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34 Chapter 3 The physiology and hemodynamics of the normal venous circulation
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Consensus Statements 3.0 of the American Venous Forum on the physiology and hemodynamics of the normal
venous circulation
No. Consensus Statement
3.1 Venous return follows a continued dynamic pressure gradient. Most of the energy imparted by the pumping action of the heart is
dissipated in distribution to the arterial circulation.
3.2 The hydrostatic pressure in the venous system is directly related to the height of the column of blood in relation to the zero point
of the right atrium.
3.3 Venous return against gravity is accomplished by the combined action of an active extremity muscle pump and one-way venous valves.
3.4 The plantar venous pump acts to prime the calf muscle pump.
3.5 The thigh muscle pump contributes little to venous return.
3.6 The anatomic structure of a vein allows for great variation in its diameter. This facilitates the capacitance function of the venous
system for adjustment to volume and temperature changes.
3.7 External pressure on collapsible proximal veins increases distal venous pressure.
3.8 Exercise therapy increases muscle strength and function of the calf pump.
REFERENCES
• Randomized controlled trial
* Systematic review or
meta-analysis
♦ Clinical practice guideline or
reporting standards
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*2. Rothe C.F. Venous system: Physiology
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*3. Shepherd J.T. Role of the veins in the circu-
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•5. Pollack A.A. and Wood E.H. Venous
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♦
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18. Arnoldi C.G. Venous pressure in the leg of
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25.
Araki C., Back T.L. and Padberg F.T.
Renements in detection of popliteal vein
reux. J Vasc Surg 1993;18:742–748.
26. VanBemellen P.J., Bedford G., Beach K. and
Strandness D.E. Quantitative segmental
evaluation of venous valvular reux with
the duplex ultrasound scanner. J Vasc Surg
1989;10:425–431.
of venous ulcers of the leg. Br J Surg
1955;43:260–278.
28. Brittenden J., Bradbury A.W., Allan
P.L., etal. Popliteal vein reux reduces
healing of chronic venous ulcer. Br J Surg
1998;85:60–62.
Dalsing M.C., Raju S., Wakeeld T.W. and
29.
Taheri S. Amulticenter, Phase Ievaluation of cryopreserved venous valvular
allografts for treatment of chronic
deep venous insufciency. J Vasc Surg
1999;30:854–866.
30. Rosfors S., Lamke L.-O., Nordström E.
and Bygdman S. Severity and location of
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Scand 1990;156:689–694.
31. Almén T. and Nylander G. Serial phlebography of the normal lower leg during
muscle contraction and relaxation. Acta
Radiol 1963;57:264–272.
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32. Christopoulos D.G., Nicolaides A.N., Szendro
G., etal. Air-plethysmography and the effect
of elastic compression on venous hemodynamics of the leg. J Vasc Surg 1987;5:148–159.
33. Ludbrook J. Musculovenous pumps
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34. Alimi Y.S., Barthelemy P. and Juhan P.
Venous pump of the calf: Astudy of
venous and muscular pressures. J Vasc Surg
1994;20:728–735.
35. Partsch B. and Partsch H. Calf Compression pressure required to achieve venous
closure from supine to standing position. J
Vasc Surg 2005;42:734–738.
36. White J.V., Katz M.L., Cisek P. and
Kreither J. Venous outow of the leg:
Anatomy and physiologic mechanism of
the plantar venous plexus. J Vasc Surg
1996;24:819–824.
37. Bishara R.A., Sigel B., Rocco K., etal.
Deterioration of venous function in normal
lower extremities during daily activity. J
Vasc Surg 1986;3:700–706.
38. Katz M.L., Comerota A.J., Kerr R.P. and
Caputo G.C. Variability of venous hemodynamics with daily activity. J Vasc Surg
1994;19:361–365.
39. Höjensgård I.C. and Stürup H. Static and
dynamic pressures in supercial and deep
veins of the lower extremity in man. Acta
Physiol Scand 1953;27:49–67.
