Deep Vein Thrombosis is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. Deep Vein Thrombosis is the primary cause of pulmonary embolism. Deep Vein Thrombosis results from condition that impair venous return, lead to endothelial injury or dysfunction, or cause hypercoagulability. Deep Vein Thrombosis may be asymptomatic or cause pain in an extremity. Diagnosis is by history, physical examination, and duplex ultrasonography with d-dimer or other testing as necessary. Treatment is with anticoagulkants. Prognosis is generally good with prompt adequate treatment; common long-term complication includes venous insufficiency with or without postphlebitic syndrome.
I.1 Venous Anatomy
The superficial veins of the lower extremity consist of the greater and the lesser saphenous veins. They contain multiple valves and exhibit significant variability in branching and location. The greater saphenous vein begins anterior to the medial malleolus with the joining of superficial draining veins from the medial aspect of the dorsum of the foot with veins from the medial aspect of the sole. It travels subcutaneously, usually in a straight line on the anteromedial aspect of the lower leg 1 or 2 cm posterior to the tibia, and passes along the medial aspect of the knee. The greater saphenous vein continues in a straight line to the thigh, where it joins the femoral vein 2 to 4 cm lateral to the pubic tubercle and inferior to the inguinal ligament at the fossa ovalis (Fig. 91.1). In the leg, the greater saphenous vein lies adjacent to and sometimes is crossed by the saphenous branch of the femoral nerve, providing cutaneous sensation to the medial aspect of the lower leg.
Fig 1. Anatomy of the lower Vein
The location of the saphenous nerve places it at risk during procedures involving the use or removal of the greater saphenous vein. The junction of the greater saphenous vein with the femoral vein is sometimes missed because the greater saphenous vein may appear to continue proximally if the superficial inferior epigastric vein or the superficial circumflex iliac vein joins the saphenous vein vertically and is large. The superficial external pudendal vein joins the saphenous vein medially, although the arrangement of this branch and other superficial saphenous venous tributaries is not constant. Usually, there are four to five branches off of the saphenous vein at this location. The saphenous vein receives a variable number of tributaries draining the posteromedial and anterolateral aspects of the leg. The medial and lateral greater saphenous branches may be large and can be confused with the main greater saphenous trunk. The greater saphenous vein may be duplicated and exist as two separate trunks that join to form a single vein at its origin and termination. This occurs in as many as 5% to 10% of patients. The lesser saphenous vein arises behind the lateral malleolus, from the confluence of veins draining the lateral aspect of the foot. It curves toward the midline of the posterior calf and then ascends in a straight line vertically to join the popliteal vein behind the knee near the head of the gastrocnemius muscle, although it has been demonstrated to terminate above the level of the knee crease in 7% to 8% of cases (1). The lesser saphenous vein lies in the subcutaneous tissues just below the skin. It may continue upward in the posterior region of the thigh and connect with tributaries of the greater saphenous vein.
The greater and lesser saphenous veins are joined in the foot by a superficial dorsal venous arch. The deep veins of the sole of the foot consist of lateral and medial plantar veins. They are joined through communicating veins to a cutaneous arch and come together to form the posterior tibial vein. Multiple communicating veins connect the superficial to the deep veins in the foot. The deep veins of the lower leg consist of venae comitantes that accompany the anterior tibial, posterior tibial, and peroneal arteries. Each of the deep veins consists of two or three venae comitantes adjacent to the artery with multiple connections that cross and surround the artery. These connecting veins make surgical exposure of the tibial arteries difficult. The anterior tibial venous drainage arises from the dorsum of the foot and lies in the anterior compartment of the calf next to the interosseous membrane. The posterior tibial veins, which drain the superficial and deep plantar veins, are inferior to the medial malleolus and follow the course of the posterior tibial artery. The peroneal veins lie directly behind and medial to the fibula and ascend along the peroneal artery. These deep veins of the calf have frequent interconnections. The soleal muscle sinusoids are without valves and are referred to as venous lakes. The venous lakes in the calf are a common site of early thrombus formation. They coalesce to join the posterior tibial and peroneal veins. These sinusoids are less apparent in the gastrocnemius muscle, where the veins tend to be linear and exhibit valves. The paired venae comitantes merge to form single trunks that unite at the knee to form the popliteal vein. Sometimes the junction occurs above the knee, resulting in a dual popliteal vein system.
