by Elif Dilek Cakal
Case Presentation
An 85-year-old woman, with a history of congestive heart failure, presented with right leg pain and swelling of 2 days’ duration. She had been hospitalized for pneumonia one week earlier. Her vitals on arrival were: Blood Pressure: 138/84 mmHg, Pulse Rate: 65 beats per minute, Respiratory Rate: 14 breaths per minute, Body Temperature: 37°C (98.6°F), Oxygen Saturation: 96%. On examination, her right calf was reddish, tender, edematous and 4 cm greater in circumference than the left when measured 10 cm below the tibial tuberosity. Her Wells’ Score for deep vein thrombosis (DVT) was 4 and suggested high-risk for DVT. Compression ultrasonography showed a thrombus in the popliteal vein. Enoxaparin (1 mg/kg, twice a day, SC) was started. No signs and symptoms of pulmonary embolism were observed. The patient was referred to a cardiovascular surgeon as an outpatient after discussion and confirmed understanding of discharge instructions.
Introduction
The annual incidence of DVT is 92 cases per 100000 persons. The rate steadily advances with increased age (32/100000 if age < 55 years, 282/100000 if age 65-74 years, 555/100000 if age >74). While 90% of DVT occurs in lower extremities, 10% of DVT occurs in upper extremities. Up to more than 40% of patients with lower extremity DVT have concomitant pulmonary embolism (PE), whether they may have related complaints or not.
Critical Bedside Actions and General Approach
DVT is mostly a relatively benign disease; nevertheless, it may cause severe symptoms and limb- or life-threatening presentations. Emergency physician (EP) must check for signs of adverse outcome. Therefore patients should be evaluated for airway, breathing, circulation sequence and EPs try to understand possible immediate life-threatening problems. Concentrating on the patient focal complaint should be followed after the initial evaluation. Check vitals for instability and fever. Check for arterial pulses and signs of acute arterial thrombosis immediately in the case of every limp pain. Also, an extremely or entirely swollen limb indicates total or near total obstruction at a more proximal level. Increased compartment pressure may potentially disrupt the arterial flow. Diagnosing DVT in the emergency department (ED) is crucial. A timely started treatment may prevent the subsequent pulmonary embolism (PE) and chronic morbidities like chronic venous stasis and recurrent clots.
Some patients may ignore PE-related mild symptoms, or they may give priority to DVT-related ones. EP must concentrate on subtle PE-related sign and symptoms. In the spectrum of DVT, phlegmasia alba dolens, phlegmasia cerulea dolens and venous gangrene are vascular emergencies. They should be managed surgically, by endovascular interventions or thrombolytic treatment, in a time-sensitive manner. Upper extremity DVT has its own risk factors and consequences. It should be managed in its own context.
Differential Diagnosis
Table 1 summarizes differential diagnoses of DVT. Unilateral and bilateral leg swelling and pain are two categories in order to differentiate the various causes. Bilateral leg swelling is more likely a clue for congestive heart failure, liver or renal failure, inferior vena cava compression than the bilateral DVT. However, patients symptoms and findings should be considered for ruling out these causes.
Differential Diagnoses of DVT.
| Unilateral Leg Swelling and/or Pain | Bilateral Leg Swelling and/or Pain |
|---|---|
| Abscess/Necrotizing Fasciitis Arterial insufficiency Baker cyst rupture/inflammation Cellulitis Claudication Compartment Syndrome DVT Erythema Nodosum Hematoma Lymphangitis Lymphedema Musculoskeletal trauma Myositis Polyarteritis Nodosa Postphlebitic Syndrome Superficial thrombophlebitis Tendinitis/Achilles tendinitis Varicose Veins | Bilateral DVT Congestive heart Failure Inferior vena cava compression Liver Failure Renal Failure |
History and Physical Examination Hints
- Neither medical history nor physical examination is specific to DVT. Clinical presentation may range from nearly asymptomatic to severely symptomatic or limb- or life-threatening.
- As a general rule, unilateral limb pain and swelling imply DVT.
