VTE
Venous thromboembolism (VTE) includes deep vein thrombosis (DVT) and pulmonary embolism (PE). As one of the most common types of cardiovascular disease, VTE is associated with long-term complications, disability and significant mortality. Discover more about VTE, including:
- The types of VTE, and their signs and symptoms
- Risk factors for VTE
- Diagnostic approaches for VTE, including tools to assess the clinical probability of VTE, and the role of D-dimer and imaging tests
Types of venous thromboembolism
Venous thromboembolism (VTE) encompasses pulmonary embolism (PE), deep vein thrombosis (DVT), as well as thrombosis in other parts of the venous system, such as superficial veins1.
Globally, VTE is the third most common type of cardiovascular disease, after myocardial infarction and stroke2
Epidemiological studies indicate the annual incidence of PE is 39–115 per 100,000 population, and 53–162 per 100,000 population for DVT2. For those who have experienced a VTE, the rate of recurrence is high, ranging from approximately 10% in the first year, and up to 30% within 5–10 years 3.
VTE is a leading cause of disability, preventable hospital death and mortality worldwide, incurring a high patient and socioeconomic burden of disease1,4,5. Of the types of VTE, PE is one of the more common causes of cardiovascular mortality2; estimates indicate that sudden death occurs in up to one-quarter of patients with PE3.
VTE is also associated with morbidity relating to long-term complications, such as post-thrombotic syndrome in 20–50% of patients with DVT, and chronic thromboembolic pulmonary hypertension in up to 5% of patients with PE3.
Venous thromboembolism (VTE) can affect any vein in the body1. Types of VTE include pulmonary embolism (PE), deep vein thrombosis (DVT) and superficial vein thrombosis (SVT), as summarised in Figure 11.
Figure 1. Types of venous thromboembolism (Adapted1,2).
Pulmonary embolism
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Signs and symptoms of venous thromboembolism
General signs and symptoms of venous thromboembolism (VTE) include pain/tenderness, redness and swelling; however, there is wide variation in symptoms, depending on location (Figure 2)1,2,6.
Figure 2. Signs and symptoms of VTE (Adapted1,2,6–8). BP, blood pressure; DVT, deep vein thrombosis; PE, pulmonary embolism.
VTE can also be asymptomatic. Up to 80% of deep vein thrombosis (DVT) cases may not be clinically apparent, and pain may be the only feature1. Catheter-related DVT is often asymptomatic; when symptoms are evident, they may range from minor pain and tenderness to superior vena cava syndrome1.
While the presence of signs and symptoms raises clinical suspicion of VTE, in most cases confirmation is required through additional tests and investigations1
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Venous thromboembolism risk factors
Key pathophysiological factors contributing to venous thromboembolism
Together with advanced age, the three main pathophysiological factors that are considered to contribute to risk of venous thromboembolism (VTE) are increased procoagulant activity in the blood, vein wall damage and impaired venous flow (Virchow’s triad; Figure 3)1,9.
Figure 3. Factors which contribute to venous thromboembolism (Adapted9).
Impaired flow (venous stasis) may be associated with immobility (prolonged sitting or resting)2,9 or may arise from external compression by tumours or aneurysms1. Haematological abnormalities in the coagulation pathway or the presence of natural anticoagulants may increase blood hypercoagulability; injury to vascular walls may also increase the levels of coagulation enzymes and cofactors9.
Risk factors for VTE
A wide range of factors can increase the risk of VTE1. These risk factors may be environmental/acquired or inherited, transient (such as surgery, pregnancy) or persistent (i.e., inflammatory bowel disease, active cancer)1. A summary of general risk factors for VTE is provided in Table 1.
Table 1. Predisposing risk factors for VTE (Adapted2). CVD, cardiovascular disease; EPO, erythropoietin; HIV, human immunodeficiency virus; HRT, hormone replacement therapy; IV, intravenous; MI, myocardial infarction; OR, odds ratio; SVT, superficial vein thrombosis; UTI, urinary tract infection; VTE, venous thromboembolism.
| Strong risk factors (OR >10) |
Moderate risk factors (OR 2–9) |
Weak risk factors (OR <2) |
| Surgery: · Hip/knee replacement History of CVD: · MI (within ≤3 months) · Previous VTE Hospitalisation for: · Heart failure · Atrial fibrillation/flutter (within ≤3 months) Injury: · Lower limb fracture · Spinal cord injury · Major trauma |
Surgery/medical procedures: · Arthroscopic knee surgery · Blood transfusion · Insertion of IV catheters · In vitro fertilisation Medical conditions: · Autoimmune disease · Congestive heart failure · Respiratory failure · Infection (UTI, HIV, pneumonia) · Thrombophilia · Metastatic cancer · Inflammatory bowel disease · Paralytic stroke · SVT Pharmacological treatment: · Chemotherapy · HRT · Oral contraceptives · EPO-stimulating agents Post-partum period |
Surgery: · Laparoscopic Medical conditions: · Diabetes mellitus · Arterial hypertension · Varicose veins Immobility: · Bed rest >3 days · Prolonged sitting (e.g. long-haul car or air travel) Patient characteristics: · Increasing age · Obesity · Pregnancy |
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Venous thromboembolism diagnosis
Venous thromboembolism diagnosis
Diagnosis of venous thromboembolism (VTE) presents a challenge for healthcare providers, as signs and symptoms can be difficult to distinguish from other conditions7. Symptoms of pulmonary embolism (PE) can be similar to those of myocardial infarction and congestive heart failure, while symptoms of deep vein thrombosis (DVT) can be difficult to distinguish from cellulitis, haematoma, superficial thrombophlebitis and congestive heart failure7.
