From the Guidelines
An isolated prolonged activated partial thromboplastin time (aPTT) with a normal International Normalized Ratio (INR) is most commonly caused by lupus anticoagulant, heparin therapy, or specific factor deficiencies, as supported by the most recent evidence 1.
Causes of Isolated Prolonged aPTT
The causes of an isolated prolonged aPTT with a normal INR can be categorized into several groups:
- Deficiencies or inhibitors in the intrinsic or common coagulation pathways, such as heparin therapy (including unfractionated heparin and sometimes low molecular weight heparin) 1
- Lupus anticoagulant, which may not correct with normal plasma and can be associated with a prolonged aPTT 1
- Specific factor deficiencies, particularly factors VIII, IX, XI, or XII, which can be diagnosed using mixing studies and specific factor assays 1
- Acquired factor inhibitors, such as factor VIII inhibitors, which can be identified using mixing studies and specific assays 1
- Certain medications, including direct thrombin inhibitors (e.g., dabigatran) and specific factor Xa inhibitors, which can affect coagulation assays and increase bleeding risk 1
Clinical Interpretation and Further Testing
Clinical context is crucial for interpreting an isolated prolonged aPTT with a normal INR. For instance, a patient on heparin therapy would be expected to have this laboratory finding. If the cause is not immediately apparent, further testing such as mixing studies can help differentiate between factor deficiencies and inhibitors. Factor deficiencies would show correction of aPTT when patient plasma is mixed with normal plasma, while inhibitors typically would not 1. Viscoelastic coagulation tests, such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM), can also be useful in detecting coagulopathy associated with direct oral anticoagulants (DOACs) and guiding reversal therapy 1.
Morbidity, Mortality, and Quality of Life
Recognizing the causes of an isolated prolonged aPTT with a normal INR is essential to prevent morbidity, mortality, and to improve quality of life. Some causes, such as factor VIII or IX deficiencies, may increase bleeding risk, while others, such as lupus anticoagulant or factor XII deficiency, generally do not. Therefore, accurate diagnosis and management are critical to minimize complications and improve patient outcomes.
From the Research
Causes of Isolated Prolonged aPTT with Normal INR
The causes of isolated prolonged activated partial thromboplastin time (aPTT) with a normal International Normalized Ratio (INR) can be attributed to several factors. These include:
- Presence of lupus anticoagulants, which are antibodies that interfere with the coagulation process 2, 3, 4, 5
- Treatment with anticoagulants, mainly heparin, which can prolong the aPTT 2, 3
- Deficiencies of specific coagulation factors, such as factors VIII, IX, XI, and XII, which are involved in the intrinsic arm of hemostasis 2, 3, 4, 5
- Presence of antiphospholipid antibodies, which can also prolong the aPTT 5
- Vitamin K deficiency or liver disease, which can affect the production of coagulation factors 5
Prevalence of Causes
The prevalence of these causes can vary, with lupus anticoagulants being the most common cause in some studies 4, while other studies found that antiphospholipid antibodies and contact pathway factor deficiencies were also common causes 5. In some cases, no definite cause can be identified 5.
Importance of Investigation
Investigating the cause of an isolated prolonged aPTT is crucial to ensure correct diagnostic workup and therapeutic choices 2, 3. Failure to recognize the underlying cause can lead to delayed surgery, emotional stress, and increased costs due to re-testing and coagulation factor assessment 3. Additionally, some causes of prolonged aPTT, such as lupus anticoagulants, can increase the risk of thrombosis, rather than bleeding 6.