40. Jacobsen B.H. Venous drainage of the foot.
Surg Gynecol Obstet 1970;131:22–24.
41. Kuster G., Lofgren E.P. and Hollinshead
W.H. Anatomy of the veins of the foot.
Surg Gynecol Obstet 1968;127:817–823.
42. Samuelhoff S.I., Browse N.L. and
Shepherd J.T. Response of capacity
vessels in human limbs to heal up tilt and
suction on the lower body. J Appl Physiol
1966;21:47–54.
43. Smith James J., Porth CM. and Erickson
M. Hemodynamic response to the upright
posture. J Clin Pharmacol 1994;34:
375–386.
44. Henry J.P. and Gauer O.H. The inuence
of temperature upon venous pressure in
the foot. J Clin Invest 1950;29:855–861.
45. Tschakovsky Michael E. and Sheriff Don D.
Immediate exercise hyperemia: Contributions of the muscle pump vs rapid vasodilation. J Appl Physiol 2004;97;739–747.
•46. Padberg F.T., Jr., Johnston M.V. and Sisto
S.A. Structured exercise improves calf
muscle pump function in chronic venous
insufciency: Arandomized trial. J Vasc
Surg 2004;39:79–87.
*47. Araujo D.N., Ribeiro C.T.D., Maciel
A.C.C., Bruno S.S., Fregonezi G.A.F.
and Dias F.A.L. Physical exercise for
the treatment of non-ulcerated chronic
venous insufciency. Cochrane Database
Syst Rev 2016;12. Art. No.: CD010637.
DOI: 10.1002/14651858.CD010637.
pub2.
3
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CHAPTER
4
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The epidemiology, genetics, and risk
factors for acute venous thrombosis
Samuel Jessula and Anahita Dua
4.1 INTRODUCTION
Venous thromboembolism (VTE) represents signicant
morbidity and mortality in the community and hospital setting and incurs substantial health care costs. The Virchow
1
is the major theory explaining VTE, which states that
triad
VTE results from three phenomena: venous stasis, vascular
endothelial injury, and a hypercoagulable state. Deep venous
thrombosis (DVT) and pulmonary embolism (PE) represent
the most common manifestations of VTE. These are multicausal diseases resulting from the interaction of both genetic
and environmental factors. Each can occur either in the
absence of recognized thrombotic risk factors, designated as
idiopathic, or secondary/provoked from an inciting incident
that raises the thrombotic risk either transiently or permanently. Up to 50% of VTEs are considered idiopathic.
2
4.2 EPIDEMIOLOGY
The annual incidence of VTE ranges from 1.04 to 1.83
per 1000 person-years.
tion of Thromboembolism Etiology study totaling 21,680
patients, the age-adjusted incidence of rst-time VTE was
1.92 per 1000 person-years.
database study, Tagalakis etal. identied an overall incidence of VTE of 1.22 per 1000 person-years of which the
DVT incidence was 0.78 per 1000 person-years and PE
0.45 per 1000 person-years.
Huang etal. reported age- and sex-adjusted annual event
rates for both lower extremity DVT and PE during nine
annual periods from 1986 to 2009 in a population of 5487
individuals. From 1986 to 2009, there was an increase in
the annual incidence of rst-time VTE from 0.73 to 1.33
per 1000 person-years. The annual incidence rate of DVT
increased from 0.49 to 0.68 per 1000 person-years, and the
annual incidence rate of PE increased from 0.14 to 0.65 per
1000 person-years during the same interval.
in incidence of PE in the twenty-rst century seems closely
linked to the improvement of diagnostic modalities for
VTE, namely computed tomography angiography (CTA).
Wiener etal. found a substantial increase in national PE
incidence prior to—0.62 per 1000 in 1993–1998—versus
after—1.12 per 1000 in 1998–2006—the introduction of
CTA diagnostic imaging.
