Venous thromboembolism

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Venous thromboembolism Microchapters

Patient Information

Deep vein thrombosis
Pulmonary embolism

Overview

Classification

Epidemiology

Risk Factors

Diagnosis

Treatment

Deep Vein Thrombosis
Pulmonary Embolism

Prevention

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [3], Iqra Qamar M.D.[4], Anmol Pitliya, M.B.B.S. M.D.[5], Aravind Reddy Kothagadi M.B.B.S[6]

Overiew

Venous thromboembolism (VTE) may be classified into deep vein thrombosis (DVT) and pulmonary embolism (PE). Pulmonary embolism may arise as a consequence of deep vein thrombosis as a result of embolization of the clot from deep veins of the legs. Pulmonary embolism (PE) is an acute obstruction of the pulmonary artery (or one of its branches). The obstruction in the pulmonary artery that causes a PE can be due to thrombus, air, tumor, or fat. Most often, this is due to a venous thrombosis (blood clot from a vein), which has been dislodged from its site of formation in the lower extremities. It has then embolized to the arterial blood supply of one of the lungs. Deep vein thrombosis (also known as deep venous thrombosis or DVT and colloquially referred to as "economy class syndrome") is the formation of a blood clot ("thrombus") in a deep vein.

Classification

Venous thromboembolism (VTE) may be classified into:[1][2]

The following table further classifies DVT and PE:[3][4][5][6][5][7][8][9]

Classification of Venous Thromboembolism
Clinical diagnosis Sub-classification Comments
Deep vein thrombosis Upper extremity
Lower extremity
Pulmonary embolism (PE) Massive PE (High risk)

OR

OR

Sub-massive PE (Intermediate risk PE)

AND

Low risk PE

Epidemiology

Incidence

  • The incidence of VTE increases with age, ranging from less than 5 cases per 100,000 people in childhood to 500 cases per 100,000 people in the elderly.[10]
  • Those who are more than 65 years of age are at three times higher risk for VTE compared to those who are 45-54 years old.[11]
  • In the United States, the annual incidence of VTE is estimated to be approximately 100 per 100,000 persons.[10]

Age

  • The incidence of VTE increases with age, ranging from less than 5 cases per 100,000 people in childhood to 500 cases per 100,000 people in the elderly.[10]
  • Those who are more than 65 years of age are at three times higher risk for VTE compared to those who are 45-54 years old.[11]

Gender

  • Studies about differences in the incidence of VTE by gender have yielded mixed results:
    • Some reported a higher incidence of DVT among young females.[12]
    • Some reported a higher incidence of DVT among older females.[13]
    • Some reported a higher incidence of DVT in men.[11][14]
  • In addition, the risk for DVT was reported to consistently increase with age across both genders.[11]

Race

  • There is a significant difference in the incidence of DVT as it relates to race. African Americans characteristically have the highest incidence of DVT while Caucasians rank as the second highest incidence of DVT.[10]
  • Compared to African Americans and Caucasians, the incidence of DVT is noted to be two to four times lower in Hispanics and Asian-Pacific Islanders.[10]
  • Lower incidence of thrombosis in non-Caucasians may be related to a lower prevalence of disorders like Factor V Leiden or Prothrombin 20210A mutation.[15][16]

