Antiphospholipid Antibodies & Osteopontin as Risk Factors for Cerebrovascular Stroke in Young Adults

The burden of stroke is increasing in many low- and middle income countries.(1) Around 10% of all thrombotic cerebrovascular events (CVE) occur in young population defined as younger than 50 years old (2)

In the majority of these patients, the cause of the ischaemic stroke remains undetermined.(3) Arterial thrombosis is a major clinical manifestation of the antiphospholipid syndrome (APS), an autoimmune condition characterised by thrombotic events and/or pregnancy morbidity with persistently positive antiphospholipid antibodies (aPL) (4).

Considering all patients with cerebral ischaemia, the prevalence of aPL seems rather high in young adults, who might constitute a subgroup at high risk for recurrence.(5)

Through the support of the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION), a systematic review aiming to estimate the frequency of clinically significant aPL profiles in the general population (no age limit) was completed. (6)

The pathogenesis of ischemic stroke is complex, and several studies documented hypercoagulable states as a significant mechanism underlying stroke. (8).

The latter include protein C, protein S, or antithrombin III deficiencies, activated protein C resistance and anti-phospholipid antibodies (aPLA), including anticardiolipin (aCL) antibodies or lupus anticoagulant (LAC), which influence stroke susceptibility owing to their capacity to disturb normal hemostatic mechanisms (9).

While aPLA are clinically associated with a state of hypercoagulation and prothrombotic disorders, the exact mechanism underlying their prothrombotic effects remains unknown (10).

aPLA are detected either functionally, owing to their ability to prolong coagulation time in a phospholipid-dependent coagulation test (LAC), or by measuring specific [anticardiolipin (aCL) and antiphosphatidylserine (aPS)] antibodies by specific immunoassays, using anionic phospholipids as antigens (11).

The contribution of LAC to the overall risk of both venous and arterial thrombosis, including ischemic stroke, is now well recognized (12).

While the contribution of aPLA (including LAC and aCL antibodies) to thrombosis is well established, their role as independent risk factors in the pathogenesis of ischemic stroke yielded apparently conflicting results. (13).

These conflicting results could be explained by differences in ethnic origin , inherent variation in aPLA levels and in the failure in some studies to account for the contribution of covariates (14).

Osteopontin (OPN) was first identified as a protein involved in bone remodelling, but later also shown to have important immunological roles. (15).

Study Overview

• Status: Unknown
• Conditions: Stroke in Young Adults
• Intervention / Treatment: Diagnostic test: antiphospholipid Abs

• Study Type: Observational
• Enrollment (Anticipated): 500

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt, 71111
    • Recruiting
    • Assiut University Hospital
    • Contact: Sally Samir Hussein, Ass. lecturer; Phone Number: 01005543417; Email: ysailly@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

stroke patients less than 50 years old

Description

Inclusion Criteria:

• A study was included if it reported on the laboratory investigation of any aPL and confirmed CVE
• Included patients aged <50 years

Exclusion Criteria:

• Exclusion criteria included non-atherosclerotic causes, rheumatic heart disease, ventricular arrhythmias, uncompensated heart failure, stroke secondary to atrial fibrillation, hematoma, brain tumors, accidental or iatrogenic stroke, arterial malformation and recent acute myocardial infarction. Information on cardiovascular and cerebrovascular risk factors will be obtained at baseline.
• Cardiovascular disease will positive if subjects reported a history of heart disease or stroke, whereas diabetes will be assessed according to fasting blood glucose and/or use of glucose-lowering drugs (including insulin).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Stroke with antiphospholipid	Diagnostic test: antiphospholipid Abs; Laboratory test
stroke without antiphospholipid	Diagnostic test: antiphospholipid Abs; Laboratory test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Stroke patients with APs	1 year

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Study Director: Eman Abbas El kady, Prof., Investigator

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2020
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: April 13, 2018
• First Submitted That Met QC Criteria: June 16, 2018
• First Posted (Actual): June 19, 2018

Study Record Updates

• Last Update Posted (Actual): July 8, 2020
• Last Update Submitted That Met QC Criteria: July 7, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: 17200187

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No