What is the appropriate approach to a medical workup?

Medical Workup Approach

The appropriate medical workup begins with a focused history and physical examination targeting specific clinical presentations, followed by essential laboratory studies (CBC with differential, comprehensive metabolic panel including liver and renal function, and inflammatory markers), with additional testing guided by the clinical context and initial findings. 1

Initial Assessment Components

History and Physical Examination

• Document constitutional symptoms systematically: unexplained weight loss, fever patterns and duration, night sweats, fatigue, anorexia, and symptom progression timeline 1
• Evaluate vital signs comprehensively: blood pressure, pulse, temperature, and respiratory rate at presentation 2, 1
• Perform targeted physical examination: examine all lymph node basins, assess for organomegaly (liver and spleen size), and evaluate skin for lesions or pallor 2, 1
• Obtain medication history: focus on high-risk drugs, recent exposures, and potential toxins 2

Essential Laboratory Studies

Core laboratory panel should include:

• Complete blood count (CBC) with differential and platelet count to evaluate for cytopenias, abnormal cell populations, or lymphocytosis 2, 1, 3
• Comprehensive metabolic panel: liver function tests (AST, ALT, alkaline phosphatase, bilirubin), renal function (creatinine, BUN), electrolytes (sodium, potassium), and glucose 2, 1
• Inflammatory markers: erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) 1
• Lactate dehydrogenase (LDH) as a marker for hemolysis or malignancy 4, 3
• Urinalysis 1

Additional Initial Testing Based on Clinical Context

For suspected hematologic abnormalities:

• Blood smear morphology with attention to schistocytes, abnormal cells, or morphologic changes 2, 3
• Reticulocyte count to assess bone marrow response 2
• Haptoglobin and direct antiglobulin test (Coombs) if hemolysis suspected 2, 3

For suspected cardiac involvement:

• Cardiac troponin and 12-lead ECG to evaluate for occult cardiovascular disease 2, 1
• Echocardiography within 48 hours if hemodynamically unstable or cardiac structure unknown 2

For suspected infectious or inflammatory processes:

• Viral studies: EBV, CMV, HIV, hepatitis B and C screening 2, 3
• Thyroid-stimulating hormone (TSH) 2, 4

Imaging Studies

Initial Imaging

• Chest radiograph as initial screening for pulmonary or mediastinal abnormalities 2, 1
• CT chest/abdomen/pelvis with contrast if history and examination suggest malignancy, infection, or lymphadenopathy requiring characterization 2, 1, 3
• Abdominal ultrasound to assess liver and spleen size, evaluate biliary system if cholestasis present 4, 5

Advanced Imaging When Indicated

• MRI brain with and without contrast for neurologic symptoms 2
• PET-CT if transformation to aggressive lymphoma suspected or for staging certain malignancies 2, 3

Disease-Specific Workup Considerations

For Suspected Malignancy

• Tissue procurement is essential: excisional lymph node biopsy or core biopsy preferred over fine-needle aspiration 2
• Immunophenotypic analysis via flow cytometry and/or immunohistochemistry 2, 3
• Bone marrow aspiration and biopsy with immunohistochemistry, cytogenetics, and molecular testing if peripheral blood abnormalities or myeloproliferative/lymphoproliferative disorder suspected 2, 4, 3
• β2-microglobulin as prognostic marker for hematologic malignancies 2, 4
• Serum protein electrophoresis to evaluate for paraproteinemia 4, 3

For Suspected Liver Disease

• Distinguish pattern of abnormality: hepatocellular (elevated AST/ALT) versus cholestatic (elevated alkaline phosphatase/GGT) 5, 6
• Confirm hepatic origin of alkaline phosphatase elevation with GGT levels 5
• Evaluate synthetic function: albumin and prothrombin time/INR to differentiate acute versus chronic disease 5, 7
• Abdominal ultrasound mandatory to evaluate biliary system and distinguish extrahepatic versus intrahepatic cholestasis 5, 6

For Suspected Coagulopathy

• Coagulation studies: PT/INR, aPTT 4
• Advanced testing if indicated: Factor VIII, IX, XI, XIII levels, von Willebrand activity 4
• Disseminated intravascular coagulation panel if hemolysis present 2

Common Pitfalls to Avoid

• Normal laboratory values do not exclude serious disease - clinical correlation is essential 1
• Avoid excessive testing without clinical indication - let initial findings guide subsequent workup 1
• Do not delay bone marrow evaluation in patients with concerning peripheral blood findings 4, 3
• Do not overlook HIV testing in patients with unexplained lymphadenopathy 3
• Liver disease can present without abnormal liver function tests - clinical context is critical 6

Algorithmic Approach to Next Steps

If initial workup suggests specific diagnosis:

• Pursue targeted additional testing based on the suspected etiology 1
• Obtain appropriate specialist consultation (hematology, gastroenterology, cardiology) 2

If constitutional symptoms persist without clear etiology:

• Consider referral to appropriate specialists for further evaluation 1, 3
• Repeat testing may be necessary to monitor trends, especially for borderline abnormalities 4

For hemodynamically unstable patients:

• Immediate transfer to facility with ICU/CCU capabilities 2
• Continuous monitoring of vital cardiorespiratory functions, pulse oximetry, blood pressure, respiratory rate, and ECG 2
• Echocardiography immediately if cardiac etiology suspected 2