Thrombophilia Testing After Ischemic Stroke

Thrombophilia testing is frequently performed after an ischemic stroke, particularly when cryptogenic. However, there is minimal evidence supporting a significant association between most conditions assessed through thrombophilia testing and ischemic stroke, and the rationale for thrombophilia testing in many clinical situations remains uncertain. In this topical review, we review and contextualize the existing data on the risks, predictors, and outcomes of thrombophilic conditions in patients with ischemic stroke. We report that inherited thrombophilias have an uncertain relationship with ischemic stroke. Conversely, antiphospholipid syndrome, an acquired immune-mediated thrombophilia, seems to be a strong risk factor for arterial thromboembolic events, including ischemic stroke, and especially among young patients. Our findings suggest that certain circumstances may warrant targeted thrombophilia testing, such as stroke in the young, cryptogenic stroke, and high estrogen states. Future prospective studies should investigate the utility and cost effectiveness of thrombophilia testing in various stroke settings, including among patients with patent foramen ovale; as well as the optimal secondary stroke prevention regimen in patients with confirmed thrombophilia, particularly if no other potential stroke mechanism is identified.

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Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO): echocardiography performance protocol

Echo Research and Practice ◽

10.1530/erp-19-0025 ◽

2019 ◽

Vol 6 (3) ◽

pp. 53-61 ◽

Cited By ~ 4

Author(s):

Sahrai Saeed ◽

Eva Gerdts ◽

Ulrike Waje-Andreassen ◽

Juha Sinisalo ◽

Jukka Putaala

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Transesophageal Echocardiography ◽

Cardiac Imaging ◽

Cryptogenic Stroke ◽

Young Patients ◽

Interatrial Septum ◽

Stroke In The Young ◽

Undetermined Etiology ◽

A Prospective Study

Background The incidence of ischemic stroke in young patients is increasing and associated with unfavorable prognosis due to high risk of recurrent cardiovascular events. In many young patients the cause of stroke remains unknown, referred to as cryptogenic stroke. Neuroimaging frequently suggests a proximal source of embolism in these strokes. We developed a comprehensive step-by-step echocardiography protocol for a prospective study with centralized reading to characterize preclinical cardiac changes associated with cryptogenic stroke. Methods and study design SECRETO (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome; NCT01934725) is an ongoing multicenter case–control study enrolling patients (target n = 600) aged 18–49 years hospitalized due to first-ever ischemic stroke of undetermined etiology and age- and sex-matched controls (target n = 600). A comprehensive assessment of cardiovascular risk factors and extensive cardiac imaging with transthoracic and transesophageal echocardiography, electrocardiography and neurovascular imaging is performed. Transthoracic and transesophageal echocardiograms will be centrally read, following an extensive protocol particularly emphasizing the characteristics of left atrium, left atrial appendage and interatrial septum. Conclusions A detailed assessment of both conventional and unconventional vascular risk factors and cardiac imaging with transthoracic and transesophageal echocardiography are implemented in SECRETO, aiming to establish indirect and direct risk factors and causes for cryptogenic stroke and novel pathophysiological brain–heart pathways. This may ultimately enable more personalized therapeutic options for these patients.

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Ipsilateral internal carotid artery web and acute ischemic stroke: A cohort study, systematic review and meta-analysis

PLoS ONE ◽

10.1371/journal.pone.0257697 ◽

2021 ◽

Vol 16 (9) ◽

pp. e0257697

Author(s):

Brian Mac Grory ◽

Erez Nossek ◽

Michael E. Reznik ◽

Matthew Schrag ◽

Mahesh Jayaraman ◽

...

Keyword(s):

