Anemia, Sickle Cell

ANEMIA: Defined by the WHO as

1. Hb ___ g/dL in men

2. Hb ___ g/dL in women

1. <13

2. <12

RED BLOOD CELL PRODUCTION

1. Complete maturation process takes about _____

2. ______ and ____ are incorporated gradually into the RBC

3. Becomes erythrocyte within a couple days, erythrocyte has a normal survival time of ____

4. Erythropoietin 90% produced by ______ → initiates and stimulates _______

1. 1 week

2. Hb, iron

3. 120 days

4. kidneys → RBC prod

Anemia clinical presentation: GENERAL (7)

1. fatigue

2. dizziness

3. tachycardia

4. SOB

5. edema

6. dry skin, chapped lips, brittle nails

7. pale mucous memb

Anemia clinical presentation: ACUTE RAPID (4)

1. palpitations/tachycardia

2. angina

3. hypotension

4. breathlessness

COMPLETE BLOOD COUNT

1. Normal Hb / Hgb range ____ g/dL

2. Hematocrit (Hct) ____%

3. MCV (mean cell volume) → represents …

4. MCH (mean cell hemoglobin) → represents …

5. Reticulocyte count (premature erythrocytes) ____%

1. 12-16

2. 36-50%

3. Hct/RBC count → avg RBC size

4. Hb/RBC count → amt of Hb in a RBC

5. 0.5-2%

MICROCYTIC ANEMIA

1. Result of a deficiency in ____ synthesis

2. Usually due to ______ or _______

3. Irons from an animal source _____ is ~3X more absorbable than ____ iron found in veggies/fruits/nuts/dietary supplements

4. ______ enhances absorption up to 100%

5. ______, _____, _____ reduces absorption

1. Hb

2. iron def, impaired iron utilization

3. heme iron > non heme

4. vit C

5. calcium, grains/brans, tea/coffee

1. ______ is a plasma protein that delivers iron to bone marrow for incorporation into Hb molecule

2. ______ represents “stored iron” in the liver, spleen, bone marrow

1. transferrin

2. ferritin

Combination of __________ and ________ is indicative of IRON DEFICIENCY

low serum iron + high TIBC (total iron binding capacity)

1. ______ is the most sensitive and earliest indicator of iron deficiency or iron overload

2. ______ only in iron deficiency

1. ferritin

2. DEC

IRON DEFICIENCY ANEMIA: PRESENTATION

1. ____ nails

2. _________

3. _____ (cracked tongue)

4. _____ (cracked lips)

5. Craving for nonfood items: ______

6. May have _________

7. Lab findings → 3

1. brittle

2. nail spooning

3. glossitis

4. angular stomatitis

5. pica

6. restless leg syndrome

7. low/normal serum iron, low ferritin, high TIBC

IRON DEFICIENCY ANEMIA: TREATMENT

1. Usually consists of dietary supplementation & administration of oral iron preparations → 6 forms of Fe2+ absorbed similarly

2. Best absorbed → 4

3. Reduced absorption with … HOWEVER, MAY IMPROVE TOLERABILITY

4. *Counseling w antacids →

5. _______ of elemental iron in 2-3 div doses/day was previously recommended

6. *New studies showed improved absorption and tolerability with ______ OR _______

7. ADES → 4

8. Strategies to improve tolerability → 4

1. sulfate, succinate, lactate, fumarate, glutamate, gluconate

2. Fe2+, meat/fish/poultry, iron-fortified cereals, ascorbic acid

3. tea, coffee, milk

4. take 2h before or 4h after antacid

5. 150-200 mg

6. lower dosing, every-other-day dosing

7. GI, dark stools, abdominal pain, dyspepsia/heartburn

8. +interval, take w food/milk, switch to lower elemental iron, switch to liquid

IRON DEFICIENCY ANEMIA-DRUG INTERXNS

1. Drugs that DECREASE iron absorption → 3

2. Drugs affected by iron → 2

MONITORING/FOLLOW UP

3. Recheck Hb/Hct, iron studies values within _____ after tx initiation

   Check ADEs, tolerability, GI side effects, symptoms

1. antacids, H2RAs, PPIs

2. methyldopa, fluoroquinolones (-floxacins)

