From the Guidelines
Prolonged activated partial thromboplastin time (APTT) is most commonly caused by anticoagulant medications, such as heparin, direct thrombin inhibitors, and direct oral anticoagulants, as well as deficiencies or inhibitors affecting the intrinsic and common pathways of coagulation, including lupus anticoagulant or antiphospholipid antibodies, as seen in COVID-19 patients 1. When considering the causes of prolonged APTT, it's essential to evaluate the patient's medical history, current medications, and laboratory results.
- Anticoagulant medications, such as heparin (unfractionated and low molecular weight), direct thrombin inhibitors (bivalirudin, argatroban), and direct oral anticoagulants (dabigatran), are well-known causes of prolonged APTT 1.
- Deficiencies of clotting factors VIII, IX, XI, and XII can also prolong APTT, with hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency) being notable examples.
- Acquired conditions, such as liver disease, vitamin K deficiency, disseminated intravascular coagulation (DIC), and the presence of lupus anticoagulant or antiphospholipid antibodies, can cause prolongation as well 1.
- Von Willebrand disease, which affects von Willebrand factor and secondarily factor VIII, may also extend APTT.
- In COVID-19 patients, prolonged APTT may be due to consumptive coagulopathy, lupus anticoagulant, or antiphospholipid antibodies 1. It's crucial to determine if the prolonged APTT represents a true bleeding risk or is simply a laboratory finding, as factor XII deficiency and lupus anticoagulant can prolong APTT without increasing bleeding risk 1.
- Mixing studies can help differentiate between factor deficiencies and inhibitors, with correction of APTT after mixing with normal plasma suggesting a factor deficiency, while persistent prolongation indicates the presence of an inhibitor.
- Viscoelastic coagulation tests, such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM), can also be useful in evaluating the coagulation status of patients with prolonged APTT 1.
From the FDA Drug Label
Various times (activated clotting time, activated partial thromboplastin time, prothrombin time, whole blood clotting time) are prolonged by full therapeutic doses of heparin; in most cases, they are not measurably affected by low doses of heparin. Patients over 60 years of age, following similar doses of heparin, may have higher plasma levels of heparin and longer activated partial thromboplastin times (aPTTs) compared with patients under 60 years of age
Prolonged APTT can be caused by:
- Full therapeutic doses of heparin 2
- Higher plasma levels of heparin in geriatric patients (over 60 years of age) compared to younger patients 2 2
From the Research
Causes of Prolonged APTT
- Isolated prolonged activated partial thromboplastin time (APTT) can be caused by several factors, including:
- Other conditions that may cause a prolonged APTT include liver disease, vitamin K deficiency, and disseminated intravascular coagulation 7
Diagnostic Approach
- The identification of the cause of an isolated prolonged APTT is crucial for ensuring the correct diagnostic workup and therapeutic choices 4
- A diagnostic algorithm can be used to differentiate between lupus anticoagulants and factor deficiencies 3
- The measurement of contact activation factors and factor inhibitors should be considered in the initial evaluation of a prolonged APTT with normal prothrombin time (PT) 5
- Specific clotting factor assays may not be necessary if an APTT with a specific reagent is normal 6
Laboratory Considerations
- Different APTT reagents display considerable differences in their sensitivity to deficiencies of coagulation factors 3
- The choice of APTT reagent can affect the detection of prolonged APTT and the subsequent diagnostic approach 7
- Laboratories should be aware of the sensitivity of their APTT reagents to heparin, lupus anticoagulant, and clotting factors to ensure accurate interpretation of results 7