Accompanied by her husband, a 28-year-old woman arrives at the emergency department presen… — USMLE Step 3

Accompanied by her husband, a 28-year-old woman arrives at the emergency department presenting with progressive lethargy, confusion, and subjective fever over the past two days. Her husband mentions she had been complaining of an intense headache and recently developed a pinpoint red rash on her calves. She has a known history of systemic lupus erythematosus (SLE) diagnosed three years ago, managed with hydroxychloroquine and a low-dose oral corticosteroid.

Her temperature is $38.1^\circ\text{C}$ ( $100.6^\circ\text{F}$ ), blood pressure is $142/88 \text{ mmHg}$ , pulse is $105/\text{min}$ , and respirations are $18/\text{min}$ . Physical examination reveals scattered petechiae on the bilateral lower extremities. Neurological examination shows she is oriented to person and place only, but there are no focal motor or sensory deficits.

Laboratory results are as follows:

Laboratory Test	Result	Reference Range
Hemoglobin	$7.8 \text{ g/dL}$	$12.0-15.5 \text{ g/dL}$
Platelets	$24,000/\text{mm}^3$	$150,000-400,000/\text{mm}^3$
Leukocytes	$6,500/\text{mm}^3$	$4,500-11,000/\text{mm}^3$
Creatinine	$1.6 \text{ mg/dL}$	$0.6-1.1 \text{ mg/dL}$
Total bilirubin	$3.2 \text{ mg/dL}$	$0.1-1.2 \text{ mg/dL}$
Indirect bilirubin	$2.7 \text{ mg/dL}$	$0.1-0.8 \text{ mg/dL}$
Lactate dehydrogenase (LDH)	$1,150 \text{ U/L}$	$140-280 \text{ U/L}$
Prothrombin time (PT)	$12 \text{ seconds}$	$11-15 \text{ seconds}$
Activated partial thromboplastin time (aPTT)	$32 \text{ seconds}$	$25-40 \text{ seconds}$
Direct antiglobulin test (DAT)	Negative	Negative

The peripheral blood smear reveals prominent schistocytes and severely decreased platelets.

Based on the clinical evaluation and laboratory data, which of the following is the most likely diagnosis?

Thrombotic thrombocytopenic purpuraAnswer
B
Systemic lupus erythematosus disease flare
C
Disseminated intravascular coagulation
D
Evans syndrome
E
Meningococcal meningitis

Answer

The most likely diagnosis is thrombotic thrombocytopenic purpura.

The correct diagnosis is thrombotic thrombocytopenic purpura (TTP). TTP is a life-threatening thrombotic microangiopathy typically caused by a severe deficiency of the ADAMTS13 protease, which leads to the formation of large von Willebrand factor multimers that shear red blood cells and consume platelets. It is classically defined by a pentad of clinical findings: microangiopathic hemolytic anemia (MAHA), thrombocytopenia, acute kidney injury, neurological abnormalities, and fever. This patient exhibits all five features. The peripheral smear showing schistocytes, combined with elevated LDH and indirect bilirubin, confirms mechanical hemolysis (MAHA). Crucially, the normal coagulation studies (PT and aPTT) differentiate TTP from consumptive coagulopathies like disseminated intravascular coagulation (DIC). Acquired TTP is often associated with autoantibodies, and patients with underlying autoimmune diseases, such as systemic lupus erythematosus (SLE), are at a higher risk of developing it.

Step-by-Step Solution

Identify the patient's primary clinical syndrome from the physical and historical findings.

The patient has altered mental status, fever, and petechiae (indicative of thrombocytopenia).

Establishing the clinical pillars helps guide the interpretation of laboratory results.

Analyze the laboratory data and peripheral smear to characterize the cytopenias.

Labs show severe thrombocytopenia and anemia. Elevated LDH, indirect hyperbilirubinemia, and schistocytes confirm a microangiopathic hemolytic anemia (MAHA).

Differentiating mechanical intravascular hemolysis (schistocytes, negative DAT) from immune extravascular hemolysis (spherocytes, positive DAT) is critical for diagnosis.

Assess the coagulation cascade markers (PT and aPTT).

Both PT and aPTT are within normal limits.

Normal coagulation times rule out consumptive coagulopathies like DIC, narrowing the differential to primary thrombotic microangiopathies.

Synthesize the findings to formulate the final diagnosis.

The classic pentad of MAHA, thrombocytopenia, fever, renal impairment, and neurological symptoms in the setting of normal coagulation studies points directly to TTP.

Patients with preexisting autoimmune conditions (like SLE) have a known increased risk of developing acquired TTP (due to autoantibodies against ADAMTS13).

Key Concept

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, neurological symptoms, renal impairment, and fever, all in the setting of normal coagulation studies (PT/aPTT).

Question

Answer

Step-by-Step Solution

Key Concept

Common Mistakes

Topics

More questions from this topic