Systematic Review ◽

Cohort Study ◽

Ischemic Stroke ◽

Carotid Artery ◽

Acute Ischemic Stroke ◽

Meta Analysis ◽

Cryptogenic Stroke ◽

Young Patients ◽

Carotid Bifurcation ◽

Stroke Patients

Introduction The carotid web is a compelling potential mechanism of embolic ischemic stroke. In this study, we aim to determine the prevalence of ipsilateral carotid web in a cohort of ischemic stroke patients and to perform a systematic review and meta-analysis of similar cohorts. Patients & methods We performed a retrospective, observational, cohort study of acute ischemic stroke patients admitted to a comprehensive stroke center from June 2012 to September 2017. Carotid web was defined on computed tomography angiography (CTA) as a thin shelf of non-calcified tissue immediately distal to the carotid bifurcation. We described the prevalence of carotid artery webs in our cohort, then performed a systematic review and meta-analysis of similar cohorts in the published literature. Results We identified 1,435 potentially eligible patients of whom 879 met criteria for inclusion in our analysis. An ipsilateral carotid web was detected in 4 out of 879 (0.45%) patients, of which 4/4 (1.6%) were in 244 patients with cryptogenic stroke and 3/4 were in 66 (4.5%) patients <60 years old with cryptogenic stroke. Our systematic review yielded 3,192 patients. On meta-analysis, the pooled prevalence of ipsilateral carotid web in cryptogenic stroke patients <60 was 13% (95% CI: 7%-22%; I2 = 66.1%). The relative risk (RR) of ipsilateral versus contralateral carotid web in all patients was 2.5 (95% CI 1.5–4.2, p = 0.0009) whereas in patients less than 60 with cryptogenic stroke it was 3.0 (95% CI 1.6–5.8, p = 0.0011). Discussion Carotid webs are more common in young patients with cryptogenic stroke than in other stroke subtypes. Future studies concerning the diagnosis and secondary prevention of stroke associated with carotid web should focus on this population.

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The research of the relationships between patent foramen ovale and ischemic stroke in elderly patients

10.21203/rs.3.rs-23628/v1 ◽

2020 ◽

Author(s):

Xu Chao Sun ◽

Wenjing Jiang ◽

Yan Zhao ◽

Lin Ma ◽

Yan Lin ◽

...

Keyword(s):

Ischemic Stroke ◽

Elderly Patients ◽

Patent Foramen Ovale ◽

Cryptogenic Stroke ◽

Young Patients ◽

Test Group ◽

Control Group ◽

Foramen Ovale ◽

Stroke Patients ◽

Shunt Volume

Abstract Background Research indicates that abnormal embolism caused by patent foramen ovale (PFO) may play an important role in cryptogenic stroke (CS). However, most researches has focused on young patients, and whether abnormal embolism caused by PFO also plays an important role in elderly CS is uncertain. The purpose of this study is to analyze the clinical characteristics of elderly patients with PFO, and to explore the correlation between elderly PFO and ischemic stroke.Methods 62 elderly patients diagnosed with ischemic stroke admitted to Qilu Hospital of Shandong University from April 2014 to April 2019 were selected as the Test Group. 62 non-stroke patients in our hospital's physical examination center and outpatient clinic were selected as the Control Group. Collect clinical data of patients for retrospective analysis.Results The incidence of PFO in the Test Group was significantly higher than that in the Control Group, the difference was statistically significant (p < 0.05). The proportion of large and medium shunt patients in the Test Group was significantly higher than that in the Control Group (p < 0.05). The proportion of patients with migraine in the PFO (+) group in the Test Group was significantly higher than the stroke patients in the PFO (-) group (p < 0.05).Conclusions The shunt volume of the PFO is related to ischemic stroke and may be a risk factor for ischemic stroke.

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Abstract WP252: Secular Trends for Etiologies of Acute Ischemic Stroke in Young Adults

Stroke ◽

10.1161/str.51.suppl_1.wp252 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Vaelan Molian ◽

Amir Shaban ◽

Aayushi Garg ◽

Kaustubh Limaye ◽

Kanika Sharma ◽

...

Keyword(s):

Young Adults ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Small Vessel Disease ◽

Cryptogenic Stroke ◽

Young Patients ◽

Diagnostic Studies ◽

Stroke In Young Adults ◽

Chi Squared ◽

Comprehensive Stroke Center

Introduction: Because acute ischemic stroke (AIS) in young adults is not rare, understanding trends in etiology may help decisions about evaluation and secondary stroke prevention. This study describes probable causes of AIS in a cohort of young adults and identifies changes in etiologies and diagnostic studies compared to 20 years ago. Methods: We retrospectively reviewed all patients aged 15-45 admitted to our comprehensive stroke center between 1/2010-11/2016 with AIS. Diagnostic studies and stroke etiologies for each patient were reviewed. We then compared our results to a historic sample of young patients who presented to our center in 1977-1993 using univariate chi-squared comparison for each etiology. Results: We identified 333 young adults, 169 (50.8%) were women. The mean age was 36.4±7.1 years. Vessel imaging was performed in 305 (91.3%) cases vs. 68.9% in the historic sample. Of these, 247 (81.0%) had magnetic resonance angiography (MRA). Transthoracic echocardiography (TTE) was performed in 101 (30.3%) and transesophageal echocardiography (TEE) was performed in 171 (51.4%) cases compared to 67.1% who underwent TTE in the historic sample. Etiologic comparisons to the historic sample yielded significant decline in small vessel disease ( P = .029) and a major increase in stroke of other identified cause ( P = .024). Other TOAST etiologies illustrated in Figure 1. The most common etiology for stroke in our sample was arterial dissection 84 (25.2%), whereas this was found in only 6.0% of patients in the historic sample ( P< .001). Conclusions: Using the TOAST classification, the most common subtype in young adults was stroke of other identified cause; a rate that reflects a marked increase in the diagnosis of dissection. Despite advancement in diagnostic studies, cryptogenic stroke remains a common category in young adults.

