What is the most likely diagnosis and immediate management for a 45‑year‑old male chronic alcoholic with fatigue, decreased appetite, oral ulcerations, peripheral edema, macrocytic anemia (hemoglobin 6.5 g/dL, MCV >100 fL), thrombocytopenia (platelet count 95 000/µL), normal white‑cell count, mildly elevated transaminases (≈2 × upper limit of normal), total bilirubin 2 mg/dL (direct 1.2 mg/dL), normal renal function, and mild splenomegaly on ultrasound?

Diagnosis and Immediate Management

This patient most likely has alcoholic liver disease (ALD) with cirrhosis, complicated by severe macrocytic anemia due to combined nutritional deficiencies (folate and possibly B12) and direct alcohol toxicity, requiring immediate alcohol cessation, nutritional supplementation, and blood transfusion. 1

Most Likely Diagnosis: Alcoholic Liver Disease with Cirrhosis

The clinical presentation strongly suggests alcoholic liver cirrhosis based on the constellation of findings 1:

• Chronic heavy alcohol use is the prerequisite for ALD diagnosis, and this patient meets criteria as a chronic alcoholic 1
• Lower extremity edema indicates portal hypertension and hypoalbuminemia, typical of cirrhosis 1
• Mild splenomegaly on ultrasound reflects portal hypertension from advanced liver disease 1
• Thrombocytopenia (95,000/µL) results from both splenic sequestration due to portal hypertension and direct alcohol toxicity 1
• Elevated bilirubin (2 mg/dL with direct 1.2 mg/dL) indicates hepatocellular dysfunction 1
• Mildly elevated transaminases (2× normal) with AST likely > ALT is characteristic of ALD, where levels rarely exceed 300 IU/L 1, 2

The oral ulcerations are likely secondary to nutritional deficiencies (folate/B12) rather than primary liver disease 1.

Macrocytic Anemia: Multifactorial Etiology

The severe macrocytic anemia (Hb 6.5 g/dL, MCV >100 fL) has multiple contributing factors in this alcoholic patient 3, 4:

• Folate deficiency is the primary cause, occurring in 14.5% of alcoholics and 35.9% of those with macrocytic anemia 5
• Direct alcohol toxicity on bone marrow causes macrocytosis when daily consumption exceeds 60 g 1
• Chronic liver disease itself causes macrocytic anemia, particularly in cirrhosis where the Child-Pugh score correlates with severity 6
• Possible B12 deficiency should be considered given the oral ulcerations 1, 3
• Possible thiamine deficiency may contribute to the peripheral edema 7

Macrocytosis occurs in 70.3% of alcoholics with liver disease versus only 23.3% of non-alcoholics with liver disease, making it highly suggestive of alcohol-related etiology 5.

Immediate Management Algorithm

Step 1: Stabilize and Assess Severity

Transfuse packed red blood cells immediately given the critically low hemoglobin of 6.5 g/dL, which poses significant morbidity and mortality risk 1:

• Target hemoglobin >7-8 g/dL initially
• Monitor for transfusion reactions and volume overload given likely hypoalbuminemia

Calculate severity scores to assess prognosis 8:

• Modified Discriminant Function (mDF) = 4.6 × (PT patient - PT control) + total bilirubin (mg/dL)
• MELD score using bilirubin, INR, and creatinine
• If mDF ≥32 or hepatic encephalopathy present, this indicates severe alcoholic hepatitis with 30-50% mortality 1

Step 2: Initiate Nutritional Supplementation Immediately

Start thiamine 100 mg IV/IM daily before any glucose administration to prevent Wernicke's encephalopathy 9, 8, 7:

• Thiamine deficiency occurs commonly in AUD and can contribute to peripheral edema 7
• Continue for at least 3-5 days, then transition to oral

Start folic acid 1-5 mg daily orally for folate deficiency 3, 4:

• Folate deficiency is inversely correlated with MCV in ALD 6
• Serum folate <3 µg/L found in 18.3% of alcoholics with macrocytosis 5

Start vitamin B12 1000 µg IM (or high-dose oral if absorption intact) 1, 3:

• Oral ulcerations suggest possible B12 deficiency
• Check B12 and folate levels before starting, but do not delay treatment

Implement aggressive nutritional support 9, 8:

• 1.0-1.5 g protein/kg/day and 30-40 kcal/kg/day 9
• Malnutrition is common in ALD and worsens outcomes 1