3
In the Longitudinal Investiga-
4
In a large administrative
5
In the Worcester VTE study,
6
The increase
7
One and ve-year survival rates after a VTE are 96%
and 88%, respectively; 94% and 83%, respectively, in
patients with non-cancer-associated VTE; and 66% and
46%, respectively, in patients with cancer-associated VTE.
The mortality from VTE appears to be decreasing in recent
years. Ording and colleagues identied progressively
decreasing mortality in both PE (HR 0.79) and DVT (HR
0.76) between the years 2006 and 2017.
9
8
4.3 RISK FACTORS FOR VTE
4.3.1 Demographic risk factors
The incidence of VTE increases with age and is rare in the
rst two decades of life. In a large population-based study,
Silverstein et al. studied age trends in 2218 VTEs (42%
DVT, 44% PE, and 14% both).
was 61.7 (SD 20.4) and increased sharply in both sexes
beyond age 60. Although both DVT and PE rates increase
sharply with older age, PE represents a larger proportion of incident VTE as age increases beyond 60. Overall,
the age-adjusted incidence is higher in men compared to
women (1.3 vs 1.1 per 1000 person-years) with a male-tofemale ratio of 1.2:1; however, incidence rates are higher
for females during childbearing years, whereas incidence
is higher in men beyond age 45.
study, the relative risk of VTE increased by 1.9 for each
additional decade of life.
with the highest prevalence found in individuals of African
descent (1.4 per 1000 person-years), followed by Caucasian (1.03 per 1000 person-years) and the lowest risk in
individuals of Hispanic (0.61 per 1000 person years) or
Asian descent (0.29 per 1000 person-years).
African Americans have a higher proportion of PE as the
manifestation of VTE (36%) compared to those of Caucasian (32%) and Hispanic descent (26%).
12
4.3.2 Anatomic risk factors
Certain anatomic congenital anomalies cause venous
compression and thus predispose individuals for VTE.
Spontaneous DVT occurs secondary to compression at
the thoracic outlet (Paget–Schroetter syndrome),
left common or external iliac vein between the right iliac
10
The mean age of onset
10,11
In the Worcester DVT
The risk of VTE varies by race,
13
Furthermore,
13
14
of the
DOI: 10.1201/9781003328971-5
3737
38 Chapter 4 The epidemiology, genetics, and risk factors for acute venous thrombosis
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artery and adjacent vertebral body (May–Thurner syndrome),
from the medial or lateral head of the gastrocnemius, bony
tumors, or hypertrophied facia.
alies, including agenesis or hypoplasia, may also cause
DVT from obstructed venous outow.
15,16
and as a result of popliteal vein entrapment
17
Inferior vena cava anom-
18
Varicose veins are
markers of venous stasis and are associated with increased
inammatory and prothrombotic markers and are believed
to be associated with VTE. In the Olmsted County study,
patients with varicose veins had a signicant increased risk
of VTE (OR 4.19 if under 45 and 1.93 if under 65).
19
In a
large recent database study from Taiwan’s National Health
Insurance of over 200,000 patients with varicose veins, the
hazard ratio for DVT was 5.3 and 1.73 for PE compared
to healthy controls.
20
4.3.3 Risk factors for atherosclerotic
disease and VTE
Although traditionally, venous thromboembolism and cardiovascular atherosclerotic disease were considered completely distinct disease entities, recent evidence suggests
that traditional risk factors for atherosclerotic disease
may increase the risk of VTE. Ageno etal. performed a
meta-analysis of 21 cohort and case control studies examining the role of traditional risk factors for cardiovascular
disease and VTE events and identied a signicant association between VTE and obesity (OR 2.3), hypertension (OR
and diabetes (OR 1.42).
1.5),
21
Of note, obesity is consistently associated with VTE.
Abdollahi etal. identied a twofold risk of VTE in individuals with a body mass index (BMI) >30 compared to ageand sex-matched controls.
