Epidemiology

In England, 35,845 hospital admissions for pulmonary embolism (PE) were reported in the 1-year period between 2022 and 2023.[8]​ The number of deaths due to PE was 7388 between 2019 and 2021.[9]

Of 317,000 deaths related to venous thromboembolism (VTE) in six European Union countries (population 454 million) in 2004, 34% were attributable to sudden fatal PE, 59% from PE-related deaths following undiagnosed VTE, and 7% from correctly diagnosed PE.[10]

Between 2007 and 2009, PE resulted in 277,549 adult (aged ≥18 years) hospitalisations in the US. Of these patients, an average of 19,297 died each year.[11] The annual rate of adult hospitalisations with a discharge diagnosis of PE during 2007 to 2009 was 121 per 100,000 population.[11]

From 1993 to 2012, US National Inpatient Sample recorded an increase in PE admissions from 23 per 100,000 to 65 per 100,000.[12] The rate of both massive PE and mortality increased (1.5 to 2.8 per 100,000, and 1.6 to 2.1 per 100,000, respectively), but not commensurate with the increase in admissions.[12] The proportion of male patients admitted with PE increased from 44.9% in 1993 to 47.3% in 2012. The majority of patients were white (62.1% in 1993, 70.2% in 2012); however, the proportion of black patients admitted increased significantly (from 8.0% to 15.9%).

Among US adults greater than 65 years of age, the adjusted PE hospitalisation rate increased from 129/100,000 person-years in 1999 to 302/100,000 person-years in 2010.[13]

Risk factors

The incidence and direct mortality from PE increases with age.[19]

Age-specific mortality rates double for every 10 years starting at age 25.[20]

Present in 45% to 50% of patients with a diagnosed PE.[21][22]

Present in 29% with confirmed PE.[21]

Present in 28% with confirmed PE.[21]

Present in 25% with confirmed PE.[21]

A family history of VTE is associated with a significantly increased rate of VTE among first-degree relatives.[23] The risk is increased more than 20-fold in patients with at least two affected siblings, making this one of the strongest risk factors identified for VTE.[24]

Present in 22% with confirmed PE.[21]

Ovarian, uterine, prostate, and brain cancers are most commonly associated with death due to PE.[20]

Present in 11% with confirmed PE.[21]

There is a more than fourfold increased risk of thrombosis throughout gestation, and this risk may increase during the postnatal period.[32][33][34]

Venous stasis and prolonged bed rest are known to increase the risk of venous thromboembolic event.[36]

Present in 11% to 21% of patients with a venous thromboembolic event (combined DVT/PE incident rate).[58] Heterozygous carriers have an estimated risk for venous thromboembolic event that is 7 times higher than those without the mutation. Homozygous carriers are at 80 times higher risk for venous thromboembolic event than non-affected individuals.[59]

The absolute risk of first pregnancy-associated VTE with heterozygous and homozygous factor V Leiden mutation is 1.1% and 6.2%, respectively.[60]

Patients with factor V Leiden are less likely to have a PE than are people with other inherited thrombophilias. This paradox highlights the differences that exist between the risk factors for DVT and PE.[61][62]

The prevalence of prothrombin G20210A mutation in patients with DVT or PE varies with geography and ethnicity.

In North America, prothrombin gene G20210A carrier rates ranging from 1% in African-Americans to between 6.4% and 10.4% in white people have been reported among those with a history of VTE.[63]

In a Dutch study, the mutation was found in 6.3% of consecutive unselected patients with a first episode of DVT.[64]

Estimated to increase the risk of a venous thromboembolic event by 2 to 5 times that of those without the mutation.[54]

The absolute risk of first pregnancy-associated VTE with heterozygous prothrombin G20210A mutation is 0.9%.[60]

Large variability to the disorder. May not significantly increase the risk of thrombosis in people without a concomitant family history. Fifty percent of patients with antithrombin deficiency and a family history of thrombosis will have a venous thromboembolic event before the age of 40.[54]

The absolute risk of first pregnancy-associated VTE in antithrombin-deficient women is 16.6%.[60]

Rare inherited thrombophilia.

In a white population, protein C deficiency is found in approximately 2% to 5% of patients with VTE and in 5% to 10% of those with recurrent VTE.[65]

The absolute risk of first pregnancy-associated VTE in protein C-deficient women is 7.8%.[60]

Found in 1% to 2% of patients presenting with a DVT.

The increase in risk associated with this disorder is not well established; the incidence of venous thromboembolic event is approximately 3.5% per year.[54]

The absolute risk of first pregnancy-associated VTE in protein S-deficient women is 4.8%.[60]

Antiphospholipid antibodies have been reported in up to 14% of patients presenting with a VTE.[66]​ Antiphospholipid antibody syndrome is strongly associated with a high risk of recurrent PE.[67]

Present in 29% of patients with a diagnosed PE.[21]

More likely to be present in patients who die from PE.

Current smoking modestly increases the risk of VTE (hazard ratio [HR] 1.19, 95% CI 1.08 to 1.32).[25]

Subtype analyses indicate that smoking is associated with provoked (but not unprovoked) VTE, possibly through comorbid conditions such as cancer.

