What to do in a patient with a prolonged Activated Partial Thromboplastin Time (APTT)?

Management of Prolonged Activated Partial Thromboplastin Time (aPTT)

When encountering a prolonged aPTT, perform a systematic diagnostic evaluation to determine the underlying cause before initiating any treatment, as the cause is more important than the degree of prolongation. 1

Initial Diagnostic Approach

1. Review medication history:

   • Check for anticoagulant use (especially unfractionated heparin, direct thrombin inhibitors)
   • Document timing of last dose relative to blood draw

2. Repeat the test to rule out pre-analytical errors:

   • Ensure proper blood collection technique (no heparin contamination)
   • Verify correct blood-to-anticoagulant ratio
   • Check for hemolysis or clotting in the sample

3. Perform mixing study:

   • Mix patient plasma with normal plasma (1:1)
   • Measure aPTT immediately and after 2-hour incubation
   • Interpretation:
     • Correction of aPTT suggests factor deficiency
     • Persistent prolongation suggests inhibitor presence (e.g., lupus anticoagulant, factor inhibitor)
     • Time-dependent prolongation (normal immediate mix but prolonged after incubation) suggests factor VIII inhibitor 2

4. Measure specific factor levels if mixing study suggests factor deficiency:

   • Factors VIII, IX, XI, and XII
   • An isolated low factor VIII level suggests acquired hemophilia A 2

Management Based on Underlying Cause

1. Therapeutic Anticoagulation (e.g., Heparin)

• Target aPTT range: 1.5-2.5 times control value (typically 46-70 seconds) 2
• Dose adjustment according to weight-based nomogram:

aPTT (s)	Bolus (U/kg)	Infusion Adjustment (U/kg/h)
<35	80	Increase by 4
35-45	40	Increase by 2
46-70	No change	No change
71-90	-	Reduce by 2
>90	-	Stop for 1h, then reduce by 3

• Monitoring frequency: Every 6 hours after starting therapy or after dosage change 2
• For patients with baseline aPTT prolongation: Use anti-Xa monitoring (target 0.3-0.7 IU/mL) instead of aPTT 3

2. Factor Deficiencies

• Congenital factor deficiencies:

  • Factor VIII, IX deficiency: Replace specific factor if bleeding or before procedures
  • Factor XI deficiency: Replace if bleeding or before high-risk procedures
  • Factor XII deficiency: No treatment needed (no bleeding risk despite prolonged aPTT) 4

• Acquired factor deficiencies:

  • Acquired hemophilia A (factor VIII inhibitor):
    • For bleeding: Use bypassing agents (recombinant factor VIIa or activated prothrombin complex concentrates)
    • For inhibitor eradication: Initiate immunosuppression with corticosteroids (1 mg/kg/day) alone or with cyclophosphamide (1.5-2 mg/kg/day) for 4-6 weeks 2
    • Consider rituximab as second-line therapy if first-line fails 2

3. Lupus Anticoagulant

• No treatment needed for the prolonged aPTT itself
• If associated with thrombosis, anticoagulate according to thrombosis guidelines
• If anticoagulation needed for other reasons, use anti-Xa monitoring rather than aPTT 3

4. Heparin-Induced Thrombocytopenia (HIT)

• Discontinue all heparin products immediately
• Monitor platelet count (should increase within 10 days)
• Switch to non-heparin anticoagulant if anticoagulation needed 2

Management of Bleeding with Prolonged aPTT

1. Identify and treat underlying cause
2. For severe bleeding:
   • If heparin-induced: Protamine sulfate (1 mg per 100 units of heparin given in previous 2-3 hours, maximum 50 mg) 3
   • If factor deficiency: Fresh frozen plasma (15 ml/kg) or specific factor replacement
   • If acquired hemophilia: Bypassing agents (rFVIIa 90 μg/kg every 2-3h or aPCCs 50-100 IU/kg every 8-12h) 2

Special Considerations

• Lupus anticoagulant is paradoxically associated with thrombosis rather than bleeding despite prolonging aPTT 3
• Factor XII deficiency causes prolonged aPTT but does not increase bleeding risk; thromboprophylaxis should not be withheld based solely on prolonged aPTT in these patients 4
• For patients requiring heparin with baseline aPTT prolongation: Use anti-Xa monitoring instead of aPTT 3
• When converting from heparin to warfarin: Overlap therapy for 4-5 days until warfarin has produced desired therapeutic response 5

Common Pitfalls to Avoid

1. Withholding thromboprophylaxis based solely on prolonged aPTT without identifying the cause
2. Assuming bleeding risk based on degree of aPTT prolongation rather than underlying cause
3. Failure to recognize acquired hemophilia in patients with spontaneous bleeding and isolated prolonged aPTT
4. Misinterpreting lupus anticoagulant as a bleeding risk when it actually increases thrombosis risk
5. Over-reliance on aPTT for heparin monitoring in patients with baseline abnormal aPTT

Remember that the cause of an abnormal aPTT is more important than the result itself for determining clinical significance and appropriate management 1.