Introduction
Thrombosis, defined as the pathological formation of blood clots within the vasculature, is a major global health concern with potentially life-threatening consequences. These thrombi may impair blood flow in veins (venous thrombosis) or arteries (arterial thrombosis), leading to complications such as deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, or cerebrovascular accidents. The incidence of venous thromboembolism (VTE) alone is estimated at 1–2 cases per 1000 individuals annually in developed nations.1 As risk factors like obesity, physical inactivity, and an ageing population continue to rise, comprehensive thrombosis prevention strategies have become increasingly important. This review discusses evidence-based approaches to thrombosis prevention, with emphasis on lifestyle modifications and pharmacological prophylaxis across various populations.
Pathophysiology of thrombosis
An understanding of thrombosis pathogenesis is key to effective prevention. Virchow’s triad, which includes hypercoagulability, endothelial injury, and venous stasis, remains the cornerstone in explaining thrombus formation.2 Hypercoagulability results from increased coagulation factor activity or systemic inflammation. Endothelial injury exposes subendothelial structures - activating platelets and the coagulation cascade, and blood stasis impedes the dilution and clearance of activated clotting factors.
Modern advances have expanded on this model, highlighting interactions between coagulation proteins, inflammatory cytokines, and the vascular endothelium. Genetic predispositions, such as Factor V Leiden, prothrombin gene mutations, and deficiencies in proteins C, S, or antithrombin, significantly elevate thrombotic risk.3 Environmental and acquired factors such as immobility, surgery, trauma, hormonal therapy, pregnancy, and pharmacological agents, can further shift the hemostatic balance towards thrombosis.4
Risk assessment
Accurate risk stratification is essential for appropriate thromboprophylaxis. Multiple validated models exist: the Wells and Geneva scores estimate DVT or PE probability;5,6 the Caprini score is used preoperatively,7 and CHADS₂ and CHA₂DS₂-VASc assess stroke risk in atrial fibrillation, while HAS-BLED evaluates bleeding risk during anticoagulation.8,9,10
Patients at high risk often exhibit multiple contributing factors, such as previous thrombosis, malignancy, surgery, immobility, obesity, and hematological disorders. In women, pregnancy, postpartum state, and hormone therapies also raise the thrombotic risk, especially when additional risk factors are present.11
Lifestyle modifications
Physical activity
Regular physical activity improves venous return, reduces blood viscosity, enhances endogenous fibrinolysis, and mitigates cardiovascular risk factors. The World Health Organisation recommends at least 150 minutes of moderate or 75 minutes of vigorous aerobic activity weekly, along with strength training on two or more days.12 For sedentary individuals, brief activity breaks during prolonged sitting can reduce VTE risk. During extended travel, periodic movement and simple exercises like calf raises or ankle rotations are beneficial. Low-impact activities like swimming and cycling are ideal for those with limited mobility.13
Nutrition and hydration
Diet influences thrombosis risk by modulating platelet activity, coagulation, inflammation, and endothelial function. The Mediterranean diet, rich in fruits, vegetables, whole grains, and healthy fats, has been associated with antithrombotic effects.14 Specific nutrients beneficial for thrombosis prevention include:
- Omega-3 fatty acids (from fatty fish, flaxseeds, walnuts) that suppress platelet aggregation and inflammation15
- Flavonoids (from berries, citrus, tea, and dark chocolate) that enhance endothelial function and reduce platelet reactivity16
- Allicin (from garlic and onions), which exhibits antiplatelet and fibrinolytic activity17
- Vitamin E, which inhibits vitamin K-dependent coagulation factors18
Adequate hydration is critical to maintaining blood viscosity and flow. Excessive alcohol intake may promote thrombosis through fibrinogen elevation and increased platelet activation, although moderate consumption has been linked to cardiovascular protection (19).
