What does a prolonged activated partial thromboplastin time (aPTT) indicate?

What Does a Prolonged aPTT Indicate?

A prolonged activated partial thromboplastin time (aPTT) primarily indicates interference with the intrinsic and/or common coagulation pathways and can be caused by anticoagulant therapy, factor deficiencies, or the presence of inhibitors like lupus anticoagulant. 1

Common Causes of Prolonged aPTT

Anticoagulant Therapy

• Unfractionated Heparin (UFH): Most common medication cause
  • Therapeutic aPTT range: 1.5-2.5 times control (approximately 45-75 seconds) 1
  • Monitored using aPTT or anti-Xa assays 2
• Direct Thrombin Inhibitors (e.g., dabigatran)
  • Can be monitored using diluted thrombin time or ecarin clotting time 2, 1

Factor Deficiencies

• Hemophilia A (Factor VIII deficiency)
• Hemophilia B (Factor IX deficiency)
• Factor XI deficiency
• Factor XII deficiency (does not cause bleeding)
• Prekallikrein or high-molecular-weight kininogen deficiency (does not cause bleeding) 3

Inhibitors

• Lupus Anticoagulant: Most common inhibitor causing prolonged aPTT 4
  • Paradoxically associated with thrombosis rather than bleeding
  • Present in up to 45% of COVID-19 patients 2
• Acquired Factor Inhibitors (e.g., acquired hemophilia)

Other Causes

• Pre-analytical errors:
  • Improper sample collection
  • Presence of clots in the sample tube 1
• Liver disease
• Vitamin K deficiency
• Disseminated Intravascular Coagulation (DIC) 3

Clinical Significance

Bleeding Risk Assessment

• Clinically Significant Prolongation: Associated with bleeding risk when due to deficiencies in factors VIII, IX, or XI 3
• No Bleeding Risk: Prolongation due to factor XII, prekallikrein, or high-molecular-weight kininogen deficiencies typically doesn't increase bleeding risk 3, 5
• Thrombotic Risk: When due to lupus anticoagulant, may actually indicate increased thrombotic risk rather than bleeding 4

Diagnostic Algorithm

1. Verify the result with repeat testing to rule out pre-analytical errors 1
2. Check PT/INR:
   • If both PT and aPTT prolonged: Consider common pathway factors, liver disease, vitamin K deficiency, or DIC
   • If isolated aPTT prolongation: Continue investigation 4
3. Perform mixing study (mix patient plasma with normal plasma):
   • If aPTT corrects: Factor deficiency likely
   • If aPTT remains prolonged: Inhibitor likely (e.g., lupus anticoagulant) 6
4. Specific factor assays to identify deficiencies if mixing study suggests factor deficiency 1
5. Lupus anticoagulant testing if mixing study suggests an inhibitor 6

Management Considerations

For Anticoagulant Therapy

• UFH monitoring:
  • Check aPTT 6 hours after any dosage change
  • When two consecutive aPTT values are therapeutic, measurements may be made every 24 hours 1
  • In inflammatory states (e.g., COVID-19), anti-Xa monitoring may be more reliable than aPTT 2

For Factor Deficiencies

• Factor replacement therapy based on severity and clinical situation 1
• Desmopressin may be useful for mild hemophilia A 1
• Fresh frozen plasma if bleeding or before invasive procedures 1

For Inhibitors

• Lupus anticoagulant: Anticoagulation therapy (typically warfarin) for patients with thrombosis 1
• Acquired hemophilia: Bypassing agents and immunosuppressive therapy 1

Important Caveats

• The degree of aPTT prolongation does not necessarily correlate with bleeding risk 5
• Unnecessary FFP administration for isolated aPTT prolongation without bleeding or planned invasive procedure should be avoided, especially with Factor XII deficiency or lupus anticoagulant 1
• In inflammatory states (like COVID-19), heparin resistance may occur due to increased acute phase reactants, making aPTT less reliable for monitoring 2
• For patients requiring heparin therapy who have baseline aPTT prolongation, anti-Xa monitoring is preferred 1

Remember that the cause of an abnormal aPTT is more important than the degree of abnormality itself when assessing clinical risk 5.