Basics
Description
- A constant balance exists between intravascular clot formation and clot dissolution, clot forming when the former overpowers the latter.
- Clot can be superficial (to the fascia) or deep. The latter is called deep vein thrombosis (DVT).
- Pulmonary embolism (PE) and DVT are different ends of the clinical spectrum of the same disease process (venous thromboembolism, VTE).
- DVT can be upper or lower extremity, as well as distal or proximal (to the popliteal vein)
- Incidence is ~2 1st time VTE episodes per 1,000 person yr.
- Prevalence increases with advancing age
- Common in both medical and surgical hospitalized patients
- Diagnosis is more accurate using active surveillance rather than clinical suspicion.
DVT in children is unusual, but when cases do occur, search for an underlying reason for hypercoagulability. Also, upper-extremity DVT is associated with central IV lines in children.
Etiology
- Clot formation/dissolution is an intricately balanced system which can be influenced by many factors which must be considered
- Hypercoagulable states:
- Cancer
- Myeloproliferative disorders
- Nephrotic syndrome
- Sepsis
- Inflammatory conditions:
- Increased estrogen:
- Pregnancy
- Exogenous hormones (OCPs, HRT)
- Antiphospholipid syndrome
- Protein S, C, and antithrombin III deficiencies, factor V Leiden, prothrombin gene mutations, lupus, others
- Stasis:
- Prolonged bed rest
- Immobility (such as from a cast)
- Long plane, car, or train rides
- Neurologic disorders with paralysis
- CHF
- Obesity
- Vascular concerns/damage:
- Trauma
- Surgery
- Anatomic anomalies (May-Thurner syndrome)
- Central lines:
- Especially with upper extremity DVT
- Multifactorial issues:
- Advancing age
- Medications (hydralazine, procainamide, phenothiazines)
- Tobacco use
- Prior DVT or PE
- Genetics:
- Important with respect to some of the risk factors; ask about family history of clotting.
- There is no consensus about which patients with VTE to test for inherited thrombophilias
Pregnancy is a risk factor for DVT, especially in the 3rd trimester up to the 2nd wk postpartum.
Age in and of itself is a risk for DVT (and PE). As with many diseases, the presentation may be atypical in the elderly.
Diagnosis
Signs and Symptoms
- Leg swelling:
- >1 cm difference is usually significant.
- Leg warmth and redness
- Leg pain and tenderness
- Palpable cord
- In superficial thrombophlebitis, a red pipe cleaner-like cord may be visible and palpable.
- Arm swelling, warmth, or tenderness:
- Upper extremity or subclavian vein involved
- Phlegmasia cerulea dolens:
- Cold, tender, swollen, and blue leg (secondary arterial insufficiency, venous gangrene)
- In phlegmasia alba dolens:
- Cold, tender, and white leg (secondary arterial insufficiency)
Essential Workup
- Determination of a patients clinical (pretest) risk is a key step in a workup for DVT.
- A careful history and physical exam, interpreted in the context of the risk-factor profile, is the most important driver of subsequent diagnostic evaluation as individual clinical findings are poorly predictive in isolation.
- Consider further evaluation for underlying malignancy when appropriate as VTE may be initial manifestation.
Diagnosis Tests & Interpretation
Lab
D-dimer testing:
- D-dimer, a byproduct of endogenous clot formation, is becoming increasingly used in evaluation of patients for DVT and PE.
- Only useful when the result is negative (to exclude DVT). Positive D-dimer does not make the diagnosis; it only mandates further testing.
- Methods of measuring D-dimer levels:
- Latex agglutination (1st-generation tests) and microlatex agglutination (2nd-generation) are generally insufficient.
- Whole-blood latex agglutination (SimpliRED) is valuable if negative in low probability patients (using Wells criteria).
- Enzyme-linked immunosorbent assay (ELISA) testing gives a quantitative result and has been validated in large clinical studies in ED patients; particularly when combined with assessment of pretest probability
Imaging
- Contrast venography:
- Once the imaging test of choice; now rarely performed because it is invasive, expensive, and has complications.
- Involves injection of contrast medium into a leg vein, which can cause thrombophlebitis in patients undergoing the procedure; as well as contrast dye reactions and possible renal damage
- Compression US:
- Standard 1st-line diagnostic test
- Venous study. Normal veins compress; those with clots do not.
