What is the diagnosis for a patient with elevated hemoglobin (16.5 g/dL), prolonged activated partial thromboplastin time (APTT), mildly elevated serum bilirubin (1.5 mg/dL), and normal vitamin B12 (190 pg/mL) levels?

Diagnostic Assessment: Elevated Hemoglobin with Prolonged APTT, Mild Hyperbilirubinemia, and Low-Normal Vitamin B12

The most likely diagnosis is vitamin K deficiency or early warfarin effect, given the isolated prolonged APTT with elevated hemoglobin and mildly elevated bilirubin, though a mixing study is essential to differentiate factor deficiency from inhibitor. 1

Immediate Diagnostic Workup Required

Systematically review all medications, particularly anticoagulants including warfarin, unfractionated heparin, low-molecular-weight heparin, and direct oral anticoagulants, as these are the most common causes of isolated APTT prolongation. 1 Additionally, check for drugs that potentiate warfarin effects: phenylbutazone, sulfinpyrazone, metronidazole, trimethoprim-sulfamethoxazole, and amiodarone. 1

Essential Laboratory Tests

• Perform a mixing study immediately - if the prolonged APTT corrects with normal plasma, this indicates a coagulation factor deficiency rather than an inhibitor (such as lupus anticoagulant or factor VIII inhibitor). 1

• Repeat PT, APTT, fibrinogen, and platelet count to fully characterize the coagulopathy pattern. 1

• Check prothrombin time (PT/INR) - if both PT and APTT are prolonged together with a corrective mixing study, this points to common pathway factor deficiencies (II, V, X, or fibrinogen) or vitamin K deficiency affecting factors II, VII, IX, and X. 1

Differential Diagnosis Analysis

Primary Consideration: Vitamin K Deficiency

Vitamin K deficiency is the single most common cause of combined PT/APTT prolongation with correction on mixing, causing depletion of vitamin K-dependent factors (II, VII, IX, X). 1 The mildly elevated bilirubin (1.5 mg/dL) may indicate early hemolysis or hepatic dysfunction contributing to vitamin K malabsorption. 2

• The elevated hemoglobin (16.5 g/dL) argues against significant hemolytic anemia but does not exclude vitamin K deficiency. 2

• Vitamin K deficiency affects multiple coagulation factors simultaneously because factors II, VII, IX, and X are all vitamin K-dependent. 3

Secondary Consideration: Early Liver Disease

Hepatic dysfunction prolongs PT/APTT through impaired synthesis of coagulation factors, typically requiring loss of >70% of synthetic function to manifest as coagulopathy. 4, 1 The mildly elevated bilirubin could represent early hepatic dysfunction. 2

• However, the elevated hemoglobin makes significant liver disease less likely, as chronic liver disease typically causes anemia, not polycythemia. 2

Vitamin B12 Deficiency Considerations

The vitamin B12 level of 190 pg/mL is at the lower end of normal (typically 200-900 pg/mL). 5 While vitamin B12 deficiency can cause:

• Pseudothrombotic microangiopathy with hemolysis, thrombocytopenia, and elevated bilirubin 6, 7
• Macrocytic anemia with elevated LDH and indirect bilirubin 8, 7

This diagnosis is unlikely here because:

• The hemoglobin is elevated (16.5 g/dL), not decreased - vitamin B12 deficiency causes anemia with mean hemoglobin around 9.7 g/dL. 5
• Vitamin B12 deficiency does not typically cause isolated APTT prolongation. 6, 7

Diagnostic Algorithm

Step 1: Mixing Study Interpretation

• If APTT corrects → Factor deficiency (proceed to Step 2)
• If APTT does not correct → Inhibitor present (lupus anticoagulant, factor VIII inhibitor) - requires hematology consultation 1

Step 2: PT Assessment (if mixing study corrects)

• PT normal, APTT prolonged → Intrinsic pathway deficiency (factors VIII, IX, XI, XII) or heparin effect 4
• Both PT and APTT prolonged → Common pathway deficiency (factors II, V, X, fibrinogen) or vitamin K deficiency 1

Step 3: Targeted Testing Based on Pattern

• For vitamin K deficiency: Administer vitamin K 2.5-10 mg subcutaneously and recheck PT/APTT in 6-8 hours - rapid correction confirms diagnosis. 1, 3
• For liver disease: Check albumin, transaminases (AST, ALT), and assess for clinical signs of chronic liver disease. 2
• For specific factor deficiencies: Measure individual factor levels (VIII, IX, XI for isolated APTT prolongation). 2

Critical Pitfalls to Avoid

• Do not assume correction on mixing study excludes all inhibitors - some weak inhibitors may still correct initially. 1

• Do not overlook specimen handling issues - underfilled tubes cause excess citrate and spuriously prolong PT/APTT. 1

• Do not use FFP empirically in non-bleeding patients - this exposes patients to unnecessary transfusion risks including TRALI, circulatory overload, and infection. 1

• Do not interpret PT/APTT in isolation - these tests only monitor the initiation phase (first 4% of thrombin production). 1

• Do not use INR for non-warfarin coagulopathies - it lacks validity for liver disease, DIC, or acute bleeding. 1

Management Based on Clinical Context

For Non-Bleeding Patients Without Urgent Procedures

• Administer vitamin K 2.5-10 mg subcutaneously or intramuscularly and recheck PT/APTT in 6-8 hours. 1
• Correction within 2-4 hours confirms vitamin K deficiency. 3

For Bleeding Patients or Urgent Procedures

• Maintain PT/APTT <1.5 times normal control. 1
• Consider fresh frozen plasma (FFP) or prothrombin complex concentrate for immediate reversal. 1
• FFP dose should be 10-20 mL/kg to maintain coagulation factors above critical levels. 3