What are the causes of a prolonged Partial Thromboplastin Time (PTT)?

From the Guidelines

Prolonged partial thromboplastin time (PTT) is primarily caused by deficiencies or inhibitors affecting the intrinsic and common pathways of coagulation, with the most common causes including heparin therapy, vitamin K deficiency, liver disease, and factor deficiencies (particularly factors VIII, IX, XI, and XII) as noted in studies such as 1 and 1. When evaluating the causes of prolonged PTT, it is crucial to consider the patient's clinical context, medication history, and family history. Key factors to assess include:

• Heparin therapy (both unfractionated and low molecular weight heparin)
• Vitamin K deficiency
• Liver disease
• Disseminated intravascular coagulation (DIC)
• Factor deficiencies, especially factors VIII, IX, XI, and XII
• Specific factor deficiencies like hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency)
• Acquired inhibitors such as lupus anticoagulant and specific factor inhibitors
• Massive blood transfusion leading to dilutional coagulopathy

A mixing study can help differentiate between factor deficiencies and inhibitors - if the PTT corrects with normal plasma, a factor deficiency is likely; if it remains prolonged, an inhibitor is suspected, as discussed in 1. The diagnosis and treatment should be guided by the most recent and highest quality evidence, prioritizing the patient's morbidity, mortality, and quality of life. Treatment depends on addressing the underlying cause, which may include vitamin K supplementation, factor replacement, or discontinuation of heparin therapy when appropriate, considering the clinical presentation and laboratory findings as outlined in studies like 1.

From the FDA Drug Label

Warfarin sodium tablets may increase the activated partial thromboplastin time (aPTT) test, even in the absence of heparin 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.

The causes of prolonged PTT include:

• Warfarin: Warfarin sodium tablets may increase the activated partial thromboplastin time (aPTT) test, even in the absence of heparin 2
• Heparin: Full therapeutic doses of heparin can prolong the activated partial thromboplastin time (aPTT) 3 3

From the Research

Causes of Prolonged PTT

• Prolonged activated partial thromboplastin time (APTT) can be caused by the presence of the lupus anticoagulant or an intrinsic or contact factor deficiency, of which only deficiencies of factors VIII, IX, or XI are associated with bleeding 4
• Isolated prolongation of APTT can be caused by lupus anticoagulant, intrinsic or contact factor deficiency, or other conditions such as prekallikrein deficiency 5, 6
• Other causes of prolonged APTT include:
  • Vitamin K deficiency 5
  • Liver disease 5
  • Factor VIII inhibitor and lupus anticoagulant coexistence 7
  • Prekallikrein (PK) deficiency, also known as Fletcher factor deficiency 6
• It is essential to evaluate the measurement of contact activation factors and factor inhibitors in the initial assessment of a prolonged APTT with normal prothrombin time (PT) 6

Diagnostic Approaches

• An algorithmic approach, termed the prolonged clot time profile (PROCT), can be used to delineate the etiology of a prolonged PT/aPTT 5
• The choice of reagent or methodology can strongly influence the resulting activity in factor VIII and factor IX activity measurements 8
• Discrepancy between one-stage and chromogenic reagents has been demonstrated in some patients with mild hemophilia A or B, and in the measurement of some standard and extended half-life factor replacement therapies 8