytopenia * SLE (lupus) * Hypersplenism * Disseminated infection

Question 133

Diagnostic Tests, Aplastic Anemia | (3)

Answer 133

1. CBC * **Pancytopenia** * Blast cells decreased 2. Reticulocyte count decreased 3. Bone marrow biopsy hypocellular

Question 134

Medical Tx, Aplastic Anemia | (4)

Answer 134

**Refer to hematologist**, who will do the following 1. Blood Transfusion 2. Platelet transfusion 3. Antibiotics 4. Cyclosporine and antithymocyte globulin *(from rabbits)* * Tx of choice for pts \> 50 yo

Question 135

Surgical Tx, Aplastic Anemia

Answer 135

Allogenic bone marrow transplant if \< 50 yo

Question 136

"Aplastic"

Answer 136

"Without plasticity," meaning inability to mold/shape/produce new cells

Question 137

Patient Ed/Prevention, Aplastic Anemia

Answer 137

Good long term prognosis – partial response in 70% of cases

Question 138

Leukocyte Classifications

Answer 138

1. Granulocytes * Neutrophils * Basophils * Eosinophils 2. Monocytes 3. Lymphocytes

Question 139

Granulocyte Maturation (

Answer 139

*Complete development in BM* 1. Blast cell 2. Myelocyte 3. Band Cell (some of these do enter circulation; 3-5% of all circulating WBC are band cells) 4. Mature WBC

Question 140

Macrophage Maturation

Answer 140

1. Begin differentiation from hematocytoblast in BM 2. Enter peripheral blood upon becoming a monocyte 3. Circulate for 12-24 hours, until it takes residency in tissue 4. Differentiate into macrophage

Question 141

Lyphocyte Maturation

Answer 141

1. Lymphoid stem cells that are stimulated by antigens precurse all lymphocytes 2. Cells separate depending on how they differentiate * B-cell and NK cells remain in the BM to mature * T-cells migrate to peripheral lymphoid tissues * **Thymus** * Spleen * Tonsils * Lymph nodes

Question 142

Neutrophils (3 alternate names, function, indication for concentration change)

Answer 142

**Names**: segs, polys, PMN's **Function**: First line of defense, phagocytize pathogens and foreign particles **Changes**: Usually 55-65% WBCs * _Increased_ - bacterial infections. Often increased c higher [band cell] for left shift (paired c metamyelocytes and myelocytes)) * _Decreased_ - chemotherapy or aplastic anemia

Question 143

Lymphocytes | (functions, changes in number)

Answer 143

**Functions**: 1. Cell mediated immunity - T lymphocytes (CD4, CD8, supressors), NK cells 2. Humoral immunity - B lymphocytes → plasma cells → antibodies **Changes**: Usually 20%, second most popular lymphcyte * Increased - lymphocytic leukemia, viral infections * Decreased - HIV

Question 144

Reactive/atypical lymphs

Answer 144

Cells that assist c infectious mono/Epstein Barr virus ## Footnote ***_Note - this will not be paired c monocyte elevation_*** **This is often a board question and Sandy will most likely ask this on the test**

Question 145

Monocytes (function, normal concentration, 4 macrophage types)

Answer 145

**Function**: Circulating phagocytes, present antigens to T lymph for immune response **Normal concentration**: 5-10% WBC **Macrophage types**: 1. Kupffer cells - liver 2. Alveolar macrophages - lungs 3. Histiocytes - CT 4. Osteoblasts - bone

Question 146

Leukemia | (gen. def, classification system)

Answer 146

**Definition**: Characterized by unrestricted growth of leukocytes and leukocyte precursors * Cells are nonfunctional in providing usual protection against infection **Classification based on**: * Cell type * Myeloid * Lymphoid * Presentation * Acute * Chronic

Question 147

Leukemia Risk Factors (4)

Answer 147

1. Family hx 2. **Exposure to ionizing radiation**, forming dangerous free radicals 3. Benzene 4. Some alkylating agents 5. Cyclophosphamide 1. Anticancer drug that undergoes hydroxylation à active compound reacts with DNA leading to cytotoxicity

Question 148

Pathophysiology, Leukemia (general)

Answer 148

Replacement of normal bone marrow with malignant cells *This is the basis for all s/sx. Logic!*

Question 149

Acute Leukemias | (list 2)

Answer 149

1. ALL - Acute Lymphocytic Leukemia 2. AML - Acute Myelogenous Leukemia

Question 150

Define Acute Lymphocytic Leukemia

Answer 150

Acute unrestricted growth of lymphocytes and their precursors

Question 151

Etiology, Acute Lymphocytic Leukemia

Answer 151

* Most common **pediatric leukemia (80%), years 3-7** * Adult, 20% of leukemias, usually posess a risk factor * Family hx * Ionizing radiation exposure * Benzene * Some alkylating agents (cyclophosphamide) * Prognosis varies upon * Age * WBC * Presence of Philadelphia chromosome

Question 152

Pathophysiology, Acute Lymphocytic Leukemia

Answer 152

Mutation to only the lymphocyte precursor. Produces excess and ineffective T, B, and NK cells. Excess cells “clog” the body and do not

Question 153

S/Sx, Acute Lymphocytic Leukemia | (5 symptoms, 4 signs)

Answer 153

* Occur over days to weeks* * Remember, all s/sx either pertain to ineffective BM or ineffective lymphocytes* **Symptoms** Reflective of dysfunctional lymphoid cells * Fatigue * Lethargy * HA * Bone pain * Joint pain **Signs** Reflective of dysfunctional lymphoid cells * Fever * Pallor * Lymphadopathy * Hematosplenomegaly

Question 154

Differential Dx, Acute Lymphocytic Leukemia (4)

Answer 154

1. CLL 2. Aplastic Anemia 3. Bacterial Infection 4. Sepsis

Question 155

Diagnostic Tests, Acute Lymphocyte Leukemia (4)

Answer 155

1. CBC – high WBC count (**lymphocytosis**) 2. **Bone marrow biopsy \> 20% nucleated BM cells are lymphoblasts** * Confirmatory test 3. CXR – mediastinal mass 4. Genetic testing – Philadelphia chromosome sometimes present * Unfavorable dx *Notes* * *Lymphoblast can be definitively named in BM but not in peripheral circulation* * *Mediastinal mass is from clogged lymph nodes* * *Philidelphia chromosome is not a landmark for this leukemia but it will change your course of tx due to a change in likely disease progression*