For most patients with suspected DVT and PE, the recommended diagnostic approach involves an initial assessment of clinical (pre-test) probability, which may involve D-dimer tests and imaging, where appropriate7
Considering around 80% of patients with PE have signs of DVT, and approximately 50% of patients with proven proximal DVT have an associated PE8, it is generally recommended to screen patients with suspected PE for DVT (and vice versa) as part of the diagnostic workup1,2,6.
Diagnosing pulmonary embolism
For patients with suspected PE, initial management is dependent on the presence or absence of haemodynamic instability2.
Suspected PE with haemodynamic instability: Emergency diagnosis required
Haemodynamic instability is a rare, life-threatening and high-risk presentation of PE2. It is characterised by the presence of at least one of cardiac arrest, obstructive shock or persistent hypotension at presentation2. If any of these conditions are present, and high-risk PE is suspected, an emergency diagnosis is required2. In such cases, a bedside transthoracic echocardiogram (TTE) or emergency computed tomography pulmonary angiography (CTPA) is recommended, with immediate referral for reperfusion treatment2.
Suspected PE without haemodynamic instability
For patients with suspected PE without haemodynamic instability, the recommended diagnostic approach is based on clinical probability of PE2,6.
Determining the clinical probability of PE
Clinical probability of PE may be determined via clinical judgement or prediction rules, informed by a combination of symptoms, clinical findings and the presence of predisposing risk factors2. Where required, a chest x-ray and electrocardiogram may also assist with diagnosis2,6.
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References
- Kakkos SK, Gohel M, Baekgaard N, Bauersachs R, Bellmunt-Montoya S, Black SA, et al. European Society for Vascular Surgery (ESVS) 2021 clinical practice guidelines on the management of venous thrombosis. European Journal of Vascular and Endovascular Surgery. 2021;61(1):9–82.
- Konstantinides S v., Meyer G, Bueno H, Galié N, Gibbs JSR, Ageno W, et al. 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). European Heart Journal. 2020;41(4):543–603.
- Ortel TL, Neumann I, Ageno W, Beyth R, Clark NP, Cuker A, et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: Treatment of deep vein thrombosis and pulmonary embolism. Blood Advances. 2020;4(19):4693–4738.
- Heit JA. Predicting the risk of venous thromboembolism recurrence. American Journal of Hematology. 2012;87(Suppl 1):S63–S67.
- Badescu M, Ciocoiu M, Badulescu O, Vladeanu M-C, Bojan I, Vlad C, et al. Prediction of bleeding events using the VTE‑BLEED risk score in patients with venous thromboembolism receiving anticoagulant therapy (Review). Experimental and Therapeutic Medicine. 2021;22(5).
- National Institute for Health and Care Excellence. Venous thromboembolic diseases: diagnosis, management and thrombophilia testing: NICE Guideline. 2020.
- Tritschler T, Kraajpoel N, le Gal G, Wells P. Venous thromboembolism - advances in diagnosis and treatment. Journal of American Medical Association. 2018;320(15):1583–1594.
- Parakh RS, Sabath DE. Venous thromboembolism: Role of the clinical laboratory in diagnosis and management. The Journal of Applied Laboratory Medicine. 2019;3(5):870–882.
- Phillippe H. Overview of venous thromboembolism. American Journal of Managed Care. 2017;23:S376–S382.
- Zuin M, Barco S, Giannakoulas G, Engelen MM, Hobohm L, Valerio L, Vandenbriele C, Verhamme P, Vanassche T, Konstantinides SV. Risk of venous thromboembolic events after COVID-19 infection: a systematic review and meta-analysis. 2023. J Thromb Thrombolysis. 1–9.
- Angelini DE, Kaatz S, Rosovsky RP, Zon RL, Pillai S, Robertson WE, Elavalakanar P, Patell R, Khorana A. COVID-19 and venous thromboembolism: A narrative review. Res Pract Thromb Haemost. 2022 Feb 15;6(2):e12666.
- Lyman GH, Carrier M, Ay C, Nisio M di, Hicks LK, Khorana AA, et al. American Society of Hematology 2021 guidelines for management of venous thromboembolism: Prevention and treatment in patients with cancer. Blood Advances. 2021;5(4):927–974.
- Fernandes CJ, Morinaga LTK, Alves JL, Castro MA, Calderaro D, Jardim CVP, et al. Cancer-associated thrombosis: The when, how and why. European Respiratory Review. 2019;28(151).
- Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111(10):4902–4907.
- le Gal G, Righini M, Roy P, Sanchez O, Aujesky D, Bounameaux H. Prediction of pulmonary embolism in the emergency department: The revised Geneva score. Annals of Interntal Medicine. 2006;144(4):165–171.
- Klok FA, Mos ICM, Nijkeuter M, Righini M, Perrier A, Grégoire LG, et al. Simplification of the revised Geneva score for assessing clinical probability of pulmonary embolism. Archives of Internal Medicine. 2008;168(19):2131–2136.
- Gibson NS, Sohne M, Kruip MJHA, Tick LW, Gerdes VE, Bossuyt PM, et al. Further validation and simplification of the Wells clinical decision rule in pulmonary embolism. Thrombosis and Haemostasis. 2008;99(1):229–234.
- Wells P, Anderson D, Rodger M, Ginsberg J, Kearon C, Gent M, et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: Increasing the models utility with the SimpliRED d-dimer. Thrombosis and Haemostasis. 2000;83:416–420.
- Price CP, Fay M, Hopstaken RM. Point-of-care testing for d-dimer in the diagnosis of venous thromboembolism in primary care: A narrative review. Cardiology and Therapy. 2021;10(1):27–40.
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