The popliteal vein continues proximally as the superficial femoral vein in proximity to the superficial femoral artery in the adductor canal. It is joined below the inguinal ligament by the deep femoral (profunda) vein and then continues as the common femoral vein. The deep femoral vein frequently connects directly or through tributary veins to the popliteal vein. The anatomy of the popliteal and femoral veins is variable, and duplication is common. The common femoral vein runs medial to the common femoral artery beneath the inguinal ligament and continues as the external iliac vein. The greater saphenous vein usually joins the common femoral vein 2 to 4 cm proximal to the junction of the deep and superficial femoral vein at the fossa ovalis. The external iliac vein is the continuation in the pelvis of the common femoral vein and is joined at the level of the sacroiliac joint medially by the internal iliac vein (hypogastric) draining the pelvis. Both internal iliac veins form a generous collateral network in the pelvis and include connections with the gluteal, obturator, and internal pudendal veins, a large number of unnamed vessels, as well as multiple extrapelvic collateral pathways. The common iliac veins arise from the joining of the external and internal iliac veins. They ascend in a medial direction and join on the right side of the fifth lumbar vertebra and the aorta, forming the inferior vena cava. The right common iliac vein ascends in an almost straight line to the inferior vena cava, whereas the left common iliac vein is more transversely oriented and joins the right iliac vein at an angle of approximately 90 degrees. The left common iliac vein may be compressed between the convexity of the lumbosacral spine posteriorly and the anterior crossing of the right common iliac artery. This variable degree of compression may be seen on venography (Fig. 91.4) and probably accounts for the higher incidence of left-sided deep venous thrombosis (DVT), varicose veins, and varicocele in men. Compression of the left iliac vein may lead to the venous obstructive condition termed the May-Thurner syndrome.
The inferior vena cava ascends from the level of the fifth lumbar vertebra and ends at the right atrium. It lies to the right of the midline and lateral to the aorta and receives a variable number of paired lumbar veins that connect with the vertebral and paravertebral venous plexus. At the level of the L-1 to L-2 interspace, the renal veins join the inferior vena cava. More proximally, the hepatic veins join the inferior vena cava. The embryogenesis of the abdominal venous system occurs between the sixth and eighth week of gestation. First, the posterior cardinal veins appear. This system regresses, leaving only the iliac vein bifurcation. Next, the subcardinal veins develop, with the cranial portion of the right subcardinal vein anastomosing with the right hepatic vein, forming the suprarenal inferior vena cava. The right and left subcardinal veins anastomose to form the left renal vein. Finally, the supracardinal veins form and an anastomosis between the supracardinal and subcardinal veins forms the renal segment of the inferior vena cava. The caudal segment of the right supracardinal vein becomes the infrarenal segment of the inferior vena cava, whereas the cranial segment develops into the azygos vein while the left system regresses.
The inferior vena cava may be duplicated below the level of the renal veins, with a left-sided cava draining into the left renal vein, which then joins to form a single proximal inferior vena cava. If unsuspected, this anomaly can cause confusion at operation and inadvertent injury may result. The incidence of inferior vena caval and renal vein anomalies is significant. Duplication of the inferior vena cava occurs in 0.2% to 3% of cases, transposition or left-sided inferior vena cava occurs in 0.2% to 0.5%, a retroaortic left renal vein in 1.2% to 2.4%, and a circumaortic left renal vein in 1.5% to 8.7% (2). The left renal vein normally crosses the aorta on its anterior surface, but it occasionally crosses posteriorly and may result in confusion and unexpected injury. Collateral circulation around an obstructed inferior vena cava occurs through many alternate pathways, including the vertebral plexus, gonadal veins, ureteral veins, the azygos system, and the extensive superficial collaterals, which include the superficial epigastric, circumflex iliac veins, and the lateral thoracic and intercostal veins.