22
Similarly, Stein etal. analyzed
patients from the national inpatient sample and found a
relative risk of 2.5 and 2.21 in obese patients compared
to nonobese for DVT and PE, respectively.
smoking is not associated with an increased risk of VTE
(OR 0.97–1.15).
21,24
23
Interestingly,
4.3.4 Genetic risk factors
Familial and twin studies suggest that genetics are responsible for 55%–60% of the risk for VTE.
is the most common hereditary risk factor for VTE and
affects 1%7% of the Caucasian American population.
Factor V is a procoagulant in the coagulation cascade
which, when interacting with thrombin, serves as a cofactor in the prothrombinase complex, cleaving prothrombin to produce more thrombin and ensuing clots. Factor
V Leiden is caused by a single point mutation in the F5
gene that results in the factor V protein becoming insensitive to activated protein c and greatly increasing the risk of
thrombosis. Initially, in the Leiden Thrombophilia Study,
homozygous individuals for factor V Leiden were believed
to have an OR of 79.4 of VTE compared to the general
population
28
; however, recent population-based studies
have identied an OR of 2.7–4.2 for heterozygous carriers
and 11.5–28 for homozygous carriers.
Prothrombin G20210A is the second most common
acquired thrombophilia. It is caused by a point mutation
in the G20210a gene responsible for prothrombin creation
25,26
Factor V Leiden
29,30
27
(factor II) and has an overall prevalence of 2.0%,
common in Caucasian populations (1%–6% prevalence)
and very rare in individuals of Asian and African descent.
Prothrombin G20210A increases the risk of VTE by an
OR of 2.8–4.8.
V Leiden and prothrombin G20210A mutations, and the
combination has an OR of VTE of up to 20.
33–35
Some patients may carry both factor
36
Protein S and C are plasma proteins that act in the anticoagulant pathway. Protein C becomes activated by the
interaction of thrombin and endothelium surface proteins
and, with protein S as a cofactor, inactivates factors V and
VIIIa. Deciency in either protein can cause a hypercoagulable state.
individuals with VTE varies from 0.9% to 8%.
37
The prevalence of protein S deciency in
38,39
Multiple Environmental and Genetic Assessment (MEGA)
study of risk factors for VTE, protein S deciency was not
associated with a statistically signicant increase in VTE
risk, suggesting that protein S deciency is a rare risk factor
for VTE when testing is performed in the absence of a family history of VTE. The prevalence of protein C deciency
is 1.45 per 1000 individuals, with a relative risk of VTE of
7.3 when compared to healthy individuals.
40
Antithrombin III inhibits the activity of thrombin,
factor Xa, and factor IXa, and administration of heparin
accelerates its activity. Thus, antithrombin III deciency is
associated with thrombosis and heparin resistance. Antithrombin III deciency can be hereditary or acquired and
is associated with a 16.3 relative risk of VTE compared to
unaffected indviduals.
41
4.3.5 Antiphospholipid syndrome
Antiphospholipid syndrome (APS) is an autoimmune condition characterized by antibodies to phospholipid-binding
proteins, including lupus anticoagulant (LA) and anticardiolipin antibodies (ACAs). These antibodies occur in up to
44% of patients with systemic lupus erythematous (SLE)
and are estimated to be responsible for 9.5% of DVTs
worldwide.
increased risk of VTE, while patients with SLE and ACA
have a twofold increase in VTE.
patients, the presence of LA is associated with a 4.6-fold
increased risk of VTE.
4.3.6 Pregnancy
Pregnancy can cause venous obstruction from decreased
mobility, an enlarged uterus, and associated hypercoagulable state due to decreased
gen and coagulation factors (von Willebrand factor, factors
II, VII, VIII, and X), a decreased protein S level and increased
resistance to activated protein C.
