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    Subjects/Pathology/Coagulation Disorders
    Coagulation Disorders
    medium
    microscope Pathology

    A 35-year-old woman presents with recurrent thrombosis and recurrent pregnancy losses. Investigations reveal prolonged aPTT that does not correct on mixing study. Which of the following is NOT a characteristic feature of Antiphospholipid Syndrome?

    A. Positive DRVVT (Dilute Russell Viper Venom Time) test
    B. Presence of lupus anticoagulant or anticardiolipin antibodies
    C. Thrombosis (arterial or venous) or pregnancy morbidity
    D. Prolonged aPTT that corrects on mixing with normal plasma

    Explanation

    Antiphospholipid Syndrome (APS): Diagnostic & Laboratory Features

    Key Point
    The hallmark laboratory finding in APS is a prolonged aPTT that does NOT correct on mixing study — this is the critical diagnostic clue that distinguishes APS from factor deficiencies.
    Why aPTT Does NOT Correct in APS

    In APS, the prolonged aPTT is caused by lupus anticoagulant (LA), an immunoglobulin that binds to phospholipid-protein complexes in vitro. When patient plasma is mixed with normal plasma:

    • The LA from the patient plasma continues to inhibit the phospholipid-dependent reactions in the normal plasma
    • The aPTT remains prolonged (non-correction)
    • This is pathognomonic for LA and APS

    In contrast, factor deficiencies (e.g., Factor VIII deficiency) will show correction on mixing because the normal plasma supplies the missing factor.

    Diagnostic Criteria for APS (Sydney 2006)
    Table
    CriterionDetails
    ClinicalThrombosis (arterial/venous) OR pregnancy morbidity (≥3 consecutive losses <10 weeks OR ≥1 unexplained fetal death ≥10 weeks)
    LaboratoryLupus anticoagulant (LA) OR Anticardiolipin (aCL) IgG/IgM ≥40 GPL/MPL units OR Anti-β2-glycoprotein-I IgG/IgM ≥40 units
    TimingLab abnormality must be present on ≥2 occasions ≥12 weeks apart
    High-YieldNEET PG
    The three characteristic lab tests for LA are:
    1. 1.
      aPTT — prolonged, non-correcting on mixing
    2. 2.
      DRVVT (Dilute Russell Viper Venom Time) — prolonged, corrects with phospholipid (confirmatory)
    3. 3.
      Platelet Neutralization Procedure — shortens aPTT (confirms LA)
    Clinical Pearl

    APS is a paradoxical thrombophilia: despite prolonged aPTT (which would suggest bleeding), patients have increased thrombotic risk. This is because the anticoagulant effect is in vitro only; in vivo, the antibodies promote thrombosis via:

    • Activation of endothelial cells
    • Platelet activation
    • Complement activation
    • Tissue factor upregulation
    Why Option 0 Is Incorrect

    The statement "Prolonged aPTT that corrects on mixing with normal plasma" is NOT a feature of APS. This is the key distinction. Correction on mixing indicates a factor deficiency, not LA. The presence of non-correcting prolonged aPTT is what makes APS unique and diagnostically important.

    Why Other Options Are Correct
    • Option 1: Lupus anticoagulant and anticardiolipin antibodies are the defining serological markers of APS.
    • Option 2: Thrombosis and pregnancy morbidity are the clinical manifestations required for diagnosis.
    • Option 3: DRVVT is a confirmatory test; it is prolonged in LA and corrects when phospholipid is added (phospholipid neutralization).

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