Silent cerebral infarction during immune TTP remission - prevalence, predictors, and impact on cognition

Chaturvedi, Shruti; Brown, Jenna; Wei, Aria; Selvakumar, Sruthi; Gerber, Gloria; Moliterno, Alison R.; Streiff, Michael B.; Kraus, Peggy S.; Logue, Claire; Yui, Jennifer; Naik, Rakhi P.; Latif, Hira; Lanzkron, Sophie; Braunstein, Evan M.; Gottesman, Rebecca F.; Lin, Doris

doi:10.1182/blood.2023019663

Cited by 6 publications

(6 citation statements)

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“…Recent data show that patients with iTTP in remission might experience cognitive symptoms and are also susceptible to TIA and stroke. These findings imply that severe deficiency of ADAMTS13 is a risk for cognitive impairment [39]. This suggests that prophylactic treatment may be appropriate for all patients with hTTP.…”

Section: Management Strategiesmentioning

confidence: 84%

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Hereditary Thrombotic Thrombocytopenic Purpura

Nusrat,

Beg,

Khan

et al. 2023

Genes

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Hereditary thrombotic thrombocytopenic purpura (hTTP), also known as Upshaw–Schulman syndrome, is a rare genetic disorder caused by mutations in the ADAMTS13 gene that leads to decreased or absent production of the plasma von Willebrand factor (VWF)-cleaving metalloprotease ADAMTS13. The result is circulating ultra-large multimers of VWF that can cause microthrombi, intravascular occlusion and organ damage, especially at times of turbulent circulation. Patients with hTTP may have many overt or clinically silent manifestations, and a high index of suspicion is required for diagnosis. For the treatment of hTTP, the goal is simply replacement of ADAMTS13. The primary treatment is prophylaxis with plasma infusions or plasma-derived factor VIII products, providing sufficient ADAMTS13 to prevent acute episodes. When acute episodes occur, prophylaxis is intensified. Recombinant ADAMTS13, which is near to approval, will immediately be the most effective and also the most convenient treatment. In this review, we discuss the possible clinical manifestations of this rare disease and the relevant differential diagnoses in different age groups. An extensive discussion on prophylaxis and treatment strategies is also presented. Unique real patient cases have been added to highlight critical aspects of hTTP manifestations, diagnosis and treatment.

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Section: Management Strategiesmentioning

confidence: 84%

“…Increased risk for stroke in patients with iTTP in remission but with low ADAMTS13 activity was recently confirmed. Among 36 patients with iTTP in clinical remission, patients with lower ADAMTS13 activity had higher risk for stroke [39].…”

Section: Ittpmentioning

confidence: 96%

Hereditary Thrombotic Thrombocytopenic Purpura

Nusrat,

Beg,

Khan

et al. 2023

Genes

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Section: Cardiovascular Disease Burden In Chronic Ittpmentioning

confidence: 99%

“…Most recently, a study reported that in a prospectively enrolled cohort of iTTP survivors, 50% demonstrated silent cerebral infarction, which is defined as magnetic resonance imaging (MRI) evidence of brain ischemic infarction without a corresponding neuro-deficit [ 35 ]. Silent cerebral infarction was strongly associated with cognitive impairment, including both major and mild cognitive impairment [ 35 ]. Given that silent cerebral infarctions are a risk factor for both cognitive impairment [ 36 ] and stroke [ 37 ] in the general population, it is likely that silent cerebral infarction also contributes to neurocognitive deficits that are a common complaint in TTP survivors (60–80%) [ 38 , 39 , 40 , 41 , 42 ].…”

Section: Cardiovascular Disease Burden In Chronic Ittpmentioning

confidence: 99%

“…Recent research links racism and discrimination to chronic stress [61], which can have an independent effect on promoting autoimmunity and inflammation [62,63]. One of the more provocative findings from observational studies is the association of lower remission ADAMTS13 activity in iTTP survivors with a number of adverse health outcomes, including stroke [15], silent cerebral infarction [35], and a trend towards higher all-cause mortality [12]. Thus, patients with both immune and congenital TTP, who share a phenotype of partial or complete ADAMTS13 deficiency, develop accelerated vascular aging and atherosclerosis that predominantly affects the cerebral circulation.…”

Section: Factors Contributing To Risk Of CV Disease In Ittpmentioning

confidence: 99%

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Cardiovascular Disease and Stroke in Immune TTP–Challenges and Opportunities

Sukumar,

Mazepa,

Chaturvedi

2023

JCM

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Advances in the management of immune thrombotic thrombocytopenic purpura (iTTP) have dramatically improved outcomes of acute TTP episodes, and TTP is now treated as a chronic, relapsing disorder. It is now recognized that iTTP survivors are at high risk for vascular disease, with stroke and myocardial infarction occurring at younger ages than in the general population, and cardiovascular disease is the leading cause of premature death in this population. iTTP appears to have a phenotype of accelerated vascular aging with a particular predilection for cerebral circulation, and stroke is much more common than myocardial infarction. In addition to traditional cardiovascular risk factors, low ADAMTS13 activity during clinical remission may be a risk factor for some of these outcomes, such as stroke. Recent studies also suggest that Black patients, who are disproportionately affected by iTTP in the United States, are at higher risk of adverse cardiovascular outcomes, likely due to multifactorial reasons. Additional research is required to establish the risk factors and mechanisms underlying these complications in order to institute optimal screening strategies and identify interventions to improve outcomes.

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Long-term health-related quality of life and mental health in patients with immune thrombotic thrombocytopenic purpura

Mulas,

Efficace,

Costa

et al. 2024

Ann Hematol

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Immune thrombotic thrombocytopenic purpura (iTTP) is a rare and potentially life-threatening disorder. Treatment advances have lowered morbidity rates, but past acute events can still cause long-term consequences, reducing health-related quality of life (HRQoL) and determining cognitive impairment, anxiety, and depression. We aimed to investigate these aspects and the role of caplacizumab and rituximab: 39 patients were evaluated using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), the FACIT-Fatigue, the Hospital Anxiety and Depression Scale, and the Functional Assessment in Cancer Therapy-Cognitive Function questionnaires. The median age at study inclusion was 50 years (IQR 38–60), and the median follow-up from diagnosis was 97 months (IQR 14–182); 82% of patients were female, and 36% had one or more recurrences. Caplacizumab was administered in 16 patients (41%), as well as rituximab. ITTP patients reported lower physical and mental HRQoL scores than the general population. No differences in physical or mental domains were observed between patients treated or not with caplacizumab, while those who received rituximab reported lower scores in mental health. Neurological impairment at diagnosis correlated with worse fatigue. The majority of patients (72%) reported anxiety or depression (82%). ITTP had a significant impact on the long-term cognitive function, fatigue, depression, and anxiety levels of patients, with a negative effect on their HRQoL. Our findings underscore the need to pay special attention to patients’ long-term physical and mental health, regardless of the medical treatments received.

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Silent cerebral infarction during immune TTP remission - prevalence, predictors, and impact on cognition

Cited by 6 publications

References 0 publications

Hereditary Thrombotic Thrombocytopenic Purpura

Hereditary Thrombotic Thrombocytopenic Purpura

Cardiovascular Disease and Stroke in Immune TTP–Challenges and Opportunities

Long-term health-related quality of life and mental health in patients with immune thrombotic thrombocytopenic purpura

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