Present in 18% with confirmed PE.[21]

Patients with stage III/IV COPD have a higher risk of VTE compared with those without COPD (HR 1.61, 95% CI 0.90 to 2.93).[26]

COPD severity (defined by airflow limitation or medication usage), rather than frequency of exacerbations, may be associated with VTE events in people with COPD.[27]

Present in 12% with confirmed PE.[21]

CHF is an independent risk factor for VTE.[28] It is present in 10% with confirmed PE.[21]

Death certificate data from the United States Census Bureau list PE as the cause of death among 2.7% of adults (20,387 of 755,807) who died with heart failure between 1980 and 1998.[29]

Studies of cancer patients have estimated the overall rate of catheter-related thrombosis to be between 14% and 18%.[30]

Among non-metastatic invasive breast cancer patients, an incidence rate of 2.18/100 patient-months has been reported for central venous catheter-related VTE.[31]

Risk of incident DVT is significantly increased in people with varicose veins compared with those without (6.55 vs 1.23 per 1000 person-years).[35] Findings regarding PE are less clear.

Long-duration travel is a weak risk factor for the development of VTE.[36]

The incidence of VTE in flights >8 hours' duration is approximately 0.5% in travellers at low to intermediate risk for development of VTE.[36]

Multiple pathophysiological factors have been attributed to increased risk including immobility, relative hypoxia in the pressure-controlled cabin, and dehydration.[37]

Individual risk factors for long-duration travel-related VTE also play an important role. Age >40 years, female sex, women who use oral contraceptives, people with chronic venous insufficiency and/or varicose veins in the lower limbs, obesity, and genetic thrombophilia are strong modulators of VTE attributed to long-distance travel.[38]

Acquired thrombophilic factors related to arterial and/or venous thrombosis are associated with recurrent miscarriage.[32][39]

Registry studies variously report that myocardial infarction is associated with a transient increased risk of VTE, independent of atherosclerotic risk factors, or that it is not an independent risk factor for VTE.[40][41]

In a small prospective study of patients with severe sepsis and septic shock, VTE incidence was 37.2% despite thromboprophylaxis.[42]

A prospective cohort study using data from the National Surgical Quality Improvement Program database of the American College of Surgeons (ACS-NSQIP) found that preoperative sepsis in patients undergoing a surgical procedure increased the risk of postoperative venous thrombosis compared with patients without any systemic inflammation (odds ratio [OR] 3.3, 95% CI 3.2 to 3.4).[43]

Transfusion of red blood cells, platelets, and fresh frozen plasma is associated with an increased risk of venous and arterial thrombotic events and mortality in hospitalised patients with cancer, acute coronary syndrome, or acute bleeding.[44][45][46]

Current exposure to a combined oral contraceptive (COC) is associated with an increased risk of VTE (adjusted OR 2.97, 95% CI 2.78 to 3.17) compared with no exposure during the previous year.[47]

The risk of VTE associated with different COCs appears to be influenced by progestogen type. COCs containing levonorgestrel, norethisterone, or norgestimate have the lowest risk (5-7 events per 10,000 women per year), whereas those containing drospirenone, desogestrel, or gestodene have the highest risk (9-12 events per 10,000 women per year). European Medicines Agency: combined hormonal contraceptives Opens in new window 

Observational studies of the combined ethinylestradiol and norelgestromin transdermal patch have reported a similar, or increased, level of VTE risk compared with COCs containing second-generation progestogens. Faculty of Sexual & Reproductive Healthcare: statement - venous thromboembolism (VTE) and hormonal contraception Opens in new window 

Progestogen-only methods of contraception do not appear to be associated with an increased risk of VTE. Faculty of Sexual & Reproductive Healthcare: statement - venous thromboembolism (VTE) and hormonal contraception Opens in new window

Oral HRT preparations containing oestrogen, or combined oestrogen-progestogen, increase the risk of VTE.[48] Risk is greater with increased oestrogen dose.

The risk of VTE is increased in patients with inflammatory bowel disease compared with those who do not have inflammatory bowel disease.[49]

More likely to be seen in those who die with a PE, with an adjusted mortality ratio double that of unaffected individuals.[20]

Serological abnormalities found in inactive Crohn's disease and ulcerative colitis, including abnormalities in fibrinolysis, may increase risk of PE.

Nephrotic syndrome increased the risk of VTE in a case-control study (OR 2.89, 95% CI 2.26 to 3.69).[50] The association was strongest within the first 3 months.

Severe nephrotic syndrome leads to hypercoagulability, resulting in thromboembolism at sites such as the renal and pulmonary vasculature.

Estimates of thrombotic events in Behcet's disease vary from 10% to 30%.[51] VTEs appear to be more common in males.

An 8-year audit in one hospital in Turkey found that venous thromboembolic events occurred in 12.8% of patients with the disease.[52]

This association may be linked to hyperhomocysteinaemia.

Prospective studies indicate that hyperhomocysteinaemia is associated with increased risk of VTE.[53] 

Homocysteinaemia may increase the relative risk of venous thromboembolic event 2.5-fold.[54]

One pooled analysis of case-control and cohort studies found that the methylenetetrahydrofolate reductase (MTHFR) C677T genetic variant (encoding a thermolabile enzyme that is less active at higher temperatures) is not independently associated with VTE risk.[55]

Studies demonstrate a significant association between JAK2V617F allele burden and venous thromboembolic events in patients with Philadelphia-negative myeloproliferative neoplasms.[56][57]

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