Question 156

Medical Tx, Acute Lymphocytic Leukemia

Answer 156

Itensive Chemotherapy * Cycles of many txs and recovery * Induces pancytopenia

Question 157

Pt Education/Prevention, Acute Lymphocytic Leukemia (1 point)

Answer 157

Prognosis – remission rate \>70%

Question 158

Define Acute Myelogenous Leukemia

Answer 158

Acute unrestricted growth of myelocytes and their precursors, characterized by short duration of s/sx

Question 159

Etiology, Acute Myelogenous Leukemia

Answer 159

1. Age – primarily a leukemia of people \>60 yo 2. Risk factors * Family hx * Ionizing radiation exposure * Benzene * Some alkylating agents (cyclophosphamide)

Question 160

Pathophysiology, Acute Myelogenous Leukemia

Answer 160

Mutation to only the myelocyte precursor. Produces excess and ineffective granulocytes, monocytes, thrombocytes, and erythrocytes. Excess cells “clog” the body and disturb all cell lines

Question 161

S/Sx, Acute Myelogenous Leukemia | (4 symptoms, 5 signs)

Answer 161

* Both reflective of dysfunctional myeloid cells and bone marrow (note lack of infectious problems due to functioning lymphocytes)* * Onset time, days to weeks* **Symptoms ** * Bleeding * GI * Epistaxis * Skin * Menorrhagia * Bacterial infections * Joint pain * Bone Pain **Signs** * Pallor * Gingival hyperplasia * Purpura * Petechiae * Lymphadopathy

Question 162

Differential Dx, Acute Myelogenous Leukemia (4)

Answer 162

1. CML 2. Aplastic Anemia 3. Bacterial Infection 4. Sepsis

Question 163

Diagnostic Tests, Acute Myelogenous Leukemia (3)

Answer 163

1. CBC – high WBC count (**leukocytosis**) 2. B**one marrow biopsy \> 20% nucleated BM cells are myeloblasts** * Confirmatory test * **Auer Rods** 3. **Peripheral smear contains myeloblasts**

Question 164

Medical Tx, Acute Myelogenous Leukemia

Answer 164

Chemotherapy

Question 165

Surgical Tx, Acute Myelogenous Leukemia

Answer 165

BM Transplant

Question 166

Pt Ed/Prevention, Acute Myelogenous Leukemia

Answer 166

Prognosis – c chemotherapy, complete remission in (depending on severity) * 80-90% pts \< 60 yo * 50-60% pts \> 60 yo

Question 167

Chronic Leukemias | (list 2)

Answer 167

1. Chronic Lymphocytic Leukemia 2. Chronic Myelogenous (Myeloid) Leukemia

Question 168

Define Chronic Myelogenous Leukemia

Answer 168

Myeloproliferative disorder of extended duration

Question 169

Etiology, Chronic Myelogenous Leukemia

Answer 169

* Young to middle aged adults (median age 55) * Risk factors * Family hx * Ionizing radiation exposure * Benzene * Some alkylating agents (cyclophosphamide)

Question 170

Pathophysiology, Chronic Myelogenous Leukemia

Answer 170

Abnormal myeloid cell production c normal cell differentiation. Bone marrow function persists in early disease. Occurs in three phases 1. Chronic * Normal BM function 2. Accelerated * Impaired neutrophil differentiation * WBC uncontrollable by chemo 3. Acute (blast crisis) * Myeloid blast proliferation * Resembles AML

Question 171

S/Sx, Chronic Myelogenous Leukemia | (5 symptoms, 2 signs)

Answer 171

**Symptoms** * Fatigue * Weight loss * Low grade fever * Night sweats * Abdo fullness **Signs** * Splenomegaly * Sternal tenderness

Question 172

Differential Dx, Chronic Myelogenous Leukemia (5)

Answer 172

1. AML 2. CLL 3. Bacterial Infection 4. Sepsis (lesser WBC count than CML) 5. Anemia, in later progression (not enough room in BM to produce funtional RBCs)

Question 173

Dx Tests, Chronic Myelogenous Leukemia | (2)

Answer 173

1. CBC * Increased WBC **(leukocytosis median count 150,000/mcl) c severe left shift** * **​Considered CML at 50,000** * Anemia – present in later stages * Thrombocytosis – present in later stages 2. Genetic testing * **Philadelphia chromosome (95% of the time)** * **Bcr/abl gene\***

Question 174

Medical Tx, Chronic Myelogenous Leukemia

Answer 174

Refer to hematologist, who will do the following 1. First line – Imatinib * Inhibits tyrosine kinase of bcr/abl oncogene * Controls chronic disease 2. Second line – Dasatinib * More potent * Effective against bcr/abl mutations

Question 175

Surgical Tx, Chronic Myelogenous Leukemia

Answer 175

Third line – BM transplant

Question 176

Pt Ed/Prevention, Chronic Myelogenous Leukemia

Answer 176

Imatinib often achieves remission x 8 years

Question 177

Clinical Pearls, Chronic Myelogenous Leukemia

Answer 177

* Pts c unexplained leukocytosis \< 50,000 can be referred to hematology/oncology for monitoring. They may start chemo at lower threshold * When patients present to in blast crisis prioritize as follows: 1. Achieve remission or at least reduce WBC count 2. Figure out exact cause

Question 178

Philidelphia Chromosome (define, 1 landmark associated condition)

Answer 178

# **Define** - translocation in chromosomes 9 and 22 **Disease** - Chronic Myeloid Leukemia (present in 95% of cases)

Question 179

CML vs. Infection | (compare 5 factors)

Answer 179

Question 180

Define Chronic Lymphocytic Leukemia

Answer 180

AKA B Cell Leukemia Clonal malignancy of B lymphocytes

Question 181

Etiology, Chronic Lymphocytic Leukemia

Answer 181

*Most prevalent leukemia* * Median age \> 70 yo * Risk factors * Family hx * Ionizing radiation exposure * Benzene * Some alkylating agents (cyclophosphamide)

Question 182

Pathophysiology, Chronic Lymphocytic Leukemia

Answer 182

B lymphocyte clone will uncontrollably proliferate, creating ineffective B cells, thus ineffective plasma cells and antibodies. ## Footnote **Note – B cell only, not entire lymphocyte line**

