Venous Thromboembolism (VTE)

Author(s): R. Samuel Mayer, MD, Mi Ran Shin, MD, W. Bernard Abrams MD

Originally published:12/27/2012

Last updated:04/28/2017

1. DISEASE/DISORDER:

Definition

  1. Venous thromboembolism (VTE) refers to blood clots that develop in veins. It includes superficial and deep venous thrombosis (DVT) and pulmonary embolism (PE).
  2. PE refers to clot within the pulmonary artery or its branches. These blood clots arise from the veins in the limbs or torso, break off and travel through the right side of the heart to lodge in the main pulmonary artery or its branches.
  3. Saddle PEs can cause shock by formation of a clot where the pulmonary artery bifurcates, occluding flow back to the left ventricle. This occurrence frequently results in sudden death.

Etiology

Virtually all rehabilitation inpatients are in high-risk groups.

Risk factors include:

  1. history of VTE
  2. major surgery (lasting > 2 hours) especially of lower limbs
  3. major trauma
  4. immobility
  5. paralysis
  6. prolonged hospitalization or nursing home residence
  7. long-distance travel
  8. cancer
  9. increased estrogen states (including from oral birth control pills or hormonal therapies)
  10. pregnancy
  11. central venous access devices
  12. smoking
  13. congestive heart failure
  14. chronic obstructive pulmonary disease
  15. stroke or other brain injury
  16. spinal cord injury
  17. obesity
  18. increased age
  19. kidney disease (e.g. nephrotic syndrome)
  20. inherited coagulopathies (Factor V Leiden deficiency, anti-thrombin III deficiency, protein S deficiency, dysfibrinogenemia) are found up to 25% of person with venous clots9.

Most DVTs (> 90%) develop in the lower limbs. Almost all PEs are associated with proximal DVTs (at or above the knee). The propagation rate of distal vein DVTs to the proximal veins is approximately 25%.

Epidemiology including risk factors and primary prevention

  1. In the US, the annual incidence of VTE is estimated to exceed 600,000 with nearly 300,000 fatalities, making it the most common preventable cause of hospital-related death.
  2. It is optimal to diagnose VTE at the stage of DVT, as PE frequently results in sudden death. PE leads to over 50, 000 death per year in the United States9.
  3. Unfortunately, only 50% of VTE events found at autopsy were diagnosed clinically prior to death, hence prevention and early diagnosis and treatment are critical.
  4. Only 33% of inpatients in US hospitals receive appropriate VTE prophylaxis.1

Patho-anatomy/physiology

  1. Virchow’s triad describes the classic pathophysiologic predisposition: stasis, endothelial injury and hypercoagulability.
  2. These factors disrupt the normal balance between thrombin formation and endothelial thrombolysis, setting off the coagulation cascade by activating factor Xa.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Post-thrombotic syndrome is a condition of chronic edema, often with venous stasis ulcers, that can arise in a limb after DVT, particularly if the patient is not given compression hose.

Specific secondary or associated conditions and complications

  1. Sudden death from PE is the most serious complication. Up to 70% of fatal PE is first diagnosed at autopsy.
  2. PE, particularly multiple PEs, can result in chronic pulmonary hypertension.
  3. Post-thrombotic syndrome predisposes to chronic edema and cellulitis.

2. ESSENTIALS OF ASSESSMENT

History

Diagnosis is difficult. Examination is unreliable. Sudden onset calf pain and/or unilateral lower limb calf swelling is the classic presentation of lower extremity DVT. For upper limb DVT, sudden swelling of the arm should trigger investigation, particularly if a central venous access device is or has been in place. For PE, dyspnea is usually the presenting symptom. Tachycardia, tachypnea, and anxiety should also raise concern for acute pulmonary embolus.

Physical examination

  1. DVT: Unilateral calf edema and tenderness are usually present. Homan’s sign is an increase in calf tenderness when the ankle is dorsiflexed with the knee in full extension. It may be more sensitive than calf tenderness alone.
  2. PE: There are no specific physical exam findings for PE. Patients frequently demonstrate have some degree of hypoxia on pulse oximetry, and are often tachycardic and tachypneic. Lungs are usually clear. Peri-oral cyanosis may be present in extreme cases.

Functional assessment

Some functional loss may occur because of edema (DVT) or because of pulmonary symptoms (PE).

Laboratory studies

Some have advocated the use of D-dimer to screen symptomatic patients before ordering an ultrasound (US). This screen may have some utility in the outpatient setting in patients at low risk, when the D-dimer result is negative; however, in postoperative patients, it is of little benefit because the positive predictive value is low, and false positives are frequent.