Weight management
Obesity is a well-established independent risk factor for VTE, due to chronic inflammation, elevated fibrinogen, impaired fibrinolysis, and venous stasis. Each unit increase in BMI above 25 kg/m² is associated with a 26% rise in VTE risk.20 Weight loss via diet changes and physical activity reduces inflammation and coagulant activity. Bariatric surgery is effective for patients with severe obesity but necessitates perioperative thromboprophylaxis due to elevated short-term risk.21
Smoking cessation
Tobacco smoking enhances thrombogenicity by damaging the endothelium, increasing platelet activity, raising fibrinogen levels, and impairing fibrinolysis. Smokers face a 23–43% greater risk of VTE than non-smokers.22 Smoking cessation interventions, including counseling, nicotine replacement, varenicline, and bupropion, significantly reduce thrombotic risk over time.23
Pharmacological prophylaxis
Antiplatelet agents
Antiplatelet drugs are primarily used for arterial thrombosis. Aspirin irreversibly inhibits cyclooxygenase-1 and thromboxane A₂, reducing platelet activation. It is recommended for secondary prevention in established atherosclerotic disease but has limited use in primary prevention due to bleeding risk.24 P2Y₁₂ inhibitors (clopidogrel, prasugrel, ticagrelor) prevent ADP-mediated platelet aggregation and are used in acute coronary syndromes or aspirin intolerance. Dual antiplatelet therapy is used in high-risk settings but can increase bleeding.25
Anticoagulants
Anticoagulants prevent venous thrombosis by inhibiting coagulation pathways. These include:
- Unfractionated heparin (UFH): Requires aPTT monitoring and is associated with heparin-induced thrombocytopenia (HIT)26
- Low molecular weight heparins (LMWH): Such as enoxaparin, with more predictable pharmacokinetics and lower HIT risk27
- Vitamin K antagonists (VKAs): Such as warfarin, which inhibits synthesis of vitamin K-dependent factors. Require INR monitoring28
Direct oral anticoagulants (DOACs), including dabigatran, rivaroxaban, apixaban, edoxaban, and betrixaban, offer fixed dosing and fewer interactions. They are non-inferior or superior to VKAs for many indications, with a reduced risk of intracranial hemorrhage.29 However, their use is limited by renal impairment and reversal challenges in major bleeding.30
Special populations
Surgical patients
Surgical procedures vary in thrombosis risk. Orthopaedic, abdominal, pelvic, and neurosurgeries have the highest risk. Prophylaxis includes early mobilisation, compression devices, LMWHs, or DOACs.31 Extended prophylaxis up to 35 days post-surgery is recommended in major orthopedic and high-risk abdominal surgeries, especially in cancer patients.32
Hospitalised medical patients
Acutely ill medical patients often have multiple thrombotic risk factors. Risk scoring tools like the Padua Prediction Score and IMPROVE Score guide prophylaxis decisions, usually involving LMWH or low-dose UFH during hospitalisation.33
Pregnancy and postpartum
Pregnancy increases thrombotic risk 4–5-fold due to hormonal and mechanical changes. LMWH is preferred in high-risk patients due to better safety compared to UFH. Extended prophylaxis for up to 6 weeks postpartum is recommended in highest-risk scenarios.34
Summary
Thrombosis prevention requires a multifaceted strategy integrating lifestyle changes and pharmacologic interventions based on individual risk profiles. Physical activity, Mediterranean dietary patterns, weight control, and smoking cessation serve as core preventive measures for the general population. High-risk individuals benefit from anticoagulation or antiplatelet therapies, with careful assessment of bleeding risk. Future developments may include genetic risk profiling, safer anticoagulants, and AI-driven personalised prevention strategies. Through such comprehensive efforts, the global burden of thrombosis can be significantly reduced.
References
- Heit JA. Epidemiology of venous thromboembolism. Nat Rev Cardiol. 2015 Aug;12(8):464–74.
- Bagot CN, Arya R. Virchow and his triad: a question of attribution. Br J Haematol. 2008 Apr;143(2):180–90.
- Kujovich JL. Factor V Leiden thrombophilia. Genet Med. 2011 Jan;13(1):1–16.
- Cushman M. Epidemiology and risk factors for venous thrombosis. Semin Hematol. 2007 Apr;44(2):62–9.
