Basics
Description
- Deep venous thrombosis (DVT) is a fibrin clot most commonly found in the deep veins of the lower extremities.
- Pulmonary embolism (PE) occurs when such clots migrate to the pulmonary venous circulation.
- Venous thromboembolism (VTE) may describe either or both conditions.
Epidemiology
Incidence
- About 1.1/1,000 person-years in adults ≥18 years for acute PE
- For DVT about 2.1/1,000 in adults ≥18 years
- Risk is similar for both sexes. The incidence doubles with every 10-year increase in age.
- 3 " 4 greater risk of VTE among women taking estrogen-containing oral contraceptive pills (OCPs)
- 2 " 6 greater risk in pregnant or postpartum women compared to nonpregnant women
Risk Factors
Virchow 's triad: Venous stasis, hypercoagulability, and/or vessel wall injury
- General risks: Age >40, personal or family history of VTE, pregnancy or recent postpartum, OCPs, tamoxifen or hormone replacement use, myeloproliferative disorders, obesity, inflammatory bowel disease, nephrotic syndrome, hypertension (HTN), congestive heart failure, stroke, pneumonia, cancer, tobacco use, surgery requiring >30 minutes of anesthesia within the last 3 months, recent air or other prolonged travel, trauma and/or fracture (of lower extremities or pelvis), shock, diabetic ketoacidosis
- Inherited/acquired hypercoagulable states:
- Major risk: Antiphospholipid antibodies, antithrombin III, protein C or S deficiency, homozygosity for factor V Leiden mutation, prothrombin G20210A mutation
- Minor risk: Heterozygosity for factor V Leiden or prothrombin G20210A mutations, hyperhomocysteinemia, high factor VIII levels
- In pregnancy, protein S and homocysteine (if taking folate supplements) levels may be decreased and factor VIII levels increased.
General Prevention
Patients who have had surgery and/or prolonged hospitalizations have a heightened risk for VTE.
- Intermittent sequential compression devices with thromboembolism-deterrent stockings, subcutaneous heparin, low-dose warfarin, low molecular weight heparins (LMWHs), fondaparinux, and other thrombin and factor Xa inhibitors decrease the risk of VTE.
- LMWHs are probably most effective when the risk of VTE is high (e.g., immediately after orthopedic surgery).
- Early mobilization of patients after surgery and during hospitalization minimizes VTE risk.
Pathophysiology
- Acute PE causes increased pulmonary vascular resistance due to:
- Physical obstruction of blood flow
- Hypoxia-induced vasoconstriction from released humoral factors (serotonin, thrombin, histamine)
- Resultant increase in pulmonary artery pressure leading to increased right ventricular (RV) afterload which in severe cases may cause RV dilation and failure
Diagnosis
History
- Pulmonary embolism: Dyspnea, chest pain (pleuritic or nonpleuritic), low-grade fever, hemoptysis, syncope, tachypnea, tachycardia, and hypotension
- >80% of PEs are associated with DVTs and some of these may be asymptomatic.
- DVT: Pain, swelling, skin discoloration, and low-grade fever
- >20% of symptomatic DVTs are associated with asymptomatic PE.
Physical Exam
- Often unrevealing
- Most common findings: Tachycardia, hypoxia
- Right heart strain (jugular venous distention, new tricuspid regurgitation murmur, accentuated P2, RV heave) and hypotension may be present.
Tests
Lab
- CBC to detect blood dyscrasias; thrombocytopenia should be ruled out prior to heparin use.
- Baseline PT/ PTT prior to anticoagulation
- EKG to rule out other causes and to evaluate for right heart strain.
- Arterial blood gas:
- Obtained only if further evaluation of respiratory status is necessary
- A normal A-a gradient can be seen in up to 20% of patients with PE.
- CXR (<0.001 rads exposure) to evaluate for alternative diagnoses and to compare with ventilation/perfusion (V/Q) scan but unnecessary if CT angiogram (CTA) ordered.
- Troponin I and BNP elevations suggest a more clinically severe PE or an alternative/additional diagnosis.
- Serum D-dimer (usual cutoff 500 ¼g/L):
- Negative predictive value is up to 99%, but positive predictive value is only 30% " use to exclude VTE in low-probability patients.
- Accuracy varies according to assay type; ELISA has highest sensitivities.
- Decreased specificity in pregnant women and older adults, but sensitivity remains high
Imaging
- Lower extremity ultrasound (US):
- Because calf veins are not well visualized with traditional US technique, repeat US 5 " 7 days later to rule out clot propagation. Repeat US should be done on day 2 or 3 in pregnant women as clots may propagate more quickly in this population.
