Smith - Sickle Cell

What are the two major pathophysiologic consequences of sickle cell disease?

Hemolytic anemia and vaso-occlusion

What is the lifespan of a normal red blood cell?

Approximately 120 days

What is the lifespan of a sickled red blood cell?

Approximately 10-20 days

What genotype represents sickle cell anemia?

HbSS

What genotype represents sickle cell trait?

HbAS

What genotype represents sickle hemoglobin-C disease?

HbSC

What hemoglobin predominates at birth and initially protects infants with SCD from symptoms?

HbF

At approximately what age does anemia usually appear in patients with HbSS?

4-6 months after birth

What happens to the reticulocyte count in SCD due to chronic hemolysis?

It is elevated

Why does SCD cause functional asplenia?

Vaso-occlusion obstructs splenic blood flow and damages splenic function

Which three encapsulated organisms are especially important in functional asplenia (SHIN)?

Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis

What is dactylitis in SCD?

Pain and swelling of the hands and feet

When should neonatal screening for SCD occur?

Before 2 months of age

What should happen after a positive neonatal SCD screen?

A second confirmatory test should be performed by 2 months of age

What are the major goals of SCD treatment?

Reduce symptoms and crises, prevent complications, improve quality of life, decrease hospitalizations and morbidity, and improve mortality

What is the penicillin VK dose for SCD patients from 2 months to 3 years old?

125 mg PO twice daily

What is the penicillin VK dose for SCD patients from 3 to 5 years old?

250 mg PO twice daily

What can be used instead of penicillin VK in a penicillin-allergic patient?

Erythromycin

Until approximately what age is prophylactic penicillin VK given in children with SCD?

Until 5 years of age

What is the major therapeutic purpose of RBC transfusion in SCD?

Lower the percentage of HbS and increase hemoglobin oxygen saturation, reducing the likelihood of vaso-occlusion

What HbS target is associated with reduced vaso-occlusive pain and acute chest syndrome in HbSS?

HbS less than 30%

What are major risks of repeated blood transfusions in SCD?

Transfusion reactions, alloimmunization, delayed hemolytic transfusion reactions, hyperviscosity, viral transmission, and iron overload

Why can excessive transfusion cause hyperviscosity in SCD?

Donor RBCs raise the hematocrit and viscosity, which can trigger vaso-occlusion

When do delayed hemolytic transfusion reactions usually occur after transfusion?

Usually 7-10 days after transfusion

What are major acute indications for transfusion in SCD?

Acute stroke, acute bleeding, symptomatic acute chest syndrome, certain surgeries, hepatic or splenic sequestration, aplastic crisis, acute symptomatic anemia, and acute multiorgan failure

Should an uncomplicated vaso-occlusive pain crisis routinely be treated with blood transfusion?

No

Should asymptomatic chronic anemia in an SCD patient automatically be treated with transfusion?

No

What two criteria from the lecture indicate chronic iron overload requiring consideration of chelation?

At least 100 mL/kg of PRBC transfusions plus serum ferritin consistently greater than 1000 mcg/L

Which iron chelator is taken orally once daily?

Deferasirox (Exjade or Jadenu)

Which iron chelator is taken orally in 2-3 divided doses?

Deferiprone (Ferriprox)

Which iron chelator is administered IV or SQ over 8-24 hours for 5-7 days per week?

Deferoxamine (Desferal)

What is the general mechanism of the iron chelators?

They bind iron to form a complex that can be excreted

What antacid ingredient should be avoided with iron chelation therapy according to the lecture?

Aluminum

What urine discoloration can occur during iron chelation therapy?

Pink, red, or orange-colored urine

What is hydroxyurea's major mechanism in SCD?

It increases HbF production, which reduces HbS polymerization and RBC sickling

What important additional effect does hydroxyurea have on RBCs and the endothelium?

It decreases RBC adhesion to the endothelium

When should hydroxyurea be considered in an adult based on frequency of pain crises?

At least 3 moderate-to-severe pain crises during a 12-month period

What pretreatment assessments should be obtained before starting hydroxyurea?

CBC with differential, reticulocyte count, MCV, quantitative HbF, renal function, liver function, and pregnancy test when applicable

What is the initial adult hydroxyurea dose?

15 mg/kg/day

What is the initial pediatric hydroxyurea dose?

20 mg/kg once daily

How is hydroxyurea titrated?

Increase by 5 mg/kg/day every 8 weeks based on clinical and laboratory findings

What is the maximum hydroxyurea dose from the lecture?

35 mg/kg/day

What is the major dose-limiting adverse effect of hydroxyurea?

Bone marrow suppression

What ANC represents the usual hydroxyurea toxicity cutoff?

ANC less than 2,000 cells/mm3

What platelet count represents the hydroxyurea toxicity cutoff?

Platelets less than 80,000 cells/mm3

What should be done if neutropenia or thrombocytopenia occurs during hydroxyurea therapy?

Hold hydroxyurea for 1-2 weeks and reassess; if counts normalize, resume at a lower dose as specified in the lecture

How long may hydroxyurea take to produce a clinical response?

Approximately 3-6 months

What laboratory value commonly increases with hydroxyurea and can correlate with adherence?

MCV

What is L-glutamine (Endari) used for in SCD?

Prevention or reduction of acute SCD complications; it is NOT useful for treating an active crisis

What is crizanlizumab used for and how is it dosed?

It reduces the frequency of vaso-occlusive crises; 5 mg/kg IV over 30 minutes at weeks 0 and 2, then every 4 weeks

How is an uncomplicated vaso-occlusive pain crisis managed?

Rapid pain management with nonopioids and/or opioids plus supportive care such as hydration, oxygen when needed, heat, and laboratory monitoring

What findings should make you suspect acute chest syndrome?

A new chest X-ray infiltrate with findings such as fever, cough, chest pain, oxygen saturation below 90%, increased work of breathing, or wheezing

What empiric antibiotics are listed for acute chest syndrome?

Ceftriaxone plus azithromycin OR moxifloxacin

What supportive treatments are used for acute chest syndrome?

Bronchodilators, pain management, IV hydration, oxygen, and incentive spirometry

At what hemoglobin level does the lecture recommend transfusion in acute chest syndrome?

Hemoglobin less than 9 g/dL

What is an aplastic crisis and how is it managed?

An acute drop in hemoglobin in response to bacterial or viral infection; treat with transfusion

What is splenic sequestration and how is it managed?

Acute anemia from trapping a large blood volume in the spleen; treat with transfusion, hydration, and potentially splenectomy with appropriate immunizations

What is priapism in SCD and what intervention is recommended?

An erection lasting more than 4 hours; obtain urology/surgical consultation

Should a new disease-modifying therapy be initiated during an acute SCD crisis?

No; disease-modifying therapy should not be initiated during the acute crisis