A 31-year-old woman is evaluated in the outpatient clinic prior to an elective laparoscopi… — USMLE Step 3

A $31$ -year-old woman is evaluated in the outpatient clinic prior to an elective laparoscopic cholecystectomy for symptomatic cholelithiasis. She has a past medical history of a left lower extremity deep vein thrombosis $3$ years ago following a long-haul flight, for which she was treated with oral anticoagulation for $6$ months. She currently takes no medications. She reports no history of abnormal bleeding with previous dental extractions or menses. Physical examination is unremarkable.

Preoperative laboratory studies show:

Laboratory Test	Result	Reference Range
Hemoglobin	$13.2$ g/dL	$12.0-16.0$ g/dL
Platelet count	$210,000$ /µL	$150,000-400,000$ /µL
Prothrombin time (PT)	$12.5$ sec	$11-15$ sec
Activated partial thromboplastin time (aPTT)	$62$ sec	$25-40$ sec

A $1:1$ mixing study with normal pooled plasma is performed. The patient's aPTT immediately after mixing is $58$ seconds, and after a $2$ -hour incubation, it remains $60$ seconds.

Which of the following is the most likely explanation for this patient's laboratory findings?

Presence of a lupus anticoagulantCevap
B
Acquired factor VIII inhibitor
C
Inherited factor VIII deficiency
D
Factor XII deficiency
E
Von Willebrand disease

Cevap

Presence of a lupus anticoagulant

The correct answer identifies that the patient has an isolated prolonged aPTT that fails to correct with a

1:1

mixing study, indicating a circulating inhibitor rather than a factor deficiency. The clinical history of a previous deep vein thrombosis without any bleeding diathesis strongly points to a lupus anticoagulant. Paradoxically, lupus anticoagulants (which are antiphospholipid antibodies) bind to the phospholipids used in the laboratory assay, artificially prolonging the aPTT in vitro, while acting as highly prothrombotic agents in vivo.

Adım Adım Çözüm

Analyze the initial coagulation panel.

The patient has an isolated prolonged aPTT with a normal PT and platelet count.

This isolates the hematologic abnormality to the intrinsic coagulation pathway (Factors VIII, IX, XI, XII) or a circulating inhibitor affecting this pathway.

Interpret the results of the 1:1 mixing study.

The aPTT fails to correct upon mixing with normal plasma both immediately and after incubation.

Failure to correct the aPTT into the normal reference range indicates the presence of a circulating inhibitor (antibody) rather than a simple clotting factor deficiency.

Correlate the laboratory inhibitor pattern with the patient's clinical history.

The patient is asymptomatic for bleeding but has a notable history of deep vein thrombosis.

Lupus anticoagulant is an inhibitor that artificially prolongs phospholipid-dependent coagulation tests (like aPTT) in vitro but promotes hypercoagulability and thrombosis in vivo, perfectly matching this patient's presentation.

Anahtar Kavram

Interpretation of a mixing study and correlation with Antiphospholipid Syndrome

Soru

Cevap

Adım Adım Çözüm

Anahtar Kavram

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