Hospitalization for VTE

  • During 2007–2009, an estimated annual average of 547,596 hospitalizations culminated in a diagnosis of VTE for adults aged ≥18 years. Estimates for DVT and PE diagnoses were not mutually exclusive. An estimated annual average of 348,558 adult hospitalizations resulted in a diagnosis of DVT, and 277,549 adult hospitalizations resulted in a diagnosis of PE. An estimated annual average of 78,511 adult hospitalizations (14% of overall VTE hospitalizations) had diagnoses of both DVT and PE.[17]
  • The estimated average annual number of hospitalizations with VTE was successively greater among older age groups: 54,034 for persons aged 18–39 years; 143,354 for persons aged 40–59 years; and 350,208 for persons aged ≥60 years. The estimated average annual number of hospitalizations with VTE was comparable for men (250,973) and women (296,623).[17]
  • Shown below is an image depicting the estimated average annual number of hospitalization with a diagnosis of DVT, PE, or VTE by age and sex.
Estimated average annual number of hospitalizations with a diagnosis of deep thrombosis (DVT), pulmonary embolism (PE), or venous thromboembolism (VTE), by patient sex and age group — National Hospital Discharge Survey, United States, 2007–2009 - Source:CDC
  • The average annual rates of hospitalizations with a discharge diagnosis of DVT, PE, or VTE among adults were 152, 121, and 239 per 100,000 population, respectively. For VTE, the average annual rates were 60 per 100,000 population aged 18–39 years, 143 for persons aged 40–49 years, 200 for persons aged 50–59 years, 391 for persons aged 60–69 years, 727 for persons aged 70–79 years, and 1,134 for persons aged ≥80 years. The rates of hospitalization were similar for men and women, and the point estimates increased for both sexes by age.[17]
  • On average, 28,726 hospitalized adults with a VTE diagnosis died each year. Of these patients, an average of 13,164 had a DVT diagnosis and 19,297 had a PE diagnosis; 3,735 had both DVT and PE diagnoses.[17]

Recurrence of VTE

  • Approximately 33% of people with VTE will have a recurrence within 10 years.[18][19]
  • The risk of recurrence of VTE in patients diagnosed with first-time VTE is estimated to be approximately 7-8% per year during an average follow up period of 2.2 years of subsequent observation.[11]
  • Among patients with a first episode of VTE, the risk of recurrence of VTE is particularly elevated in the first 6 to 12 months following the first episode of VTE. The risk of recurrent VTE remains up to 10 years, with a estimated cumulative incidence of first overall VTE recurrence of 30%. Predictors for recurrence of VTE include malignancy, neurological diseases, and paresis.[20]
  • The recent increase in thrombosis incidence may be related to improved diagnostic modalities and increased awareness by clinicians.[10]

Complications of VTE

  • Estimates suggest that 60,000-100,000 Americans die of VTE, 10 to 30% of which will die within one month of diagnosis.[18][19]

Risk Factors

Shown below is a list of predisposing factors for VTE.[21][22] The risk factors are classified as moderate or weak depending on how strongly they predispose for a VTE.

Moderate risk factors Weak risk factors
Chemotherapy
Obesity

Chronic heart failure
Respiratory failure
Hormone replacement therapy
Cancer
Oral contraceptive pills
Stroke
Pregnancy
Postpartum
❑ Prior history of VTE
Thrombophilia

Hospitalization

❑ Advanced age

Laparoscopic surgery
❑ Prepartum
Varicose veins

Risk factors of VTE may be categorized in to modifiable, non-modifiable, temporary and other risk factors.

Modifiable Risk Factors Non-Modifiable Risk Factors Temporary Risk Factors Other Risk Factors

❑ Modifiable risk factors are reversible based upon lifestyle/behavior modification.
Obesity is defined as a body-mass index (BMI) above 30 kg/m2.[23] [24] [25]
Smoking:[23] Smoking significantly increases the risk of DVT, particularly among women who are taking oral contraceptive pills as well as among obese people.
❑ Use of oral contraceptives[26]
Hyperhomocysteinemia:[27] Hyperhomocysteinemia can be reduced with vitamin B supplementation.