- Color Doppler can be useful for identifying the vein but does not add substantially to accuracy. Duplex scanning refers to the combination of compression B-mode US and color Doppler.
- Has a sensitivity in the high 90% range
- Should be repeated (or followed up with contrast venography) in high-risk patients with negative US.
- Other tests include radionuclide venography and impedance plethysmography; however, these are not commonly used in clinical practice
Differential Diagnosis
- Superficial thrombophlebitis
- Cellulitis
- Torn muscle and/or ligaments (including plantaris and gastrocnemius tears)
- Ruptured Baker cyst
- (Bilateral) edema secondary to heart, liver, or kidney disease
- Venous valvular insufficiency
- Drug-induced edema (calcium channel blockers)
- (Unilateral) edema from abdominal mass (gravid uterus or tumor) or lymphedema
- Postphlebitic syndrome (from prior thrombophlebitis)
Treatment
Initial Stabilization/Therapy
In cases of phlegmasia cerulean, or alba dolens:
- IV access
- Supplemental oxygen
- Surgical or vascular consultation
Ed Treatment/Procedures
- Systemic anticoagulation:
- In patients without contraindications as PE will occur in ~50% of untreated DVT
- Use either unfractionated heparin or low-molecular-weight heparin (LMWH), fondaparinux or adjusted dose subcutaneous heparin
- Carefully selected patients can be primarily treated with as outpatients
- Warfarin:
- Started shortly after a heparin has been administered
- Not before heparin because of the theoretic risk for inducing a transient hypercoagulable state
- Insufficient evidence exists to safely recommend other oral anticoagulants (e.g., dabigatran, rivaroxaban, apixaban)
- Vena cava filters:
- Two main indications:
- Contraindications to systemic anticoagulation
- New thromboembolic event while on adequate anticoagulation
- Vena cava filters can be placed transcutaneously, usually by a vascular or trauma surgeon or radiologist.
- Empiric filter placement may be useful in certain settings:
- Ongoing risk such as cancer, polytrauma.
- Risk for a recurrent PE could be fatal because of poor cardiopulmonary reserve or a recent PE.
- Randomized data suggest that filter placement is no more effective than anticoagulation.
- Filters can also be deployed in the superior vena cava in the setting of upper-extremity DVT.
- Thrombolysis:
- Rarely indicated
- Roughly a 3-fold increase in bleeding complications
- Catheter-administered lytic therapy is used more commonly in upper-extremity DVT
- Thrombectomy (surgical or percutaneous):
- Occasionally recommended for patients with extensive disease
- Consult a vascular surgeon
- Septic thrombophlebitis:
- Surgical excision of the vein or IV antibiotics
Medication
- Maintain treatment with IV or SQ therapy until INR has been therapeutic for 2 consecutive days.
- Warfarin: 5 mg/d starting dose with a prothrombin time being checked on the 3rd day.
- Heparin (unfractionated): 80 U/kg bolus followed by an 18 U/kg/h drip, with the activated partial thromboplastin time (aPTT) titrated 1.5-2.5 times normal.
- LWMH (enoxaparin): 1 mg/kg SC BID for outpatients (alternative: 1.5 mg/kg SCQD).
- Tinzaparin: 175 U/kg/d SC.
- Dosing regimens are based on total body weight; however, in obese patients alternative dosing should be considered.
- Treatment usually maintained for at least 3 mo, total length is individualized.
Follow-Up
Disposition
Admission Criteria
- Patients with DVT unable to receive LMWH as an outpatient or poor follow-up
- Patients with concomitant PE or other serious diseases (i.e., renal failure)
- Patients thought to be at especially high bleeding risk
- Patients with phlegmasia
Discharge Criteria
- Outpatient treatment with an LMWH:
- No serious concomitant disease that requires hospitalization.
- Patient has means of communication and transportation to return to the hospital if needed, as well as appropriate follow-up.
- Patient (or family member) is willing and able to inject the medication.
- aPTT does not need to be checked.
- Heparin-induced thrombocytopenia is less common with the LMWH but still occurs.
- Patients with superficial or distal thrombophlebitis can be discharged with close follow-up.