Important communicating veins exist at the termination of the greater and lesser saphenous veins where they join the deep venous system in the popliteal fossa and in the fossa ovalis. The perforating veins of the lower leg are important to the pathophysiologic process of venous disease and chronic venous insufficiency (CVI), especially the three or four perforating veins at the level of the medial and lateral malleolus in the so-called gaiter area of the lower leg. Other perforating veins are located in the upper medial calf and along the posterolateral aspect of the lower leg, connecting the lesser saphenous vein with the deep veins of the calf. A small but variable number of communications exists in the mid-thigh between the greater saphenous vein and the superficial femoral vein. The locations of perforating veins can be accurately determined only by venous duplex imaging or venography.
Venous valves direct the flow of blood to the heart and prevent valvular reflux. These valves consist of two delicate leaflets composed of an intimal fold with a small amount of connective tissue in between. Venous valves in the lower extremity are more numerous in the distal extremity, decrease in number proximally, and are absent in the superior and inferior vena cava. The valves in the upper extremity appear less important for venous function, and the influence of the venous muscle pump is less significant. The loss of valvular function in the upper extremity after thrombosis less frequently produces problems, in marked contrast to the lower extremity, where the valves play an important role. There are no valves present in the soleal and gastrocnemius sinusoids, but all other deep veins of the calf contain multiple valves. The popliteal vein contains one or two valves whose function is essential to the normal venous return from the calf. Valves in the deep veins of the thigh vary in number and position. There is a constant valve in the femoral vein just distal to its junction with the deep femoral vein and in the proximal portion of the popliteal vein just distal to the adductor hiatus. The greater and lesser saphenous systems contain 8 to 10 valves, with a constant valve present at the proximal end of the greater saphenous vein just at or slightly distal to its junction with the common femoral vein. A third set of valves is present in the perforating veins, which communicate between the superficial and deep veins. Valves are oriented so that they direct venous flow from the superficial to the deep system and, in the deep system, from the foot to the heart. They prevent reflux of the higher-pressure deep venous circulation into the superficial saphenous system. The valves in these perforating veins lie both deep and superficial to the muscle fascia.
Deep Vein thrombosis can develop in deep veins of the upper extremities,lower extremities or pelvis.Lowe extremity Deep Vein Thrombosis is much more likely to cause pulmonary embolism (PE), possibly because of the higher clot burden. The superficial femoral and popliteal veins in the thighs and the posterior tibial veins in the calves are most commonly affected. Calf Vein Deep Vein Thrombosis is less likely to be a source of large emboli but can cause repeated showers of small emboli or propagate to the proximal thigh veins and from there cause Pulmonary Embolism.
The common locations are:
◦ 10% at Poplitea artery
◦ 42% at Poplitea and superficial femoralis artery
◦ 35 % at all of proximal venous
◦ 5% at superficial femoralis or illiaca
I.3 Etiology and Pathophysiology
There are many factors that can contribute to Deep Vein Thrombosis:
1. Age > 60 years
2. Cigarette smoking (including passive smoking)
3. Estrogen receptor modulators (Tamoxifen,Raloxifene)
4. Heart Failure
a. Antiphospholipid antibody syndrome
b. Antithrombin III deficiency
c. Factor V Leiden mutation (Activated protein C resistance)
d. Hereditary fibrinolytic defects
f. Heparin induced thrombocytopenia and thrombosis
g. Increase in factor VIII
h. Increase in factor XI
i. Increase in von willebrand’s factor
7. Indwelling venous catheters
8. Limb Trauma
10. Myeloproliferative disease
11. Nephrotic syndrome
13. Oral contraceptives or estrogen theraphy
14. Pregnancy and postpartum
15. Prior venous thromboembolism
16. Surgery within past 3 months
Millions of tiny injuries occur within normal blood vessels each day, and millions of tiny microthrombi are formed and lysed in a dynamic balance of functional hemostasis without clinically apparent venous or arterial thrombosis. The German pathologist Virchow demonstrated in 1846 that flow stasis, altered coagulability, or extensive vessel wall injury may cause microthrombi to propagate, resulting in macroscopic thrombi. Vessel wall endothelial damage is the most important of these 3 factors because even minor endothelial injury often results in an accumulation of macroscopic thrombi in the veins.
