SCD Flashcards
Which chain of hemoglobin is defective in SCD?
Beta chain
What are the possible defects in the beta chain in SCD?
HbSS
HbSC
SB+-thalassemia (some beta-globulin produced)
SB(null)-thalassemia (no beta-globulin produced)
What are the clinical features of HbSS?
Pain crises Microvascular disruption of organs Gallstone Priapism Leg ulcers Anemia
What are the clinical features of HbSC?
Painless hematuria
Pain crises less common and occur later in life
Mild anemia
What are SB+-thalassemia clinical features?
Rare crises
Less severe than SCD (production of HbA)
What are SB(null)-thalassemia clinical features?
Similar severity to HbSS
Anemia
What are the clinical features for sickle cell trait?
Generally asx
What element is a sickled RBC lacking?
Oxygen
What are the outcomes of sickled cells?
Increased viscosity
Adhesion
Occlusion
When do s/sx appear after birth?
4-6 months
What are lab findings for SCD?
Decreased hgb
Increased retic count
Sickled cells on peripheral blood smear
What is the clinical presentation for SCD?
Acute pain Dactylitis Pallor Weakness Splenomegaly Hepatomegaly Abdominal pain
What infections are we worried about in SCD?
SHiNS Step pneumoniae H influenzae type b Neisseria meningitides Salmonella
What vaccinations do patients with SCD receive?
Pneumococcal
Hib
Meningococcal
Flu
If a patient has HbSS, SB(null) thalassemia, or HbSC, and is 2 months to 3 years old, what penicillin dose do we prophylax with?
Oral penicillin VK 125mg PO BID
If a patient has HbSS, SB(null) thalassemia, or HbSC, and 3 years old to 5 years old, what penicillin dose do we prophylax with?
Penicillin VK 250 mg PO BID
Which vitamins (and their doses) do we regularly replace?
Folic acid 1 mg PO/day
B12 up to 1000mcg PO/day
What are the types of chronic blood transfusion therapy?
Simple
Exchange
What are indications for blood transfusions?
May reduce stroke risk in children at high risk
Symptomatic severe acute chest syndrome
Acute splenic sequestration and severe anemia
What are risks of chronic blood transfusions?
Alloimmunization
Infection transmission
Iron overload
How can we reduce risks in chronic blood transfusions?
Blood cross-matching
Immunizations and screening
Iron chelation therapy
When is iron chelation therapy used after chronic transfusions?
Consider after a year of transfusions
OR
When ferritin > 1500 mcg/L
What are the types of iron chelation therapies?
Deferoxamine
Deferasirox
Deferiprone
Which iron chelation therapies are not oral?
Deferoxamine (IV/SQ)
What is the common dose of deferoxamine?
20-50 mg/kg/d over 8-24 hours
What is the common dose for deferasirox?
Exjade: 20-40 mg/kg/d
Jadenu: 14-28 mg/kg/d
What is the common dose for deferiprone?
75-99 mg/kg/d
What is the frequency of deferoxamine dosing?
5-7 days/week
What is the frequency of deferasirox dosing?
Daily
What is the frequency of deferiprone dosing?
TID
What are the AEs of deferoxamine?
Injection site reactions Arthralgias Ocular and ototoxicities Growth retardation Renal disturbances
What are the AEs of deferasirox?
Renal and hepatic failure
Agranulocytosis
Gastrointestinal hemorrhage
What are the AEs of deferiprone?
QT prolongation
GI upset
Elevated LFT
Agranulocytosis
What is the rationale for use of hydroxyurea of SCD?
Increased HbF levels
Increased HbF-containing reticulocytes and intracellular HbF
Ribonucleotide reductase inhibitor
Antioxidant properties
What are the baseline labs?
CBC, reticulocyte count, WBC differential
HbF measurement
Renal and liver function tests
Pregnancy test
What is the dosing for hydroxyurea?
15 mg/kg PO QD
Max = 35 mg/kg
How can hydroxyurea be increased/
5 mg/kg/day every 12 weeks
What is the dosing of the liquid hydroxyurea suspensions?
100mg/ml
How do we monitor for hydroxyurea?
