🧠 Sickle Cell Disease for USMLE Step 1: Pathophysiology, Crises, and Treatment

Sickle Cell Disease (SCD) is one of the most tested genetic hemoglobinopathies on Step 1. It integrates:

• Molecular mutation → protein dysfunction

• Clinical crises

• Microvascular complications

• High-yield management concepts

Let’s walk through everything you need to dominate this topic on exam day.

🧬 Genetic Mutation and Pathogenesis

Mutation	Point mutation in β-globin gene (Glu → Val at position 6)
Inheritance	Autosomal recessive
Protein Change	Hemoglobin S (HbS) polymerizes under low O₂, acidosis, or dehydration
Effect	Distorted, rigid RBCs cause hemolysis and microvascular occlusion

🧠 Step 1 Clue: Sickle shape = crescent RBCs, best seen on peripheral smear

🔥 Vaso-Occlusive Crisis (VOC)

Trigger	Examples
↓ Oxygen	Infection, high altitude, acidosis
Dehydration	Vomiting, diarrhea, low fluid intake
Cold exposure	Vasoconstriction reduces perfusion
Stress	Inflammatory cytokine response

Symptoms:

• Acute pain (esp. in long bones, chest)

• Dactylitis in children

• Priapism

• Acute chest syndrome

• Stroke

• Splenic infarction → autosplenectomy

📉 Chronic Complications

Organ/System	Effect
Spleen	Autosplenectomy → ↑ infection risk
Bone	Avascular necrosis (femoral head)
Lungs	Pulmonary hypertension
Brain	Stroke, silent infarcts
Kidneys	Papillary necrosis, hematuria
Eyes	Retinopathy

💊 Treatment & Management

Strategy	Purpose
Hydroxyurea	↑ HbF → ↓ sickling frequency
Folate supplementation	Supports RBC production in chronic hemolysis
Pain control	Manage vaso-occlusive crises
Blood transfusion	Severe anemia, stroke, or acute chest syndrome
Vaccination	Prevent infection (encapsulated organisms)
Penicillin prophylaxis	For children <5 years old

🧠 Mnemonics to Master

“SICKLE” Triggers for Crisis:

• Stress

• Infection

• Cold

• Ketosis (acidosis)

• Low O₂

• Exercise (exertion)

“HbS = Sticky Hemoglobin S”

→ Stickiness causes microvascular plugging

⚠️ Step 1 Clinical Clue

A 5-year-old with anemia, hand swelling, and a family history of hemoglobinopathy has dactylitis and a low hematocrit. What’s the next step?

✅ Answer: Sickle cell screen (Hb electrophoresis)
✅ Diagnosis clue: Pain + autosomal recessive + African descent

🎯 Call-To-Action

Need to visually memorize all hemoglobinopathies for Step 1?

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