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Abstract TP215: Clinical Utility of Hypercoagulability Screening in Young Adults With Ischemic Stroke

Stroke ◽

10.1161/str.48.suppl_1.tp215 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Setareh Salehi Omran ◽

Michael P Lerario ◽

Alexander E Merkler ◽

Gino Gialdini ◽

Antonio Moya ◽

...

Keyword(s):

Risk Factors ◽

Young Adults ◽

Ischemic Stroke ◽

Clinical Management ◽

Medical Center ◽

Cryptogenic Stroke ◽

Young Patients ◽

Hypercoagulable State ◽

Secondary Outcome ◽

Stroke Subtype

Introduction: We aimed to evaluate the ability of current genetic and serological testing to diagnose clinically relevant thrombophilic states in young adults with ischemic stroke. Methods: We performed a retrospective cohort study of patients aged 18 to 65 years who presented to Weill Cornell Medical Center between 2011 and 2014 with an ischemic stroke and had laboratory testing for a hypercoagulable state within six months of the index stroke. A hypercoagulable state was diagnosed by the criteria listed in Table 1. The primary outcome was any positive thrombophilia test. The secondary outcome was a change in clinical management based on the thrombophilia testing, defined as a change in antithrombotic selection or patent foramen ovale (PFO) closure. Using Fisher’s exact or Mann-Whitney U tests, we assessed whether the following prespecified risk factors were associated with our outcomes: age, sex, prior venous thromboembolism, family history of stroke, stroke subtype, and presence of PFO. Results: Of 146 ischemic stroke patients who met inclusion criteria, the mean age was 47 (±10) years and 47% were women. Of these patients, 61 (42.0%, 95% CI 33.7-49.9%) had at least one positive thrombophilia test and 8 (5.5%, 95% CI 1.7-9.2%) had a resultant change in management. A cryptogenic stroke subtype was documented in 87 patients, of whom 40 (46.0%, 95% CI 35.3-56.7%) had an abnormal hypercoagulability screen and 5 (5.7%, 95% CI 0.8-10.7%) had a change in management. There was no association between cryptogenic stroke subtype and a positive hypercoagulability test (p=0.2). No prespecified risk factors were associated with a positive hypercoagulability screen or a change in clinical management. Conclusions: Hypercoagulability screening among young patients with cryptogenic stroke changed clinical management in roughly one of every twenty patients tested. Cryptogenic stroke subtype and other clinical factors were not associated with a positive hypercoagulable screen.

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Abstract TP222: Prevalence of Carotid Web in Patients With Cryptogenic Stroke

Stroke ◽

10.1161/str.51.suppl_1.tp222 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Anusha Boyanpally ◽

Sleiman El Jamal ◽

Michael Reznik ◽

Tina Burton ◽

Shawna Cutting ◽

...

Keyword(s):

