Which condition is most consistent with an elevated prothrombin time (PT) and activated partial thromboplastin time (aPTT)?

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Elevated PT and APTT: Diagnostic Answer

Liver disease (Option C) is the most consistent condition with simultaneous elevation of both PT and APTT, as hepatic dysfunction impairs synthesis of multiple coagulation factors across both the extrinsic and intrinsic pathways. 1, 2, 3

Why Liver Disease Causes Both PT and APTT Elevation

  • Liver disease affects PT earlier and more significantly than APTT because factor VII (measured by PT) has the shortest half-life among coagulation factors. 2

  • The liver synthesizes all coagulation factors except factor VIII, so progressive hepatic dysfunction leads to deficiencies affecting both the extrinsic pathway (factors II, V, VII, X) and intrinsic pathway (factors II, V, IX, X), causing prolongation of both tests. 4, 5

  • In a retrospective study of outpatients with prolonged coagulation times, liver disease was the most common cause of combined PT and APTT prolongation, accounting for 14% of cases. 4

  • Simultaneous elevation of both PT and APTT indicates either deficiency or dysfunction affecting the common coagulation pathway (factors II, V, X, fibrinogen), which occurs characteristically in liver disease. 3

Why the Other Options Are Incorrect

Congenital Factor VIII Deficiency (Option A)

  • Factor VIII deficiency (hemophilia A) causes isolated APTT prolongation only, with normal PT results. 2, 5

  • PT measures the extrinsic pathway (factors VII, X, V, II, fibrinogen) and remains normal in hemophilia A because factor VIII is part of the intrinsic pathway only. 2

Acquired Factor VIII Deficiency (Option B)

  • Acquired hemophilia A also produces isolated APTT prolongation without PT elevation. 6

  • Like congenital factor VIII deficiency, acquired inhibitors to factor VIII affect only the intrinsic pathway, leaving the extrinsic pathway (and thus PT) intact. 6

Factor XIII Deficiency (Option D)

  • Factor XIII deficiency does not prolong either PT or APTT, as both tests measure only the initiation phase of coagulation, representing merely the first 4% of thrombin production. 3

  • Factor XIII is a transglutaminase that cross-links fibrin after clot formation, functioning downstream of the coagulation cascade measured by PT and APTT. 3

  • Patients with factor XIII deficiency present with delayed bleeding and poor wound healing despite completely normal PT and APTT values. 2

Clinical Context and Additional Considerations

  • When both PT and APTT are prolonged, the differential diagnosis includes: common pathway factor deficiencies (II, V, X, fibrinogen), severe liver disease, disseminated intravascular coagulation (DIC), vitamin K deficiency, or warfarin therapy. 2

  • Perform a 50:50 mixing study with normal plasma to distinguish factor deficiency (which corrects) from inhibitors (which fails to correct). 2, 6

  • In liver disease specifically, PT/INR is a poor predictor of actual bleeding risk despite its use in prognostic scores like MELD, and viscoelastic testing (TEG/ROTEM) provides more comprehensive coagulation assessment. 3

  • In pregnancy, use PT ratio and APTT ratio ≥1.5 as the coagulopathy threshold rather than absolute values in seconds, as coagulation factors increase toward term. 1, 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Coagulation Tests: PT and APTT

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Coagulation Factor Targets for Central Procedures

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Diagnostic Approach to Prolonged aPTT Due to Factor Deficiency

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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