What is the management approach for a patient with anorexia nervosa presenting with elevated hemoglobin (hyperhemoglobinemia) and prolonged activated partial thromboplastin time (APTT)?

Management of Elevated Hemoglobin and Prolonged APTT in Anorexia Nervosa

The elevated hemoglobin represents hemoconcentration from volume depletion rather than true polycythemia, and the prolonged APTT requires immediate mixing study to distinguish between factor deficiency (which resolves with nutritional rehabilitation) versus lupus anticoagulant (which paradoxically increases thrombotic risk). 1, 2

Initial Assessment of Hemoglobin Elevation

Recognize Hemoconcentration as the Primary Mechanism

• Elevated hemoglobin in anorexia nervosa is almost always pseudopolycythemia from plasma volume depletion, not true erythrocytosis. 1
• Hemoconcentration occurs in 64% of severely malnourished anorexia nervosa patients (BMI <13 kg/m²) due to chronic sodium and fluid restriction used as weight control methods. 1
• The elevated hemoglobin masks underlying anemia—once volume is restored with intravenous fluids, hemoglobin typically drops below 12 g/dL, revealing true anemia in approximately 43% of these patients. 1
• Serum urea nitrogen/creatinine ratio >25 confirms plasma volume depletion, though standard hematocrit and hemoglobin may appear falsely normal due to severe malnutrition. 1

Immediate Management Steps

• Initiate intravenous fluid supplementation to restore plasma volume; hemoglobin and hematocrit will decrease significantly within hours of adequate hydration. 1
• Monitor hemoglobin after fluid resuscitation—expect values to drop and reveal underlying normocytic, normochromic anemia (present in 83% of severe anorexia nervosa patients). 3, 4
• Do not pursue polycythemia workup (JAK2 mutation, erythropoietin levels) as this represents volume contraction, not bone marrow overproduction. 1

Evaluation of Prolonged APTT

Perform Mixing Study Immediately

• Order a 1:1 mixing study (patient plasma with normal plasma) immediately and after 2-hour incubation to distinguish factor deficiency from inhibitor presence. 2
• Immediate correction of APTT indicates factor deficiency from malnutrition-induced gelatinous bone marrow transformation, which resolves with nutritional rehabilitation. 2, 5
• Failure to correct suggests lupus anticoagulant (present in up to 45% of certain populations) or acquired factor inhibitor. 2, 6
• Calculate Rosner index: values <11% support factor deficiency, while ≥11% indicate inhibitor presence. 2

Critical Pitfall to Avoid

• Do not assume immediate mixing study correction completely excludes acquired hemophilia A—if clinical bleeding is present, proceed with Factor VIII inhibitor testing (Bethesda assay) regardless of mixing study results. 2
• Elderly patients and postpartum women with anorexia nervosa are at highest risk for acquired hemophilia A, which can present with isolated prolonged APTT without bleeding symptoms initially. 2

Management Based on Mixing Study Results

If Mixing Study Corrects (Factor Deficiency)

• This indicates starvation-mediated gelatinous marrow transformation causing factor deficiencies, which resolves with proper nutritional rehabilitation. 5, 3
• Measure Factor VIII activity level to exclude hemophilia A or von Willebrand disease. 2
• No immediate correction of APTT is required unless active bleeding or planned surgery—89% of neutropenia and associated coagulopathy resolves with nutritional rehabilitation alone. 3
• Monitor APTT during refeeding; expect normalization within 2-4 weeks as bone marrow function recovers. 5, 3

If Mixing Study Does Not Correct (Inhibitor Present)

• Proceed with lupus anticoagulant testing even when mixing study corrects, as both conditions can coexist. 2, 6
• If lupus anticoagulant is confirmed, recognize this paradoxically indicates thrombotic risk, NOT bleeding risk—these patients require anticoagulation for thrombosis prevention if they meet antiphospholipid syndrome criteria. 2, 6
• Critical: Prolonged APTT from lupus anticoagulant is NOT a contraindication to anticoagulation therapy. 2, 6
• If acquired hemophilia A is suspected (bleeding symptoms present), order Factor VIII inhibitor assay (Bethesda) and consult hematology urgently. 2

Nutritional Rehabilitation Protocol

Address Underlying Malnutrition

• Initiate gradual nutritional rehabilitation targeting weekly weight gain of 0.5-1 kg for adults, as recommended by the American Psychiatric Association. 7
• Monitor for refeeding syndrome with daily phosphate, magnesium, and calcium levels during the first week—hypophosphatemia is characteristic and potentially life-threatening. 5
• Expect hematologic abnormalities (anemia, leukopenia, thrombocytopenia, prolonged APTT) to resolve within 2-4 weeks of adequate nutritional rehabilitation. 5, 3

Avoid Unnecessary Interventions

• Do not transfuse blood products for isolated cytopenias or prolonged APTT in the absence of active bleeding—these resolve with nutritional rehabilitation alone. 3, 4
• Do not perform bone marrow biopsy unless cytopenias fail to improve after 4 weeks of adequate nutritional rehabilitation or if atypical features suggest alternative diagnosis. 3, 4

Monitoring During Treatment

Serial Laboratory Assessment

• Obtain complete blood count, comprehensive metabolic panel, and coagulation studies (PT, APTT) on admission, after initial fluid resuscitation (24-48 hours), and weekly during nutritional rehabilitation. 7, 5
• Expect hemoglobin to decrease by 1-2 g/dL after fluid resuscitation, revealing underlying anemia. 1
• Monitor for development of thrombocytosis (platelets >400 k/μL) during refeeding, which occurs in 17% of patients and typically resolves spontaneously. 3

Red Flags Requiring Hematology Consultation

• APTT remains prolonged >4 weeks despite adequate nutritional rehabilitation and weight gain. 5, 3
• Active bleeding develops with prolonged APTT (suggests acquired hemophilia A requiring urgent factor replacement). 2
• Pancytopenia develops or worsens during refeeding (consider hemophagocytic syndrome requiring immunosuppressive treatment). 7
• Severe thrombocytopenia <50 × 10⁹/L persists beyond 2 weeks of nutritional rehabilitation. 3