❑ Advanced age
Heart failure
Thrombophilia or hypercoagulable state
Polycythemia vera

Factor V Leiden
Prothrombin G20210A mutation
Protein C deficiency
Protein S deficiency
Activated protein C resistance
Antithrombin III deficiency
Factor VIII mutation
Antiphospholipid syndrome
Heparin induced thrombocytopenia
Nephrotic syndrome
Paroxysmal nocturnal hemoglobinuria

Pregnancy and the peri-partum period
❑ Active cancer
Central venous catheterization

❑ Other possible factors associated with VTE include:[28]

❑ Nutrition low in fish
Psychological stress
❑ Cardiovascular risk factors such as diabetes and hypercholesterolemia

Diagnosis

The diagnostic guidelines for venous thromboembolism are as follows:[29]

 
 
 
 
 
 
 
 
Suspected DVT
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical probability
likely
 
 
 
 
 
 
 
Clinical probability
unlikely
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ultrasound
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Normal
 
Abnormal
 
 
 
 
 
D-dimer
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
D-dimer
 
Treat
 
 
 
 
 
 
 
 
 
Positive
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Negative
 
Positive
 
 
 
 
Negative
 
 
 
Ultrasound
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Stop
 
Repeat ultrasound in 1 week
 
 
 
 
Stop
 
Abnormal
 
Normal
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treat
 
Stop
 


 
 
 
 
 
 
 
 
Suspected pulmonary embolism
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
D-dimer
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Negative
 
 
 
 
 
 
 
 
 
 
 
Positive
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Stop
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CXR
 
 
 
 
 
 
Ultrasound
If signs of DVT present
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Normal
PE unlikely with positive D-dimer or PE likely
 
 
 
 
 
 
 
 
Abnormal
PE unlikely with positive D-dimer or PE likely
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
V/Q scan
 
 
 
 
 
 
 
CTPA
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nnormal
 
Non diagnostic
 
High probability
 
PE present
 
PE absent
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Stop
 
 
 
 
 
 
Treat
 
Treat
 
Stop
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PE unlikely
 
 
 
PE likely
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serial ultrasound
 
 
 
CTPA or serial ultrasound
 
 
 

Prevention

The follwoing table summarizes the major scoring criterias used for risk assessment of VTE and their prophylaxis options:[30]

Patient population Sub-population Scoring criteria for risk assessment Major predisposing risk factors and their score Prophylaxis recommendations
Padua score IMPROVE score IMPROVE bleeding risk score IMPROVE Associative score Caprini score
Non-surgical patients Acutely ill patients - IMPROVE:
  • Previous VTE: 3
IMPROVE bleeding risk:
Cancer in outpatient - - - - -
  •  Does the patient have a solid tumor 

AND 

  • Additional risk factors for VTE?
  • Previous VTE
  • Hormonal therapy
  • Immobilization
  • Angiogenesis inhibitors
  • Thalidomide
  • Lenalidomide
  • If major predisposing risk factors present:
  • If no major predisposing risk factors present:
    • No VTE prophylaxis
Chronically immobilized patients - - - - - -
  • Not indicated
Long travel
  • Frequent ambulation
  • Calf muscle excercise
  • Sitting in an isle seat
  • Below knee compression stockings (15-30 mm Hg pressure at ankle)
Asymptomatic thrombophilia - - - - - -
  • Not indicated
Surgical patients Orthopedic surgery patients - - - - - -
General and abdominal pelvic surgeries - - - - Caprini:
Cardiac surgery - - - -
Thoracic surgery - - - -
Craniotomy - - - -
Spinal surgery - - - -
Trauma - - - -

Abbreviations: LDUH: low dose unfractionated heparin; LMWH: low molecular weight heparin; VTE: Venous thromboembolism

Padua Score IMPROVE score IMPROVE bleeding risk score IMPROVE Associative score Caprini score

(Score≥ 4: High risk for VTE

Score< 4: Low risk for VTE)

0 0.5% 1 1.0%

2 1.7%

3 3.1%

4 5.4%

5-8 11%

(Score ≥7: Elevated risk of bleeding

Score <7: Not elevated risk of bleeding)

(Score 0-1: Low risk for VTE

Score 2-3: Intermediate risk for VTE

Score 4-10: Hight risk for VTE)

(Score 0-1: Low risk of VTE

Score 2: Moderate of VTE

Score 3-4: High risk of VTE

Score ≥ 5: Highest risk for VTE)

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