3. 4 weeks

PARENTERAL IRON

Iron dextran, sodium ferric gluconate, iron sucrose, Ferumoxytol, Ferric carboxymaltose

1. Indications → 3

2. BBW WARNING → It is recommended that resuscitation equipment and trained staff be available during administration

1. intolerance to oral, malabs (gastric bypass, IBS), long term nonadherence

2. iron dextran, fermoxytyl → sev allergic rxns

MACROCYTIC ANEMIA: VIT B12 DEFICIENCY

1. Lab findings →

2. Presentation → 6

3. Oral Dosing →

4. IM/deep SQ preferred for patients exhibiting _____ or impaired absorption

5. Intranasal gel $$$ → avoid with …

6. ^ DONT admin the spray ____ before/after ingestion of hot foods or beverages (may impair cobalamin abs)

7. MONITORING/FOLLOW UP → Recheck vit B12, Hb/Hct within …

8. Counsel on foods high in vit B12 → 3

1. -B12, +MCV, -reticulocyte/Hct

2. neuropsych, paresthesias, -vibratory sensation in LE, irritability, dementia-like, psychosis

3. 1000-2000 mcg/day

4. neurologic

5. avoid nasal disease or pts w nasal meds

6. 1h

7. 4 weeks then q 3-6m

8. fortified cereal, salmon, trout

MACROCYTIC ANEMIA: FOLATE DEFICIENCY

1. Body stores primarily in ____

2. Food rich in folate (destroyed by cooking or processing) → 6

3. Presentation → SIMILAR TO B12 EXCEPT…

4. Lab findings →

5. Treatment/dosing →

6. ^ why that duration?

7. MONITORING/FOLLOW UP → Recheck folate, Hg/Hct within …

1. liver

2. green leafy veggies/citrus, dairy, yeast, mushrooms, liver, kidney

3. NO neurologic

4. normal vit B12, +MCV, -reticulocyte/Hct, -folate

5. 1-5 mg daily for 4 months

6. clear folate def cells

7. 4 weeks

Folate deficiency in pregnancy

1. Periconceptional folic acid supplementation recommended to DECREASE the occurrence of __________

2. ^ occurs during _____ of life

1. neural tube defects (brain/spinal cord)

2. 3-4th week

T or F:

Folate labs should be initially rechecked in 4 mos to allow time for folate deficient cells to be cleared from circuit.

F (check in 4 weeks, be treated for 4 mos)

Important info to collect for SICKLE CELL patient

patient history →

freq of pain ep/hospitlizations

(determines tx)

SICKLE CELL ANEMIA:

1. Autosomal _______ genetic disorder

2. single gene mutation leads to development of ____

3. SCT =

4. SCD =

5. Ex: if both parents only have SCT, the off spring will have a ____ risk of inheriting SCD

6. ____ risk of SCT

1. recessive

2. HbS

3. hetero (carries trait, HbAS)

4. homo rec (has SC disease, HbSS)

5. 25%

6. 50%

_________ is present predominately in fetal RBCs, prior to birth and is RESISTANT to sickling

fetal Hb (HbF)

CLINICAL MANIFESTATIONS PATHOPHYS

1. 3 known problems of SCD are primarily responsible for various clinical manifestations →

