What causes an increased Activated Partial Thromboplastin Time (APTT)?

From the Guidelines

Increased Activated Partial Thromboplastin Time (APTT) is caused by anticoagulant therapy, such as heparin, direct oral anticoagulants (DOACs), and other factors that affect coagulation pathways.

Causes of Increased APTT

• Heparin therapy: Heparin binds to and enhances the activity of antithrombin III, reducing thrombin generation and inhibiting coagulation factors (XIIa, IXa, XIa, and Xa) 1.
• Direct Oral Anticoagulants (DOACs): DOACs, such as dabigatran, rivaroxaban, apixaban, and edoxaban, specifically inhibit thrombin or activated factor X (FXa), affecting global coagulation assays and select special coagulation tests 1.
• Factor deficiencies or inhibitors: Prolongation of APTT can be caused by deficiencies or inhibitors of coagulation factors, such as factor X deficiency 1.
• Lupus anticoagulants: Presence of lupus anticoagulants can prolong APTT 1.
• Other factors: Consumptive coagulopathy, liver or hematological disorders, and certain medications can also increase APTT 1.

Monitoring APTT

• Frequency of monitoring: APTT should be monitored regularly in patients on heparin therapy, with adjustments made to achieve a therapeutic range 1.
• Target range: The target range for APTT varies depending on the laboratory and the specific heparin preparation being used, but is typically between 1.5 to 2.5 times the control value 1.
• Limitations of APTT monitoring: APTT monitoring has limitations, including variability between laboratories and reagents, and may not accurately reflect the anticoagulant effect of DOACs 1.

From the Research

Causes of Increased Activated Partial Thromboplastin Time (APTT)

• An isolated, prolonged APTT can be caused by several factors, including:
  • Lupus anticoagulants 2, 3, 4, 5
  • Deficiencies of specific coagulation factors, such as contact pathway factor deficiencies or other coagulation factor deficiencies 2, 3, 4
  • Treatment with anticoagulants, mainly heparin 2, 3
  • Antiphospholipid antibodies 4
  • Vitamin K deficiency or liver disease 4, 5
  • Congenital or acquired conditions, such as hemophilia 2
  • Laboratory artifacts, such as poor sample collection or preanalytical interferences 3, 6, 5

Prevalence of Causes

• The most common causes of an isolated prolonged APTT vary, but may include:
  • Lupus anticoagulants, found in 4-5% of cases 5
  • Antiphospholipid antibodies, found in 22.6% of cases 4
  • Contact pathway factor deficiencies, found in 17.4% of cases 4
  • Other coagulation factor deficiencies, found in 11.6% of cases 4
  • Vitamin K deficiency or liver disease, found in 11.6% of cases 4

Importance of Identifying the Cause

• Identifying the underlying cause of an isolated prolonged APTT is crucial for ensuring the correct diagnostic workup and therapeutic choices 2, 3, 4
• The cause of an abnormal APTT is more important than the result itself, as it can indicate a hemostatic defect or no particular risk 6