Family Medicine Board Review · Hematology · Source: Prof. Salam Slides + UpToDate
Sickle Cell Disease: High-Yield Board Summary
Genotype definitions, the seven core complications, vaccination schedule, lab diagnostics, transfusion decision rules, screening calendar, and hydroxyurea safety — all in one board-oriented pass.
Definition & Clinical Features
Sickle cell disease occurs when an individual has two HbS genes, or one HbS gene + another mutant β-globin gene.
Most common compound heterozygous forms: HbS-β-thalassemia and HbSC disease.
HbAS (Sickle Cell Trait)
Asymptomatic
except during extreme hypoxia or infection.
Increased risk of
renal medullary carcinoma.
SCD-SS (HbSS)
Chronic hemolytic anemia · Jaundice in the first year of life · Retarded growth/development ± skeletal changes · Splenomegaly in childhood → splenic atrophy (autosplenectomy) in adulthood
Board trap: sickle trait (HbAS) is generally benign, but don't forget its association with renal medullary carcinoma — a rare but classic single-fact board link.
Complications
1) Acute Chest Syndrome
Presents with chest pain, cough, dyspnea, fever, and a new infiltrate on CXR.
Management: oxygen therapy, antibiotics, fluids, exchange transfusion if needed.
2) Stroke
Children and older adults → more prone to ischemic stroke.
Young adults → more prone to hemorrhagic stroke.
Requires exchange transfusion + routine stroke management.
3) Splenic Sequestration
Presents with LUQ pain + sudden drop in Hb.
4) Liver Sequestration
Analogous hepatic pooling of sickled cells.
5) Aplastic Crisis
Caused by viral infection — classically parvovirus B19. Other viruses: EBV.
6) Painful (Vaso-occlusive) Crisis
The most common acute complication requiring evaluation and management.
7) Infection
Risk driven by functional asplenia — susceptibility to encapsulated bacteria: Streptococcus pneumoniae, Klebsiella, Haemophilus influenzae, Neisseria meningitidis, and Pseudomonas aeruginosa.
Exam pearl: stroke type flips with age — children and elderly = ischemic, young adults = hemorrhagic. This age-based reversal is a classic board trap.
Causes of Sudden Drop in Hemoglobin
1. Splenic sequestration
LUQ pain + rapidly falling Hb
2. Aplastic crisis
Parvovirus B19 (or EBV) suppressing erythropoiesis
3. Hemolytic anemia
Ongoing baseline hemolysis, acutely worsened
Board trap: a sudden Hb drop is a 3-item differential — memorize all three (sequestration, aplastic crisis, hemolysis) rather than anchoring on just one.
Vaccination
- Prophylactic daily penicillin V — start at 2 months of age; may be safely stopped at age 5 if not splenectomized
- Annual influenza vaccination — starting after 6 months of age
- Meningococcal vaccine — for asplenic children
- Pneumococcal vaccine (PPV) — if age ≥2 years; consider revaccination 5 years later
- Before splenectomy: vaccinate against S. pneumoniae, N. meningitidis, H. influenzae type b, and influenza — at least 2 weeks before elective surgery, or at least 2 weeks after emergency surgery
Exam pearl: the pre-/post-splenectomy vaccine timing rule (2 weeks before elective, 2 weeks after emergency) is a frequently tested logistics point — don't just know what to give, know when.
Investigations in SCD
| Test | Key Value / Note |
|---|
| Sickle solubility test | Can be positive in trait or disease — cannot distinguish between the two |
| HPLC | Quantifies sickle hemoglobin and other hemoglobin types — the definitive quantitative test |
| Sickle cell trait (SCT) | HbS 45% and less |
| Sickle cell disease (SCD) | HbS 65% and above |
| Acceptable HbA2 in SCD | <5.5% — if higher, consider concomitant sickle cell beta-thalassemia |
Board trap: a positive sickle solubility (Sickledex) test does not confirm disease — it can't differentiate trait from disease. HPLC is required for definitive quantification.
Type of Blood Transfusion
| Simple Transfusion | Chronic Simple Transfusion | Exchange Transfusion | Chronic Exchange Transfusion |
|---|
| Symptomatic anemia; acute neurological event; acute chest syndrome; preparation for major surgery; acute splenic or hepatic sequestration; sepsis and meningitis |
Prevention of recurrent stroke; recurrent acute chest syndrome; recurrent multi-organ failure; symptomatic anemia with renal failure; pulmonary hypertension or chronic hemolysis; chronic heart failure |
Acute neurologic event; severe acute chest syndrome; preparation for major surgery; avoiding iron loading |
Maintenance of HbS level below 30%; primary prevention of stroke as determined by transcranial Doppler; secondary prevention of stroke; repeated episodes of ACS despite hydroxyurea therapy; pulmonary hypertension; recurrent priapism |
Decision rule — memorize exactly:
• If vital signs unstable → go for simple transfusion, provided Hb is below 7 g/dL; do an exchange afterward if still needed.
• If Hb is 9 g/dL or above → always go for exchange transfusion (never simple — risk of hyperviscosity from raising Hb further on top of an already adequate level).
Screening for Complications
Regular blood work
CBC, reticulocytes, iron indices, BUN, LFTs, creatinine
Urinalysis
Annually — proteinuria, glomerulopathy
Transcranial Doppler
Annually,
age 2–16 — stroke prevention
Retinal exam
Annually starting
age 8 — retinopathy screening
Echocardiography
Once in late childhood/early adulthood — pulmonary hypertension screening
DXA scan
No clear indication for timing
Board trap: transcranial Doppler (age 2–16) and retinal exams (starting age 8) have different start ages and different age ranges — don't merge them into one generic "annual screening" answer.
Supplements
- Folic acid — given to all patients
- Multivitamin without iron — for all patients
- Vitamin D and calcium — if deficient
- Zinc — replace if deficient, as SCD patients are more prone to zinc deficiency
Exam pearl: multivitamin is specifically given without iron — SCD patients undergo chronic hemolysis and often receive transfusions, both of which predispose to iron overload, so routine iron supplementation is avoided unless deficiency is confirmed.
Hydroxyurea
Side Effects (Table 1)
Toxic
Myelosuppression — leukopenia/neutropenia, thrombocytopenia, anemia; megaloblastic erythropoiesis
Idiosyncratic
Nausea, vomiting, stomatitis, anorexia, diarrhea, constipation, skin rash, erythema, hair loss
Effects reported in animals
Carcinogenesis, teratogenesis
Long-term effects
Unknown
- Can be started as young as 9 months old
- Should be stopped 3 months before planning pregnancy — for both males and females
- Not recommended during breastfeeding
Board trap: the pregnancy-planning stop rule applies to both partners (male and female), not just the mother — a detail boards specifically test given hydroxyurea's reported teratogenic potential.
SCD and Diabetes Mellitus
Best test to monitor DM in a patient with SCD: fructosamine levels.
Exam pearl: HbA1c is unreliable in SCD due to altered RBC turnover/hemolysis and the presence of abnormal hemoglobin. Fructosamine remains unaffected by hemoglobinopathies and should be used instead to monitor glycemic control in SCD patients with diabetes.