Question 183

S/Sx, Chronic Lymphocytic Leukemia | (2 symptoms, 2 signs)

Answer 183

Often detected when asymptomatic **Symptoms** * Fatigue * Recurrent infections **Signs** * Splenomegaly *(spleen is in overdrive, usually lymphocytes last for years and rate of destruction is low)* * Lymphadopathy

Question 184

Differential Dx, Chronic Lymphocytic Leukemia (4)

Answer 184

1. ALL 2. Infection 3. CML 4. Sepsis

Question 185

Diagnostic Tests, Chronic Lymphocytic Leukemia (2)

Answer 185

1. CBC * High WBC count (**leukocytosis \> 20,000/ml**) * +/- anemia * +/- thrombocytosis * **peripheral lymphocytosis** 2. **Peripheral smear reveals smudge cells**

Question 186

Medical Tx, Chronic Lymphocytic Leukemia (3)

Answer 186

1. Early disease – observation 2. Tx indications – S/sx that interfere c quality of life * Progressive fatigue * Symptomatic lymphadopathy, anemia, thrombocytopenia 3. Chemotherapy * Fludarabine - purine neucleotide analog * Rituxamib (Retuxan) - monoclonal antibody directed against CD20 antigen on normal and malignant B lymphocytes

Question 187

Surgical Tx, Chronic Lymphocytic Leukemia

Answer 187

Allogenic stem cell transplant for pts who do not respond to chemo

Question 188

Pt Ed/Prevention, Chronic Lymphocytic Leukemia

Answer 188

Mean survival time = 6 years. Choice to treat depends on quality of life and is completely up to the patient . Prognoses: * Stages 0 or 1 = 10-15 years * Stages 3 or 4 = 2 years

Question 189

Smudge Cells | (def, associated condition)

Answer 189

**Definition**: Ruptured Lymphyocytes **Condition**: this is a hallmark of CLL *Smude cell is pictured in square, normal lymphocytes in circles*

Question 190

Most Prevelant WBC in Chronic Inflammation

Answer 190

**Monocytes** are first line ## Footnote * Other "big players" - neutrophils and lymphocytes* * (neutrophils will predominate in an acute flair up)* * Remember, they reside in the tissue. Basophils and eosinophils are not very numerous, so they are not a big player. *

Question 191

When may a Pt Possess High Eosinophil Count?

Answer 191

Parasites

Question 192

Define Hodgkin's Lymphoma

Answer 192

Neoplasm (cancer) of the lymphatic system characterized by the presence of Reed Sternberg cells

Question 193

Etiology, Hodgkin's Lymphoma

Answer 193

* Largely unknown, although Epstein Barr virus is suspected * **Bimodal age distribution** (ages vary depending on source) * 15-45 yo c mean age in 20’s * \> 50 yo

Question 194

Pathophysiology, Hodgkin's Lymphoma

Answer 194

* Tumor formation due to specific cell proliferation 1. Normal lymphocytes (majority) 2. Malignant B lymphocytes 3. **Reed Sternberg cells** * Lymph node enlargement from cell infiltration 1. Eosinophil 2. Plasma cells * Presents in stages (don't need these for our exam) 1. Stage I – singular lymph node or extralymphatic site 2. Stage II – 2+lymph nodes and/or extralymphatic tissue on ipsilateral side of diaphragm 3. Stage III – lymph nodes on contralateral sides of diaphragm. May include spleen or extranodal disease * III1 – limited to upper abdomen (spleen, celiac, portohepatic nodes) * III2 – limited to lower abdomen (periaortic, pelvic, inguinal nodes) 4. Stage IV – diffuse extralymphatic disease. Commom sites include * Liver * BM * Lung * Skin

Question 195

S/Sx, Hodgkin's Lymphoma | (5 symptoms, 3 signs)

Answer 195

_Symptoms_ *These are vague. Keep a high index of suspiscion when encountered c these symptoms* 1. Fever 2. Night sweats 3. Fatigue 4. Weight loss 5. Pruritis _Signs_ 1. **Painless, rock hard, swollen lymph nodes**. Disease usually starts in the following nodes: * Cervical * Supraclavicular * Mediastinal 2. Splenomegaly *(contains lymphoid tissue)* 3. Potential hepatomegaly *(contains lymphoid tissue)*

Question 196

Differential Dx, Hodgkin's Lymphoma | (4)

Answer 196

1. Non-Hodgkin’s Lymphoma 2. HIV 3. Hypersensitivity Rxns 4. Other solid tumors

Question 197

Diagnostic Tests, Hodgkin's Lymphoma | (3 + 1 bonus)

Answer 197

1. Lymph node biopsy * **Reed Sternberg cells** * Necrosis * Fibrosis 2. Bone marrow biopsy * Lymphocytosis only present in progressive disease 3. Scans to evaluate disease stage * CXR or chest CT * Abdo CT * Bone scan 4. *Bonus - US to evaluate cystic vs solid/complex*

Question 198

Medical Tx, Hodgkin's Lymphoma | (3 general, 2 specifics each)

Answer 198

1. Chemotherapy and/or radiation (varies c histologic interpretation/staging) * AVBD – front line * MOPP – alternative 2. Experimental – targeted therapies * Monoclonal antibodies * Target-specific aids 3. Symptomatic tx * Antiemetics * Sedatives

Question 199

Surgical Tx, Hodgkin's Lymphoma

Answer 199

Autologous bone marrow transplant

Question 200

Reed Sternberg Cell | (definition, associated condition)

Answer 200

**Definition**: gigantic, multi-nucleated, bilobed lymphocyte c characteristic "owl eye" formation **Associated Condition**: Hodgkin's Lymphoma

Question 201

Define Non-Hodgkin's Lymphomas

Answer 201

Hematogenous group of malignancies originating in l ymph nodes and other lymph node tissues

Question 202

Etiology, Non-Hodgkin's Lymphomas

Answer 202

* Common pt populations * Autoimmune disorders * HIV * Immunosuppressive tx * Definitive etiology unknown. Some patterns in pts c * Viral etiology (virus may alter B cell) * Toxin exposure * Benzene * Pesticides * Herbicides

Question 203

Pathophysiology, Non-Hodgkin's Lymphoma | (3 steps)

