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Venous Thromboembolism (VTE)

  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.

    1. 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 birth control pills. 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. inherited coagulopathies( Factor V Leiden deficiency, antithrombin III deficiency, protein S deficiency, dysfibrinogenemia)
    2. 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.
    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)

    Postphlebitic syndrome can arise in a limb after DVT, 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. Postphlebitic 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.

    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 almost always 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; however, in postoperative patients, it is of little benefit because the positive predictive value is low, and false positives are frequent.

    Imaging
    1. DVT
      1. The gold standard for the diagnosis of lower limb DVT is venography; however, it is seldom used clinically outside the research setting.
      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, it has become the optimal test for diagnosing DVT in patients with symptoms.
      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
    2. Pulmonary Embolism
      1. Pulmonary angiography is the gold standard for diagnosing PE but, similarly 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.
      3. Spiral computerized tomography (SCT) is recommended in patients who do not have a contraindication to this test, the primary contraindications being renal insufficiency, use of metformin, or 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.
    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.
    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 (eg, active bleeding, thrombocytopenia, hereditary bleeding disorder).
    At different disease stages
    1. Pre-disease/prevention: 
      1. Complex medical patients: In a meta-analysis of hospitalized internal medicine patients, LMWH and UFH (5000 units subcutaneously three times daily) were found equally efficacious in preventing VTE, with similar risks of bleeding.
      2. Neurosurgical patients
      3. 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.
      4. 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
      5. 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.
      6. Cancer: The National Comprehensive Cancer Center Network released guidelines in 2007 recommending VTE prophylaxis in all hospitalized cancer patients under active therapy who do not have contraindications to anticoagulation.
      7. Orthopedic patients: Joint replacement or major fracture patients may have  prophylaxis with either LMWH or warfarin adjusted to INR of 2-3. Some orthopedists like to follow the AAOS recommendations, which for total knee replacements permit aspirin 325 mg twice daily.
      8. Intermittent compression devices (ICDs) have some effectiveness in preventing VTE when used alone compared with no intervention, and should be used when contraindications to anticoagulation exist.  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.
      9. 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.
    2. 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 postthrombotic syndrome. Their intended use is to prevent the propagation of DVT to PE.     
      3. Location of treatment: In ACP/AAFP guidelines most cases of DVT, and some cases of PE, can be safely treated in the outpatient setting. 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.
    3. Subacute/chronic/stable stage
      1. Duration of treatment: A systematic review of VTE management recommends 3 months of treatment with a vitamin K antagonist (warfarin) for VTE patients with transient risk factors (eg, postoperatively) and 12 months for patients with “unprovoked” VTE or those with ongoing risk (eg, tetraplegia). LMWH was found to be an equally efficacious alternative, especially in cancer patients.
      2. Compression hose and progressive ambulation are the best preventative and treatment methods for the post-phlebitic syndrome.
    4. Pre-terminal or end of life care (N/A)
    Patient & family education
    1. Anticoagulation medications and monitoring
    2. Importance of mobility and compression hose
    3. Diet if on warfarin: need consistent intake of foods high in vitamin K (leafy vegetables).
    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.
      2. Implement order sets for prophylaxis.
  4. Cutting edge/emerging and unique concepts and practice
    Cutting edge concepts and practice
    1. Intravenous warfarin
    2. New vitamin K antagonists to replace warfarin (darbigatran).
  5. Gaps in the evidence-based knowledge
    Gaps in the evidence-based knowledge
    1. Duration of prophylaxis is poorly established for many diagnoses.
    2. Risk/benefits and costeffectiveness 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. Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines. 8th ed. Chest. 2008;133(6)(suppl):381.
    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.
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