Ischemic Stroke ◽

A Priori ◽

Cryptogenic Stroke ◽

Stroke Patients ◽

Stroke Subtype ◽

Anterior Circulation ◽

Web Based ◽

Calcified Tissue ◽

History Of ◽

Stroke Mechanism

Introduction: Carotid web is a putative mechanism of cryptogenic ischemic stroke. We aimed to determine the prevalence of carotid web based on assigned stroke mechanism, and hypothesized that carotid webs would be found more frequently in younger cryptogenic stroke patients. Methods: We performed a single-center retrospective cohort study using institutional registry data from consecutive patients with confirmed anterior circulation ischemic stroke between July 2015-September 2017. We reviewed all available computed tomography angiogram (CTA) studies of the neck, and excluded patients who did not have a high-quality CTA of the neck performed. Carotid web was defined as a thin shelf of non-calcified tissue protruding into the lumen of the internal carotid artery immediately distal to the bifurcation, best visualized on sagittal oblique imaging and evident as a small septum on axial imaging. Stroke subtype was adjudicated a priori using validated methods, and we compared relevant risk factors in patients with cryptogenic stroke with and without carotid web. Results: We identified 882 patients with anterior circulation stroke who had a CTA neck available for review (49.3% male, 30% cryptogenic). A total of 7 patients (0.8%) were found to have carotid webs, of which 4 were ipsilateral to a patient’s stroke; all patients with ipsilateral carotid webs were adjudicated to have cryptogenic stroke. Patients with carotid web were younger than other patients in our cohort (age 49.0±14.6 vs. 72.2±14.9 years, p=0.003), and none of them had a history of hypertension (0% vs. 72%, p=0.04). In patients with cryptogenic stroke, overall prevalence of carotid webs was 1.5%, but the prevalence was significantly higher in younger cryptogenic stroke patients (age <60: 4.8%; age ≥60: 0.5%; p=0.01). Imaging findings that mimicked carotid webs, including non-calcified atherosclerosis and small protruding lesions, were prevalent in 8.3% of all patients. Discussion: Carotid web may represent an under-recognized occult mechanism of cryptogenic stroke, particularly amongst younger patients.

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Diagnostic Strategies in Young Patients with Ischemic Stroke in Canada

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100052215 ◽

2000 ◽

Vol 27 (2) ◽

pp. 120-124 ◽

Cited By ~ 27

Author(s):

Michael T.Y. Chan ◽

Zurab G. Nadareishvili ◽

John W. Norris ◽

Keyword(s):

Ischemic Stroke ◽

Cerebral Angiography ◽

Laboratory Data ◽

Young Patients ◽

Diagnostic Algorithm ◽

Diagnostic Strategies ◽

Diagnostic Uncertainty ◽

High Incidence ◽

Stroke In The Young ◽

Detailed Questionnaire

ABSTRACT:Background:A preliminary national survey of ischemic stroke in the young (15-45 years) undertaken by the Canadian Stroke Consortium indicated that in 44% of 356 patients, no cause was found.Objective:To determine the reason for this high incidence of diagnostic uncertainty in young patients with ischemic stroke.Methods:Neurologists in the ten Canadian stroke centers completed a detailed questionnaire for patients aged 15-45 years admitted to hospital between January 1993 and December 1997. Using a step-wise diagnostic algorithm incorporating clinical, neuroimaging, neurovascular and laboratory data, we divided patients into three groups: (1) those with established cause for the ischemic stroke, (2) those who remained unexplained despite adequate investigation, (3) those who remained unexplained but were, in our opinion, under-investigated.Results:In 197 patients (56%), an identified cause was established including cardioembolic sources (14%), extracranial arterial dissection (13%), lacunar infarcts (8%) atherosclerosis (6%). A miscellaneous group of 15%, included cerebral venous thrombosis, coagulopathies, vasculitis and others. In 159 patients (44%) with no apparent cause for their stroke, we considered only 81 (23%) adequately investigated, and 78 (21%) inadequately investigated.Conclusion:About one in five young patients was inadequately investigated by a stroke-oriented group of neurologists. The major problem appears to be restriction of investigations to neuroimaging alone (usually computerized cerebral tomography), without further tests such as cerebral angiography and cardiac imaging.

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Thrombophilia testing in young patients with ischemic stroke

Thrombosis Research ◽

10.1016/j.thromres.2015.11.006 ◽

2016 ◽

Vol 137 ◽

pp. 108-112 ◽

Cited By ~ 17

Author(s):

Sidse Høst Pahus ◽

Anette Tarp Hansen ◽

Anne-Mette Hvas

Keyword(s):

Ischemic Stroke ◽

Young Patients ◽

Thrombophilia Testing

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Role of Hypercoagulable Studies in Cryptogenic Stroke: A Retrospective Study

Blood ◽

10.1182/blood-2020-136723 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 33-33

Author(s):

Amulya Prakash ◽

Sindhuja Korem ◽

Sindhura Inkollu ◽

Haresh Gandhi ◽

Farrukh Iqbal ◽

...

