A Closer Look At Deep Vein Thrombosis

By Allan B. Grossman, DPM and Matt Sowa, DPM

   Venous thromboembolism (VTE) or deep vein thrombosis (DVT) is a common medical condition associated with considerable morbidity and mortality. Undiagnosed and untreated VTE can put patients at an unacceptable risk for a pulmonary embolism, which can be fatal. Thromboemboli account for 600,000 new cases, 300,000 admissions and approximately 100,000 deaths a year. Given that VTE has a recurrence rate of approximately 30 percent, early diagnosis and treatment are imperative.    In order to understand the risk factors of deep vein thrombosis (DVT), one must first appreciate Virchow’s triad. He noted there is a triad of hypercoagulability, venous stasis and endothelial damage with DVT. Clinical risk factors for DVT include immobility from surgery, prolonged automobile rides or airplane flights, age, pregnancy (usually in the third trimester or immediately following delivery), oral contraceptives and obesity. Endothelial damage is caused by injuries or leg trauma, hypoxia and infection.    Additional risk factors for DVT include inherited clotting disorders (which include factor V and prothrombin gene mutations), previous DVTs, varicose veins, inflammatory diseases, cancer and smoking.

How To Differentiate Between DVT And Other Conditions

   The differential diagnosis of DVT includes lymphedema, cellulitis/infection, compartment syndrome, popliteal cyst rupture, congestive heart failure, venous insufficiency and arterial occlusive disease.    Patients with cellulitis or infection can present with edema, erythema, pain and a low-grade fever, symptoms that are shared by those who may have DVT. One can differentiate between these conditions by obtaining a complete blood count (CBC) and differential, sed rate and blood cultures. Keep in mind that patients who have an infection will also have more cardinal signs such as chills, sweats, a high-grade fever, nausea or vomiting.    When it comes to compartment syndrome, patients who have this condition will have out of proportion pain, parasthesias, absent pulses and swelling. One can make this diagnosis by checking the compartment pressures of the foot and leg. Compartment pressures greater than 30 mm Hg are indicative of compartment syndrome.    A popliteal or Baker’s cyst lies in the head of the gastrocnemius muscle belly. When these cysts rupture, the leg swells and becomes painful, and clinicians will note a positive Homan’s sign. The clinical signs of DVT may include unilateral edema, pain, color and temperature changes, a positive Homan’s sign and a low-grade fever. One can confirm the presence of a popliteal or Baker’s cyst via radiographs, ultrasound or magnetic resonance imaging. Clinicians can differentiate between the cyst and DVT by obtaining a CBC and differential, blood cultures and/or sed rate.    Arterial vascular disease may be acute or chronic. Patients with acute arterial disease present with asymmetric symptoms such as absent pulses, severe pain, less movement of the extremity and a cold, pale limb, but little edema. Those who have chronic arterial disease can present with skin and hair atrophy, ulcers or intermittent claudication. Acute venous insufficiency has symptoms that are asymmetric with moderate edema, deep muscle pain and normal pulses. The symptoms get worse at the end of the day and improve with elevation.    Lymphedema can appear to have similar clinical symptoms to DVT, but usually starts out as soft and pitting edema. It is usually bilateral, unlike DVT, which is usually unilateral. Congestive heart failure can also cause pitting edema in the lower extremity.

Measuring DVT And Recognizing Potential Sequelae

   There is a multitude of diagnostic tests to measure DVT. The most common test is the venous duplex ultrasound, which is accurate, noninvasive and cost effective. It is 95 percent specific, but only 75 percent sensitive. Be aware that the duplex scan cannot differentiate non-compressibility of an old DVT and an acute DVT. While venography is sometimes considered the gold standard, it is painful, invasive and mostly used when there is an unclear ultrasound. Additional tests include magnetic resonance imaging, which has more of an indication for proximal DVT, and impedance plethysmography.    Sequela of DVT include recurrent DVT, emboli and post-thrombotic syndrome. Emboli form when a piece of thrombus breaks off and lodges in the pulmonary vasculature. This damages the valves in the vein so the blood pools into the lower leg instead of flowing upward. Post-thrombotic syndrome occurs in 25 percent of DVT cases. It is most common in the posterior tibial vein and can cause edema, pain, hyperpigmentation and leg ulcers.    The biggest complication of DVT is a pulmonary embolism. Symptoms of a pulmonary embolism include difficulty with breathing/shortness of breath, chest pain, syncope and a change in mental status. One can diagnose a pulmonary embolism via a ventilation perfusion scan or a spiral CT.

