Relevance of Blood Coagulation Factors IX and X to Thrombin Generation Profile and Biomarkers of Thrombogenesis in Pulmonary Embolism Patients


The study investigated the relationship of FIX and FX levels to the thrombin generation profile (endogenous thrombin potential (ETP), peak thrombin, and Lag-time) and thrombogenesis biomarkers (D-Dimer, prothrombin fragment 1+2 (F1+2), thrombin antithrombin complex (TAT)). Biomarker levels would be compared to patient clinical outcomes: PE severity (low risk, sub-massive, and massive), 30 mortality, and overall mortality.

Background and significance

Pulmonary embolism, a pulmonary artery clot, is a catastrophic complication of venous thrombo-embolism. Coagulation Factor X is essential for clot formation. Intrinsic processes activate Factor IX subsequently activating FX, generating thrombin from prothrombin.

Theoretical/Conceptual framework

Untreated PE has high morbidity and mortality rates. Nurses are fundamental for PE patient care through proper medication administration of anticoagulants and thrombolytics, assessments, and prevention education of recurrent thrombotic events. Focus on the coagulation cascade in PE patients may deepen understanding of complex pathophysiology. Any findings may improve clinical outcomes whilst reinforcing nursing interventions.


At Loyola University Medical Center, under an approved IRB, PE patients’ plasma samples (n=400) were collected. Healthy donor plasma (n=60) served as the control. ELISA assays measured FIX, FX, and the three thrombogenesis biomarkers. A calibrated automated thrombogram measured the three thrombin generation profile markers.


PE patient characteristics were gathered. FIX and FX showed a wider scattering compared to control. The thrombin generation profile showed a statistically significant decrease while thrombogenesis biomarkers showed significant increase versus the control. The Spearman correlation analysis showed various degrees of significant associations. FIX showed moderate correlation with FX (r=0.26) and Lag-time (r=0.26). TAT was strongly correlated with D-Dimer (r=0.43) and F1+2 (r=0.53). Eight biomarker levels were statistically analyzed against PE severity, 30-day mortality, and overall mortality. With increasing PE severity, D-Dimer, F1+2, and TAT (P<0.01) were increased while Peak Thrombin (P<0.05), ETP (P=0.01), and FX (P<0.01) decreased. D-Dimer (P=0.04) and FX (P<0.01) was associated with 30-day mortality. TAT (p=0.03) and FX (p<0.01) was associated in overall mortality.


Biomarker levels suggest consumption of prothrombin due to increased thrombogenesis biomarkers and a decreased thrombin generation profile in PE patients. There are significant associations between relevant thrombotic biomarkers and FX compared to clinical outcomes for pulmonary embolism severity, 30-day, and overall patient mortality.



Relevance of Blood Coagulation Factors IX and X to Thrombin Generation Profile and Biomarkers of Thrombogenesis in Pulmonary Embolism Patients