Objective:

To describe paroxysmal nocturnal hemoglobinuria (PNH) as a rare cause of ischemic stroke.

Background:

PNH is a rare hematological disease (incidence ~1/100,000) caused by impaired inhibition of complement. Complement dysregulation typically targets CD55/59 markers on erythrocytes and leads to high levels of intravascular hemolysis and thrombosis. Descriptions of ischemic stroke secondary to PNH are rare and limited to case reports mostly involving young and middle-aged adults. This is an illustrative case of an 89-year-old man presenting with ischemic stroke in the setting of previously undiagnosed PNH.

Design/Methods:

Case Report

Results:

The patient described increasing fatigue over recent weeks but was otherwise in baseline health upon presentation to the hospital for syncope and left-sided vision loss. Medical history included carotid stenosis, ocular migraine, remote episode of peri-procedural atrial fibrillation, urothelial carcinoma, and hypertension. Initial examination demonstrated left-sided homonymous inferior quadrantanopia with NIHSS score of 1. Thrombolysis was not administered since onset was 36 hours prior. Imaging revealed acute right occipital infarction without large vessel occlusion. Cardiac workup was unrevealing for atrial fibrillation. Contrasted CT scan of the chest, abdomen, and pelvis was negative for cancer recurrence. Initial hemoglobin was 6.9 (baseline=13) with undetectable haptoglobin, elevated indirect bilirubin and LDH, and significant hemoglobinuria. PNH panel confirmed the diagnosis. Ravulizumab was started without complication. There has been no additional manifestation of PNH since initiating treatment.

Conclusions:

Extracellular hemoglobin in a PNH crisis predisposes to ischemic stroke via induced hyperthrombotic state and enhanced propensity for arterial vasospasm. Few cases of cerebral infarction secondary to PNH have been described in the literature and predominate in individuals aged <60 years. Thus, our case represents the oldest reported individual to suffer a stroke secondary to PNH and as a primary manifestation of disease. The case underscores the importance of thorough investigation for uncommon metabolic contributors to stroke etiology.