Answer 203

1. Oncogene becomes juxtaposed next to * Immunoglobulin gene (B-cell lymphoma) * 85% of cases * T-cell receptor gene (T-cell lymphoma) 2. Oncogene over-expression 3. Excess T- or B-cell production, causing lymphoma

Question 204

S/Sx, Non-Hodgkin's Lymphomas | (6 symptoms, 3 signs)

Answer 204

_Symptoms_ * **“B Symptoms” (present in B- and T-cell lymphomas)** * Weight loss * Fever * Drenching night sweats * Other * Fatigue * Pruritis * Abdo pn _Signs_ * Uneven enlargement of tonsils and adenoids * **Painless uneven lymphadenopathy** * Cervical * Suprascapular * Dramatic infections

Question 205

Differential Dx, Non-Hodgkin's Lymphomas (2)

Answer 205

1. Hodgkin’s Lymphoma 2. Infectious mononucleosis

Question 206

Diagnostic Tests, Non-Hodgkin's Lymphomas (3 broad)

Answer 206

1. **Lymph node biopsy – _No_ Reed Sternberg Cells** 2. Tissue biopsy or enlarged lymphatic tissues * Tonsils * Adenoids 3. Scans to evaluate disease stage * Bone scan * Chest CT * Abdo CT * PET scan

Question 207

Medical Tx, Non-Hodgkin's Lymphomas | (3)

Answer 207

Varies c histology and disease progression * Radiation therapy, if localized * In combo c chemotherapy if advanced * Chemotherapy * CHOP * Advanced cases only * Rituximab – binds to B cell receptors to stim. apoptosis * For relapse or refractory follicular lymphoma

Question 208

Classification, Non-Hodgkin's Lymphoma | ("2")

Answer 208

Classification system is still evolving. Existing systems 1. Clinical features 2. Pathologic features

Question 209

Prevelance, Non-Hodgkin's Lymphoma vs. Hodgkin's Lymphoma

Answer 209

Non-Hodgkin's 3x more common than Hodgkin's

Question 210

PET Scan (definition, clinical use in hematology)

Answer 210

**Definition**: Imaging technique that evaluates tagged glucose and its position in the body. Helps evaluate physiology **Use**: Diagnosis of Non-Hodgkin's Lymphomas

Question 211

Define Multiple Myeloma

Answer 211

Disseminated malignant neoplasm of plasma cells that infiltrates BM

Question 212

Etiology, Multiple Myeloma

Answer 212

* Male \> female * Exact etiology unknown. Some hypotheses * Genetics * Autoimmune disease * Environmental toxins * Agricultural chemicals * Herbicides * Pesticides

Question 213

Pathophysiology, Multiple Myeloma | (7 steps, 8 end results)

Answer 213

1. Malignant **plasma cells** invade BM 2. Abnormal cells consume BM and progress to invade bone matrix (cortex) 3. Formation of **osteolytic lesions** 4. Simultaneous co-infiltrations due to wide distribution of plasma cells 5. Plasma cells produce excessive immunoglobulins 6. High circulating protein from immunoglobulins degrade kidney and bone 7. Result in various complications * Dec. functional antibodies - infection * Protein overload in kidney * Pyelonephritis * Renal failure * Renal calculi (stones due to inc. calcium or uric acid) * Bone destruction * Hematologic imbalance (anemia, abnml WBC leukocytosis) * Fractures at osteolytic lesions * Hypercalcemia from bone degradation byproduct * Hyperuricemia from cell degradation products

Question 214

S/Sx, Multple Myeloma | (6 symptoms, 4 signs)

Answer 214

_Symptoms_ * Pts typically present c complaints concerning * Anemia * **Bone pn, most severe in** * **Back** * Ribs * Hips * Infection * Fever * Malaise * Weight loss _Signs_ * Anemia s/sx * Pallor * Bone destruction * Osteoporosis * Pathologic fx * **Vertebral compression fx**

Question 215

Differential Dx, Multiple Myeloma | (6)

Answer 215

1. Anemia 2. MSK dysfunction 3. Malignant lymphoma 4. Metastatic carcinoma 5. Monoclonal gammopathies or uncertain origin

Question 216

Diagnostic Tests, Multiple Myeloma | (6)

Answer 216

1. X-ray – **lytic lesions in skull, pelvis, spine** 2. CBC 1. Moderate-severe anemia 2. **Rouleaux formation of RBC** 3. **Bence Jones urinalysis – positive** 4. Electrolyte levels - Hypercalcemia 5. **Serum protein electrophoresis – hallmark test** 1. **Monoclonal spike in beta or gamma region** (“M spikes”) 2. Note- can be spiked in other diseases, must go with other dx tests 6. Bone marrow aspirate – inc. plasma cell precursors

Question 217

Medical Tx, Multiple Myeloma | (3)

Answer 217

Only with more progressive disease. May be monitored at first 1. Chemotherapy to suppress plasma cell growth, thus dec. pn * VAD * TD 2. Adjunctive radiation 3. Dialysis if kidneys fail

Question 218

Surgical Tx, Multiple Myeloma

Answer 218

BM Transplant

Question 219

Patient Education, Multilple Myeloma

Answer 219

1. Prognosis is improving. Currently 4-6 years c tx 2. Avoid the following to prevent irritation * Heavy lifting * Dehyrating

Question 220

Platelets (origin, function, normal count, normal lifespan)

Answer 220

_Origin_: fragment from megakaryocytes after prdcn stimulation via thrombopoietin (synth in liver) _Function_**: hemostasis** * occlude small BV openings * contribute factor III to extrinsic clotting pathway _Count_: 250,000-500,000/ml blood, although counts vary c geographic location and lab equipment _Lifespan_: * formation - 5 days * half life - 8→12 days

Question 221

Platelet Disorders | (2 "categories", general defs)

Answer 221

1. Essential Thrombocytosis - inc. platelets 2. Thrombocytopenia - dec. platelets

Question 222

Define Essential Thrombocytosis

Answer 222

Myeloproliferative disorder characterized by increased platelets with no other direct cause

Question 223

Etiology, Essential Thrombocytosis | (2)

Answer 223

1. Median age 50-60 yo 2. Correlation c JAK2 mutation (same mutation as CML)

Question 224

Pathophysiology, Essential Thrombocytosis (2)