2. result of 2 MAJOR DISTURBANCES involving RBCs →

1. impaired circulation, destruction of RBCs, stasis of blood flow

2. abnormal Hb polymerization, memb dmg

HBS POLYMERIZATION

1. HbS polymerizes only with ______

2. HbS becomes “_____” (-solubility, +viscosity)

   Deoxy-HbS begin to stick together

3. Leads to ______ and loss of deformability

MEMBRANE DAMAGE

4. ______ damage, cells lose ability to become normal again

5. sickle cell life span ______ leads to anemia

DEOXY HBS POLYMERIZATION IS THOUGHT TO DRIVE MOLCULAR PATHOGENESIS OF SCD

1. deoxygenation

2. sticky

3. sickling

4. irreversible

5. 10-20 days

SCD COMPLICATION

1. ___________: caused by adhesion of sickled erythrocytes and leukocytes to endothelium

2. Results in …

3. Adhesion to endothelium during inflam is initiated by ______ → contributes to adhesion of sickled RBCs

1. vaso-occlusion

2. vasc obstruction → ischemia → pain

3. P-selectin

SCD: DIAGNOSIS

1. Identified by neonatal screening _________

2. Anemia usually appears ______ after birth in those who are HbSS

3. Infants can present with pain/swelling of hands and feet →

   HbF is primary Hb at gestation, HbA replaces HbF in normal; HbS replaces HbF in sickle

4. HbF is ________ to polymerization like HbS

1. before 2m

2. 4-6m

3. hand-and-foot syndrome, dactylitis (sausage fingers)

4. not susceptible

SICKLE CELL HALLMARK SYMPTOMS

1. hemolytic anemia

2. vaso-occlusion

SCD: ACUTE PAIN CRISIS MANAGEMENT

1. Pain →

   Patient preferences should drive clinical decisions

2. Supportive care →

1. nonopioids, opioids

2. hydration, O2, heat compresses, oral antihistamines for itching

SCD: BLOOD TRANSFUSION THERAPY

appropriate = life saving

inappropriate = potentially harmful

1. Thought to _________ and _______

2. RISKS →

1. -HbS%, +Hb O2 sat

2. iron overload

SCD: INDICATIONS FOR TRANSFUSION

1. acute _____

2. acute _____

3. acute ________, symptomatic

4. Prior to surgical procedures using general anesthesia, consult hematologist to bring pre-op Hb level to ____ g/dL

5. _____ or _____ sequestration

6. ________

7. acute _______

8. acute symptomatic anemia → 4

1. stroke

2. bleeding

3. chest syndrome

4. 10

5. hepatic, splenic

6. aplastic crisis

7. multi-organ failure

8. HF, dyspnea, hypotension, marked fatigue

SCD: NO TRANSFUSION RECOMMENDED →

1. _________

2. _________

3. _________ anemia

4. _______ in the ______ of multisystem organ failure

1. uncomplicated pain crisis

2. priapism

3. asymptomatic

4. AKI, absence

SCD: IRON OVERLOAD

1. _____ should be used to measure iron stores

2. Goal is to maintain a value NO GREATER THAN _____

3. Chronic iron overload =

4. Iron chelators MOA: bind iron and form a complex that can be _____

5. *1ST LINE FOR IRON OVERLOAD IN SCD →

6. Monitoring →

7. ADEs → 3

1. ferritin

2. 1000-1500 ng/mL

3. >1000 mcg/L

4. excreted

5. deferasirox → Exjade tab for susp, Jadenu tab/granule

6. ferritin after 3m

7. renal, CBC, LFTs

SCD: IRON OVERLOAD (continued)

