A 42-year-old woman is brought to the emergency department by her husband due to sudden-on… — USMLE Step 3

A $42$ -year-old woman is brought to the emergency department by her husband due to sudden-onset difficulty speaking and weakness in her right arm that began $2$ hours ago. Her medical history includes systemic lupus erythematosus managed with hydroxychloroquine, as well as two spontaneous first-trimester abortions. Vital signs are within normal limits. Neurological examination reveals an expressive aphasia and $2/5$ motor strength in the right upper extremity. A non-contrast head CT demonstrates no acute intracranial hemorrhage. Laboratory studies reveal:

Hemoglobin: $12.1 \text{ g/dL}$
Platelet count: $92,000/\text{mm}^3$
Prothrombin time (PT): $12 \text{ s}$ (Normal: $11-15 \text{ s}$ )
Partial thromboplastin time (PTT): $55 \text{ s}$ (Normal: $25-40 \text{ s}$ )

A mixing study with normal plasma is performed, and the patient's PTT remains prolonged at $52 \text{ s}$ .

Which of the following is the most likely diagnosis?

Antiphospholipid syndromeAnswer
B
Thrombotic thrombocytopenic purpura
C
Acquired hemophilia A
D
Disseminated intravascular coagulation
E
Central nervous system lupus vasculitis

Answer

Antiphospholipid syndrome

The correct diagnosis is antiphospholipid syndrome. This patient's presentation of an acute ischemic stroke combined with a history of recurrent first-trimester miscarriages and systemic lupus erythematosus is highly suggestive of a hypercoagulable state. The laboratory evaluation provides the definitive clue: an isolated prolonged PTT that fails to correct when mixed with normal plasma. A mixing study differentiates between a factor deficiency (which corrects) and an inhibitor (which fails to correct). In this patient, the inhibitor is the lupus anticoagulant. Paradoxically, while the lupus anticoagulant prolongs the PTT in the laboratory by interfering with the phospholipid-dependent coagulation assays, it is highly thrombogenic inside the human body. The presence of mild thrombocytopenia is also a frequent accompanying feature in antiphospholipid syndrome.

Step-by-Step Solution

Identify the primary clinical presentation.

The patient is having an acute ischemic stroke (aphasia, focal weakness, normal non-contrast CT).

Establishing the primary acute problem narrows the differential to causes of cerebral ischemia or thrombosis.

Interpret the laboratory findings.

Mild thrombocytopenia and an isolated prolonged PTT that does not correct with a mixing study.

Failure to correct with normal plasma indicates the presence of a coagulation inhibitor (such as an autoantibody) rather than a clotting factor deficiency.

Synthesize the history and objective findings.

The combination of stroke, recurrent miscarriages, SLE, and an inhibitor (lupus anticoagulant) strongly supports antiphospholipid syndrome.

Integrating the patient's rheumatologic history with the paradoxical in vitro PTT prolongation clarifies the etiology of the in vivo thrombosis.

Key Concept

The diagnosis of antiphospholipid syndrome is highly likely in a patient with a history of SLE, recurrent miscarriages, and arterial thrombosis, especially when laboratory evaluation reveals an isolated prolonged PTT that fails to correct on a mixing study due to the lupus anticoagulant.

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