Original Article
Immune-Thrombotic Thrombocytopenic Purpura is a Rare Cause of Ischemic Stroke in Young Adults: Case Reports and Literature Review

https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.07.017Get rights and content

Abstract

Introduction

Immune thrombotic thrombocytopenic purpura (i-TTP), related to acquired ADAMTS-13 dysfunction, can lead to various neurological symptoms including ischemic stroke. To date the clinical, radiological, and biological characteristics of patients having a stroke as the inaugural manifestation of i-TTP are largely unknown.

Methods

Probable immune-TTP was defined by a low ADAMTS-13 activity associated with the presence of ADAMTS-13 inhibitors and/or favorable clinicobiological response under immunological treatments. The clinical, radiological, biological data and outcome under treatment are described in a cohort of 17 patients coming from 3 local cases and a literature review.

Results

Fourteen of the 17 patients were female and the mean age was 41 years. None of the patients had the classical pentad of TTP. Only 41% had a combination of thrombocythemia and hemolysis. Stroke was multifocal in 35% and included large artery strokes. No adverse event was observed following intravenous thrombolysis. Refractory and relapsing forms were observed in 47%.

Discussion

The clinical, radiological, and biological presentation of patients with stroke as the inaugural presentation of i-TTP is heterogeneous. This diagnosis should be discussed in every young adult with ischemic stroke of undetermined source.

Introduction

About 35% of ischemic strokes (IS) are of undetermined source after first-line investigations.1 This rate includes a large number of rare diseases, including coagulation disorders that account for less than 5% of stroke mechanisms.2 Thrombotic thrombocytopenic purpura (TTP), which is a consequence of an inherited or acquired ADAMTS-13 dysfunction, is part of the thrombotic microangiopathy (TMA) syndromes.3 TTP has been historically associated with a pentad associating thrombocytopenia, microangiopathic hemolytic anemia (MAHA), fever, neurological symptoms, and renal insufficiency. However, this full spectrum is observed in less than 10% of the patients.4 Herein we report 3 cases of IS associated to probable immune-TTP and make a literature review of the clinical and biological characteristics reported in patients having an IS as the inaugural clinical presentation of this rare disorder. ADAMTS-13 inhibitor was determined using a neutralizing inhibitor approach as previously described5 and anti-ADAMTS-13 IgG was determined by Enzyme Linked ImmunoSorbent Assay (ELISA) (TECHNOZYME ADAMTS-13 INH, Technoclone, Austria). Our laboratory cut-off for a positive value was >35IU/mL.

Section snippets

Case 1

A 33-year-old patient was admitted for a sudden binocular diplopia, related to a left oculomotor nerve palsy, and right ataxia (National Institute of Health Stroke Score [NIHSS] = 2). General examination was normal with no fever. He was an occasional smoker, and had a pertussis vaccination 1 month before. Admission MRI (Fig 1, A,B) showed a right punctiform cerebellar infarct on diffusion-weighted sequences. CT-angiography of the supra-aortic vessels was normal. Intravenous thrombolysis was

Literature Review

We identified 26 cases published since 1988 that reported, among adults, ischemic stroke as the inaugural manifestation of probable immune-TTP (at diagnosis or inaugurating a relapse) defined by a low ADAMTS-13 activity associated with the presence of ADAMTS-13 inhibitors and/or favorable biological response under immunological treatments. Patients without demonstration of low ADAMTS-13 activity or without available information about the biological outcome were not included.6,7, 8, 9, 10, 11, 12

Discussion

Ischemic stroke (IS) is part of the spectrum of vascular events reported among patients with a low ADAMTS-13 activity, reported in 31% of cases.17 For comparison heart and mesenteric ischemia have been reported in 25%-63% and 13%-35% of cases, respectively.4, 17 The 17 patients reported in this paper confirm the strong heterogeneity of the clinical presentation of patients admitted for an IS related to an immune-TTP. Clinically, most of the patients were under 50-year-old at stroke onset, and

Conclusion

Immune ADAMTS-13 deficiency is a potential cause of IS in young adults. Absence of renal involvement or MAHA, moderate thrombocytopenia and large artery stroke should not rule out this diagnosis that could delay the initiation of specific treatments.

Acknowledgments

No organization funded this paper.

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