# ADAMTS13 and Late Neurologic Morbidity after Thrombotic Thrombocytopenic Purpura

> **NIH NIH K99** · JOHNS HOPKINS UNIVERSITY · 2020 · $213,300

## Abstract

PROJECT SUMMARY/ABSTRACT
 Acquired autoimmune thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disorder
characterized by acute episodes of systemic microvascular thrombosis caused by deficiency of ADAMTS13, a
von Willebrand factor cleaving protease. TTP is more common in women and African Americans. Plasma
exchange has improved survival of acute TTP from <10% to 80-90%; however, long-term adverse health
outcomes in adults following recovery from TTP are under recognized. Recent data indicate that TTP survivors
have higher mortality than age and sex matched controls and over 60% of TTP survivors demonstrate
neurocognitive impairment. In a cohort of 157 TTP survivors at Johns Hopkins Hospital, we found a high rate of
incident stroke unrelated to an acute TTP relapse during long-term follow up.Intriguingly, over 50% of TTP
survivors did not recover ADAMTS13 activity in remission and low ADAMTS13 activity in remission was
associated with a higher risk of stroke. Silent cerebral infarcts are ischemic lesions seen on MRI in patients
without neurologic symptoms, which are associated with future stroke and cognitive impairment in the general
population. Currently, there are no published studies evaluating the prevalence of silent infarcts in TTP
survivors, and their association with future stroke and cognitive impairment. The association of ADAMTS13 in
remission with ischemic cerebral events (silent infarct and stroke) is also unknown.
 Dr. Chaturvedi has established a large prospective cohort of patients with TTP, generated compelling
preliminary data regarding the risk of stroke in TTP survivors, and established collaborations throughout Johns
Hopkins Hospital to answer these questions. We will use the existing Johns Hopkins Thrombotic
Microangiopathy Registry to test the hypothesis that silent cerebral infarcts more common in TTP survivors
than an age and sex-matched control population, and are a risk factor for stroke and cognitive impairment (Aim
1). We will evaluate whether low ADAMTS13 activity during TTP remission is associated with cerebral
ischemic events (silent infarcts and stroke) (Aim 2). Finally, we will evaluate the association of traditional
cardiovascular risk factors and germline variants in ADAMTS13 and complement genes with silent infarcts and
stroke (Aim 3). Understanding the epidemiology and risk factors for cerebrovascular and cognitive sequelae of
TTP will lead to a pilot study of an intervention (low dose anticoagulation or antiplatelet therapy) to reduce the
incidence of silent cerebral infarcts and stroke in high-risk TTP patients and has implications for understanding
the role of ADAMTS13 in cerebrovascular disease in other populations. Dr. Chaturvedi's mentors, Dr. Robert
Brodsky and Dr. Michael DeBaun, have extensive expertise in thrombotic microangiopathies, rare disease
research, and evaluation of cerebrovascular disease. Her additional training proposed will enable her to
transition to an independent...

## Key facts

- **NIH application ID:** 9883453
- **Project number:** 1K99HL150594-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Shruti Chaturvedi
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $213,300
- **Award type:** 1
- **Project period:** 2020-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9883453

## Citation

> US National Institutes of Health, RePORTER application 9883453, ADAMTS13 and Late Neurologic Morbidity after Thrombotic Thrombocytopenic Purpura (1K99HL150594-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9883453. Licensed CC0.

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