Diagnostic Tests for Cystic Fibrosis, DVT, HIV, and Sickle Cell Anemia

Cystic Fibrosis

The sweat chloride test via pilocarpine iontophoresis is the gold standard diagnostic test for cystic fibrosis, with values >60 mmol/L confirming the diagnosis in patients with compatible clinical features. 1

Diagnostic Algorithm for CF

Initial test: Sweat chloride measurement by pilocarpine iontophoresis with collection on gauze, filter paper, or Macroduct coil 1
Diagnostic threshold: Sweat chloride >60 mmol/L on two separate occasions confirms CF in patients with characteristic clinical features (chronic respiratory symptoms, malabsorption, positive family history, or positive newborn screening) 2, 3
Borderline results (30-60 mmol/L): Require CFTR mutation analysis to identify two disease-causing mutations 3
Normal sweat chloride (<30 mmol/L) with clinical suspicion: Perform nasal potential difference measurement on two separate days to document CFTR dysfunction 2

Supporting Tests

CFTR genetic testing: Identifies specific mutations, essential for mutation-specific therapies and useful when sweat chloride is borderline or normal 1, 4
Nasal potential difference or intestinal current measurement: Bioassays of CFTR function for diagnostically complex cases 1

Common Pitfalls

Less than 5% of patients have inconclusive initial results requiring referral to expert centers 1
CF has a wide disease spectrum; diagnosis is increasingly made in adults with milder phenotypes 1
Newborn screening is not foolproof and can miss diagnoses or yield screen-positive inconclusive diagnoses (CFSPID) 1

Deep Vein Thrombosis (DVT)

For suspected first lower extremity DVT, the diagnostic approach depends on pretest probability assessment, with D-dimer testing and proximal compression ultrasound (CUS) as the primary diagnostic modalities. 5

Diagnostic Algorithm Based on Pretest Probability

Low Pretest Probability

Initial test: Moderately or highly sensitive D-dimer 6, 5
If D-dimer negative: No further testing required 6, 5
If D-dimer positive: Proceed to proximal CUS 6
If proximal CUS negative: No further testing needed 6

Moderate Pretest Probability

Initial test: Highly sensitive D-dimer or proximal CUS 6, 5
If D-dimer negative: DVT excluded, no further testing 6
If proximal CUS negative: No further testing required 6

High Pretest Probability

Initial test: Proceed directly to proximal CUS or whole-leg ultrasound 6, 5
If positive: Treat for DVT 6
If negative: Consider serial CUS at day 3 and day 7, or highly sensitive D-dimer 6

Alternative Imaging

When ultrasound is impractical (leg casting, excessive subcutaneous tissue): CT venography, MR venography, or MR direct thrombus imaging 6
Venography: Historical gold standard but not routinely used 6

Special Populations

Pregnant patients: Initial proximal CUS preferred over D-dimer (which has reduced specificity in pregnancy) 6, 5
Upper extremity DVT: Combined modality ultrasound (compression with Doppler or color Doppler) as initial test 6
Suspected isolated iliac vein thrombosis: Doppler US of iliac vein, venography, or direct MRI if standard proximal CUS is negative 6

Common Pitfalls

D-dimer has high sensitivity but limited specificity; falsely elevated in pregnancy, inflammation, malignancy, and advanced age 7, 5
Initial ultrasound may be preferred over D-dimer in patients with comorbid conditions likely to cause elevated D-dimer 5
Age-adjusted D-dimer thresholds (age × 10 ng/mL) should be used in patients >50 years to improve specificity 7
Never initiate anticoagulation based solely on elevated D-dimer without confirmatory imaging 7

HIV (Human Immunodeficiency Virus)

The diagnostic test for HIV involves a two-step algorithm: initial screening with a fourth-generation antigen/antibody immunoassay, followed by confirmatory testing with HIV-1/HIV-2 antibody differentiation assay and HIV-1 RNA testing if discordant.

Standard Diagnostic Algorithm

Initial screening: Fourth-generation HIV-1/2 antigen/antibody combination immunoassay (detects both HIV antibodies and p24 antigen)
If positive: Perform HIV-1/HIV-2 antibody differentiation immunoassay
If differentiation assay is negative or indeterminate: Perform HIV-1 RNA nucleic acid test (NAT)
Window period: Fourth-generation tests can detect infection 2-4 weeks post-exposure

Confirmatory Testing

HIV-1 RNA viral load: Confirms active infection and quantifies viral burden
Western blot: Largely replaced by differentiation immunoassays but may still be used in some settings

Common Pitfalls

Acute HIV infection may be missed by antibody-only tests during the window period
False positives can occur; always confirm with supplemental testing
Rapid point-of-care tests require laboratory confirmation if positive

Sickle Cell Anemia

Hemoglobin electrophoresis or high-performance liquid chromatography (HPLC) is the definitive diagnostic test for sickle cell anemia, identifying hemoglobin S (HbS) and distinguishing between sickle cell disease and sickle cell trait.