- Wells PS et al. Value of assessment of pretest probability of deep-vein thrombosis. Lancet. 1997;350(9094):1795–8.
- Le Gal G et al. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med. 2006;144(3):165–71.
- Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005 Feb;51(2–3):70–8.
- Gage BF et al. Validation of clinical classification schemes for predicting stroke. JAMA. 2001 Jun;285(22):2864–70.
- Lip GY et al. Refining clinical risk stratification for predicting stroke and thromboembolism. Chest. 2010 Feb;137(2):263–72.
- Pisters R et al. A novel user-friendly score to assess bleeding risk in atrial fibrillation. Chest. 2010 Nov;138(5):1093–100.
- James AH. Venous thromboembolism in pregnancy. Arterioscler Thromb Vasc Biol. 2009 Mar;29(3):326–31.
- WHO. Global recommendations on physical activity for health. Geneva: WHO; 2010.
- Belcaro G et al. Venous thrombosis from air travel: prevention with pycnogenol. Clin Appl Thromb Hemost. 2004 Apr;10(1):73–7.
- Schwingshackl L, Hoffmann G. Mediterranean dietary pattern and cardiovascular risk. Nutr Metab Cardiovasc Dis. 2014 Sep;24(9):929–39.
- Calder PC. Omega-3 fatty acids and inflammatory processes. Nutrients. 2010 Mar;2(3):355–74.
- Erdman JW Jr et al. Flavonoids and heart health. J Nutr. 2007 Mar;137(3 Suppl 1):718S–737S.
- Rahman K, Lowe GM. Garlic and cardiovascular disease. Curr Nutr Food Sci. 2006;2(4):309–26.
- Meydani SN et al. Vitamin E supplementation and in vivo immune response. Am J Clin Nutr. 1990 May;51(5):807–15.
- Mukamal KJ, Rimm EB. Alcohol consumption and risk for coronary heart disease. JAMA. 2001;285(10):1238–45.
- Stein PD et al. Obesity as a risk factor in venous thromboembolism. Am J Med. 2005;118(9):978–80.
- Hager K et al. Impact of bariatric surgery on venous thromboembolism. Obes Surg. 2007;17(9):1194–9.
- Cheng YJ et al. Smoking and risk of venous thromboembolism. Arch Intern Med. 2011 Jan;171(3):183–9.
- Cahill K et al. Pharmacological interventions for smoking cessation. Cochrane Database Syst Rev. 2013 May;2013(5):CD009329.
- Antithrombotic Trialists’ Collaboration. Aspirin in prevention of cardiovascular events. Lancet. 2009;373(9678):1849–60.
- Wiviott SD et al. Prasugrel vs. clopidogrel in acute coronary syndromes. N Engl J Med. 2007 Nov;357(20):2001–15.
- Hirsh J et al. Heparin: Mechanism and management. Chest. 2001 Jan;119(1 Suppl):64S–94S.
- Weitz JI. Low-molecular-weight heparins. N Engl J Med. 1997 Apr;337(10):688–98.
- Holbrook A et al. Evidence-based management of anticoagulant therapy. Chest. 2012 Feb;141(2 Suppl):e152S–84S.
- Ruff CT et al. Comparison of new oral anticoagulants with warfarin. Lancet. 2014 Mar;383(9921):955–62.
- Majeed A et al. Management of bleeding complications in patients on DOACs. Blood. 2013 Jul;122(15):2457–64.
- Falck-Ytter Y et al. Prevention of VTE in orthopedic surgery patients. Chest. 2012 Feb;141(2 Suppl):e278S–325S.
- Bergqvist D et al. Extended thromboprophylaxis in cancer surgery. N Engl J Med. 2002;346(14):975–80.
- Barbar S et al. Risk assessment model for VTE in hospitalized medical patients. J Thromb Haemost. 2010 Apr;8(11):2450–7.
- Bates SM et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy. Chest. 2012 Feb;141(2 Suppl):e691S–736S.
