Prothrombin G20210A and Factor V Leiden Variants Not Linked to Thrombosis in Congenital Heart Di

04 Mar 20264 min read0 viewsJournal Feed

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Journal of the American Heart Association, Volume 15, Issue 6 , March 17, 2026. BackgroundThrombotic events, including acute ischemic stroke, are more common in individuals with congenital heart disease (CHD).

Whether common thrombophilia variants contribute to thrombotic risk in this population remains unclear. We evaluated whether prothrombin G20210A (F2c.97G>A) and factor V Leiden (F5c.1601G>A; p.Arg534Gln) are associated with thrombotic events in CHD.MethodsParticipants in the Pediatric Cardiac Genomics Consortium with exome sequencing and electronic medical record data were identified.

Individuals were stratified by prothrombin G20210A and factor V Leiden genotypes, ventricular physiology, and antithrombotic therapy. The primary outcome was the presence ofInternational Classification of Diseases(ICD) or Phecodes (phenotype codes) for thrombotic events.ResultsAmong 4008 participants (median age, 11.4 [interquartile range, 5.1–17.9] years; 44.4% boys), thrombotic events occurred in 737 (18%), including 93 (13%) with acute ischemic stroke.

Compared with the Genome Aggregation Database, the CHD cohort had a lower prevalence of heterozygous prothrombin G20210A and factor V Leiden variants. Variant prevalence did not differ between participants with and without thrombotic events.

Clinical Editorial

Dominant Research Question and Population Context

The cohort comprises 4008 participants with a median age of 11.4 years (IQR 5.1–17.9) and 44.4% male.

This observational study probes whether common thrombophilia variants, prothrombin G20210A and factor V Leiden, contribute to thrombotic events in individuals with congenital heart disease (CHD).
The analysis uses participants from the Pediatric Cardiac Genomics Consortium who had exome sequencing and electronic medical record data.

Study Design and Data Framework

Stratification was performed by: (1) genotypes for prothrombin G20210A and factor V Leiden, (2) ventricular physiology, and (3) antithrombotic therapy status.
The primary outcome captured thrombotic events via International Classification of Diseases (ICD) codes or phenotype codes (Phecodes) associated with thrombosis.

Major Signal and Comparative Context

Thrombotic events occurred in 737 participants (18%), including 93 cases (13% of those with events) of acute ischemic stroke.
Relative to the Genome Aggregation Database (gnomAD) reference, the CHD cohort showed a lower prevalence of heterozygous prothrombin G20210A and factor V Leiden variants.
Importantly, the prevalence of these variants did not differ between participants who experienced thrombotic events and those who did not.

Subgroup Observations

Single-ventricle CHD patients exhibited a higher frequency of thrombosis (35%) compared with those with biventricular CHD (16%), an association with thrombotic events that was independent of variant status.

Interpretation, Limitations, and Practical Relevance

The study reports no significant association between prothrombin G20210A or factor V Leiden variants and thrombotic outcomes in the CHD cohort.
Authors note that, given the relatively low prevalence of these variants, the study was powered to exclude only large effect sizes.
They acknowledge potential survivorship bias, as reduced variant frequency could reflect selection pressures beginning in fetal life.