0.76–1.72 per 1000 pregnancies, and PE remains the leading cause of maternal death in the developed world.
factors within this population include inherited thrombophilia, antiphospholipid syndrome, black race, heart disease, diabetes, lupus, smoking, multiple pregnancies, age
over 35, obesity, and cesarean delivery.
percent of cases of DVT in pregnancy occur in the left leg,
presumably from compression of the left iliac vein under
the right iliac artery by the growing uterus.
42
Patients with LA and SLE have a sixfold
43
In otherwise healthy
44
45
brinolysis, increases in brino-
45
The incidence of VTE is
46
Seventy to ninety
47
31
more
In the
46
Risk
32
4.3 Risk factors for VTE 39
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4.3.7 Malignancy
Malignancy is associated with a hypercoagulable state, secondary to increased production of procoagulants such as
tissue factor and cancer procoagulant, platelet activation,
microparticle shedding by circulating cells, and generation
of neutrophil extracellular traps.
48
Additionally, treatments
for malignancy such as surgery, central venous catheters,
and chemotherapy increase the risk of VTE. The incidence
of a malignancy diagnosis within 1year of idiopathic DVT
or PE is 1.3 times higher than in the general population.
In the Rochester Epidemiology Project, malignancy was
responsible for 20% of VTEs.
50
In a large California regis-
49
try-based study, VTE was found in 1.6% of patients with
cancer. Metastatic disease at the time of diagnosis was the
strongest risk factor for VTE, and the malignancies with
the highest rate of VTE included metastatic pancreatic,
stomach, bladder, and uterine cancer (20, 10.7, 7.9, and 6.4
per 100 person-years, respectively). VTE is associated with
decreased overall survival in the cancer population, even
after adjusting for stage of disease (HR 1.6–4.2), and complications of VTE are the second leading cause of death
among cancer patients, likely secondary to the association
between cancer progression and procoagulant activity.
51
4.3.8 Medical illness, trauma, and surgery
Hospitalization or connement to a nursing home is associated with an eightfold risk increase in VTE compared to
healthy individuals.
talized patients, Stein etal. identied DVT in up to 1.1%
and PE in 0.3%–0.4%% of admissions of African American and Caucasian individuals.
miology Project, hospitalization or nursing home residency
was responsible for 61% of VTEs.
ting, Samama etal. identied that 85% of patients with
any illness had at least one risk factor for DVT and over
50% had at least two.
Trauma carries a particularly high risk of VTE and was
identied in up to 58% of venography studies and 65%
of autopsies performed on traumatically injured patients.
Risk factors include older age, blood transfusion, surgery,
femoral central venous access, lower extremity or pelvic
fracture, and spinal cord injury.
of VTE exists even with minor traumatic injuries. In the
MEGA population-based study, minor traumatic injuries
within 4 weeks were associated with a threefold increase in
VTE, even after excluding patients who underwent surgery,
casting, bed rest, and were aficted with malignancies.
Surgical intervention commonly involves acute medical
illness, injury to the vasculature, immobilization, activation of coagulation, and decreased brinolysis and thus is
associated with an increased risk of VTE. In the Olmsted
County study, Heit etal. identied a 22-fold increased risk
of VTE if institutionalized with recent surgery.
study of over 1.5million procedures, VTE occurred within
3 months in 0.8% of the population, of which 37% were
PE and less than half were diagnosed prior to discharge.
Procedures with the highest risk of VTE included neurosurgery, total hip arthroplasty, major vascular surgery, and
radical cystectomy. Risk factors included older age, malignancy, and prior VTE.
52
In a large database analysis of hospi-
53
In the Rochester Epide-
50
In the outpatient set-
54
55,56
The increased risk
52
In a large
58
55
57
58
4.3.9 Physical activity and immobility
Individual surveys, including the Longitudinal Investigation of Thromboembolism Etiology Study, the Nurse’s
Health Study, the E3N cohort study, and the Tromsø
study, did show an effect of physical activity on VTE.
