Sickle Cell Disease

Question 1

HbS Phenotype

Answer 1

Single base substitution (valine –> glutamic acid)

HbS is less soluble than normal Hb when deoxygenated –> polymerize and block tissues (end-organ ischemia and necrosis) + more fragile RBCs so lysed

Question 2

Vaso-Occlusive Crisis (what are they and what causes them?)

Answer 2

• acute episodes of intense hemolysis and trapping
• Main Factors - hypoxemia, RBC dehydration, RBC conc/viscosity
• Ex) inadequate fluid replacement, surgical or psych stress, thermal changes, exposure to loq O2 environment, infections

Question 3

SCD Tx Options

Answer 3

• Acute - hydroxyurea (for VOE, pain, acute chest) - inc fetal Hb
• HSC Transplant is curative (stabilizes or reverses end organ damage)
• Indications for HSC transplant- stroke, recurrent acute chest, frequent pain crisis

Question 4

Heme Symptoms

Answer 4

hemolysis –> anemia

if dec Hb is out or proportion to anemia then suspect splenic sequestration (multiple splenic infarcts and even auto-splenectomy is common)

inc neutrophils and platelets but chronically suppressed haptoglobin

if severe VOE then can have bone marrow infarcts –> fat embolization

Question 5

What are the possible negative outcomes of transfusions in these patients?

Answer 5

alloimmunization against RBCs and hemosiderosis (iron deposition in heart, liver, endocrine glands)

Question 6

Neuro Symptoms

Answer 6

• inc risk of stroke

- accelerated brain aging and vascular dementia in 40s

Question 7

Optho Symptoms

Answer 7

retinal disease (occlusion of arteriole –> vascular proliferation and neo-vascularization –> retinal hemorrhage and detachment)

• Esp in HbSC (inc blood viscosity)

Question 8

Kidney Symptoms

Answer 8

• hematuria from papillary necrosis
• proteinuria (primarily FSGS - inc risk AA)
• inability to conc urine (predisposes to dehydration)
• tubular acidoses –> hyperkalemia (bad b/c inc K+ in lysis and if on ACEi)
• hyperphosphatemia and hyperuricemia

Question 9

GI Symptoms

Answer 9

-nausea, vomiting, gastroparesis (may be due to microvasculature sickling of ANS), diarrhea from chelating agents, liver sequestration

Question 10

Immune Issues

Answer 10

-functional asplenia so susceptible to encapsulated organisms (Strep pneumo, H flu, N meningitidis); prophylaxis and vaccinate

Question 11

Pulm Symptoms

Answer 11

• acute chest syndrome (fever, pleuritic chest pain, oxygen desaturation and multi-lobar infiltrates); often comes few days after VOE crisis, infection or fat embolus
• Must dx sep from pneumonia b/c give transfusion in addition to abx
• Chronic pulm fibrosis and pulm HTN

Question 12

What allele combinations are possible?

Answer 12

HbSS, HbS/beta+, HbSC