Genetics of Coagulopathy

Coagulopathy refers to impaired blood clotting regulation, encompassing both hypercoagulable states (increased clotting risk) and hypocoagulable states (bleeding tendency). Post-COVID coagulopathy including microclotting and fibrinogen abnormalities has been extensively documented.

This page is for educational and informational purposes only. Not a diagnostic tool. Always consult a qualified healthcare provider.

What is Coagulopathy?

COVID-19 is associated with a prothrombotic coagulopathy characterised by elevated D-dimer, fibrinogen, and von Willebrand factor, along with microclot formation and increased thromboembolic risk. In Long COVID, persisting coagulopathy — including fibrinogen-amyloid microclots and elevated platelet activation markers — has been documented months after acute infection. Genetic variants in clotting factors, fibrinolytic enzymes, and natural anticoagulants may predispose individuals to more severe or persistent post-COVID coagulopathy.

Biological pathways commonly discussed in relation to Coagulopathy

Research into Coagulopathy 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.

Procoagulant Factors

Coagulation factors (II, V, VII, VIII, IX, X, XI, XII) activate the clotting cascade. Factor V Leiden (F5 rs6025) and prothrombin G20210A (F2 rs1799963) are the most common thrombophilia variants.

Fibrinolytic System

Plasminogen (PLG) and tissue plasminogen activator (PLAT) dissolve clots. PAI-1 (SERPINE1) inhibits this process. Variants increasing PAI-1 may impair clot dissolution and contribute to microclot persistence.

Natural Anticoagulants

Protein C (PROC), Protein S (PROS1), and Antithrombin (SERPINC1) limit coagulation. Deficiencies or variants reducing their activity increase thrombotic risk.

Platelet Coagulation

Platelets provide the surface for coagulation complex assembly. Platelet activation abnormalities in Long COVID may amplify the local procoagulant environment.

Key genes studied in relation to Coagulopathy

The following genes have been studied in relation to Coagulopathy and Clotting Disorders. These genes span the biological pathways most commonly discussed in this area of research.

CYP2C19

CYP2C19 activates clopidogrel and metabolizes proton pump inhibitors, antidepressants, and antifungals. Poor metabolizers have reduced clopidogrel activation (elevated cardiovascular risk) while ultrarapid metabolizers have increased drug clearance.

CYP2C9

CYP2C9 metabolizes warfarin, NSAIDs, phenytoin, and glipizide. The *2 and *3 alleles reduce enzymatic activity, causing higher drug exposure and increasing bleeding risk with warfarin.

VKORC1

VKORC1 regenerates vitamin K hydroquinone needed for carboxylation of coagulation factors II, VII, IX, and X. It is the target of warfarin anticoagulation, and rs9923231 is the major genetic determinant of warfarin dose requirements.

P2RY12

P2Y12 is an ADP-activated Gi-coupled receptor on platelets that amplifies platelet aggregation and is the target of clopidogrel, prasugrel, and ticagrelor antiplatelet therapy. It is also expressed on microglia.

SELP

P-selectin (CD62P) is stored in platelet alpha-granules and endothelial Weibel-Palade bodies. Rapid surface expression upon activation mediates platelet-leukocyte-endothelium interactions initiating inflammatory thrombosis.

EPCR

EPCR (PROCR) accelerates protein C activation by thrombin-thrombomodulin complexes and participates in cell signaling through PAR1. It maintains the anticoagulant and cytoprotective effects of activated protein C on endothelium.

THBD

Thrombomodulin is an endothelial receptor that binds thrombin and converts it from a procoagulant to an anticoagulant enzyme that activates protein C. It is a critical regulator of the thrombin-protein C anticoagulant pathway.

PROC

Protein C is the zymogen of activated protein C (APC), the major physiological anticoagulant that inactivates factors Va and VIIIa. It requires vitamin K-dependent carboxylation and is activated by the thrombin-thrombomodulin complex.

41 genes total studied in relation to Coagulopathy across the ChronicDNA dataset.

Genetic variants commonly discussed

The following genetic variants (SNPs) are found in genes that have been studied in relation to Coagulopathy. Each variant represents a position in the genome where individuals may carry different alleles.

rs5985F13A1 rs4244285CYP2C19 rs1799853CYP2C9 rs1057910CYP2C9 rs9923231VKORC1 rs2359612VKORC1

142 variants total across genes studied in relation to Coagulopathy.

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 Coagulopathy.

This is not a diagnostic service. Genetic variants do not determine whether you have Coagulopathy, 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

Coagulopathy shares biological pathways and genetic associations with the following related conditions and areas of research.

Coagulation Vascular Long Covid Platelet Activation Cardiovascular

Frequently asked questions

What is Long COVID coagulopathy?

Long COVID coagulopathy refers to persisting abnormalities in clotting and fibrinolysis documented in Long COVID patients, including fibrinogen-amyloid microclots, elevated platelet activation markers, and von Willebrand factor abnormalities, which may impair microcirculation.

Which thrombophilia variants are most clinically relevant?

The most common thrombophilia variants are Factor V Leiden (F5 rs6025, present in 2–8% of Europeans) and prothrombin G20210A (F2 rs1799963, present in 1–3% of Europeans). Both increase venous thromboembolism risk, particularly in combination with other risk factors.

What is PAI-1 and why does it matter in Long COVID?

PAI-1 (plasminogen activator inhibitor-1, encoded by SERPINE1) is the primary inhibitor of fibrinolysis. The 4G/5G promoter polymorphism affects PAI-1 expression levels. Higher PAI-1 activity may impair dissolution of microclots, potentially contributing to their persistence in Long COVID.

Should Long COVID patients with thrombophilia variants be concerned?

Thrombophilia variants modify baseline clotting risk. Their interaction with Long COVID coagulopathy is an area of active research. Any concerns about clotting risk should be discussed with a qualified healthcare provider — ChronicDNA provides educational context only.

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 Coagulopathy and connected biological pathways.

Get Your Personalised DNA Report

Informational and educational only · Not a diagnostic tool · GDPR compliant

41 genes · 142 variants analysed in relation to Coagulopathy