Workup of Hypoalbuminemia with Anasarca
The workup should prioritize identifying the underlying cause through a systematic evaluation of the three major mechanisms: protein loss (renal, GI, or dermal), decreased synthesis (liver disease), or redistribution (inflammation/capillary leak), with initial laboratory assessment including urinalysis with protein quantification, comprehensive metabolic panel with liver function tests, and inflammatory markers to guide further targeted investigation.
Initial Laboratory Assessment
The minimum essential workup includes:
- Complete blood count with differential to assess for anemia, thrombocytopenia, or signs of bone marrow pathology 1
- Comprehensive metabolic panel including serum creatinine, BUN, electrolytes, glucose, and liver function tests (AST, ALT, bilirubin, alkaline phosphatase) 1
- Serum albumin level (target normal ≥4.0 g/dL by bromcresol green method) 2
- C-reactive protein (CRP) to distinguish inflammation-driven hypoalbuminemia from pure protein loss 3
- Urinalysis with 24-hour urine protein quantification to assess for nephrotic-range proteinuria (>3.5 g/day) 1
- Serum ferritin and transferrin saturation to evaluate iron status 1
Algorithmic Approach Based on Initial Results
If Nephrotic-Range Proteinuria Present (>3.5 g/day):
- Renal ultrasound to assess kidney size and structure 1
- Serum and urine protein electrophoresis with immunofixation to evaluate for AL amyloidosis 1
- Serum free light chains (kappa and lambda) with ratio calculation 1
- Consider nephrology referral for potential kidney biopsy if diagnosis remains unclear 1
If Liver Dysfunction Present (elevated bilirubin, transaminases, or INR):
- Hepatitis panel (HBsAg, anti-HCV) 1
- Abdominal ultrasound with Doppler to assess liver parenchyma, portal vein patency, and ascites 1
- Echocardiography to evaluate for right heart failure causing hepatic congestion 1
- Consider hepatology referral for further evaluation of cirrhosis or chronic liver disease 1
If Elevated CRP with Normal Renal/Hepatic Function:
This pattern suggests inflammation-driven hypoalbuminemia rather than true protein loss 3, 4:
- Chest X-ray to evaluate for pulmonary pathology, pleural effusions, or cardiomegaly 1
- ECG to assess for cardiac abnormalities (rarely normal in acute heart failure) 1
- Echocardiography (preferably within 48 hours) to evaluate cardiac structure, function, and valvular disease 1
- BNP or NT-proBNP if heart failure suspected 1
- Thyroid-stimulating hormone (TSH) to exclude thyroid disease 1
If Normal CRP, Renal Function, and Liver Function:
This pattern suggests gastrointestinal protein loss 3:
- Fecal alpha-1 antitrypsin clearance to confirm protein-losing enteropathy 5, 6
- Vitamin B12 and folate levels (especially if small bowel disease suspected) 3
- Antinuclear antibody (ANA) with titer to evaluate for systemic lupus erythematosus 5, 6
- Serum complement levels (C3, C4) if ANA positive 6
- Consider gastroenterology referral for endoscopic evaluation 3
Additional Specialized Testing Based on Clinical Context
If Cardiac Amyloidosis Suspected:
- Cardiac biomarkers (troponin, BNP/NT-proBNP) 1
- Serum and urine immunofixation with free light chains 1
- Echocardiography with strain imaging 1
- Cardiac MRI or nuclear scintigraphy (technetium pyrophosphate scan) 1
If Malnutrition or Chronic Disease Suspected:
- Reticulocyte count to assess bone marrow response 1
- Red cell distribution width (RDW) and mean corpuscular volume (MCV) 1
- Vitamin B12, folate, and haptoglobin if macrocytosis present 1
- Lactate dehydrogenase if hemolysis suspected 1
Critical Pitfalls to Avoid
Do not assume hypoalbuminemia equals malnutrition – in most hospitalized patients with anasarca, hypoalbuminemia reflects inflammation and capillary leak rather than nutritional deficiency 3, 4. Inflammatory cytokines directly downregulate hepatic albumin synthesis even with adequate protein intake 4.
Do not order albumin infusions to "correct the number" – treatment should target the underlying cause rather than the albumin level itself 2, 3. Albumin infusion is expensive ($130/25g) and carries risks including fluid overload, hypotension, and anaphylaxis 2.
Do not overlook fluid overload as a cause – hemodilution from excess fluid decreases serum albumin concentration and should be corrected with diuretics rather than albumin 3.
Do not miss rare causes – intravascular lymphoma can present with severe anasarca and hypoalbuminemia due to vascular obstruction 7. Consider hematology referral if unexplained cytopenias or elevated RDW with thrombocytopenia 8.