Answer 224

1. Excessive platelet formation without trigger 2. Abnormal and excess platelets c attempted removal by spleen

Question 225

S/Sx, Essential Thrombocytosis | (1 symptom, 3 signs)

Answer 225

**Symptoms** Increased bleeding **Signs** 1. _Thrombosis_ in normal and abnormal _venous_ clotting locations * Typical (for other clotting disorders) – DVT * Atypical (for other clotting disorders) * Mesenteric vein * Hepatic vein * Portal vein 2. Bleeding, mucosal 3. Splenomegaly

Question 226

Differential Dx, Essential Thrombocytosis (5, 1 important one)

Answer 226

1. **Chronic myelogenous leukemia** 2. Agnogenic myeloid metaplasia c myelofibrosis 3. Myelodysplastic syndrome 4. Polycythemia vera 5. Secondary thrombocytosis

Question 227

Diagnostic Tests, Essential Thrombocytosis (3)

Answer 227

1. CBC * _Platelet count \> 500,000/mcl (can be in the millions)_ * Large, abnormal platelets on peripheral smear * WBC count – slightly increased c increased blasts 2. Bone marrow biopsy – increased megakaryocytes 3. Genetic testing – No Philadelphia chromosome, unless this is early CML

Question 228

Medical Tx, Essential Thrombocytosis | (1)

Answer 228

Refer to hematologist, who will prescribe Hydroxyurea for myelosuppression ## Footnote *Requires regular monitoring via CBC*

Question 229

Pt Education/Prevention, Essential Thrombocytosis (2)

Answer 229

1. 5% cases transform to leukemia, esp CML 2. Prognosis, avg \>15 years

Question 230

Clinical Pearls, Essential Thrombocytosis (2)

Answer 230

1. Test for Philadelphia chromosome to R/O CML 2. If platelet count in the realm of 500,000 and there are no other s/sx you can have your pt return in a couple weeks to retest platelet counts * Decreased – continue to monitor * Increased/remained – refer to hematologist

Question 231

Thrombocytopenia | (definition, 3 general causes)

Answer 231

**Definition:** Decreased platelet count, c risk of spontaneous hemorrhage if plt count \< 20,000/mcl **Causes**: 1. Decreased platelet production 2. Increased platelet destruction 3. Platelet dysfunction

Question 232

Causes of Dec. Platelet Production in Thrombocytopenia (3)

Answer 232

* Bone marrow failure * Congenital disorders * Acquired * Aplastic anemia * Bone marrow infiltration * Massive replacement of bone marrow by leukemic cells, myeloma, lymphoma * Radiation or chemotherapy exposure

Question 233

Platelet Destructive/Dysfunctional Thrombocytopenias (list 5)

Answer 233

* Immune Thrombocytpoenic Purpura * Thrombotic microangiopathies * Thrombotic Thrombocytopenic Purpura * Hemolytic Uremic Syndrome * Heparin Induced Thrombocytopenia * Disseminated Intravascular Coagulopathy

Question 234

Define Immune Thrombocytopenia Purpura (ITP)

Answer 234

Isolated thrombocytopenia secondary to anti-platelet antibodies

Question 235

Etiology, Immune Thrombocytopenia Purpura

Answer 235

*Diagnosis of exclusion* * Usually idiopathic * Associated c the following * Lupus * Lymphoma * Hep B * Hep C * HIV * Drugs * Sulfa * Thiazides (anti-convulsive) * Cimetidine

Question 236

S/Sx, Immune Thrombocytopenia Purpura (ITP) (1 symptom, 3 signs within 1 category)

Answer 236

**Symptoms** Spontaneous bleeding **Signs** Mucocutaneous bleeding, spontaneous when plt count \< 20,000-30,000 1. Bruising 2. Nosebleeds 3. Gingival bleed

Question 237

Pathophysiology, Immune Thrombocytopenia Purpura (ITP) (3 steps)

Answer 237

a. Anti-platelet antibodies attach to normal platelets b. Macrophages in liver and spleen phagocytize platelets c. Resulting thrombocytopenia

Question 238

Differential Dx, Immune Thrombocytopenia Purpura (ITP)

Answer 238

Other destructive/dysfunctional platelet thrombocytopenias * Thrombotic microangiopathies * Thrombotic Thrombocytopenic Purpura * Hemolytic Uremic Syndrome * Heparin Induced Thrombocytopenia * Disseminated Intravascular Coagulopathy

Question 239

Diagnostic Tests, Immune Thrombocytopenia Purpura (ITP) (3)

Answer 239

1. CBC – **Isolated thrombocytopenia** 1. **Platelet Count** 1. Acute: 10,000 – 20,000/mcl 2. Chronic: 25,000 – 75,000/mcl 2. RBC studies – potential mild anemia 2. Coagulation studies – normal 3. Disease specific testing, varies upon etiology 1. Hep B 2. Hep C 3. HIV

Question 240

Medical Tx, Immune Thrombocytopenia Purpura (ITP) (6)

Answer 240

Refer to a hematologist **as soon as levels drop below normal. **He/she will 1. Monitor, if chronic. Spontaneous resolution often occurs 2. Steroids 3. IV immunoglobulin 4. Rituximab 5. Splenectomy 6. **Treat underlying co-morbidity or eliminate offending agent**

Question 241

Emergency Tx, Immune Thrombocytopenia Purpura (ITP)

Answer 241

Platelet transfusion for life threatening bleeding

Question 242

Rituximab | (MOA, role in ITP)

Answer 242

**MOA**: genetically engineered monoclonal antibody agnst CD20 ag on surface of normal and malignant B cells **Role in ITP**: attack dysfunctional B cells to decrase severity of thrombobytopenia

Question 243

Thrombotic Microangiopathies | (definition, list 2)

Answer 243

**Def**: Potentially fatal thrombocytopenia due to incorporation of plts into thrombi in microvasculature. Forms tiny clots in circulatory system. Results in 1. blockage of normal cell circulation 2. lack of available platelets for necessary clotting **Diseases**: 1. Thrombotic Thrombocytopenic Purpura (TTP) 2. Hemolytic Uremic Syndrome (HUS)

Question 244

Etiology, Thrombotic Thrombocytic Purpura (6)

Answer 244

**Know all of these** 1. Viruses (HIV) 2. Bacteria 3. Pregnancy 4. Autoimmune 5. Cancer 6. Medications * Cyclosporine * Clopidogrel

