What is the interpretation of a normal International Normalized Ratio (INR) with an elevated Partial Thromboplastin Time (PTT)?

From the FDA Drug Label

1. 2 Pharmacodynamics 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. Specific Populations Geriatric patients 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

A normal INR with an elevated PTT may indicate that heparin is present in the system, as heparin primarily affects the activated partial thromboplastin time (aPTT).

• Heparin inhibits Factor Xa and thrombin (Factor IIa), which are involved in the clotting sequence, thereby prolonging the aPTT.
• A normal INR suggests that the prothrombin time is not significantly affected, which may be due to the dose of heparin being low or the patient's individual response to heparin.
• It is essential to consider the patient's age, as geriatric patients may have higher plasma levels of heparin and longer aPTTs compared to younger patients 1.
• In this scenario, it is crucial to monitor the patient's coagulation parameters closely and adjust the heparin dose accordingly to minimize the risk of bleeding complications.

From the Research

An elevated PTT with a normal INR suggests a coagulation abnormality in the intrinsic or contact activation pathway, and additional testing such as mixing studies, specific factor assays, or tests for lupus anticoagulant is necessary to evaluate this finding. This combination typically indicates a problem in the intrinsic or contact activation pathway of coagulation, while the extrinsic pathway remains intact. Common causes include heparin therapy (including low molecular weight heparin), lupus anticoagulant, hemophilia A (factor VIII deficiency), hemophilia B (factor IX deficiency), von Willebrand disease, or factor XII deficiency 2. To properly evaluate this finding, it is essential to consider the clinical context and the potential effects of heparin therapy on PTT results, as increased factor VIII levels can shorten APTT under therapeutic doses of heparin 3. The normal INR indicates that the vitamin K-dependent factors (II, VII, IX, X) and the common pathway are functioning properly, which helps narrow down the diagnostic possibilities.

Some key points to consider in the evaluation of an elevated PTT with a normal INR include:

• The potential for heparin therapy to cause an elevated PTT, and the need to consider alternative tests such as anti-Xa activity to monitor the anticoagulant effect of heparin 3
• The importance of specialized testing such as mixing studies to distinguish between factor deficiencies and inhibitors, specific factor assays, or tests for lupus anticoagulant 2
• The need to consider the clinical context and the potential for underlying bleeding disorders or autoimmune conditions that require specific management
• The potential for increased factor VIII levels to shorten APTT under therapeutic doses of heparin, and the need to consider this when interpreting PTT results 3

Overall, the evaluation of an elevated PTT with a normal INR requires a careful consideration of the clinical context and the potential causes of this coagulation abnormality, as well as the use of specialized testing to determine the underlying cause and guide management.