A Primer On Anticoagulation Therapy For DVT

   Treatment of DVT includes physical measures, prophylaxis, anticoagulation therapy, catheter-directed thrombolysis and thrombolytics. Physical measures include bed rest, anti-embolytic position, moist warm heat, analgesics, diet, exercise and hydration. Lowering saturated fats in one’s diet is important for decreasing cholesterol levels in the blood. Increased cholesterol can lead to plaque formation. Anticoagulation therapy prevents the onset of future clots, but does not dissolve the clots that have already formed. Thrombolytic medications include streptokinase and urokinase.    Most advances in the treatment and prophylaxis of DVT have been with anticoagulation therapy. Retrospectively, the first heparin trial for acute thromboemboli was done in 1960. Warfarin and other anticoagulant medications slow down the formation of clots by lowering clotting factors in the blood.    Standard unfractionated heparin (UH) is a mixture of polysaccharide chains with a mean molecular weight of 15,000 daltons. A random pentasaccharide sequence in heparin binds to the natural anticoagulant protein called antithrombin. This binding leads to an inactivation of two coagulation enzymes, thrombin and factor Xa.1 This promotes the release of tissue factor pathway inhibitor from the endothelial cells.    The traditional treatment for DVT is UH for five to seven days. In addition, one should initiate oral anticoagulant therapy with warfarin between 2 and 10 mg PO once a day for three to four days and then adjust the dose according to the PT and INR. Then continue the treatment for at least three months. Be aware that administering UH requires hospitalization for intravenous infusion in association with careful partial thromboplastin time monitoring.    In the 1970s, researchers noted that low molecular weight heparin (LMWH) had similar antithrombotic properties as UH, but not the same anticoagulant effect. It was not until 1985 that LMWH underwent trials with a positive outlook. The Food and Drug Administration approved LMWH in 1998 for the treatment of thromboemboli in inpatient and outpatient settings.    LMWH is made of fragments of UH produced by alkaline depolymerization and benzylation with a mean molecular weight of 4,500 daltons. This is much less than the 15,000 daltons of UH. LMWH also activates antithrombin, but less than half of the pentasaccharide chains are long enough to bind to both antithrombin and thrombin. This allows increased activity against factor Xa. It also releases tissue factor pathway inhibitors from endothelial cells. The bioavailability for low doses of UH is only 30 percent. The bioavailability of LMWH is 90 percent. At higher doses, the bioavailability of the two seems to equalize. Examples of LMWH are enoxaparin, tinzaparin, ardeparin and dalteparin.    Patients with LMWH have a recurrence rate of 1.5 percent at 10 days versus a 10.4 percent recurrence rate with UH.2 One of the most dramatic differences between both is the hospital stay. The mean length of stay with LMWH was 1.1 days versus 6.5 days with UH. Almost half of the patients were treated on an outpatient basis.