Question 245

Pathophysiology, Thrombotic Thrombocytic Purpura (5 steps)

Answer 245

1. Antibodies against vonWillenbrand factor cleaving protease (**ADAMTI-13)** 2. Multimer accumulation within vasculature 3. Bridging of multimer 4. Excessive plt aggregation 5. Circulating clots prevent platelet use in necessary clots

Question 246

S/Sx, Trombotic Thrombocytic Purpura | (3 symptoms, 5 signs)

Answer 246

**Symptoms** Anemia symptoms, bleeding difficulties, DVT **Signs** 25% of patients will have ***_pentad_***: 1. Thrombocytopenia 2. Hemolytic anemia 3. Fever 4. Neuro defects (HA, somnolence, delirium, seizures) 5. Renal insufficiency

Question 247

Differential Dx, Thrombotic Thrombocytic Purpura (4)

Answer 247

*Other thrombocytopenias* * Immune thrombocytopenia purpura * Thrombotic microangiopathies * _Hemolytic Uremic Syndrome_ * Heparin Induced Thrombocytopenia * Disseminated Intravascular Coagulopathy

Question 248

Diagnostic Tests, Thrombotic Thrombocytic Purpura | (6)

Answer 248

1. CBC * **Hemolytic anemia** * Schistocytes s sickled cells * Normocytic, normochromic RBC * Elevated WBC count * Thrombocytopenia, platelets \< 20,000 2. LDH – increased 3. Bilirubin (direct and indirect) – increased 4. Reticulocyte count – increased 5. **Coagulation studies – normal** 6. BUN/Cr – increased only in very severe TTP

Question 249

Medical Tx, Thrombotic Thrombocytic Purpura (3)

Answer 249

1. **Plastmapheresis** 2. Steroids 3. IV immunoglobulin

Question 250

Surgical Tx, Thrombotic Thrombocytic Purpura

Answer 250

Splenectomy

Question 251

Pt Ed/Prevention, Thrombotic Thrombocytic Purpura

Answer 251

Prognosis - 5% s plasmapheresis

Question 252

Define Hemolytic Uremic Syndrome

Answer 252

Thrombocytopenia due to incorporation of plts into thrombi in microvasculature c **associated RBC shearing in microcirulation**

Question 253

Etology, Hemolytic Uremic Syndrome | (3 aspects, 2 major takeaways)

Answer 253

* Predominantly **_pediatric_** population * Usually associated c current/recent diarrhea (usually due to food poisoning) * Typical causative agents * **_Toxigenic E. Coli (0157:H7)_** * Viruses (HIV) * Bacteria * Pregnancy * Autoimmune * Cancer * Medications * Cyclosporine * Clopidogrel

Question 254

Pathophysiology, Hemolytic Uremic Syndrome (6 steps)

Answer 254

1. Endothelial damage from toxigenic **E Coli (0157:H7)**, cancer, HIV 2. Circulating small platelet aggregations 3. Extension of aggregates throughout vessel walls 4. RBC lyse when passing through vessels, creating ineffective schystocytes 5. Platelets unavailable for necessary clotting 6. Renal insufficiency

Question 255

S/Sx, Hemolytic Uremic Syndrome | (3 symptoms, 5 signs)

Answer 255

**Symptoms** Anemia symptoms, bleeding difficulties, DVT **Signs** 25% of patients will have ***_pentad_***: 1. Thrombocytopenia 2. Hemolytic anemia 3. Fever 4. Neuro defects (HA, somnolence, delirium, seizures) 5. Renal insufficiency

Question 256

Differential Dx, Hemolytic Uremic Syndrome (4)

Answer 256

*Other thrombocytopenias* * Immune thrombocytopenia purpura * Thrombotic microangiopathies * **Thrombotyc Thrombocytic Purpura** * Heparin Induced Thrombocytopenia * Disseminated Intravascular Coagulopathy

Question 257

Diagnostic Tests, Hemolytic Uremic Syndrome (6)

Answer 257

1. CBC * **Hemolytic anemia** * Schistocytes s sickled cells * Normocytic, normochromic RBC * Elevated WBC count * Thrombocytopenia, platelets \< 20,000 2. LDH – increased 3. Bilirubin (direct and indirect) – increased 4. Reticulocyte count – increased 5. **Coagulation studies – normal** 6. BUN/Cr – increased

Question 258

Medical Tx, Hemolytic Uremic Syndrome | (4)

Answer 258

1. *Avoid antibiotics c E. Coli etiology, due to risk of resistance and increased toxin release from lysed cells* 2. **Plastmapheresis** 3. Steroids 4. IV immunoglobulin

Question 259

Surgical Tx, Hemolytic Uremic Syndrome

Answer 259

Splenectomy

Question 260

Pt Ed/Prevention, Hemolytic Uremic Syndrome

Answer 260

Prognosis – 5% s Plasmapheresis

Question 261

Clinial Pearls, Hemolytic Uremic Syndrome (2)

Answer 261

1. **Avoid platelet transfusions – worsens thrombotic microangiopathy** 2. Vicious cycle – these pts need platelets because they are bleeding but platelets will advance the disease

Question 262

Define Heparin Induced Thrombocytopenia (HIT)

Answer 262

Decline in baseline platelet count of **50% or greater within 5-10 days of heparin exposure**

Question 263

Etiology, Heparin Induced Thrombocytopenia (HIT) (1)

Answer 263

Heparin patients

Question 264

Pathophysiology, Heparin Induced Thrombocytopenia (HIT) (4 steps)

Answer 264

1. IgG antibody formation against heparin platelet factor 4 (PF4) complexes 2. Antigen-antibody complex formation and activation 3. Macrophage phagocytosis, destroying the platelet 4. Inability of BM to keep up c destruction, thus thrombocytopenia an dpro-thrombic state

Question 265

S/Sx, Heparin Induced Thrombocytopenia (HIT) (1 symptom, 3 signs)

Answer 265

**Symptoms** Pain in the event of thrombosis **Signs** 1. Usually asymptomatic 2. **Thrombosis – 50% cases** 3. Bleeding is uncommon

Question 266

Differential Dx, Heparin Induced Thrombocytopenia (HIT) (4)