Efficacy: less pain episodes and hospitalizations, improved well being
HbF: Every 3 months x 2, then every 6 months
CBC w/diff
Periodic renal and liver function tests
What are the toxicity cut offs for hydroxyurea?
ANV < 2,000 Plt < 80,000 Hgb < 5 or 20% reduction SCr > 50% above baseline ALT 100% increase
If there is a toxicity with hydroxyurea, what is the course of action?
Stop for 1-2 weeks and resume (if normal counts) at 5 mg/kg/d less than previous dose
If toxicity does not recur after 12 weeks on lower dose, the dose may be increased
What is the counseling for hydroxyurea?
Bleeding risk
Infections
Status regarding pregnancy
Wash hands before and after handling
What oral powder was approved to reduce severe complications associated with SCD in > age 5?
L-glutamine
What is the MOA of Crizanlizumab?
Monoclonal antibody binds to P-selectin and blocks interaction with PSGL-1 (may prevent vasoocclusion by inhibiting adhesion of erythrocytes to vessel walls
What SCD affect does crizanlizumab work on?
Significantly lower rate of pain crises
What are the strategies to modify disease outcomes?
Hydroxyurea
L-glutamine
Crizanlizumab
HSCT
What causes vasoocclusive crisis or acute pain crisis?
Bone or muscle infarction d/t vasoconstriction
What is the most common reason for hospitalization?
Vasoocclusive crisis or acute pain crisis
What is the treatment for vasoocclusive crisis or acute pain crisis?
Hydration and pain management
What are acute complications of SCD?
Vasoocclusive crises/acute pain crisis
Fever and acute infection
Acute chest syndrome
Compared to normal, how must we increase hydration in an acute pain crisis or vanoocclusive crisis?
1.5 times maintenance
What is the regular hydration maintenance requirement for adults?
30-35 ml/kg
What is the regular hydration maintenance requirement for children?
For the first 10kg: 100ml/kg per day
For the 2nd 10kg: 1000ml + 50Ml/kg per day
For more than 20kg: 1500mL + 20 ml/kg per day for each kg over 20 kg
Why do we monitor fluid status during hydration?
Volume overload can lead to acute chest syndrome
What are chronic complications of SCD?
Retinopathy Anemia, leukocytosis OSA Pulmonary hypertension Indirect hyperbilirubinemia Cardiomegaly Chronic renal failure Functional asplenia Avascular necrosis Delayed puberty Skin ulcers
What are acute complications of SCD?
Stroke, meningitis Post-hyperma glaucoma, retinal infarction Acute chest syndrome Sickle hepatopathy Splenic sequestration, splenic infarction Cholelithiasis Priapism Bone marrow infarction, osteomyelitis
Does Fetal Hgb (HgF) sickle?
No
What are non pharm approaches for pain management in SCD?
Hydration
Heating pads
Ect
What are pharm options for pain management of SCD?
Opioids 1st line for mod-sev pain
Morphine sulfate or hydromorphone most common
PCA with basal and on demand options
NSAIDs in combo with opioids - esp for bone pain
Bowel regimen
Antihistamines for itching
Antiemetics for n/v
Which medications are used for bowel regimens?
Senna-colace
Polyethylene glycol
Why are fever and acute infection increased in SCD?
Loss of splenic function
What are the manifestations of fever and acute infection in SCD?
Pneumonia
Osteomyelitis
Meningitis
Bacteremia
What are the likely organisms that occur in SCD?
SHiNS
Mycoplasma pneumonia
Viral influenza
How do we diagnose infections and fever in SCD?
Fever WBC Cultures Imaging Lumbar punctures
What leads to acute chest syndromes?
Vasoocclusive crisis of pulmonary vasculature
What are the etiologies of acute chest syndrome?
Infection
Pulmonary vascular occlusion
Pulmonary edema
What is the presentation of acute chest syndrome?
Acute fever Respiratory symptoms New infiltrates on chest x-ray Hypoxia Pain Wheezing
What other condition is radiologically indistinguishable from acute chest syndrome?
Pneumonia
What are the antimicrobials used in acute chest syndromes?
Ceftriaxone Or Cefotaxime + Azith Or Moxifloxacin
What is the management for acute chest syndrome?
Bronchodilators Hydration Pain management O2 etc
