Genetics of Thrombosis and Clotting
Thrombosis involves abnormal blood clot formation within vessels, driven by hypercoagulability, endothelial dysfunction, and impaired fibrinolysis. Genetic variants in clotting factors — particularly F5 (Factor V Leiden) and F2 (prothrombin G20210A) — substantially increase thrombotic risk.
This page is for educational and informational purposes only. Not a diagnostic tool. Always consult a qualified healthcare provider.
What is Thrombosis and Clotting?
The coagulation cascade produces fibrin clots through sequential activation of coagulation factors. Key genetic risk variants include F5 rs6025 (Factor V Leiden), which causes activated protein C resistance and increases venous thromboembolism (VTE) risk 3–8 fold, and F2 rs1799963 (prothrombin G20210A), which increases prothrombin levels and VTE risk 2–3 fold. COVID-19 is strongly prothrombotic, and Long COVID patients have shown evidence of persistent microclotting, elevated fibrinogen, D-dimer, and platelet activation. Genetic predisposition to coagulation may amplify COVID-associated thrombotic risk.
Biological pathways commonly discussed in relation to Thrombosis and Clotting
Research into Thrombosis, Hypercoagulability, and Clotting Disorders has highlighted several biological pathways that may be relevant. Genetic variants within these pathways may influence individual susceptibility, symptom severity, or the trajectory of the condition.
Coagulation Cascade
The intrinsic and extrinsic coagulation pathways converge at Factor X activation, leading to thrombin generation and fibrin clot formation. F5 (Factor V), F8 (Factor VIII), F11 (Factor XI), and F2 (prothrombin) variants affect cascade efficiency.
Fibrinolysis
Fibrinolysis dissolves clots via plasmin generated from plasminogen by tPA and uPA. PAI-1 (SERPINE1) inhibits fibrinolysis — the 4G/5G promoter variant affects PAI-1 expression and fibrinolytic capacity.
Platelet Activation
Platelets are activated by collagen, ADP, and thromboxane A2. Integrin alpha2beta1 (ITGA2 807C/T) affects platelet-collagen interaction. GPIa-IIa variants modulate platelet adhesion and thrombotic risk.
Endothelial Function
Healthy endothelium maintains antithrombotic tone via prostacyclin, nitric oxide (NOS3/eNOS), and thrombomodulin (THBD). NOS3 variants reducing NO production impair anticoagulant endothelial function.
Key genes studied in relation to Thrombosis and Clotting
The following genes have been studied in relation to Thrombosis, Hypercoagulability, and Clotting Disorders. These genes span the biological pathways most commonly discussed in this area of research.
19 genes total studied in relation to Thrombosis and Clotting across the ChronicDNA dataset.
Genetic variants commonly discussed
The following genetic variants (SNPs) are found in genes that have been studied in relation to Thrombosis and Clotting. Each variant represents a position in the genome where individuals may carry different alleles.
71 variants total across genes studied in relation to Thrombosis and Clotting.
How personal DNA data may provide educational insights
Consumer DNA files from 23andMe, AncestryDNA, and MyHeritage contain raw SNP data. When you upload your file to ChronicDNA, the analysis engine checks your genotype against a curated panel of 80+ genes selected for their relevance to Long COVID, ME/CFS, and connected biological pathways - some of which may relate to areas such as Thrombosis and Clotting.
This is not a diagnostic service. Genetic variants do not determine whether you have Thrombosis and Clotting, nor do they predict your clinical outcomes. The report is educational - it explains which variants you carry, what the research says about them, and how they fit into the biological pathways most relevant to chronic illness. All results should be discussed with a qualified healthcare provider.
Related conditions and pathways
Thrombosis and Clotting shares biological pathways and genetic associations with the following related conditions and areas of research.
Frequently asked questions
What is Factor V Leiden and how does it increase clot risk?
Factor V Leiden (F5 rs6025) is a variant that prevents Factor V from being inactivated by protein C (activated protein C resistance). This prolongs thrombin generation and increases venous thromboembolism risk approximately 3–8 fold in heterozygotes and 50–100 fold in rare homozygotes. It is the most common inherited thrombophilia in European populations (carrier frequency ~5%).
How does COVID-19 increase thrombotic risk?
COVID-19 triggers a prothrombotic state via endothelial activation, platelet hyperactivation, elevated fibrinogen and D-dimer, NET formation, and complement activation. Long COVID patients show evidence of persistent microclotting, with amyloid-containing fibrin microclots identified in some studies. Genetic thrombophilia variants may compound COVID-associated clotting risk.
What is the PAI-1 4G/5G polymorphism?
The SERPINE1 4G/5G promoter polymorphism affects PAI-1 expression levels. The 4G allele produces more PAI-1, reducing fibrinolytic capacity and increasing risk for thrombosis and microclot persistence. This variant has been studied in Long COVID, cardiovascular disease, and PCOS research.
Which thrombosis genes are most clinically relevant?
Key genes include F5, F2, SERPINE1, F8, F11, THBD, NOS3, ITGA2, and PROC/PROS1 (Protein C and S). F5 and F2 are routinely tested in clinical thrombophilia workups.
Explore DNA insights
If you already have DNA data from 23andMe, AncestryDNA, or MyHeritage, upload your raw file to ChronicDNA and receive a personalised educational report covering genes studied in relation to Thrombosis and Clotting and connected biological pathways.
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19 genes · 71 variants analysed in relation to Thrombosis and Clotting