Answer 266

* Immune thrombocytopenia purpura * Thrombotic microangiopathies * Thrombotyc Thrombocytic Purpura * Hemolytic Uremic Syndrome * Disseminated Intravascular Coagulopathy

Question 267

Dx Studies, Heparin Induced Thrombocytopenia (HIT)

Answer 267

1. CBC – significant **thrombocytopenia, \>50% decline from baseline** * This is carefully monitored when heparin is initiated; often caught before s/sx occur 2. Heparin PF4 antibodies – present only after thrombocytopenia (order after thrombosis)

Question 268

Medical Tx, Heparin Induced Thrombocytopenia (3)

Answer 268

1. Discontinue heparin 2. Anticoagulate c argatroban until platelet count \>100,000 * This is the threshold for safe Warfarin initiation, **contraindicated otherwise**

Question 269

Surgical Tx, Heparin Induced Thrombocytopenia

Answer 269

Limb amputation is thrombosis is significant and untreated

Question 270

Eergency Tx, Heparin Induced Thrombocytopenia (1)

Answer 270

Initiate medical tx quickly as to avoid emboli

Question 271

Pt Eduacation/Prevention, Heparin Induced Thrombocytopenia (HIT) (1)

Answer 271

Monitoring will be done by hospital staff any time heparin is initiated

Question 272

Define Disseminated Intravascular Coagulopathy (DIC)

Answer 272

Platelet consumptive syndrome characterized by simultaneous thrombosis and bleeding

Question 273

Etiology, Disseminated Intravascular Coagulopathy (DIC) (6)

Answer 273

Severe underlying systemic illness * Sepsis * OB complications * Cancer * Severe transfusion rxn * Trauma * Burns

Question 274

Pathophysiology, Disseminated Intravascular Coagulopathy (DIC) (4 steps)

Answer 274

1. Systemic blood coagulation activation 2. Fibrin generation and deposition 3. Microvascular thrombi in various organs 4. **Consumption and subsequent exhaustion of coagulation PRO and platelets via microclot formation**

Question 275

S/Sx, Disseminated Intravascular Coagulopathy (DIC) (1 symptom, 3 signs)

Answer 275

**Symptoms** Extreme discomfort **Signs** * **Mucocutaneous bleeding at multiple sites (all orifices)** * Shock * Digital ischemia leading to gangrene (depending on thrombosis location)

Question 276

Differential Dx, Disseminated Intravascular Coagulopathy (DIC) (4)

Answer 276

* Immune thrombocytopenia purpura * Thrombotic microangiopathies * Thrombotyc Thrombocytic Purpura * Hemolytic Uremic Syndrome * Heparin Induced Thrombocytopenia

Question 277

Diagnostic Tests, Disseminated Intravascular Coagulopathy (DIC) (5)

Answer 277

**All are vital for dx** 1. PT/INR – prolonged 2. PTT – prolonged 3. CBC * Thrombocytopenia * Hemolytic anemia * Schystocytes on peripheral smear 4. D-Dimer assay – elevated 5. Fibrinogen assay – decreased

Question 278

Medical Tx, Disseminated Intravascular Coagulopathy (DIC) (4)

Answer 278

**This is emergent** 1. **Correct underlying problem** * Antibiotics for sepsis * Surgery for trauma/burns 2. Blood product in the presence of clinically significant hemorrhage * Goal = plt count 20,000 – 30,000 3. Fresh Frozen Plasma (FFP) in patients c * Inc PT * Inc PTT * **Significant bleeding** 4. Cryoprecipitate to replace fibrinogen

Question 279

Clinical Pearls, Disseminated Intravascular Coagulopathy (3)

Answer 279

1. Primary goal is to achieve hemodynamic balance in these pts 2. Prognosis is very low 3. Paradoxical condition; the tx will worsen the condition

Question 280

Define Hemophilia A

Answer 280

Genetic congenital Factor VIII deficiency, characterized by excessive clotting time

Question 281

Etiology, Hemophilia A

Answer 281

X-linked recessive trait therefore mostly males

Question 282

Pathophysiology, Hemophilia A | (3 steps)

Answer 282

1. Lack of factor VIII interrupts the intrinsic pathway of the clotting cascade 2. Platelets start to plug 3. Definitive clot never forms

Question 283

S/Sx, Hemophilia A | (1 symptom, 1 sign c 5 common examples)

Answer 283

**Symptoms** Reports of _spontaneous_ hemorrhage **Signs** Hemorrhagic episodes s appropriate injury. Typical bleeds: 1. Hemarthoses 2. Epistaxis 3. Intracranial bleeding 4. Hematemesis 5. Melana

Question 284

Differential Dx, Hemophilia A | (3)

Answer 284

1. Hemophilia B 2. vW Disease 3. Vitamin K deficiency

Question 285

Dx Tests, Hemophilia A | (7)

Answer 285

1. PTT – prolonged 2. PT – normal 3. Bleeding time – normal 4. Fibrinogen – normal 5. Platelets – normal 6. Factor VIII Assay – decreased 7. Factor IX Assay - normal

Question 286

Medical Tx, Hemophilia A | (2)

Answer 286

1. Recombinant Factor VIII, periodic injections 2. Desmopressin (DDAVP)

Question 287

Pt Education/Prevention, Hemophilia A | (2)

Answer 287

1. Patients must be very careful and attentive c injuries. Example – every head injury warrants a CT 2. Avoid aspirin; different MOA but reduced mechanisms for coagulation are always helpful

Question 288

Clinical Pearls, Hemophilias A and B | (2)

Answer 288

* Only distinguishable factors between Hemophilias A and B are the CF assays and prevalence. Everything else is identical * Prevalence * Hemophilia A – 1/5,000 life male births * Hemophlia B - 1/25,000 male births

Question 289

Define Hemophilia B (Christmas Disease)

Answer 289

Genetic congenital Factor IX deficiency, characterized by excessive clotting time

Question 290

Etiology, Hemophilia B (Christmas Disease)

Answer 290

X-linked recessive trait therefore mostly males

Question 291

Pathophysiology, Hemophilia B (Christmas Disease) (3 steps)

Answer 291

1. Lack of factor IX interrupts the intrinsic pathway of the clotting cascade 2. Platelets start to plug 3. Definitive clot never forms

Question 292

S/Sx, Hemophilia B (Christmas Disease) | (1 sypmtom, 1 sign c 5 examples)