A Closer Look At Enoxaparin

   Enoxaparin is the LMWH medication I use most frequently for patients with DVT. Some of the advantages of enoxaparin are once-a-day or twice-a-day dosing subcutaneously. The indications for enoxaparin are DVT, non-Q wave myocardial infarctions and unstable angina. Most patients do not need monitoring or dose adjustments unless they are pregnant, morbidly obese or in renal failure.    Some contraindications to enoxaparin are hypersensitivity to heparin and pork products, and thrombocytopenia. One should be careful using this drug for patients with recent GI ulcerations, diabetic retinopathy, epidural/spinal anesthesia, mechanical prosthetic heart valves, pregnancy and renal failure with a creatinine clearance of less than 30 ml/min. Due to the fact that the drug is almost exclusively excreted by the kidney, one must ensure appropriate patient selection.    Keep in mind that patients with cancer and those who are pregnant have less osteoclast activation and bone density loss. A small prospective study of UH-induced osteoporosis in pregnancy showed UH adversely affected bone density in nearly a third of the patients receiving the drug.    DVT/PE prophylaxis with enoxaparin is 30 mg SC q12h or 40 mg SC QD at a cost of approximately $12 to $18 per day. Baseline lab monitoring should include a CBC, INR and a PTT (at the physician’s discretion). Initiating LMWH preoperatively may be more effective than administering prophylaxis postoperatively, without an increased risk of major bleeding. One would administer LMWH for thromboprophylaxis between two hours preoperatively and six to eight hours postoperatively. The majority of studies and research have shown that administering LMWH is a safe and cost-effective way of treating DVT.

Case Study: When A Patient Presents With Recent Pain And Edema In The Lower Leg

   A 45-year-old female presented with a recent history of pain, tenderness and edema involving the left lower leg. She noted increased pain in the calf with standing and walking, and relief of the pain with rest and leg elevation.    She noticed the onset of the symptoms following a period of cast immobilization. The patient was previously immobilized in order to treat a metatarsal fracture involving the left foot. Otherwise, the patient denied a more recent traumatic episode involving the leg or foot. There was also no history of fever, chills, nausea or vomiting. She also denied symptoms such as dyspnea, syncope, chest pain, tachycardia or hemoptosis that would suggest pulmonary embolism. The patient’s past medical history was significant for type 2 diabetes mellitus, obesity and hypertension.    An exam demonstrated palpable pedal pulses bilaterally and no evidence of sensory deficits or muscle weakness. Further examination revealed an exacerbation of symptoms with extension of the knee and dorsiflexion of the ankle. The calf was positive for edema, erythema, increased warmth and pain.    We admitted the patient to the hospital for further evaluation. Initial treatment included maintaining anti-embolytic position, warm moist heat application and analgesics. A CBC with differential was in normal range and blood cultures were negative. This enabled us to rule out infection.    We also performed a venous ultrasound to determine the presence of DVT and reported a positive result. Prior to instituting anticoagulant therapy, we first determined that the patient had no active intestinal ulcerative disease or known hemorrhagic risk, no history of renal insufficiency and no allergy to porcine products. (Keep in mind that heparin and enoxaparin are derived from pork intestinal mucosa.)    We began a dosing regimen for enoxaparin at 1 mg/kg every 12 hours sc as well as warfarin until the patient achieved adequate anticoagulant levels. The original symptoms eventually abated and the patient was discharged. On subsequent visits to the outpatient clinic, the patient had no evidence of thrombocytopenia, minor or major hemorrhage, or recurrent DVT. Dr. Grossman is a Fellow of the American College of Foot and Ankle Surgeons and a Diplomate of the American Board of Podiatric Surgery and the American Board of Podiatric Orthopedics. Dr. Grossman is a member of the teaching faculty at the Pinnacle Health System and is in private practice at Harrisburg, Pa. Dr. Sowa is in private practice in Harrisburg, Pa.



1. Grossman AB. New Insights on Detecting Deep Vein Thrombosis. Podiatry Today 2001; 14(7):67-72.
2. Deitcher S. Overview of Enoxaparin in the Treatment of Deep Vein Thrombosis. American Journal of Managed Care. Nov 2000.
Additional References
3. Turpie A. Review of Enoxaparin and its clinical applications in Venous and Arterial Thromboembolism. Expert Opinion Pharmacotherapy. 2002; 3(5): 575-598.
4. Spyropoulos A. Management of Acute Proximal Deep Vein Thrombosis. Chest. July, 2002.
5. Litin Scott C, Heit J, Mees K. Use of Low Molecular Weight Heparin in the Treatment of Venous Thromoembolic Disease; Answers to Frequently asked Questions. Mayo clin proc. 1998; 73:545-551.
6. Harvey D. Management of Venous and Cardiovascular Thrombosis: Enoxaparin. Hospital Medicine. Sept, 2000.


Add new comment