Step 3: Confirm Diagnosis and Exclude Complications

Obtain complete laboratory workup 2:

• AST, ALT, GGT to confirm AST/ALT ratio >2 (highly suggestive when >2, very high probability when >3) 1, 2
• Albumin, INR/PT to assess synthetic liver function 1, 8
• Serum folate, vitamin B12, RBC folate to confirm nutritional deficiencies 1, 3
• Reticulocyte count to assess bone marrow response (should be low in nutritional deficiency) 1, 3
• TSH to exclude hypothyroidism as a cause of macrocytic anemia 1, 3

Perform upper endoscopy if not contraindicated to screen for esophageal varices given splenomegaly and thrombocytopenia indicating portal hypertension 8:

• Do not delay if patient has hematemesis or melena
• Variceal bleeding is a major complication of cirrhosis 1

Consider liver biopsy only if diagnosis uncertain or if severe alcoholic hepatitis requiring corticosteroids is suspected 1, 9:

• Biopsy is not routinely required for ALD diagnosis 2
• Transjugular approach preferred if coagulopathy or ascites present 9

Step 4: Initiate Alcohol Cessation Strategy

Implement immediate alcohol abstinence counseling using motivational interviewing 2:

• Abstinence is the single most effective intervention for long-term survival 9, 2, 8
• Use the "5 As" model: Ask, Advise, Assess, Assist, Arrange 2
• Present objective feedback linking alcohol to liver enzymes, thrombocytopenia, and cirrhosis risk 2

Consider pharmacotherapy for alcohol use disorder 2:

• Naltrexone, acamprosate, or disulfiram for patients with alcohol dependence
• Improves abstinence rates and long-term outcomes

Monitor for alcohol withdrawal and treat prophylactically if indicated:

• Benzodiazepines (e.g., lorazepam, diazepam) for withdrawal prophylaxis
• CIWA-Ar protocol for symptom-triggered therapy

Step 5: Assess for Advanced Fibrosis and Initiate Surveillance

Arrange FibroScan or non-invasive fibrosis assessment 2:

• 50% of patients with advanced fibrosis have normal or minimally elevated transaminases 2

• FibroScan >12-15 kPa suggests advanced fibrosis 2
• FibroScan >16 kPa requires hepatology referral 2

If cirrhosis confirmed, initiate surveillance protocols 2, 8:

• Upper endoscopy for variceal screening (already recommended above)
• Ultrasound ± AFP every 6 months for hepatocellular carcinoma surveillance 2
• Recheck labs in 2-4 weeks if abstinence achieved: AST, ALT, GGT, albumin, bilirubin, INR, platelets 2

Step 6: Manage Peripheral Edema

Initiate diuretic therapy for peripheral edema if no contraindications:

• Spironolactone 100 mg daily (aldosterone antagonist, first-line for ascites/edema in cirrhosis)
• Add furosemide 40 mg daily if inadequate response (maintain 100:40 spironolactone:furosemide ratio)
• Monitor electrolytes, renal function closely

Sodium restriction to <2 g/day 1:

• Essential for managing fluid retention in cirrhosis

Common Pitfalls and Caveats

Do not assume macrocytic anemia is solely due to alcohol 3, 4:

• Always check B12 and folate levels, as deficiency is common and treatable
• Exclude hypothyroidism and myelodysplastic syndrome (MDS), especially if pancytopenia present 4

Do not delay thiamine supplementation 9, 7:

• Must be given before glucose to prevent Wernicke's encephalopathy
• Thiamine deficiency can cause severe peripheral edema and should be treated empirically 7

Do not use AST/ALT levels alone to exclude cirrhosis 2:

• Transaminases are often normal or only mildly elevated in advanced fibrosis
• Non-invasive fibrosis assessment (FibroScan) is essential 2

Do not correct coagulopathy with FFP prophylactically 8:

• Correcting abnormal coagulation tests with blood products to prevent bleeding lacks evidence and is not recommended 8
• Only correct if active bleeding or before invasive procedures

Monitor for infection before considering corticosteroids 8:

• If mDF ≥32, infection (SBP, pneumonia, UTI) must be definitively excluded before starting prednisolone 8
• Infection is a contraindication to corticosteroid therapy 8

Expect slow recovery of MCV and GGT 1, 2:

• MCV returns to normal after several months of abstinence 1
• GGT recovers slowly over months, making it useful for monitoring compliance 2
• In one study, macrocytosis persisted in 40% of patients at 3 months despite abstinence 5