What is the diagnosis and treatment for a 59-year-old female patient with macrocytosis (Mean Corpuscular Volume (MCV) of 102), elevated Mean Corpuscular Hemoglobin (MCH) of 34.1, thrombocytopenia (platelet count of 137), elevated Alanine Transaminase (ALT) of 55, and elevated Aspartate Transaminase (AST) of 66?

Diagnosis: Alcohol-Related Liver Disease with Macrocytic Anemia

This patient's laboratory pattern—macrocytosis (MCV 102), elevated MCH (34.1), mild thrombocytopenia (137), and AST/ALT ratio >1 (66/55)—strongly suggests alcohol-related liver disease as the primary diagnosis. 1

Diagnostic Reasoning

Liver Disease Pattern

• The AST/ALT ratio of 1.2 with both enzymes mildly elevated (AST 66, ALT 55) is characteristic of alcoholic liver disease, where AST elevation typically exceeds ALT but both remain below 300 IU/L 1
• AST/ALT ratios >2 make alcoholic hepatitis highly probable, and ratios >3 are nearly diagnostic 1
• The mild thrombocytopenia (137) occurs in 53% of chronic inflammatory liver disease and over 60% of cirrhotic liver disease 2

Macrocytosis Pattern

• Macrocytosis (MCV >95 fL) occurs in 70.3% of alcoholics with liver disease versus only 23.3% of non-alcoholics with liver disease 3
• MCV values of 100-110 fL (this patient has 102) are most commonly caused by alcohol-related liver disease 1, 3
• The combination of macrocytosis with liver enzyme abnormalities in this demographic makes alcohol the leading diagnosis 4, 5

Essential Diagnostic Workup

Immediate Laboratory Tests Required

• Complete blood count with reticulocyte count to assess bone marrow response and distinguish between deficiency states versus hemolysis 6, 7
• Serum vitamin B12 and folate levels are mandatory, as 18.3% of alcoholics with macrocytosis have concurrent folate deficiency 1, 6, 3
• Serum ferritin and transferrin saturation to identify coexisting iron deficiency, which can mask macrocytosis 1, 7
• C-reactive protein (CRP) to assess inflammation, which affects ferritin interpretation 1, 7
• Peripheral blood smear examination to identify target cells (present in 41% of cirrhosis) and assess for megaloblastic changes 1, 2

Critical Alcohol Assessment

• Detailed alcohol history using standardized questionnaires, calculating average daily intake: [amount (mL) × alcohol % × 0.785 × drinking days/week] ÷ 7 1
• Alcohol-related liver disease threshold: >40 g/day in men, >20 g/day in women 1
• Gamma-glutamyltranspeptidase (GGT) is elevated in 75% of habitual drinkers and useful for monitoring abstinence 1

Additional Hepatic Evaluation

• Hepatitis B surface antigen (HBsAg), hepatitis C antibody, and hepatitis A IgM to exclude viral hepatitis 1
• Abdominal ultrasound to assess liver architecture, exclude biliary obstruction, and evaluate for complications 1
• Prothrombin time and serum albumin to assess hepatic synthetic function 1

Treatment Algorithm

If Vitamin B12 Deficiency Confirmed (Serum B12 <200 pg/mL)

Critical Warning: Always exclude vitamin B12 deficiency before treating folate deficiency, as folate supplementation may mask severe B12 depletion and allow irreversible neurological damage to progress 7, 8, 9

With Neurological Symptoms

• Hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement 7
• Then hydroxocobalamin 1 mg intramuscularly every 2 months for life 7

Without Neurological Symptoms

• Hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks 7
• Followed by maintenance of 1 mg intramuscularly every 2-3 months for life 7

If Folate Deficiency Confirmed (Serum Folate <3 μg/L)

• Oral folic acid 5 mg daily for minimum 4 months 7
• Only after B12 deficiency has been excluded 8, 9

Alcohol-Related Liver Disease Management

• Immediate and complete alcohol cessation is the cornerstone of treatment 1
• Nutritional supplementation including thiamine, multivitamins, and adequate protein intake 1
• Monitor MCV serially: In alcoholics who abstain, MCV typically decreases over 3 months, though changes are independent of serum folate values 3

Monitoring Response to Treatment

• Reticulocyte count should increase within 5-7 days of appropriate vitamin replacement 8
• Hematocrit and reticulocyte counts should be repeated daily from days 5-7 of therapy, then frequently until hematocrit normalizes 8
• If reticulocytes have not increased or do not reach at least twice normal while hematocrit <35%, reevaluate diagnosis and treatment 8
• Serial MCV, MCH, and reticulocyte monitoring assesses response to vitamin or iron replacement 7

Mandatory Hematology Referral Criteria

• Cause remains unclear after complete workup 7
• Suspicion for myelodysplastic syndrome (MCV >120 fL without vitamin deficiency) 7, 5
• Pancytopenia present 7
• No response to appropriate vitamin or iron replacement after 2-3 weeks 7

Common Pitfalls to Avoid

• Do not administer folic acid before excluding B12 deficiency: Folic acid doses >0.1 mg daily may produce hematologic remission while neurologic manifestations progress 8, 9
• Do not assume macrocytosis is solely due to alcohol: 18.3% of alcoholics with macrocytosis have concurrent folate deficiency requiring treatment 3
• Do not overlook concurrent iron deficiency: Inflammatory states can elevate ferritin up to 100 μg/L despite true iron deficiency 1
• Do not delay workup in patients with MCV >120 fL: This level usually indicates vitamin B12 deficiency or myelodysplastic syndrome requiring urgent evaluation 1, 5