What is the appropriate workup and treatment for a patient presenting with paleness and fatigue, suspected of having anemia or other underlying conditions?

Workup for Paleness and Fatigue

Begin with a complete blood count (CBC) to assess for anemia, followed by serum ferritin to evaluate iron stores, and then systematically investigate reversible causes including nutritional deficiencies, thyroid dysfunction, sleep disturbances, and medication effects. 1, 2

Initial Laboratory Assessment

Screen with CBC and ferritin first:

• Obtain hemoglobin, hematocrit, and red blood cell indices to identify anemia 3, 4
• Measure serum ferritin as the most efficient test for iron deficiency 3
• Check electrolytes including sodium, potassium, calcium, magnesium, and iron levels, as imbalances are often reversible and may reduce fatigue 1

Expand testing based on initial findings:

• Vitamin B12, folate, and vitamin B6 levels (particularly if macrocytic anemia or malabsorption suspected) 1
• Vitamin D, as low levels are linked to muscle fatigue 2
• Thyroid function tests (TSH) to exclude thyroid dysfunction 2
• Inflammatory markers if chronic disease suspected 1, 5

Systematic Assessment of Contributing Factors

Evaluate concurrent treatable conditions that commonly cause or worsen fatigue:

Anemia and Iron Deficiency

• Iron deficiency is one of the most common causes of anemia and fatigue 3
• Anemia can dramatically decrease physical functioning, particularly when fatigue intensity reaches level 7 or higher on a 0-10 scale 2
• Identify the source: menstrual blood loss in women or gastrointestinal bleeding (most common etiologies) 3
• Note that isolated iron deficiency without anemia is not a clinically relevant contributor to fatigue 1

Nutritional Status

• Assess weight changes, caloric intake, and impediments to nutritional intake 1
• Screen for deficiencies in copper, zinc, phosphate, and magnesium 1
• Refer to a dietitian if substantial nutritional abnormalities are identified 1

Sleep Disturbances

• Query about sleep quality, duration, and patterns 1
• Assess for depression, as this commonly manifests with sleep disturbances 1
• Evaluate for obstructive sleep apnea, particularly if risk factors present 1
• Screen for poor sleep hygiene: irregular sleep schedule, daytime napping, caffeine/alcohol intake before bed, excessive screen time 1

Medications

• Review all current medications including over-the-counter, herbal supplements, and vitamins 1
• Note recent medication changes 1
• Identify medications that may contribute to fatigue: β-blockers (causing bradycardia), narcotics, antidepressants, antiemetics, antihistamines 1
• Consider adjusting dosage or dosing intervals rather than discontinuing when possible 1

Functional and Activity Assessment

• Determine if the patient can accomplish normal daily activities 1
• Assess current exercise patterns and whether activity has decreased since fatigue onset 1
• Evaluate for deconditioning, which can perpetuate fatigue 1

Psychosocial Factors

• Screen for depression and anxiety 1, 2
• Assess for alcohol or substance abuse 1
• Evaluate work or school-related stress 1

Treatment Approach Based on Findings

For confirmed iron deficiency anemia:

• Oral iron supplementation: ferrous sulfate 324 mg (65 mg elemental iron) provides 362% of the U.S. RDI 6
• Intravenous iron is more effective for filling iron stores and should be chosen when adherence is essential or oral iron is not tolerated 5
• Monitor response to treatment with repeat CBC and ferritin 5, 3

For reversible causes:

• Correct electrolyte imbalances with appropriate supplementation 1
• Restore nutrient deficiencies (vitamin B12, folate, vitamin D, magnesium) 1, 2
• Treat underlying conditions (thyroid dysfunction, sleep apnea, depression) 2

Non-pharmacologic interventions:

• Recommend moderate-intensity exercise (walking, running, swimming, cycling) 2-3 times per week for 30-60 minutes, starting with low-level activities if significantly deconditioned 1
• Provide sleep hygiene education: maintain regular sleep schedule, create dark/quiet sleep environment, avoid screens before bed 1
• Consider referral to physical therapy for exercise programming in deconditioned patients 1

Common Pitfalls to Avoid

• Do not discharge anemic patients without iron supplementation recommendations: More than 80% of patients are discharged with anemia, but less than 20% receive iron supplementation recommendations 5
• Do not assume fatigue will resolve with anemia correction alone: Fatigue often has multiple contributing factors that require concurrent management 2, 5
• Do not overlook medication review: Polypharmacy and drug interactions frequently contribute to fatigue but are easily modifiable 1
• Do not skip nutritional assessment: Even well-nourished appearing patients may harbor significant vitamin and mineral deficiencies 1
• Failing to reassess fatigue after anemia treatment: Regular follow-up is essential to ensure treatment effectiveness 2

Follow-Up Strategy

• Recheck hemoglobin and ferritin at 13 weeks after initiating iron therapy 5
• Use a 0-10 numeric rating scale to grade fatigue intensity at each visit (mild 0-3, moderate 4-6, severe 7-10) 1
• Refer to specialists if fatigue persists despite treatment of identified causes or if new symptoms appear 2
• Establish collaborative care between primary care and specialists for ongoing surveillance 2