Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal hematological disorder leading to red blood cells hemolysis and thrombosis. PNH has been reported to be the cause of cerebral venous thrombosis and embolic ischemic strokes and is sometimes diagnosed after the ischemic event. In young patients with embolic ischemic stroke of undetermined source (ESUS), thrombophilia is usually investigated. However, access to PNH testing is limited. PNH is rarely investigated in stroke patients and its contribution to the pathophysiology of ESUS is unknown. The investigators hypothesize that this condition is underdiagnosed, resulting in potential preventive opportunities being lost, since PNH can be successfully treated.~This observational study aims to determine the frequency of PNH among young (≤50 years old) patients with recent ESUS or embolic transient ischemic attacks (TIA) of undetermined source (ETUS) and patients with SSS-CVT of undetermined source (SSS-CVTUS).~Patients with ESUS or ETUS will be first screened for: (a) evidence of hemolysis based on their plasma lactate dehydrogenase (LDH) levels, (b) unexplained anemia based on their hemoglobin (Hb) levels, and (c) unexplained cytopenia (e.g., neutropenia and thrombocytopenia). Flow cytometry analysis for PNH will be performed with blood samples collected from subjects with abnormal level of plasma LDH (1.5X ULN) or unexplained anemia or cytopenia.~Patients with SSS-CVTUS will undergo flow cytometry without prior screening.~In addition, plasma and DNA samples will be collected in an optional sub-study for future analysis of DNA mutations related to specific PNH phenotypes in patients with stroke.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal hematological disorder, which can cause arterial or venous thrombosis. The frequency of PNH in young patients (< 50 years old) with embolic stroke (ESUS), transient ischemic attack (ETUS) or superior sagittal sinus cerebral venous thrombosis (SSS-CVTUS) of undetermined source, is currently unknown. This study proposes to recruit ESUS, ETUS, SSS-CVTUS patients to determine the frequency of PNH diagnosis confirmed by flow cytometry in these patient populations.