Imaging

DVT

  1. The gold standard for the diagnosis of lower limb DVT is venography; however, it is seldom used clinically outside the research setting. This test involves dye injected into a vein via catheter. It is used when ultrasound or other tests are negative but there remains strong suspicion of DVT9. However, this study carries a risk of creating a DVT..
  2. Doppler US has almost as high positive and negative predictive values as venography. Because its negative predictive value (99.5%) is even higher when duplex color technology is used, and has become the test of choice for patients with suspected DVT.
  3. Surveillance Doppler US: Screening all high risk patients for VTE with US upon admission to inpatient rehabilitation is generally not considered costeffective,4 although some limited evidence exists showing that some asymptomatic DVTs may be found.5

Pulmonary Embolism

  1. Pulmonary angiography is the gold standard for diagnosing PE but, similar to venography, it is seldom used clinically, since noninvasive testing has nearly matched its sensitivity and specificity.
  2. Ventilation-perfusion (V/Q) scintographic studies can have diagnostically definitive results in most patients, but a subset of patients will have intermediate probability. This test may also be useful for patients challenged to physically fit into a computerized tomography machine.
  3. Spiral computerized tomography (SCT) with contrast is recommended in patients who do not have a contraindication to this test. The most common contraindications being renal insufficiency, use of metformin, or contrast dye allergy.

Professional Issues

Undiagnosed PE is one of the most common reasons for malpractice suits against physiatrists.

3. REHABILITATION MANAGEMENT AND TREATMENTS

Available or current treatment guidelines

  1. The American College of Chest Physicians (ACCP) has established the most widely used guidelines.2 The guides are individualized to diagnosis or predict risk of surgical procedure. The most recent update was the 10th edition released in February 2016.  Recommendation for treatment of DVT of the leg or chest is to use a Direct Oral Anticoagulant (DOAC) instead of warfarin6. LMWH is recommended over DOAC in the setting of cancer6,8.
  2. Other guidelines exist: Alternative guidelines from the American Academy of Orthopedic Surgery (AAOS) reflect the concern among some orthopedic surgeons about the risk of postoperative hematomas in joint replacement patients who are using low molecular weight heparins (LMWH) for VTE prophylaxis. They focus on hip and knee surgeries. The last guideline release was in 2012.
  3. American College of Physicians (ACP)/American Academy of Family Physician (AAFP) Guidelines:3 These guides recommend the preferential use of LMWH for DVT, and find equal efficacy for the use of LMWH and unfractionated heparin (UFH) for PE. The exceptions are patients with renal insufficiency, who should be treated with UFH, and patients with contraindications to anticoagulation (e.g., active bleeding, thrombocytopenia, hereditary bleeding disorder).
  4. Guidelines for the management of VTE in cancer patients can be found in the American Society of Clinical Oncology (ASCO) guidelines and also the National Comprehensive Cancer Network (NCCN) VTE panel guidelines. Again, LMWH are recommended in cancer patients due to the lower risk of recurrence and mortality compared to UFH and warfarin8.

At different disease stages:

Pre-disease/prevention:

  1. Complex medical patients: In a meta-analysis of hospitalized internal medicine patients, Low Molecular Weight Heparin (LMWH) and Unfractionated Heparin (UFH) [5000 units subcutaneously three times daily] were found equally efficacious in preventing VTE, with similar risks of bleeding.
  2. Neurosurgical patients: A meta-analysis of 18 studies indicated that LMWH could prevent VTE in patients without a contraindication to its use; whereas, intermittent compression devices could also prevent VTE when the contraindication existed. Furthermore, UFH had a higher risk of complications.
  3. Data from brain injury model systems revealed only 56% of centers routinely used anticoagulants prophylactically. The same study reported an incidence of fatal PE of 0.42 per practice year, emphasizing the need for guidelines.5
  4. Spinal cord injuries (SCI): LMWH prophylaxis in SCI patients undergoing acute rehabilitation reduced VTE incidence to 7.9%, compared to 21% using low dose UFH.
  5. Cancer: The NCCN released guidelines in 2007 recommending VTE prophylaxis in all hospitalized cancer patients under active therapy who do not have contraindications to anticoagulation.
  6. Orthopedic patients: Joint replacement or major fracture patients, without a personal history of VTE, may have prophylaxis with mechanical prophylaxis plus one of the following: LMWH, fondaparinux, apixaban, dabigatran, rivaroxaban, low-dose unfractionated, heparin (LDUH), adjusted-dose vitamin K antagonist or aspirin 325 mg twice daily for 10-14 days. LMWH is the preferred treatment. For hip fractures, apixaban, dabigatran, and rivaroxaban are not recommended.2
  7. Sequential compression devices (SCDs) have some effectiveness in preventing VTE when used alone compared with no intervention, and should be used when contraindications to anticoagulation exist, such as patients with bleeding disorders or those with history of acute intracranial bleeding ICDs were substantially less effective than pharmacologic prophylaxis, but had additional benefit when used in combination with anticoagulation. In stroke patients, no benefit to the use of mechanical prophylaxis has been demonstrated. These need to be used > 18 hours per day to have any benefit.
  8. Inferior vena cava filters (IVCFs) can be used to prevent DVT from propagating to a PE in patients with contraindications to anticoagulation. However, there is no demonstrated benefit to using them as a primary prophylaxis. Otherwise, IVC are not recommended for those using anticoagulation6.

