What are the causes of an elevated Partial Thromboplastin Time (PTT)?

From the Guidelines

Elevated partial thromboplastin time (PTT) can result from several causes, including anticoagulant medications, clotting factor deficiencies, liver disease, and certain autoimmune conditions, with the most common medications being heparin, direct thrombin inhibitors, and warfarin, as well as direct oral anticoagulants (DOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban 1. The causes of an elevated PTT can be broadly categorized into the following:

• Anticoagulant medications:
  • Heparin, which is a glycosaminoglycan that binds to and enhances the activity of antithrombin III, thereby reducing thrombin generation via inhibiting coagulation factors (XIIa, IXa, XIa, and Xa) 1
  • Direct thrombin inhibitors like dabigatran, which competitively inhibits thrombin and thus prevents the conversion of fibrinogen to fibrin 1
  • Direct FXa inhibitors like rivaroxaban, apixaban, and edoxaban, which prevent the conversion of prothrombin to thrombin, thereby preventing fibrin formation 1
• Clotting factor deficiencies:
  • Inherited deficiencies, particularly of factors VIII (hemophilia A), IX (hemophilia B), XI, and XII, can prolong PTT 1
  • Acquired deficiencies, which can occur in liver disease due to decreased synthesis of clotting factors, vitamin K deficiency, or disseminated intravascular coagulation (DIC) 1
• Liver disease:
  • Decreased synthesis of clotting factors can lead to an elevated PTT 1
• Autoimmune conditions:
  • Lupus anticoagulant, despite its name, increases clotting risk while paradoxically prolonging PTT in laboratory testing 1
  • Von Willebrand disease, which affects platelet function and factor VIII levels, can also elevate PTT 1 Other causes of elevated PTT include massive blood transfusions, which can dilute clotting factors, and severe infections or sepsis, which can activate coagulation pathways, consuming factors and prolonging PTT 1. When investigating elevated PTT, it's essential to consider the patient's medication history, family history of bleeding disorders, and clinical context to determine the underlying cause and appropriate management 1. The most recent and highest quality study, published in 2024, highlights the importance of considering the effects of DOACs on PTT, as well as the need for careful monitoring and management of patients with elevated PTT 1.

From the FDA Drug Label

Warfarin sodium tablets may increase the activated partial thromboplastin time (aPTT) test, even in the absence of heparin A severe elevation (>50 seconds) in activated partial thromboplastin time (aPTT) with a PT/INR in the desired range has been identified as an indication of increased risk of postoperative hemorrhage. The causes of an elevated Partial Thromboplastin Time (PTT) or aPTT include:

• Warfarin sodium tablets
• Heparin Note that the label does not provide a comprehensive list of causes of elevated PTT, only that warfarin and heparin can increase aPTT 2

From the Research

Causes of Elevated Partial Thromboplastin Time (PTT)

• Prolonged PTT can be caused by various factors, including:
  • Use of anticoagulants, such as heparin 3, 4, 5, 6
  • Congenital or acquired deficiencies of specific coagulation factors, such as factors VIII, IX, and XI 4, 5, 6
  • Presence of circulating anticoagulants, such as lupus anticoagulant 4, 5, 6
  • Liver disease 5, 7, 6
  • Vitamin K deficiency 5, 7
  • Disseminated intravascular coagulation 5, 6
  • Factor inhibitors, such as lupus anticoagulant 5
• Other causes of prolonged PTT may include:
  • Weight-based unfractionated heparin (UFH) dose 3
  • Length of UFH therapy 3
  • Baseline PTT value 3
• It is essential to identify the cause of an elevated PTT to ensure correct diagnostic workup and therapeutic choices 4, 6

Preanalytical Interferences

• Preanalytical interferences can also affect PTT results, and it is crucial to consider these factors when interpreting results 4, 6
• Factors such as patient history, medication use, and laboratory procedures can influence PTT results 4, 6

Diagnostic Approach

• A thorough medical history, physical examination, and laboratory tests, including PTT, prothrombin time (PT), and fibrinogen, can help diagnose the cause of an elevated PTT 5, 7
• Further testing, such as factor assays and lupus anticoagulant testing, may be necessary to confirm the diagnosis 5, 6