- A negative US and a negative D-dimer rule out DVT as effectively as serial US.
- Serial negative US do not abrogate need for lung imaging when the pretest probability is moderate or high (1)[A].
- While pedal edema is most pronounced in third trimester, the risk of VTE is nearly uniform throughout gestation and greatest in the postpartum period (see "Pregnancy, Venous Thromboembolism " chapter).
- V/Q scan:
- Normal scan rules out PE
- Safest option in pregnant women
- Does not require IV contrast
- Ventilation is associated with 0.01 " 0.02 rads exposure; perfusion with 0.01 " 0.03.
- Approximately 50 " 70% of test results are nondiagnostic (only 20% in pregnant women as they tend to be younger and have fewer comorbidities).
- Low- and intermediate-probability tests should be followed by leg US.
- CTA:
- The test of choice to rule out PE (1)[A]
- Accuracy may be comparable to pulmonary angiogram (PA gram) (1)[A].
- When V/Q scan and CTA reveal discordant results, CTA demonstrated correct diagnosis 92% of the time.
- IV contrast load and radiation exposure (0.2 " 0.3 rads) equivalent to that of PA gram
- May rule in alternative diagnosis
- May help diagnose right heart strain
- PA gram:
- Gold standard, though not commonly used
- Complication rate in 4 studies:
- Rate of death was 0.0 " 0.5%
- Major complication rate ≤3% (severe contrast reaction, renal failure, cardiac arrest)
Surgery
Assess the pretest probability for PE
- Wells ' score:
- PE more likely than competing diagnoses (3 points)
- Swelling/pain on palpation of legs (3 points)
- HR >100 (1.5 points)
- Previous DVT and/or PE (1.5 points)
- Immobilization >3 days or surgery within last month (1.5 points)
- Hemoptysis (1 point)
- Malignancy, active or treated within the last 6 months (1 point)
- <2 points = low pretest probability
- 2 " 6 points = intermediate probability
- >6 points = high probability
- For low pretest probability:
- Intermediate or high pretest probability:
- Lung imaging for possible PE
- Lower extremity US if possible DVT
Differential Diagnosis
- PE: Pneumonia, asthma, chronic obstructive pulmonary disease exacerbation, myocardial infarction, pulmonary edema, anxiety, aortic dissection, pericarditis, lung cancer, pulmonary HTN, rib fracture, pneumothorax, and/or musculoskeletal pain
- DVT: Cellulitis, superficial thrombophlebitis, calf muscle strain or tear, popliteal cyst, venous insufficiency, knee or ankle pathology, asymmetric cardiac edema, drug-induced edema, lymphedema, and/or lipedema
Treatment
Medication
- Heparins [LMWH and unfractionated heparin (UFH)]:
- Current standard of care for acute DVT/PE including during pregnancy
- LMWH:
- Starting dose is 1 mg/kg SC b.i.d. or 1.5 mg/kg/day (not recommended in malignancy or iliofemoral DVT).
- Has been associated with fewer deaths and major bleeds than UFH (2)[A]
- UFH:
- Higher risk of heparin-induced thrombocytopenia (HIT) and osteoporosis with long-term use than LMWH
- Used in patients with conditions which may require rapid reversal of anticoagulation and/or creatinine clearance <30 cc/minute
- Dosed by weight and monitored by PTT
- Neither UFH nor LWMH cross the placenta nor are they secreted into breast milk.
- Warfarin (vitamin K antagonist):
- Generally started once therapeutic on LWMH (or UFH) at doses of 2.5 " 10 mg/day depending on patient 's age and comorbidities
- Overlapped with heparin for 5 days and until the INR is 2 " 3 for 24 hours, at which point heparin can be discontinued
- Probably safe in first 6 weeks of gestation but increased risk of bone, facial, and CNS abnormalities if used later. Since it crosses placenta, can lead to neonatal bleeding on delivery.
- Thrombolytics:
- Indications:
- Massive pulmonary embolus
- Cardiogenic shock
- Right heart strain by Echocardiogram
- No decrease in mortality in hemodynamically stable patients with right heart strain
- Possible decrease in likelihood of chronic pulmonary HTN
- Direct thrombin and factor Xa inhibitors are emerging as a new treatment for VTE.
Additional Treatment
General Measures
- Treatment of pain associated with VTE/PE:
- NSAIDs should be used with caution as may exacerbate bleeding risk.
- Acetaminophen in high doses associated with an elevation in INR with warfarin.
- Judicious use of opioids may be required for symptomatic management.