New onset/acute

  1. LMWH enables VTE to be treated with less intensive monitoring than intravenous unfractionated heparin (UFH).
  2. Patients for whom anticoagulation is contraindicated can be safely treated with IVCFs. These filters now are removable where long-term use is not needed. It should be remembered that IVCFs do not treat DVT, and indeed may worsen edema and pain; they frequently lead to post-thrombotic syndrome. Their intended use is to prevent the propagation of DVT to PE.
  3. Location of treatment: ACCP and ACP guidelines advocate that most cases of DVT, and some cases of PE, can be safely treated in the outpatient setting, and is preferred. The implication for physiatrists is that most patients with acute DVT, and some with hemodynamically stable PE, can be managed on the rehabilitation unit without transfer to acute care.
  4. Bed rest and compression hose: Traditionally physicians have recommended bed rest and the removal of compression devices for several days after DVT, for fear of propagation to PE. This approach is being challenged: according to a retrospective study in Italy, DVT patients who were immobilized and did not receive compression devices actually had a higher risk of developing PE subsequently. Evidence now shows that mobilization can now begin as early as 4 hours after diagnosis and management of lower extremity DVT.

Subacute/chronic/stable stage

  1. Duration of treatment: A systematic review of VTE management recommends consistently overall treatment of 3 months of treatment over shorter or longer periods (6-24 months) or extended therapy (no stop date) for known risk factors and up to 6 months for unprovoked VTE6.
  2. Compression hose is not recommend for the prevention of post thrombotic syndrome (formerly post-phebitic syndrome) but is acceptable for the management of its symptoms. Progressive ambulation is acceptable6.

Pre-terminal or end of life care 

(N/A)

Special Circumstances.

Other factors affect the choice of initial or long term (3-24 months) anticoagulation such as:

  1. Cancer
  2. frequency
  3. renal disease
  4. coronary artery disease
  5. peptic ulcer disease
  6. compliance
  7. cost
  8. fall risk
  9. recurrence:
    1. Consider increasing the dose of LMWH if already using or switch to LMWH if using Vitamin K antagonists or Direct Thrombin Inhibitors (DTI).

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

  1. Environmental interventions: early mobilization is an important part of primary prevention and decreasing recurrence.
  2. Clinical pearls
    1. Tachycardia and tachypnea need urgent attention.
    2. PE often presents with vague complaints of anxiety.
  3. Performance improvement in practice
    1. Monitor guideline adherence in your inpatient program (MOC 4 available in AAPMR Me site).
    2. Implement order sets for prophylaxis.

4. Cutting edge/emerging and unique concepts and practice

Intravenous warfarin coming to market soon.

Direct Oral Anticoagulants (Factor Xa inhibitors: apixaban, rivaroxaban) and DTIs (darbigatran) are now indicated for VTE as well as atrial fibrillation.

5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE

Gaps in the evidence-based knowledge

Duration of prophylaxis is poorly established for many diagnoses.

Risk/benefits and cost effectiveness of prophylaxis in the disabled population is poorly established.

References

  1. Amin AN, Stemkowski S, Lin J, Yang G. Preventing venous thromboembolism in US hospitals: are surgical patients receiving appropriate prophylaxis? Thromb Haemost. 2008; 99(4):796-797.
  2. Guyatt GH, Akl EA, Crowther M et al. Executive Summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th Ed: American College of Chest Physicians. Chest 2012; 141(2)(Suppl):7S–47S
  3. Snow V, Qaseem A, Barry P, Hornbake ER, Rodnick JE, Tobolic T, et al. Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2007; 146(3):204-210. .
  4. Furlan JC, Fehlings MG. Role of screening tests for deep venous thrombosis in asymptomatic adults with acute spinal cord injury. Spine. 2007; 32(17):1908-1916.
  5. Carlisle MC, Yablon SA, Mysiw WJ, Frohl AB, Lo D, Diaz-Arrostia R. Deep venous thrombosis management following traumatic brain injury: a model systems survey. J Head Trauma Rehabil. 2008; 21(6):483-490.
  6. Kearon et al. Antithrombotic Therapy for VTE Disease. CHEST Guideline and Expert Panel Report. Chest. 2016; 149(2): 315-52
  7. 2010 VTE Guideline. http://www.aaos.org/uploadedFiles/PreProduction/Quality/Guidelines_and _Reviews/guide
  8. Lyman et al. ASCO Guideline: Recommendation for Venous Thromboembolism Prophylaxis and Treatment in Patients with Cancer. Jo of Clinical Oncology. 2007; 25 (34).
  9. Douketis, James and Menaka Pai. Deep Venous Thrombosis (DVT). Up To Date. Aug 16.

Original Version of the Topic

R. Samuel Mayer, MD. Venous Thromboembolism (VTE). 12/27/2012.

Author Disclosure

R. Samuel Mayer, MD
Nothing to Disclose

MD, Mi Ran Shin, MD
Nothing to Disclose

W. Bernard Abrams, MD
Nothing to Disclose

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