Factor XI in Thrombosis: Insights and Research Products

Mechanisms of Thrombin Generation

Following vascular injury, thrombin generation is initiated by the tissue factor / factor VIIa complex which activates factor X to Xa.¹ Tissue factor / factor VIIa also activates factor IX to IXa, which sustains the hemostatic response by activation of additional factor X. Factor IX can also be activated by factor XIa generated by proteolytic activation of the zymogen factor XI.¹ In contact pathway-initiated thrombin generation, factor XIa is generated following exposure of plasma to a negatively charged surface leading to factor XIIa formation.² In concert with prekallikrein and high molecular weight kininogen, factor XIIa activates factor XI, which in turn activates factor IX and is a major contributor to thrombin generation via this pathway. As factor XII deficiency does not result in excessive bleeding,³ it is likely that factor XI is activated by other proteases, such as thrombin in normal hemostasis.⁴

Clinical Implications of Factor XI Deficiency

Individuals with deficiency of factor XI have pronounced prolongations in the aPTT while clinically they experience only a mild bleeding diathesis³ suggesting that factor XI has a diminished role in normal hemostasis. Interestingly, and in contrast, several studies using animal models suggest that factor XI plays an important role in venous and arterial thrombosis.² This is supported by epidemiological studies where plasma factor XI concentrations correlated with incidences of venous thrombosis, myocardial infarction and ischemic stroke.² In addition, individuals with factor XI deficiency have lower rates of venous and arterial thrombotic events than the general population.⁵

Research and Pharmaceutical Developments

Based on these combined observations drugs targeting factor XI or XIa have been a focus of pharmaceutical companies in clinical trials looking for safer anticoagulants that will cause less severe bleeding. As these trials are ongoing, future studies will be important to understand the contributions of factor XI and XIa to not only normal and abnormal coagulation, but also to other (patho)physiological processes, which may be affected by these drugs.

Prolytix Research Products for Factor XI

Prolytix has been providing customers with high quality research reagents and custom collection devices for more than 35 years including several products and services for factor XI research that are discussed below and summarized in Table 1.

• Human factor XI (HCXI-0150) is isolated from pooled plasma screened for potential viral contaminants. Its purity, assessed by SDS-PAGE, is ≥95%. Its activity is assessed by an aPTT assay. Custom formulations, modifications and conjugations are available.

• Human factor XIa (HCXIA-0160) is produced by factor XIIa activation of factor XI. Its purity, assessed by SDS-PAGE, is ≥95%. Its activity is assessed by an aPTT assay. Custom formulations, modifications and conjugations are available.
• Factor XI-deficient plasma (FXI-ID) is prepared from pooled human plasma screened for potential viral contaminants and contains <1% factor XI clotting activity. Each lot is further assayed to ensure the activity of the remaining  factors is 50-150% and for fibrinogen, PT, aPTT and clarity.
• Anti-human factor XI antibody (AHXI-5061) is a mouse monoclonal antibody directed against the factor XIa heavy chain that recognizes human factor XI and XIa. It is inhibitory in an aPTT, and is useful for factor XI purification, and factor XI and XIa detection by RIA, ELISA, and western blotting (nonreduced conditions). Its purity, assessed by SDS-PAGE, is ≥95%. Custom formulations, modifications and conjugations are available.
• Sheep anti-human factor XI antibody (PAHFXI-S) is a sheep polyclonal antibody that recognizes human factor XI and XIa. It is inhibitory in an aPTT and is useful for factor XI and XIa detection by ELISA and western blotting. Its purity, assessed by SDS-PAGE, is ≥95%. Custom formulations, modifications and conjugations are available.

Learn more about these reagents and others such as our custom collection devices in our extensive product catalog.

References

1. Smith SA, Travers RJ, Morrissey JH. How it all starts:  initiation of the clotting cascade. Crit Rev Biochem Mol Biol. 2015; 50(4):326-336.
2. Gailani D, Gruber A. Targeting factor XI and factor XIa to prevent thrombosis. Blood. 2024; 143(15):1465-1475.
3. Gailani D, Tillman BF, Wheeler AP.  Rare coagulation factor deficiencies. In:  Molecular basis of blood coagulation. In:  Hoffman R, Benz EJ, Silberstein LE, et al., eds. Hematology: Basic Principles and Practices. 8^th ed. Elsevier; 2023:2125-2143.     
4. Moellmer SA, Puy C, McCarty OJT. Biology of factor XI. Blood. 2024; 143(15):1445-1454.
5. Preis M, Hirsch J, Kotler A, et al. Factor XI deficiency is associated with lower risk for cardiovascular and venous thromboembolism events. Blood. 2017; 129(9):1210-1215.