What is the significance of elevated Prothrombin Time (PT) and Partial Thromboplastin Time (PTT) in a healthy young patient?

From the Guidelines

Elevated Prothrombin Time (PT) and Partial Thromboplastin Time (PTT) in a healthy young patient most commonly indicates the presence of an anticoagulant effect, and a thorough history and physical examination are essential to identify the underlying cause, with consideration of laboratory error, specimen collection issue, or the use of anticoagulant medications, such as direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) 1.

Key Considerations

• The presence of elevated PT and PTT values may indicate an increased risk of bleeding, particularly in patients taking anticoagulant medications, and it is crucial to assess the patient's bleeding risk and consider the potential need for reversal therapy 1.
• A normal aPTT and/or PT cannot rule out the effect of DOACs, and viscoelastic coagulation tests, such as thromboelastography (TEG) or rotational thromboelastometry (ROTEM), may be useful in detecting coagulopathy associated with DOACs [1, @226@].
• The use of specific factor assays, such as ecarin clotting time (ECT) or anti-Xa activity, may be necessary to identify the exact deficiency or to monitor the effects of reversal therapy [1, @202@].

Potential Causes

• Laboratory error or specimen collection issue
• Inherited clotting factor deficiencies, such as hemophilia A or B (factor VIII or IX deficiency), von Willebrand disease, or vitamin K deficiency
• Medication effects, including anticoagulants, certain antibiotics, or herbal supplements
• Liver disease, which can cause coagulation abnormalities even in young patients

Recommendations

• Repeat testing is recommended before pursuing extensive workup to rule out laboratory error or specimen collection issue 1.
• A thorough history focusing on bleeding tendencies, family history of bleeding disorders, and medication use is essential to identify the underlying cause 1.
• Consideration of viscoelastic coagulation tests, such as TEG or ROTEM, may be useful in detecting coagulopathy associated with DOACs [1, @226@].
• Specific factor assays, such as ECT or anti-Xa activity, may be necessary to identify the exact deficiency or to monitor the effects of reversal therapy [1, @202@].

From the Research

Significance of Elevated Prothrombin Time (PT) and Partial Thromboplastin Time (PTT)

Elevated PT and PTT in a healthy young patient can be indicative of various conditions, including:

• Congenital factor VII deficiency, as seen in a case report of a two-month-old infant with an elevated PT and normal aPTT 2
• Vitamin K deficiency, which can cause a prolonged PT 3, 4, 5
• Liver disease, which can cause a prolonged PT and/or aPTT 3, 4, 5
• Lupus anticoagulant, which can cause a prolonged aPTT 4, 5
• Coagulation factor deficiencies or inhibitors, which can cause a prolonged PT and/or aPTT 4

Diagnostic Approach

A thorough history and physical examination, combined with laboratory tests, are essential in diagnosing the cause of elevated PT and PTT. This may include:

• PT and aPTT mixing studies to determine if the prolongation is due to a factor deficiency or inhibitor 4
• Reflexive testing, such as factor assays or lupus anticoagulant testing, to further investigate the cause of the prolongation 5
• Verification of reference intervals for PT and aPTT in children, as adult-based reference intervals may not be applicable 6

Clinical Implications

Elevated PT and PTT can have significant clinical implications, particularly in patients undergoing high-risk surgery. It is crucial to:

• Confirm abnormal preoperative lab values before proceeding with surgery 2
• Develop a multidisciplinary plan to manage patients with coagulopathies, including the use of recombinant factor VIIa in cases of factor VII deficiency 2
• Consider the use of a prolonged clot time profile (PROCT) to efficiently diagnose the cause of prolonged PT and/or aPTT 5