61
However, a recent meta-analysis of 14 studies demonstrated an RR of VTE of 0.87 when comparing the most
physically active compared to the least physically active
cohorts, suggesting marginal benets of exercise in pooled
data.
62
Immobility, such as participating in long haul travel,
is a well-described risk factor for VTE. Lapostolle et al.
reviewed all cases of PE coming through the international
airport in Paris from 1993 to 2000 and found 56 symptomatic PEs out of over 135million passengers from 145
countries. The distance traveled was a signicant risk factor for PE in this study.
63
On meta-analysis of 14 studies,
travel was associated with a relative risk of VTE of 2.0,
and a dose response of 18% increased risk for each 2-hour
increase in travel duration by any mode and 26% increase
for each 2-hour increase in duration by air travel.
4.3.10 Drugs
Medications alter the coagulation prole of the body, and
multiple drugs have been associated with VTE. Of these,
hormonal-based medications particularly increase the risk
of VTE. Athreefold to vefold increase in VTE has been
identied in oral contraceptive users, with an incidence
of 1.3 per 1000 person-years.
in the rst year of use and increasing doses of estrogen.
Similarly, postmenopausal hormonal replacement therapy
(HRT) is associated with a twofold increase in VTE. In the
Women’s Health Initiative study of 16,608 participants
randomized to estrogen-progestin replacement vs placebo,
VTE rates were 3.5 and 1.7 per 1000 person-years in the
replacement and placebo groups, respectively. The risk of
VTE was highest in the rst year of use and increased with
older age, obesity, and the presence of factor V Leiden.
In a meta-analysis of 22 RCTs examining HRT, risk of
VTE was increased from 2 to 10 per 1000 person-years
for combined estrogen-progestin therapy and from 4 to 11
per 1000 person-years for unopposed estrogen therapy.
Tamoxifen, the selective estrogen receptor modulator, has
also been implicated in VTE events. Both the NSABP-1
Breast Cancer Prevention trial and the Eastern Cooperative Oncology Group trials demonstrated a threefold
increased risk of VTE in the tamoxifen group compared
to placebo.
69,70
Although the Food and Drug Administration warns
about the risk of VTE in testosterone replacement therapy,
a recent meta-analysis of 11 studies including six RCTs
showed no evidence of an association between testosterone and VTE (OR 1.41).
of increased VTE with the administration of tranexamic
acid, a recent meta-analysis in trauma and orthopedic
surgery did not display a signicant increase in VTE with
tranexamic acid use.
72,73
include antipsychotics, antidepressants,
bodies such as angiogenic tyrosine kinase inhibitors,
glucocorticoids.
76
65
The VTE risk is highest
71
Similarly, despite initial reports
Other drugs associated with VTE
74
monoclonal anti-
4
24,59–
64
66
67
68
75
and
40 Chapter 4 The epidemiology, genetics, and risk factors for acute venous thrombosis
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4.3.11 History of previous VTE
Approximately 15%–17% of patients with VTE will experience recurrence. The risk of recurrence appears similar if the
index event is a PE or a DVT (15% vs 18%).
77
In a recent
large Canadian administrative database study, the 30-day
case fatality rate of VTE was 2.0% (3.9% in patients with
PE compared to 1.3% in patients with DVT) and the 1-year
case fatality rate was 9.2% (12.9% in PE compared to 7.8%
in DVT) and increased with increasing age.
8
4.3.12 COVID-19
Although the understanding of the hypercoagulability
resulting from COVID-19 is still emerging, it is believed
to be secondary to the interaction with the angiotensin II–
converting enzyme receptor on endothelial cells, causing
endothelial damage and severe microvascular inammation
from severe acute respiratory distress, stasis from critical illness, and elevation in several coagulation factors including
factor VIII, brinogen, neutrophil extracellular traps, and
antiphospholipids in addition to hyperviscosity.
degree of microthrombi found on autopsy studies suggests
that COVID-19–related PE are not only caused by increased
rates of emboli from the extremity but also in situ thrombosis within the lungs.
