A 32-year-old woman is evaluated in the preoperative clinic before an elective laparoscopi… — USMLE Step 3

A 32-year-old woman is evaluated in the preoperative clinic before an elective laparoscopic cholecystectomy. She has no history of abnormal bleeding after tooth extractions or minor cuts. Her only medication is an oral contraceptive pill. Vital signs are within normal limits. Physical examination is unremarkable.

Laboratory results are as follows:

Test	Result	Reference Range
Hemoglobin	$13.2$ g/dL	$12.0-15.5$ g/dL
Platelet count	$210,000/\mu L$	$150,000-400,000/\mu L$
Prothrombin time (PT)	$12$ seconds	$11-14$ seconds
Activated partial thromboplastin time (aPTT)	$68$ seconds	$25-35$ seconds

Because of the isolated prolonged aPTT, a mixing study is performed using a 1:1 ratio of the patient's plasma and normal pooled plasma. The aPTT immediately after mixing is $64$ seconds, and after a 2-hour incubation at $37^\circ C$ , it remains $66$ seconds.

Which of the following is the most likely explanation for these laboratory findings?

Presence of a lupus anticoagulantAnswer
B
Factor VIII deficiency
C
Acquired factor VIII inhibitor
D
Von Willebrand disease
E
Factor XI deficiency

Answer

Presence of a lupus anticoagulant

The correct answer identifies the presence of a lupus anticoagulant. The diagnostic approach to an isolated, prolonged activated partial thromboplastin time (aPTT) involves a mixing study. When the patient's plasma is mixed in a 1:1 ratio with normal pooled plasma, a factor deficiency (such as Factor VIII, IX, or XI deficiency) will correct to a normal aPTT because the normal plasma provides at least

50\%

of the necessary factors. If the aPTT fails to correct, it indicates the presence of a circulating inhibitor (an antibody). Inhibitors can be specific (directed against a single factor, usually Factor VIII) or non-specific (such as a lupus anticoagulant). Patients with specific factor inhibitors typically present with severe, spontaneous bleeding. In contrast, patients with a lupus anticoagulant (an antiphospholipid antibody that binds to phospholipids in the assay) have an artifactually prolonged aPTT in vitro but do not have a bleeding diathesis; in fact, they are at an increased risk for thromboembolic events in vivo. Given this patient's completely asymptomatic status and lack of bleeding history, a lupus anticoagulant is the most likely etiology.

Step-by-Step Solution

Analyze the initial coagulation profile

The patient has an isolated prolongation of the activated partial thromboplastin time (aPTT) with a normal prothrombin time (PT) and platelet count.

This localizes the abnormality to the intrinsic or common coagulation pathway.

Interpret the mixing study results

The aPTT remains prolonged immediately after mixing and after a 2-hour incubation.

Failure to correct with normal pooled plasma indicates the presence of a circulating inhibitor (antibody) rather than a factor deficiency.

Correlate laboratory findings with the clinical presentation

The patient is asymptomatic with no history of abnormal bleeding.

An inhibitor causing a prolonged aPTT without clinical bleeding is highly characteristic of a lupus anticoagulant, an antiphospholipid antibody that paradoxically increases the risk of thrombosis in vivo.

Key Concept

Interpretation of mixing studies for prolonged aPTT

Estimated Time:1m 30s

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