Issues for Referral
- Consult vascular surgery if there is any question about arterial insufficiency.
- Consider need for inferior vena cava filter in patients who have contraindications to full anticoagulation or form new clots on adequate anticoagulation.
When the clinical suspicion is high but the US is negative, remember to advise the patient to follow-up with his or her primary care physician, and to have a follow-up US in ~1 wk.
Followup Recommendations
Outpatient treatment with an LMWH:
- Patient needs hematocrit, platelet count, and INR checked in 2-3 days.
- INR needs to be checked at about day 3.
Pearls and Pitfalls
- Do not use a negative Homans sign to exclude the diagnosis of DVT.
- Use some measure (whether clinical gestalt or a formal scoring system such as the Wells score) to determine pretest probability for DVT.
- In high pretest probability patients, do not rely on D-dimer testing; instead, perform venous imaging, generally compression US.
- In medium-risk patients with a negative D-dimer or negative US, arrange or recommend a repeat study in 1 wk.
Additional Reading
- Cushman M, Tsai AW, White RH, et al. Deep vein thrombosis and pulmonary embolism in two cohorts: The longitudinal investigation of thromboembolism etiology. Am J Med. 2004;117:19-25.
- Goodacre S, Sutton AJ, Sampson FC. Meta-analysis: The value of clinical assessment in the diagnosis of deep vein thrombosis. Ann Intern Med. 2005;143:129-139.
- Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e419S-494S.
- Kyrle PA, Eichinger S. Deep vein thrombosis. Lancet. 2005;365(9465):1163-1174.
- Lawall H, Hoffmanns W, Hoffmanns P, et al. Prevalence of deep vein thrombosis (DVT) in non-surgical patients at hospital admission. Thromb Haemost. 2007;98(4):765-770.
- Tracy JA, Edlow JA. Ultrasound diagnosis of deep venous thrombosis. Emerg Med Clin North Am. 2004;22:775-796.
Codes
ICD9
- 453.40 Acute venous embolism and thrombosis of unspecified deep vessels of lower extremity
- 453.41 Acute venous embolism and thrombosis of deep vessels of proximal lower extremity
- 453.82 Acute venous embolism and thrombosis of deep veins of upper extremity
- 453.42 Acute venous embolism and thrombosis of deep vessels of distal lower extremity
- 453.4 Acute venous embolism and thrombosis of deep vessels of lower extremity
ICD10
- I82.409 Acute embolism and thrombosis of unspecified deep veins of unspecified lower extremity
- I82.609 Acute embolism and thombos unsp vn unsp upper extremity
- I82.4Y9 Acute emblsm and thombos unsp deep vn unsp prox low extrm
- I82.4Z9 Acute emblsm and thombos unsp deep vn unsp distal low extrm
- I82.401 Acute embolism and thombos unsp deep veins of r low extrem
- I82.402 Acute embolism and thombos unsp deep veins of l low extrem
- I82.403 Acute embolism and thombos unsp deep veins of low extrm, bi
- I82.40 Acute embolism and thombos unsp deep veins of low extrm
- I82.4Y1 Ac emblsm and thombos unsp deep veins of r prox low extrm
- I82.4Y2 Ac emblsm and thombos unsp deep veins of left prox low extrm
- I82.4Y3 Ac emblsm and thombos unsp deep veins of prox low extrm, bi
- I82.4Y Acute emblsm and thombos unsp deep veins of prox low extrm
- I82.4Z1 Ac emblsm and thombos unsp deep veins of r dist low extrm
- I82.4Z2 Ac emblsm and thombos unsp deep veins of left dist low extrm
- I82.4Z3 Ac emblsm and thombos unsp deep veins of dist low extrm, bi
- I82.4Z Acute emblsm and thombos unsp deep veins of distal low extrm
SNOMED
- 128053003 Deep venous thrombosis (disorder)
- 404223003 deep venous thrombosis of lower extremity (disorder)
- 128054009 Deep venous thrombosis of upper extremity (disorder)
- 444325005 Deep vein thrombosis of bilateral lower extremities
- 427775006 Deep venous thrombosis of profunda femoris vein (disorder)
- 438785004 Deep venous thrombosis of tibial vein
- 443210003 Deep venous thrombosis of peroneal vein