Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic disorder caused by the production of anti-ADAMTS13 antibodies that leads to a severe decline in ADAMTS13 activity. Without proper treatment, it has a mortality rate of approximately 90%.1 A combination regimen of plasma exchange (PEX), using fresh frozen plasma and corticosteroids, has reduced iTTP-associated mortality to below 20%. The emerging therapeutic options, including anti-human CD20 antibody, rituximab and anti-von Willebrand factor (VWF) A1 domain nanobody, and caplacizumab,2 have demonstrated efficacy in the management of acute iTTP. Although some iTTP patients may relapse and receive additional treatments, the overall treatment outcomes for iTTP have improved significantly in the past three decades––from an unknown fetal disease to a well-understood and treatable autoimmune disorder. In contrast, there are multiple, unexpected, long-term comorbidities related to iTTP that have gradually emerged, including the risks of developing systemic lupus erythematosus, hypertension, diabetes, renal impairment and neuropsychiatric disorders (including cognitive disorders and depression).3-5 Among these comorbidities, identifying cognitive symptoms can be challenging to physicians unless they pay careful attention. Alwan et al. investigated cerebral magnetic resonance imaging (MRI) findings in 131 patients (119 iTTP and 12 congenital TTP) who complained of various neurological symptoms, ranging from persistent headache to seizures, during acute episodes of TTP. The data showed that 56% of patients had abnormal image findings, and those with severe neurological symptoms were more likely to have abnormal MRI findings than those with headaches only (80% vs. 18%, respectively). All the patients with iTTP received a combination of PEX and immunosuppressors (steroids and rituximab), while none received caplacizumab. Subsequent extensive neuropsychology assessments of 35 survivors at a median of 33 months after the acute episode revealed the following conditions: 63% had deteriorated executive function, 57% had memory impairment, and 43% had intellectual impairment (verbal and non-verbal). The MRI findings at the acute phase and neuropsychology assessments at the remission phase revealed a link between hyper-intense white matter lesions, mainly seen in the frontal and supratentorial regions in MRI images, and severe cognitive impairment. To the best of my knowledge, this is the first study to show the relationship between abnormal findings in cerebral MRI and cognitive impairments, identified by detailed neuropsychological assessments. Intriguingly, depression was not associated with the cerebral abnormalities that could be detected by MRI in the acute phase of the disease. The results of this study highlight the importance of recognising cognitive impairments as long-term comorbidities, suggesting that we should carefully follow not only haemolytic markers, but also the neuropsychiatric status in iTTP patients with cerebral MRI abnormalities at the first presentation. Previous studies have shown that a higher degree of memory impairment in remission detected in patients with neurological events during acute iTTP,5 and the symptoms associated with cognitive impairment did not improve over time.3 Hence, attention is focussed on understanding whether VWF blockage with caplacizumab in the very early phase of the disease could avoid ischaemic cell damage in the brain, preventing cognitive impairment in remission. In fact, standard therapy with caplacizumab could reduce thrombotic events in newly diagnosed iTTP significantly as has been shown in the phase III study.2 In addition, it has been previously reported that an impaired Glasgow Coma Scale at the acute phase indicates poor outcome.6 If caplacizumab could be effective in treating both acute neurological symptoms and cognitive impairments during long-term follow-up, then it might be a reasonable option for iTTP patients who develop severe neurological abnormalities, such as coma, seizure and other stroke-like symptoms, and have abnormal findings on cerebral MRI in the first presentation. When we see patients with iTTP in remission at the outpatient clinic, an extensive assessment from multiple points of view, including neurological and psychiatric evaluations, will help to indicate long-term comorbidity. The author declares no conflict of interest.