- Lower extremity DVT
- Unilateral leg pain and swelling are indicators of lower extremity DVT. Some patients may define fullness or cramping in the posterior aspect of the lower extremity. Bilateral symptoms are more likely in the course of other diseases. However, simultaneous bilateral DVT or obstruction of the inferior vena cava may cause bilateral symptoms.
- Edema, redness, and tenderness are possible signs. None is specific. Homans sign refers to calf pain elicited by passive dorsiflexion of the ankle. It is insensitive and nonspecific, therefore, useless.
- Because only history and examination are indeterminate, risk factors for DVT are essential to predict clinical probability. Known risk factors for DVT are as follows:
- Previous history of PE or DVT
- Recent Trauma or surgery
- Cancer
- Central or long-term vascular catheter
- Age
- Oral contraceptives
- Hormone replacement therapy
- Pregnancy
- Immobility
- Factor V Leiden mutation
- Antiphospholipid antibody syndrome
- Prothrombin mutation
- Hyperhomocysteinemia
- Deficient levels of clotting factors
- Congestive heart failure
- Chronic obstructive pulmonary disease
- Air travel
- Obesity
- Phlegmasia alba dolens and phlegmasia cerulea dolens are vascular surgical emergencies. The features of these conditions are summarized in Table 2.
Surgical Emergencies Secondary To DVT
| Phlegmasia alba dolens | Phlegmasia cerulea dolens | |
|---|---|---|
| Appearance | Pale, cool, edematous (An example is available at https://www.thrombosisadviser.com/html/images/library/vte/deep-vein-thrombosis-right-leg-HR.jpg) | Cyanosed, edematous, purple ecchymosis (An example is available at http://circ.ahajournals.org/content/125/8/1056/F1.expansion.html) |
| Distal pulses | Poor/Absent | Hard to palpate because of edema Absent if advanced |
| Pain | Positive | Positive |
| Mechanism | Massive iliofemoral venous thrombosis and associated arterial spasm | Arterial flow disruption due to venous congestion and increased tissue pressure |
| Thrombus location | In major veins (collaterals are generally spared) | In major veins and collaterals |
| Advances to | Phlegmasia cerulea dolens | Venous gangrene |
Please read following references for more information (http://lifeinthefastlane.com accessed at 10.05.2016, https://www.thrombosisadviser.com accessed at 10.05.2016, and Mumoli N, Invernizzi C, Luschi R, Carmignani G, Camaiti A, Cei M. Phlegmasia Cerulea Dolens. Circulation. 2012; 125: 1056-1057.)
- Upper extremity DVT:
- Upper extremity DVT is infrequent and accounts for approximately 10% of all DVTs. Its prevalence is increasing due to indwelling central catheters.
- Primary Upper extremity DVT is rare. A well-known form of primary upper extremity DVT is effort-related thrombosis named Paget-Schroetter syndrome. Paget-Schroetter syndrome generally occurs in otherwise healthy young men, after vigorous arm exercise or repetitive overhead activities. Patients with effort-related upper extremity DVT suggests an underlying venous thoracic outlet syndrome. In the absence of an obvious risk factor or underlying venous thoracic outlet syndrome, it is called idiopathic DVT.
- Catheter-associated DVT is the predominant secondary upper extremity DVT. Indwelling central venous lines, port systems and pacemaker or defibrillator are leading predisposing factors in descending order. Cancer, surgery, trauma, immobilization, pregnancy, oral contraceptive use and the ovarian hyperstimulation syndrome are the other predisposing factors for secondary upper extremity DVT.
- Severe upper extremity DVT may result in superior vena cava syndrome.
Emergency Diagnostics Tests and Interpretation
- Approximately 90% of DVTs occur in lower extremities. Determination of pretest probability (PTP), D-dimer testing and bedside compression ultrasound are the milestones of management in ED.
- Wells’ Criteria for DVT (link) stratifies patients according to their DVT risk. Scores ≥2 qualify a patient as “High Risk.”