79
Ameta-analysis of 28,173 COVID-19
patients identied a prevalence of VTE of 9.5% when no
ultrasound screening of upper and lower extremities was
performed and 40.3% when ultrasound screening was performed.
care setting and 7.9% in the hospitalized but nonintensive
care population.
80
The prevalence of VTE was 22.7% in the intensive
80
As the understanding of COVID-19 grew
and different doses of therapeutic anticoagulation were
administered to affected patients, rates of VTE in COVID19 patients declined.
COVID-19 population include elevated D-dimer >2450 ng/
mL and elevated alkaline phosphatase.
81
Risk factors for DVT within the
82
Although VTE was
associated with an increase in risk of admission to intensive
care when hospitalized with COVID-19, VTE did not confer
an increase in mortality from COVID-19.
78
The high
83
4.3.13 Other risk factors
Other risk factors for VTE include blood type, with a
higher preponderance of type A and a decreased pro-
84
portion of type O blood in patients with DVT.
Additionally, inammatory bowel disease ares are associated
with an increased hazard of VTE of 3.2 if hospitalized and
85
8.4 in the ambulatory setting.
Environmental risk factors of VTE are poorly studied and inconsistent. Steffen
etal. analyzed data from the Longitudinal Investigation
of Thromboembolism and correlated VTE events with
results of a food questionnaire. VTE was associated with
decreased fruit and vegetable intake and increased red
meat intake, while eating sh at least once per week was
86
associated with 30%–45% lower VTE incidence.
In the
Health Professionals Follow-up study, a Western diet consisting of a high intake of rened grain, cured or red meat,
and high-fat dairy had a 40% increased risk of VTE (HR
1.3) compared to diets higher in fruits and vegetables and
87
lower in meat/fat.
Conversely, the Iowa Women’s Health
Study did not nd any associations between diet and risk
88
of VTE after adjusting for obesity and diabetes.
Psychosocial factors have also been associated with VTE. In a
Swedish questionnaire-based study in 6958 patients and
follow-up of 28years, individuals with persistent stress
had an HR for VTE of 1.66 compared to individuals with
no stress.
4.4 CONCLUSION
Given the multitude of risk factors for VTE, it is not surprising that it is a common disorder affecting a large proportion of the population. Identication of risk factors
allows for more accurate screening and treatment recommendations targeted not only to the thrombotic event but
also the risk factors and causative circumstances of thrombosis, thus decreasing the incidence of and recurrence of
thrombosis.
Consensus Statements 4.0 of the American Venous Forum on the epidemiology, genetics, and risk factors for acute
venous thrombosis
No. Consensus Statements
4.1 The incidence of VTE ranges from 1.04 to 1.83 per 1000 person-years.
4.2 The risk of VTE increases with age, and it is affected by gender and race.
4.3 Anatomic factors, such as vein compression in the thoracic outlet, in the pelvis or popliteal fossa predispose to VTE. Inferior
vena cava anomalies (agenesis or hypoplasia), lower limb varicosities also increase the risk of VTE.
4.4 Genetics are responsible for 55%–60% of the risk for VTE. Factor V Leiden is the most common hereditary risk factor,
affecting 1%–7% of the Caucasian American population. Prothrombin G20210A is the second most common, with an overall
prevalence of 2.0%. Protein S and C and antithrombin III are additional risk factors for VTE.
4.5 Antiphospholipid syndrome, pregnancy, malignancy, medical illness, trauma, surgery, immobility, and COVID-19 infection are
associated with hypercoagulable state and increase the risk of VTE.
4.6 Several drugs, particularly hormonal-based medications, like oral contraceptives, hormonal replacement therapy, and tamoxifen, increase the risk of VTE.
4.7 The risk of recurrent VTE is about 15%–17%.
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