1. SQ/IV chelator →

2. Dosing interval

3. Side effects → 4

4. Monitoring →

5. →

6. →

7. →

8. →

9. *Other agents (oral) → can use in kidney disease

1. deferoxamine

2. DAILY

3. dose-related visual/aud neurotox, N/V/D, hypotension, anaphylaxis

4. ferritin

5. audiology → prior, q 6m in office, annually audiogram

6. ophthalmology → annual

7. nephrology → +SCr/BUN, urine protein+SCr q 3m

8. LFTs

9. deferiprone

Routine _______ are crucial preventive care in managing SCD

Patients are considered “high risk” for certain infections

immunizations

SCD: PNEUMOCOCCAL (Prevnar) INFECTION PREVENTION

ORAL PENICILLIN until age 5 for children with HbSS

1. dosing →

2. dosing →

3. Use ____ for PCN allergy

4. Ensure completion of _________ before DC

5. Adults 19+ →

6. Other vaccinations to consider

1. <3yo → 125 mg BID

2. 3+ → 250 mg BID

3. erythromycin

4. pneumococcal vax series

5. follow CDC guidelines

6. meningococcal, HIB

CURRENT TXS FOR SCD: Fetal Hemoglobin (HBF) inducer

1. Drug name →

2. MOA:

3. When to initiate: ADULTS with _____ mod-sev pain crises associated with SCD during a ______

4. Pain or severe ____________ that interferes w daily activities/quality of life

5. History of severe or recurrent _____

6. OFFERED FOR ALL … with sickle cell anemia

7. Clinical response to dosing may take up to _______, thorougly educate patient on this before+during therapy

8. MCV (RBC size) correlates with _________

9. STOP IMMEDIATELY IF …

10. It is estimated that approx ____ of adults may be nonresponders

1. hydroxyurea/Hydrea

2. +HbF prod

3. 3+, 12m

4. Symptomatic chronic anemia

5. ACS

6. 9m+, children, adolescents

7. 3-6m

8. dose + adherence

9. STOP if neutropenia or TC → symptoms typically mild/reversible w DC or -dose → may restart following blood count recovery at lower dose

10. 1/3

HYDROXYUREA (HYDREA) PATIENT EDUCATION

1. EFFICACY is correlated with ______

2. Missed dose?

3. All patients should be counseled on the use of _______ while taking hydroxyurea

4. ADEs → 4

1. compliance

2. do not double

3. contraception

4. bone marrow supp, dry skin, leg ulcerations, hyperpig skin/nail

CURRENT TXS FOR SCD (2)

1. Drug =

2. Supplied as _____

3. MOA =

4. Dose =

1. L-glutamine/Endari

2. oral powder

3. +free glutamine to help generate antioxidants

4. <30 kg = 5g BID, 30-65 kg = 10g BID, >65 kg = 15g BID

CURRENT TXS FOR SCD (3)

1. ANTI P-SELECTIN →

2. MOA: binds P-selectin on surface of _____ and ________

3. Dose →

1. crizanlizumab/Adakveo

2. platelets, endothelium in blood vessels → +flow

3. 5 mg/kg IV over 30min on weeks 0, 2, and q 4 weeks after W OR W/O hydroxyurea

SUMMARY OF TREATMENT OPTIONS OF SCD:

Indication →

1. Hydroxyurea (HYDREA)

2. L-glutamine (ENDARI)

3. Crizanlizuman (ADAKVEO)

1. -freq of crises and need for transfusions

2. -acute complications age 5+

3. -freq of VOCs age 16+

GENE THERAPIES → 2

1. Lyfgenia

2. Casgevy

GENE THERAPIES:

LYFGENIA (LOVOTIBEGLOGENE AUTOTEMCEL)

1. Approved for patients _____ with SCD and history of VOEs

2. Patient’s blood stem cells are collected and genetically modified to produce _______ → lower risk of sickling and occluding blood flow

1. 12+

2. HbAT87Q

GENE THERAPIES:

CASGEVY (EXAGAMGLOGENE AUTOTEMCEL)

1. Utilizes _________ genome editing technology

2. Edits portions of __________ which is responsible for repression of HbF

3. MOA: used to induce _____

1. CRISPR/Cas9

2. DNA BCL11A

3. HbF prod

1. CURATIVE THERAPY FOR SCD

2. Must have well-matched ______

3. Most transplants are performed in ____________ but also healthy enough to undergo

1. hematopoietic stem cell transplantation (HSCT)

2. donor

3. children w complications