Additional Therapies
- No compelling evidence that early ambulation promotes DVT propagation. Some guidelines recommend that normal ambulation can begin after LMWH is started.
- Evidence suggests that graduated compression stockings decrease incidence of post-thrombotic syndrome after DVT (2)[A].
- Typical symptoms include leg pain, aching, heaviness/fatigue, swelling, cramping, itching, bluish discoloration of affected leg.
- Symptoms worsen with standing or walking and improve with rest and leg elevation.
Surgery
- Surgical or catheter embolectomy may be attempted in patients who are otherwise at high risk for bleeding.
- Inferior vena cava filter:
- May be temporary or permanent
- Indications:
- Patients with known DVT when a clear contraindication to anticoagulation exists
- Adjunctive therapy for significant proximal propagation of DVT in a patient on appropriate anticoagulation
- May itself become nidus for clot:
- Risk of PE decreases acutely with known DVT but this benefit is lost within 2 years.
- Associated with increased risk of chronic venous disease and recurrent DVTs within 2 years of placement
In-Patient Considerations
Discharge Criteria
- Patients with PE can be discharged safely if hemodynamically stable and therapeutic on warfarin (INR = 2 " 3).
- Clinically stable patients with acute DVT and with good social support can be managed as outpatients on LWMH and warfarin (2)[A].
Ongoing Care
Follow-Up Recommendations
- In provoked VTE (associated with reversible risk factor) or unprovoked isolated distal DVT, duration of anticoagulation may be 3 months (2)[B].
- In unprovoked proximal DVT or PE, risk of recurrent event is high if anticoagulation stopped after 3 months.
- For a first unprovoked VTE, optimal length of treatment is at least 6 months.
- Long-term treatment should be considered with its benefits weighed against risks of bleeding and patient preference.
- In most cases, second unprovoked VTE should be treated with lifetime anticoagulation (2)[A].
- LMWH may be preferred over warfarin in cancer-related VTE. Long-term anticoagulation generally recommended in active cancer.
Patient Monitoring
- Close monitoring as outpatients to detect recurrence and to maintain therapeutic INR in patients taking warfarin
- If INR is therapeutic on 2 consecutive measurements, interval between blood checks can be increased but generally not >1 month.
Patient Education
- Patients should be aware that many foods and medications can alter INR.
- Should report any new medications including over-the-counter and herbals
- May benefit from nutrition consult and handouts on high Vitamin K foods
Prognosis
- Good prognosis for VTE with timely treatment
- For a first unprovoked VTE, recurrence rate off anticoagulants is high and optimal length of treatment is at least 6 months.
Complications
- Post-thrombotic syndrome
- Recurrent clot or new clot
- Therapy-related bleeding or HIT
- Chronic thromboembolic pulmonary HTN
References
1Elliot CG, Lovelace TD, Brown LM. Diagnosis: Imaging techniques. Clin Chest Med. 2010;31:641 " 657.2Segal JB, Streiff MB, Hofmann LV. Management of venous thromboembolism: A systematic review for a practice guideline. Ann Intern Med. 2007;146:211 " 222. [View Abstract]
Additional Reading
1Kearon C. Long-term anticoagulation for venous thromboembolism: Duration of treatment and management of warfarin therapy. Clin Chest Med 2010;31:719 " 730. [View Abstract]2Marik PE, Plante LA. Venous thromboembolic disease and pregnancy. N Engl J Med. 2008;359:2025 " 2033. [View Abstract]3Stein PD, Matta F. Epidemiology and the incidence: The scope of the problem and risk factors for development of venous thromboembolism. Clin Chest Med. 2010;31:611 " 628. [View Abstract]
Codes
ICD9
- 415.19 Other pulmonary embolism and infarction
- 453.9 Other venous embolism and thrombosis of unspecified site
- 453.40 Acute venous embolism and thrombosis of unspecified deep vessels of lower extremity
ICD10
- I26.99 Other pulmonary embolism without acute cor pulmonale
- I82.90 Acute embolism and thrombosis of unspecified vein
- I82.409 Acute embolism and thombos unsp deep vn unsp lower extremity
SNOMED
- 429098002 thromboembolism of vein (disorder)
- 404223003 deep venous thrombosis of lower extremity (disorder)
- 59282003 pulmonary embolism (disorder)
Clinical Pearls
- Venous thromboembolism (VTE) is a common, dangerous but highly treatable disease.
- Pregnancy and the use of oral contraceptive pills increase the risk of VTE significantly.
- Decisions on duration of anticoagulation, especially in unprovoked VTE, should be made on a case-by-case basis.