- A diagnostic algorithm is shown here (accessed at 10.05.2016)
- D-dimer is useful for its negative predictive value. When negative, it rules out DVT in the low-risk group. It does not confirm DVT when positive.
- Many ultrasound protocols for DVT are available. Related ultrasound videocasts can be found here (accessed at 10.05.2016)
- Upper-extremity DVT is diagnosed by Doppler ultrasonography.
A tutorial about diagnosing DVT with US.
Normal and Abnormal US findings for DVT
Emergency Treatment Options
- The mainstay of medical therapy in ED is anticoagulation.
- Possible anticoagulation options are summarized in Table 3.
Medication For Anticoagulation in DVT.
| Class of Agent | Dose | Comments |
|---|---|---|
| Unfractionated heparin | 80 U/kg IV bolus, then 18 U/kg/h IV infusion (Dose adjustment based on APTT) | Consider in inpatient therapy and in severe renal failure |
| Low Molecular Weight Heparins | ||
| Dalteparin | 100 IU/kg, twice a day, SC 200 IU/kg, once a day, SC | A standard treatment for DVT, preferred in outpatients as a first line therapy if not contraindicated |
| Enoxaparin | 1 mg/kg, twice a day, SC 1.5 mg/kg, once a day, SC | A standard treatment for DVT, preferred in outpatients as a first line therapy if not contraindicated |
| Tinzaparin | 175 IU/kg, once a day, SC | A standard treatment for DVT, preferred in outpatients as a first line therapy if not contraindicated |
| Factor Xa inhibitors | ||
| Fondaparinux | < 50 kg - 5 mg, once a day, SC 50-100 kg - 7.5 mg, once a day, SC > 100 kg - 10 mg, once a day, SC | Do not use in renal failure |
- The indications for more advanced therapies like catheter-directed thrombolysis, percutaneous mechanical thrombectomy, conventional surgery or systemic thrombolysis are as follows:
- Phlegmasia cerulea dolens
- Inferior vena cava thrombosis
- Subacute and chronic iliofemoral DVT
- Acute iliofemoral or femoropopliteal DVT
- Though all are useful, endovascular interventions are preferred over more invasive interventions in capable centers so as to minimize the consequent risks. (Bleeding or perioperative complications, etc.)
- The pain medication is advised for patients who are suffering from severe pain.
Pediatric, Geriatric, Pregnant Patient and Other Considerations
Pediatric Considerations
DVT is infrequent in children and almost always associated with risk factors. Central venous catheter-associated upper extremity DVT is relatively common in children. LMWH is the mainstay of the therapy.
- Enoxaparin:
- <2 months: 1.5 mg/kg/dose SC, twice a day
- >2 months: 1.0 mg/kg/dose SC, twice a day
Geriatric Considerations
DVT management does not alter in the elderly. Frequency and severity of DVT increase. Anticoagulation complications are more frequent than younger counterparts. Concomitant diseases and possible drug interactions complicate the management.
Pregnant Patients
DVT management does not alter in pregnant. Pregnant women are susceptible to DVT. LMWHs are the drug of choice during pregnancy. All pregnant patients with DVT should be admitted to hospital.
Patients With Isolated Calf Vein Thrombosis
The need for treatment is controversial.
Disposition Decisions
Admission Criteria
Most patients with DVT can be treated as outpatients. EP can decide the patients that need admission based on four questions (link).
- Does the patient have massive DVT?
- Does the patient have symptomatic pulmonary embolism?
- Is the patient at high risk for anticoagulant-related bleeding?
- Does the patient have major comorbidity or other factors that warrant in-hospital care
- One or more positive answers should lead EP to admission.
Consider admission if any is present:
- Suspected or proven concomitant PE
- Significant cardiovascular or pulmonary comorbidity
- Iliofemoral DVT
- Contraindications to anticoagulation
- Familial or inherited disorder of coagulation
- Familial bleeding disorder
- Pregnancy
- Morbid obesity (>150 kg)
- Renal failure (creatinine >2 mg/dL)
- Unavailable or unable to arrange close follow-up care
- Unable to follow instructions
- Homeless patient
- No contact telephone
- Geographic location (too far from the hospital)
- Patient/family resistant to outpatient therapy
Discharge Criteria
All patients lacking admission criteria may be treated as outpatients after a confirmed understanding of discharge instructions. Several discharge instructions are available online.