In a sense, thrombus formation at the site of injury is like normal cicatrization of a dermal wound. In a patient with increased coagulation or defective anticoagulation, thrombus formation can be overly exuberant, similar to the formation of a hypertrophic scar. If fibrinolysis is inhibited, the thrombus extends away from the area of the original vascular injury to invade areas of normal endothelium, similarly to keloid formation. Disorders of hemostasis, coagulation, anticoagulation, or fibrinolysis occur in a variety of clinical settings that can cause recurrent DVT or PE and premature arteriosclerotic syndromes or myocardial infarction at an early age.
For the resume, There are 3 factors that contribute Thrombus formation. The factors are:
◦ Blood Vessels
◦ Blood Component
Those three factors are called Vircow Triad
1. Blood Vessels
2. Blood Coagulation
Deep vein Thrombosis usually begins in venous valve cusps. Thrombi consist of thrombin,fibrin,and RBCs with relatively few platelets (red thrombi); Without treatment thrombi may propagate proximally,embolize within days, or both.
Fig 2. Coagulation Cascade
Most deep vein thrombosis occur in the small calf veins and are asymptomatic and never detected. When present, symptoms and signs are non specific (e.g vague aching pain,tenderness along the distribution of the veins,edema,erythema). Dilated collateral superficial veins may become visible or palpable. Calf discomfort elicted by ankle dorsoflexion with the knee extended (Homan’s sign) occasionally occurs with distal legDeep Vein Thrombosis but is neither sensitive nor specific. Leg tenderness,swelling of the whole leg,>3 cm difference in circumference between calves,pitting edema and collateral superficial veins may be most predictive.
Common cause of asymmetric leg swelling that mimic Deep Vein Thrombosis are superficial phlebitis,soft tissue trauma,cellulitis,pelvic venous or lymphatic obstruction, and popliteal bursitis (Baker’s Cysts) that obstructs venous return
Fig 3. The Picture of Deep Vein Thrombosis
How to diagnose Deep Vein Thrombosis? History and physical examination help determine probability of Deep Vein Thrombosis before testing. We can use these test:
◦ Venography (Gold Standard)
◦ MRI Angio
◦ D-Dimer test
◦ complete blood count
◦ Primary coagulation studies: PT, APTT, Fibrinogen
◦ liver enzymes
◦ Renal function and electrolytes
We can use diagram / flow chart to determine whether it is DVT or not
We can also use probability scoring to determine.
Wells score or criteria: (Possible score -2 to 9)
1) Active cancer (treatment within last 6 months or palliative) — 1 point
2) Calf swelling >3 cm compared to other calf (measured 10 cm below tibial tuberosity) — 1 point
3) Collateral superficial veins (non-varicose) — 1 point
4) Pitting edema (confined to symptomatic leg) — 1 point
5) Swelling of entire leg – 1 point
6) Localized pain along distribution of deep venous system — 1 point
7) Paralysis, paresis, or recent cast immobilization of lower extremities — 1 point
8) Recently bedridden > 3 days, or major surgery requiring regional or general anesthetic in past 12 weeks — 1 point
9) Previously documented DVT — 1 point
10) Alternative diagnosis at least as likely — Subtract 2 points
Score of 2 or higher – deep vein thrombosis is likely. Consider imaging the leg veins.
