Interpretation of Prothrombin Time and Activated Partial Thromboplastin Time Mixing Studies Using Predefined...

Area of Science:

• Hematology
• Clinical Pathology
• Diagnostic Laboratory Science

Background:

• Mixing studies are vital for differentiating clotting factor deficiencies from inhibitors.
• Current clinical practice often relies on the upper reference interval (URI) for interpreting these studies.
• This study evaluates updated ICSH guidelines for improved diagnostic accuracy.

Purpose of the Study:

• To validate and implement the 2024 ICSH recommendations for interpreting PT/aPTT mixing studies.
• To compare the diagnostic performance of ICSH criteria against the traditional URI method.
• To assess the detection rates of clotting factor deficiencies and inhibitors using different interpretive criteria.

Main Methods:

• Plasma samples with prolonged PT/aPTT were mixed 1:1 with normal pooled plasma.
• ICSH criteria (≥70% correction or ≤15% Rosner Index) were applied and compared with URI.
• Results were correlated with clotting factor assays in 243 patients.

Main Results:

• The ICSH recommendations accurately identified clotting factor deficiencies post-validation.
• Inhibitor detection rates varied: URI (4.9%), 70% correction (8.2%), Rosner Index (3.7%).
• High agreement (≥90%) was observed between different interpretive methods.

Conclusions:

• Validated ICSH guidelines provide accurate identification of clotting factor deficiencies.
• Method-dependent discordance in inhibitor detection highlights the need for careful interpretation.
• Clinical correlation remains essential for comprehensive diagnosis of coagulation disorders.