Answer 292

**Symptoms** Reports of _spontaneous_ hemorrhage **Signs** Hemorrhagic episodes s appropriate injury. Typical bleeds: 1. _Hemarthoses_ 2. Epistaxis 3. Intracranial bleeding 4. Hematemesis 5. Melana

Question 293

Differential Dx, Hemophilia B (Christmas Disease) (3)

Answer 293

1. Hemophilia B 2. vW Disease 3. Vitamin K deficiency

Question 294

Diagnostic Tests, Hemophilia B (Christmas Disease) (7)

Answer 294

1. **PTT – prolonged** 2. PT – normal 3. Bleeding time – normal 4. Fibrinogen – normal 5. Platelets – normal 6. **Factor VIII Assay – reduced** 7. Factor IX Assay - normal

Question 295

Medical Tx, Hemophilia B (Christmas Disease) (2)

Answer 295

1. Recombinant Factor IX, periodic injections

Question 296

Pt Education/Prevention, Hemophilia B (Christmas Disease) (2)

Answer 296

1. Patients must be very careful and attentive c injuries. Example – every head injury warrants a CT 2. Avoid aspirin; different MOA but reduced mechanisms for coagulation are always helpful

Question 297

Define vonWillebrand Disease

Answer 297

Autosomal dominant congenital bleeding disorder, most common congenital coagulopathy

Question 298

Etiology, vonWillebrand Disease

Answer 298

Autosomal dominant disease

Question 299

Pathophysiology, vonWillebrand Disease | (2 steps)

Answer 299

1. Origin depends on type * Type 1: Quantitative defect, not enough vWF production * Type 2: Qualitative defect, lack of vWF cofactor, **ristocetin**. While there is adequate vWF present it will not activate 2. Without adequate functioning vWF, glycoprotein bridges cannot form in a coagulative event, preventing platelet plug formation and inhibiting effectiveness of the clotting cascade

Question 300

S/Sx, vonWillebrand Disease | (2 symptoms, 2 signs)

Answer 300

**Symptoms** More predictable hemorrhage than hemophilia Prolonged heavy menstrual bleeding **Signs** Mucosal bleeding Skin bleeding/easy bruising

Question 301

Differential Dx, vonWillebrand Disease | (3)

Answer 301

1. Hemophilia A 2. Hemophilia B 3. Vitamin K deficiency

Question 302

Diagnostic Tests, vonWillebrand Disease | (5)

Answer 302

1. Bleeding time – prolonged 2. PT – normal 3. PTT – normal 4. CBC – normal, including platelet count 5. Specific assays depend on type * Type 1: decreased vonWillebrand factor assay * Type 2: decreased ristocetan assay

Question 303

Medical Tx, vonWillebrand Disease | (2)

Answer 303

1. Desmopression (DDAVP, Stimate), PO or nasal spray 2. vW concentrates, reserved for severe disaease or surgery

Question 304

Define Vitamin K Deficiency

Answer 304

Disruption in the clotting cascade due to deficient vitamin K

Question 305

Etiology, Vitamin K Deficiency | (3)

Answer 305

1. Almost always due to decreased dietary intake of vitamin K * Dark leafy greens * Oils (soybean, cottonseed, canola, olive) 2. Underlying liver disorder may also be a culprit – hepatitis, chronic alcoholism, etc. 3. Post operative pts on broad spectrum bacteria that suppress colonic bacteria

Question 306

Pathophysiology, Vitamin K Deficiency | (1 c 4 aspects)

Answer 306

Inability to synthesize clotting factors vital cofactor in liver. Clotting factors affected: II VII IX X

Question 307

S/Sx, Vitamin K Deficiency | (1 sign, 1 symptom)

Answer 307

**Symptoms** Increased bleeding times **Signs** Increased bleeding when encountered c offending agent

Question 308

Diagnostic Tests, Vitamin K Deficiency | (4)

Answer 308

1. **PT/INR – prolonged** 2. **aPPT – normal** 3. Liver function test – elevated, esp c chronic alcoholism 4. CF II, VII, IX, X assays – decreased

Question 309

Medical Tx, Vitamin K Deficiency | (2)

Answer 309

1. Vitamin K (Phytonadion) 2. Fresh frozen plasma if hemorrhaging

Question 310

Define Congential Venous Thrombosis (Group of Disease)

Answer 310

Abnormal clotting due to inheritable condition that leads to permanent hypercoaguable state if untreated

Question 311

Etiology, Congenital Venous Thrombosis Group (5)

Answer 311

Not an exhaustive list, but these are rare genetic diseases pertaining to stoppage in hemorrhage. All contain **positive family hx**: 1. **Factor V Leiden (most common)** 2. Antithrombin III deficiency 3. Protein S deficiency 4. Protein C deficiency 5. Antiphospholipid antibody syndrome * Anticardiolipin antibodies * Lupus anticoagulant

Question 312

Pathophysiology, Congenital Venous Thrombosis Group (3 differnt options)

Answer 312

* Factor V Leiden – mutated factor V cannot deactivate c Protein C * Antithrombin III/Pro S/Pro deficiency – vital ingredients for clotting cascade are absent * Antiphospholipid antibody syndromes – autoimmune attack on clotting ingredients

Question 313

S/Sx, Congenital Venous Thrombosis Group (3 symptoms, 2 signs)

Answer 313

**Symptoms** 1. Thrombotic event at young age s predisposition 2. Recurrence within individual 3. Extreme pn **Signs** 1. Erythema at clot location 2. Swelling at clot location

Question 314

Differential Dx, Congenital Venous Thrombosis Group (2)

Answer 314

* Immune thrombocytopenia purpura * Thrombotic microangiopathies * Thrombotyc Thrombocytic Purpura * Hemolytic Uremic Syndrome

Question 315

Diagnostic Tests, Congenital Venous Thrombosis Group (3)

Answer 315

1. PTT – increased 2. Factor assays, results vary c etiology 3. US

Question 316

Medical Tx, Congenital Venous Thrombosis Group (2)

Answer 316

1. Anticoagulation c heparin, warfarin, and asprin (in heterozygous Factor V Leiden) 2. Avoid hormone replacement therapy

Question 317

Clinical Pearl, Congenital Venous Thrombosis Group

Answer 317

These diseases can cause fetal demise. Genetic screening recommended for