Editorial - Hematology and Blood Disorders (2025) Volume 8, Issue 3

Thrombophilia Explained: Genetics Behind Hypercoagulation

Carlos James ^*

Department of Medicine, University of Texas Grande Valley, United States

*Corresponding Author:

Carlos James
Department of Medicine,
University of Texas Grande Valley, United States
E-mail: Jamesc@utrgv.edu

Received: 01-Aug-2025, Manuscript No. AAHBD-24-171323; Editor assigned: 03-Aug-2025, PreQC No. AAHBD-24-171323(PQ);Reviewed:16-Aug-2025, QC No. AAHBD-24-171323; Revised:18-Aug-2025, Manuscript No. AAHBD-24-171323(R); Published: 24-Aug-2025, DOI:10.35841/AAHBD-8.3.226

Citation: James C. Thrombophilia explained: Genetics behind hyper coagulation. Hematol Blood Disord. 2025;8(3):226

Introduction

Thrombophilia refers to an increased tendency to form abnormal blood clots due to inherited or acquired abnormalities in the coagulation system. While clotting is essential to prevent excessive bleeding, hypercoagulation can lead to serious complications such as deep vein thrombosis (DVT), pulmonary embolism (PE), stroke, and recurrent pregnancy loss. Understanding the genetic underpinnings of thrombophilia is crucial for early diagnosis, risk assessment, and personalized treatment strategies [1].

Thrombophilia is a disorder of hemostasis where the balance between clot formation and breakdown is disrupted, favoring thrombosis. It can be: Caused by mutations in genes regulating coagulation. Triggered by conditions like cancer, autoimmune diseases, or prolonged immobility. Genetic thrombophilias are often lifelong and may remain asymptomatic until provoked by external factors such as surgery, pregnancy, or hormonal therapy [2].

Several well-characterized genetic mutations contribute to hypercoagulability: This is the most common inherited thrombophilia in Caucasians. It results from a single-point mutation in the F5 gene, making factor V resistant to inactivation by activated protein C (APC). This leads to prolonged clotting activity and increased risk of venous thromboembolism (VTE). A mutation in the F2 gene increases prothrombin levels, enhancing thrombin generation and clot formation. Individuals with this mutation have a two- to threefold increased risk of VTE [3].

Treatment depends on the type and severity of thrombophilia and the clinical context: Standard treatments for acute and long-term management. Increasingly used for convenience and safety. Recommended during high-risk situations such as surgery, pregnancy, or prolonged immobility. Regular exercise, smoking cessation, and weight management help reduce thrombotic risk. First-degree relatives may benefit from genetic counseling and testing, especially if planning pregnancy or surgery. Living with a genetic clotting disorder can be emotionally challenging. Anxiety about future clotting events, medication side effects, and lifestyle restrictions may affect mental health. Support groups and counseling can provide valuable coping mechanisms. Protein C is a natural anticoagulant that deactivates factors Va and VIIIa. Deficiency, either due to genetic mutation or acquired conditions, impairs this regulation and promotes clot formation. Protein S acts as a cofactor to protein C. Its deficiency similarly leads to unchecked coagulation and increased thrombotic risk. Antithrombin inhibits thrombin and factor Xa. Genetic mutations in the SERPINC1 gene reduce its activity, significantly elevating the risk of thrombosis [4].

Recent studies have identified additional genetic variants that may contribute to hypercoagulability: Affect endothelial regulation of coagulation. Linked to thrombotic microangiopathies and may interact with coagulation pathways. Combinations of minor variants can compound thrombotic risk, especially in conditions like paroxysmal nocturnal hemoglobinuria (PNH). Thrombophilia is diagnosed through a combination of: Early-onset thrombosis, recurrent events, or family history. Measure levels of protein C, protein S, antithrombin, and screen for genetic mutations [5].

Conclusion

Identifies specific mutations like Factor V Leiden or prothrombin G20210A. Testing is recommended in patients with unexplained thrombosis, thrombosis in unusual sites (e.g., cerebral veins), or recurrent pregnancy loss. Genetic thrombophilias have wide-ranging health impacts: The most common manifestation. Less common but possible, especially with coexisting risk factors. Increased risk of miscarriage, preeclampsia, and placental abruption. Estrogen-containing contraceptives and hormone replacement therapy can exacerbate clotting risk in genetically predisposed women. Thrombophilia prevalence varies by ethnicity. Factor V Leiden is common in Europeans but rare in Asians and Africans. Research is expanding into: To predict thrombosis risk based on multiple genetic variants. Understanding how lifestyle and genetics combine to influence clotting. Personalized anticoagulants based on genetic profiles.

References

1. Gatta G, Botta L, Rossi S et al.Childhood cancer survival in Europe 1999–2007: Results of EUROCARE-5—A population-based study.Lancet Oncol. 2014;15(1):35-47.

Indexed at, Google ScholarCross Ref

2. Hudson MM, Ness KK, Gurney JG et al.Clinical ascertainment of health outcomes among adults treated for childhood cancer JAMA. 2013; 309(22):2371-81.

Indexed at, Google Scholar,Cross Ref

3. Morley JE, Vellas B, Van Kan GA et al.Frailtyconsensus: A call to action.Am J Med. 2013;14(6):392-7.

Indexed at, Google Scholar,Cross Ref

4. Van Iersel L, Li Z, Srivastava DK et al.Hypothalamic-pituitary disorders in childhood cancer survivors: Prevalence, risk factors and long-term health outcomesJ Clin Endocr. 2019;104(12):6101-15.

Indexed at, Google Scholar,Cross Ref

5. Aaronson NK, Muller M, Cohen PD et al.Translation, validation, and norming of the Dutch language version of the SF-36 Health Survey in community and chronic disease populations.J Clin Epidemiol. 1998;51(11):1055-68.

Indexed at, Google Scholar,Cross Ref