Elsevier

Thrombosis Research

Volume 127, Issue 2, February 2011, Pages 85-90
Thrombosis Research

Regular Article
Thrombophilic screening in young patients (< 40 years) with idiopathic ischemic stroke: A controlled study

https://doi.org/10.1016/j.thromres.2010.11.013Get rights and content

Abstract

Introduction

Despite extensive clinical and laboratory investigations, the etiology of ischemic stroke remains unknown in approximately one third of patients.

Materials and Methods

Thirty-four consecutive patients less than 40 years old (Males 13, Females 21, mean age 26.6 years, range 2-39) with documented ischemic stroke underwent, one year after the acute event, laboratory evaluation of antithrombin, protein C, free and total protein S, activated protein C resistance, fibrinogen, factor VII:C, homocysteine levels and antiphospholipid antibodies (APA). Moreover, prevalence of F5 R506Q, F2 G2021A and homozygosis for thermolabile variant C677T of the methylenetetrahydrofolate reductase (MTHFR) were also evaluated and compared to the results obtained in 120 normal controls.

Results

Antithrombin and protein C levels resulted normal in all cases. One patient (2.9%) showed free protein S deficiency and 3 patients (8.8%) had activated protein C resistance. Homocysteine levels above 15 μmol/L were found in one patient (2.9%). APA were found in 21 patients (61.7%) and in only 2 out of 120 (1.66%) controls (OR = 95.31; 95% C.I.: 18.22-667.81). The multivariate analysis selected that the presence of APA was significantly associated with an increased risk of stroke (OR = 156.60; 95% C.I.: 25.99-943.47) in this cohort of patients. The combination between APA and cardiovascular risk factors determined a risk of 29-fold (OR = 29.31; 95% CI: 3.28-261.69).

Discussion

Our data suggest that the presence of APA is associated with an increased risk of idiopathic ischemic stroke in young patients. Furthermore, also the combination of APA and cardiovascular risk factors is significantly associated with development of idiopathic ischemic stroke.

Introduction

Cerebral ischemia is an emergent health problem especially in developed countries. In fact, approximately 80% of the burden of cerebrovascular disease stems from ischemic stroke, therefore preventive strategies have important public health implications [1], [2]. Moreover, ischemic stroke in young adults aged between 15 and 45 years old has a prevalence ranging from 3 to 5% [3], [4], [5]. However, despite extensive clinical and laboratory investigations, the etiology of cerebral thrombosis is complex and remains unknown in about one third of patients. The presence of primary hypercoagulability has been accurately investigated in patients with idiopathic ischemic stroke obtaining controversial results. In particular, two case reports and a family study have suggested a role for protein C (PC) [6], [7] and protein S (PS) [8] deficiency as a risk factor for cerebral ischemia. Retrospective evaluations have reported an association between focal ischemic stroke and the presence of antiphospholipid antibodies (APA) [9], [10]. This association has been confirmed in prospective controlled studies conducted in young patients [11], [12], [13], [14]. Other studies have evaluated the relationship between inherited thrombophilic risk factors such as F5 R506Q, F2 G20210A and the thermolabile variant C677T of methylenetetrahydrofolate reductase (MTHFR) and the development of ischemic stroke. The results from these studies revealed that these thrombophilic inherited factors may [15], [16], [17], [18] or may not [19], [20], [21], [22] have a role in the development of idiopathic ischemic stroke. As for mild hyperhomocysteinemia, whose blood levels are influenced by nutritional factors and daily vitamins intake, is actually considered an independent risk factor for peripheral, coronary and cerebral vascular disease [23], [24], [25], [26]. However, so far the role of inherited and acquired thrombophilic factors has been scarcely investigated in young patients with ischemic stroke. The aim of this study was to contemporaneously evaluate inherited and acquired thrombophilic factors in a cohort of young patients with a diagnosis of ischemic stroke in order to evaluate the role of these thrombophilic factors in the development of the disease.

Section snippets

Study population

Fifty-two consecutive patients with ischemic stroke were evaluated for inherited and acquired thrombophilic factors.

Inclusion criteria for entering this study were:

  • 1)

    Less than 40 years old;

  • 2)

    Presence of ischemic stroke diagnosed by computerized tomography scan and/or magnetic resonance;

  • 3)

    Normal cardiac structure and function;

  • 4)

    Absence of any heart malformations and disease;

  • 5)

    Absence of arrhythmias as assessed by clinical evaluation, electrocardiography and echocardiography in all patients;

  • 6)

    A normal

Results

Out of a total of fifty-two consecutive patients with documented ischemic stroke, 15 were over 40 years old and 3, less than 40 years old , had cardiac abnormalities. Therefore, a total of 34 patients (Males 13, Females 21, mean age 26.6 years, range 2-39) fulfilled the inclusion criteria and were prospectively evaluated. Their characteristics are reported in Table 1. As for conventional risk factors for arterial disease, 7/34 (20.6%) patients had a smoking habit, 1 (2.9%) had hyperlipidaemia and

Discussion

Idiopathic ischemic stroke is an important cause of death in general population and it is also emerging as a prominent health problem in developed countries [1], [2]. Therefore, the correct identification of risk factors related to the development of cerebral ischemia could have important social health implications. Genetic and environmental factors responsible for primary hypercoagulability have been associated to the development of idiopathic ischemic stroke. Indeed, these deficiencies are

Conflict of interest statement

The Authors declare the absence of any commercial or other associations that might pose a conflict of interest in connection with the submitted article. Moreover, the Authors declare that photographs of organs or body parts of the evaluated patients have not been used to perform this paper. This paper includes only new data which have not been published elsewhere and not under editorial consideration in another journal.

Acknowledgments

We would like to thank Mr. Michael Redante, 6015 Lower Mountain Rd., New Hope, PA, USA, for the revision of the English form of this manuscript.

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