Referral: Patients must be referred to cardiovascular surgeons.
References and Further Reading
- Spencer FA, Lessard D, Emery C, et al. Venous thromboembolism in the outpatient setting. Arch Intern Med. 2007;167:1471-1475.
- Engelberger RP, Kucher N. Management of Deep Vein Thrombosis of the Upper Extremity. Circulation. 2012; 126: 768-773.
- Moser KM, Fedullo PF, LitteJohn JK, Crawford R. Frequent asymptomatic pulmonary embolism in patients with deep venous thrombosis. JAMA. 1994;271(3):223–225.
- Meignan M, Rosso J, Gauthier H, et al. Systematic lung scans reveal a high frequency of silent pulmonary embolism in patients with proximal deep venous thrombosis. Arch Intern Med. 2000;160(2):159–164.
- Courtney DM. Venous Thrombosis. In: Adams JG, Barton ED, Collings JL, DeBlieux PMC, Gisondi MS, Nadel ES, editors. Emergency Medicine: Clinical Essentials. Philedephia: Elsevier; 2013:611-617.
- Ferri FF. Deep Vein Thrombosis. In: Ferri FF, et al, editors. Ferri’s Clinical Advisor 2015: 5 Books In 1. Philedephia: Elsevier; 2015:348-350.
- http://lifeinthefastlane.com accessed at 10.05.2016
- https://www.thrombosisadviser.com accessed at 10.05.2016
- Mumoli N, Invernizzi C, Luschi R, Carmignani G, Camaiti A, Cei M. Phlegmasia Cerulea Dolens. Circulation. 2012; 125: 1056-1057.
- Joffe HV, Goldhaber SZ. Upper-Extremity Deep Vein Thrombosis. Circulation. 2002; 106: 1874-1880.
- http://emedicine.medscape.com accessed at 10.05.2016
- https://www.acep.org/Clinical—Practice-Management/Focus-On–Emergency-Ultrasound-For-Deep-Vein-Thrombosis/ accessed at 10.05.2016
- http://www.mdcalc.com accessed at 10.05.2016
14. Wells PS, Anderson DR, Rodger M, et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med. 2003:25;349(13):1227-35. - http://www.uwhealth.org/files/uwhealth/docs/pdf2/anticoag_dus_eval_algo.pdf accessed at 10.05.2016
- Lewiss RE, Kaban NL, Saul T. Point-of-Care Ultrasound for a Deep Venous Thrombosis. Glob Heart. 2013;8:329-333.
- http://www.sonosite.com accessed at 10.05.2016
- Kucher N. Clinical practice: deep-vein thrombosis of the upper extremities. N Engl J Med. 2011; 364: 861– 869
- Righini M: Is it worth diagnosing and treating distal deep vein thrombosis? No. J Thromb Haemost. 5 (Suppl 1):55-59 2007
- Schellong SM: Distal DVT: worth diagnosing? Yes. J Thromb Haemost. 5 (Suppl 1):51-54 2007
- Douketis JD. Treatment of deep vein thrombosis: What factors determine appropriate treatment? Can Fam Physician. 2005: 10; 51(2): 217–223.
- http://www.summitmedicalgroup.com/library/adult_care/dvt_dc/) accessed at 10.05.2016)
Link To More Information
- A discussion on the hospitalization of the patients (http://www.aafp.org/afp/2005/1101/p1845.html accessed at 10.05.2016)
- A discussion on Phlegmasia alba dolens and phlegmasia cerulea dolens (https://www.youtube.com/watch?v=Jea_um6Syv8 accessed at 10.05..2016)
- For ultrasound and ct images (http://radiopaedia.org/articles/deep-vein-thrombosis 10.05.2016)