Okay, let's tackle this question about the investigation of choice for confirming sickle cell disease. First, I need to recall the diagnostic methods for sickle cell disease. I know that sickle cell is an inherited disorder caused by a mutation in the beta-globin gene, leading to abnormal hemoglobin (HbS). The main diagnostic tests involve detecting the presence of HbS.

The core concept here is that the gold standard for diagnosing sickle cell disease is hemoglobin electrophoresis. This test separates different types of hemoglobin based on their charge, allowing the identification of HbS. Another possible test might be isoelectric focusing, which is a more refined method of electrophoresis. Alternatively, genetic testing could be used, but that's more for confirming specific mutations rather than the primary diagnosis.

Looking at the options, the correct answer is likely hemoglobin electrophoresis. The other options might include things like peripheral blood smear, which can show sickle cells but isn't as definitive. CBC might show anemia but doesn't confirm the disease. Urine tests aren't relevant here. So, the correct answer is hemoglobin electrophoresis.

Wait, but some sources mention that newborn screening uses Hb electrophoresis. Also, in a symptomatic patient, a peripheral blood smear under low oxygen conditions can show sickled cells, but that's not as reliable. So the investigation of choice is definitely hemoglobin electrophoresis. The other options would be incorrect because they don't specifically detect HbS. For example, CBC can show microcytic anemia but isn't diagnostic. Urinalysis is unrelated. Genetic testing is more for confirming mutations in specific cases but not the first-line test. So, the correct answer is hemoglobin electrophoresis.

**Core Concept**
Sickle cell disease (SCD) is diagnosed by identifying abnormal hemoglobin (HbS) caused by a point mutation in the β-globin gene. The gold standard is **hemoglobin electrophoresis**, which separates hemoglobin variants based on charge differences, allowing specific detection of HbS and HbA2 levels.

**Why the Correct Answer is Right**
**Hemoglobin electrophoresis** confirms SCD by demonstrating **HbS as the predominant hemoglobin** (>90%) and elevated HbA2. In sickle cell trait (heterozygous), HbA and HbS are present in a 1:1 ratio. The test is specific, sensitive, and widely available, making it the investigation of choice. For newborn screening, isoelectric focusing (a more precise electrophoretic technique) is often used.

**Why Each Wrong Option is Incorrect**
**Option A: Peripheral blood smear** – Shows sickled RBCs but requires deoxygenation to visualize sickling and is not definitive alone.
**Option B: Complete blood count (CBC)** – May reveal anemia, microcytosis, or nucleated RBCs but does not confirm HbS.
**Option C: Urinalysis** – Unrelated to diagnosing SCD; used for complications like hemoglobinuria.
**Option D: Genetic testing** – Detects β-globin gene mutations (e.g., GAG→GTG) but is not first-line for routine diagnosis

✓ Correct Answer: C. High performance liquid chromatography