Hypercoagulability and the risk of myocardial infarction and ischemic stroke in young women

Siegerink, Bob; Maino, Alberto; Algra, Ale; Rosendaal, Frits R.

doi:10.1111/jth.13045

Cited by 38 publications

(41 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…62 The incidence of MI in 96 individuals with severe fXI deficiency was similar to the expected incidence for age-matched controls. 63 The data are in line with recent work by Siegerink et al showing that an elevated level of fXIa correlated more closely with risk for ischemic stroke than for MI in young women, 64 and suggest that the contribution of fXI to thrombus formation is greater in some vascular beds than in others.…”

Section: The Intrinsic Pathway and Thrombosissupporting

confidence: 88%

The Intrinsic Pathway of Coagulation as a Target for Antithrombotic Therapy

Wheeler

Gailani

2016

Hematology/Oncology Clinics of North America

View full text Add to dashboard Cite

Plasma coagulation in the activated partial thromboplastin time assay is initiated by sequential activation of coagulation factors XII, XI and IX – the classical intrinsic pathway of coagulation. It is well recognized that this series of proteolytic reactions is not an accurate model for hemostasis in vivo, as factor XII deficiency does not cause abnormal bleeding, and fXI deficiency causes a relatively mild propensity to bleed excessively with injury. Despite their limited roles in hemostasis, there is mounting evidence that fXI and fXII contribute to thrombosis, and that inhibiting them can produce an antithrombotic effect with a relatively small effect on hemostasis. In this chapter the contributions of components of the intrinsic pathway to thrombosis in animal models and humans are discussed, and results of early clinical trials of drugs targeting factors IX, XI and XII are presented.

show abstract

Section: The Intrinsic Pathway and Thrombosissupporting

confidence: 88%

The Intrinsic Pathway of Coagulation as a Target for Antithrombotic Therapy

Wheeler

Gailani

2016

Hematology/Oncology Clinics of North America

View full text Add to dashboard Cite

show abstract

“…One of the most examined aggregate of risk factors is the combination of PFO and prothrombotic mutations. 9 However, with or without PFO, the role of known prothrombotic mutations and other investigated candidate genes remains inconclusive, [10][11][12] whereas data suggest that genetic factors have a much stronger influence in early-onset rather than late-onset IS. 13 Due to the large proportion of cryptogenic events, the evidence base to guide prevention and treatment of early-onset IS remains poor.…”

Section: Introductionmentioning

confidence: 99%

Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design

Putaala

Martinez‐Majander

Saeed

et al. 2017

European Stroke Journal

View full text Add to dashboard Cite

Background: Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged <50 years. Of these early-onset strokes, up to 50% can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies. Key hypotheses/aims: (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. Design: Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case-control study enrolling patients aged 18-49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age-and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patientcontrol pairs enrolled by the end of 2018. Summary: SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.

show abstract

“…While MI and PAOD are (mainly) caused by atherosclerosis, stroke etiology remains undefined (“cryptogenic”) in about 25% of all stroke patients (14). Interestingly, published studies give reason to postulate that a prothrombotic state may play an important role in the pathophysiology of ischemic stroke (9, 10). …”

Section: Discussionmentioning

confidence: 99%

“…This introduces the concept of comparing the overall prothrombotic predisposition—as previously used in venous thrombosis—in distinct cardiovascular diseases (8). Previous research indicates that hypercoagulability might play a different role in different subforms of arterial thrombosis (9). A recent meta-analysis suggests that a prothrombotic state has a greater impact on the risk of ischemic stroke compared to MI (10).…”

Section: Introductionmentioning

confidence: 99%

A Prothrombotic Score Based on Genetic Polymorphisms of the Hemostatic System Differs in Patients with Ischemic Stroke, Myocardial Infarction, or Peripheral Arterial Occlusive Disease

Herm

Hoppe

Siegerink

et al. 2017

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

BackgroundWhile twin studies indicate a genetic component in arterial thrombosis such as ischemic stroke, myocardial infarction (MI), or peripheral arterial occlusive disease (PAOD), the clinical relevance of hemostatic polymorphisms in arterial thrombosis is a matter of debate.MethodsWe analyzed the prevalence of 13 hemostatic polymorphisms [PAI-1, PLAT, F5 (including factor V Leiden and HR2 haplotype), F2, F7, F13A, FGB, TFPI, THBD, MTHFR, ACE, and ITGA2] in patients referred to a tertiary referral center. A “prothrombotic score” was calculated by dividing the number of risk-increasing polymorphisms for thrombosis minus the number of risk-lowering polymorphisms (F7 and F13A) by the number of polymorphisms tested.ResultsDatasets of 144 patients with prior ischemic stroke (mean age 44 ± 13 years; 65% female) were compared to 62 patients with MI or PAOD (mean age 54 ± 14 years; 47% female). The prothrombotic score was lower in MI and PAOD patients compared to stroke patients [odds ratios 2.7 (95% confidence intervals 1.1–6.2)]. Frequencies of individual polymorphisms did not differ between both groups.ConclusionPatients with MI or PAOD had a lower burden of prothrombotic mutations compared to patients with prior stroke, indicating that a prothrombotic state might play a different role in distinct forms of arterial thrombosis.

show abstract

Hypercoagulability and the risk of myocardial infarction and ischemic stroke in young women

Cited by 38 publications

References 46 publications

The Intrinsic Pathway of Coagulation as a Target for Antithrombotic Therapy

The Intrinsic Pathway of Coagulation as a Target for Antithrombotic Therapy

Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design

A Prothrombotic Score Based on Genetic Polymorphisms of the Hemostatic System Differs in Patients with Ischemic Stroke, Myocardial Infarction, or Peripheral Arterial Occlusive Disease

Contact Info

Product

Resources

About