Keyword(s):

Ischemic Stroke ◽

Retrospective Study ◽

Clinical Management ◽

Conflicts Of Interest ◽

Cryptogenic Stroke ◽

Secondary Outcome ◽

Poor Correlation ◽

Inherited Thrombophilia ◽

Thrombophilia Testing

Introduction: Hypercoagulable states are recognized, although uncommon, etiology of ischemic stroke especially in young adults under the age of 40 and children. Currently, there are no specific guidelines related to screening patients for inherited thrombophilia who are diagnosed with ischemic stroke without any identifiable risk factors. Typically, patients to be screened for thrombophilia will have prior unexplained thromboembolic events. We evaluated the association between thrombophilia and cryptogenic stroke and the role of serologic and genetic testing to establish the diagnosis. Material and methods: We performed a retrospective study through a review of EHR of patients diagnosed with ischemic stroke at our hospital between 2015- 2019 with laboratory testing for thrombophilia. The primary outcome was to identify any positive association between thrombophilia and cryptogenic stroke. The secondary outcome was to identify any change in clinical management based on thrombophilia testing results. Results: Among 35 patients included, who had an average age of 58.5 years ± 16.37 years with 36.6% under the age of 55 and 63.3% above the age of 55. Sex distribution was 40% female and 60%, male. Of 35 patients who had thrombophilia studies ordered, 9 patients had at least one positive thrombophilia test identified but none of them had any resultant change in management. 2 patients had protein C deficiency, 3 patients had protein S deficiency and 4 patients had antithrombin III deficiency, however, they were measured during the acute phase and were not repeated as an outpatient. None of the patients were found to have any Factor V and PT gene G20210A gene mutation. Lupus anticoagulant, antiphospholipid antibodies, homocysteine level were not uniformly tested. Conclusion: Only 8% of all patients who had thrombophilia testing had at least one positive study with no change in clinical management. We concluded that there is a poor correlation between inherited thrombophilia and cryptogenic stroke. The majority of our patients who had worked up done were above the age of 55 years who didn't display any symptom of thrombophilia previously. It raises a question of reflexive and inappropriate testing in the absence of clear guidelines for thrombophilia workup in the setting of cryptogenic stroke. Disclosures No relevant conflicts of interest to declare.

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Safety and efficacy of endovascular patent foramen ovale closure: the first results of a Russian multicenter study

Neurology neuropsychiatry Psychosomatics ◽

10.14412/2074-2711-2020-6-26-32 ◽

2020 ◽

Vol 12 (6) ◽

pp. 26-32

Author(s):

D. V. Ognerubov ◽

A. S. Tereshchenko ◽

A. N. Samko ◽

G. К. Arutyunyan ◽

O. A. Sivakova ◽

...

Keyword(s):

Ischemic Stroke ◽

Secondary Prevention ◽

Patent Foramen Ovale ◽

Cryptogenic Stroke ◽

Young Patients ◽

Paradoxical Embolism ◽

Atrial Septal Aneurysm ◽

Foramen Ovale ◽

History Of ◽

Pfo Closure

Patent foramen ovale (PFO) is detectable in more than 25% of the adult population and is generally clinically insignificant. However, it can be a cause of paradoxical embolism in some cases. Randomized trials indicate that endovascular PFO closure in patients with a history of cryptogenic stroke is an effective method for the secondary prevention of catastrophic brain damage.Objective: to study the safety and efficiency of endovascular PFO closure in young patients with a history of cryptogenic stroke.Patients and methods. Sixty-two patients, including (22 males and 40 females) women, underwent percutaneous PFO closure in May 2018 to March 2020. The patients' mean age was 37.4±7.6 years. The inclusion criteria were a prior cryptogenic ischemic stroke lasting less than 12 months and PFO with a high risk for paradoxical embolism (PFO concurrent with atrial septal aneurysm or hypermobility; PFO, ≥2 mm size; the presence of the Chiari network and/or the Eustachian valve).Results and discussion. The technical success of the operation was achieved in all cases. In 50 (80.6%) patients, the right chamber of the heart was completely isolated from the left one in the first 3 months. During the first year, the atria were also completely isolated in 10 (16.1%) patients. A left-to-right shunt persisted in 2 (3.2%) patents 12 months later. Two patients were found to have main procedural complications: one had perioperative atrial fibrillation and the other had pseudoaneurysm formation at the puncture site.Conclusion. Endovascular PFO closure is a safe and effective operation for the secondary prevention of recurrent ischemic stroke. In our study, blood shunting through the PFO was stopped in 96.6% of patients at less than 6 months after surgery, which suggests that there is a rapid and effective reduction in the risk of paradoxical embolism.

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