We present a case of unexpected severe neutropenia in a patient prescribed a 21-day course of double antiplatelet therapy (aspirin and clopidogrel) for ischemic stroke.

Antiplatelet agents are the cornerstone of atherosclerotic stroke prevention. In recent years, trials such as CHANCE and POINT have popularized the use of a short (3-4 week) course of dual antiplatelet therapy (aspirin plus a P2Y12 inhibitor) after minor stroke or high-risk transient ischemic attack. While some P2Y12 inhibitors such as ticlopidine have been associated with neutropenia, this side effect is exceedingly rare with clopidogrel and has primarily been reported with prolonged use after coronary stenting.

An 88-year-old woman presented with acute onset of left face, arm, and leg numbness. National Institutes of Health Stroke Scale was 1 for mild sensory loss. Non-contrast computed tomography (CT) of head showed no evidence of hemorrhage or acute ischemia. Brain magnetic resonance imaging revealed a small area of diffusion positivity in the right thalamus consistent with acute ischemic stroke. She was already taking aspirin 81mg daily; clopidogrel 75mg daily was added for a 21-day course. WBC count during admission had ranged from 4.11-6.27 K/uL. On post-stroke day 23, she presented with three days of malaise, abdominal pain, and fever to 102 °F. WBC and absolute neutrophil count were now markedly low (0.67, <0.01 K/uL, respectively). CT scan of abdomen revealed enterocolitis and early appendicitis. She was diagnosed with febrile neutropenia and treated with broad-spectrum antibiotics and filgrastim. As there was no evidence of hematologic malignancy, it was concluded that her neutropenia was drug-induced secondary to clopidogrel. She gradually recovered and cell counts had normalized at follow-up.

While rare, severe neutropenia can occur with even brief use of clopidogrel. With the widespread adoption of short course dual antiplatelet therapy after stroke, neurologists should be aware of this association.