Score of less than 2 – deep vein thrombosis is unlikely. Consider blood test such as d-dimer test to further rule out deep vein thrombosis
◦ Dorsiflexion of foot elicits pain in posterior calf
◦ Pratt’s sign: Squeezing of posterior calf elicits pain.
Fig 4. Homan’s test
Imaging the leg veins
Fig 5.Impedance plethysmography
Fig 6. Doppler ultrasonography
compression ultrasound scanning of the leg veins, combined with duplex measurements (to determine blood flow
Duplex Ultrasonography,due to its high sensitivity, specificity and reproducibility, has replaced venography as the most widely used test in the evaluation of the disease.
Fig 7. Duplex Ultrasonography
All patients with Deep Vein Thrombosis are given anticoagulants, initially an inject able heparin (unfractioned or low molecular weight), followed by warfarin started within 24-28 hours. Inadequate anticoagulation in the first 24 hours may increase risk of pulmonary embolism. Acute Deep Vein Thrombosis can be treated on an outpatient basis unless Pulmonary Embolism is suspected, severe symptoms require parenteral analgesics, other disorders preclude safe outpatient discharge, or other factors (eg,functional,sosioeconomics) might prevent the patient from adhering to prescribed treatments.
General supportive measures include pain control with analgesics other than aspirin and NSAIDS (because of their antiplatelet effects) and, during periods of inactivity, elevation of legs (supported by a pillow or other soft surface to avoid compression). Patient may be as physically active as they can tolerate; there is no evidence that early activity increases risk of clot dislodgement and Pulmonary Embolism.
Low Molecular Wight Heparin is typically given sub cutaneus in a standard weight-based dose:
1. Enoxaparin 1.5 mg/kg s.c once/day or 1 mg/kg s.c q 12 hours to a maximum of 200 mg/day
2. Dalteparin 200 units/kg sc once/day
• Obese patients may require higher doses.
• Cathetic patients require lower doses
• Patients with renal failre are best treated with Unfractioned Heparin
Monitoring is unnecessary because Low Molecular Weight Heparin do not significantly prolong the activated partial thromboplastin time,responses are predictable,and there is no clear relationship between Low Molecular Weight Heparin overdose and bleeding. Treatment is continued until full anticoagulation is achieved with warfarin. However,early evidence suggests that Low Molecular Weight Heparin is effective for long term Deep Vein Thrombosis treatment in high-risk patients, and thus Low Molecular Weight Heparin may become an acceptable alternative to warfarin for some patients, although warfarin is likely to be the treatment of choice because of its low cost and ease of administration
Unfractioned Heparin may be used instead of Low Molecular Weight Heparin for hospitalized patiens and for patients who have renal insufficiency or failure (creatinine clearance 10 to 50 ml/min) because Unfractioned Heparin is not cleared by the kidneys. Unfractioned Heparin is given as a bolus and infusion to achieve full anticoagulation, defined as aPTT 1.5 to 2.5 times that of the reference range. Unfractioned Heparin 3500 to 5000 units’ sc q 8 to 12 hours can be substituted for parenteral Unfractioned Heparin to facilitate patient mobility.
Inferior cava Vein filter
◦ Inferior vena cava filter reduces pulmonary embolism
◦ an option for patients with an absolute contraindication to anticoagulant treatment (e.g., cerebral hemorrhage) or those rare patients who have objectively documented recurrent PEs while on anticoagulation
◦ an inferior vena cava filter (also referred to as a Greenfield filter) may prevent pulmonary embolisation of the leg clot
◦ IVC filters are viewed as a temporizing measure for preventing life-threatening pulmonary embolism
Fig 8. Inferior Cava Vein Filter
Streptokinase,urokinase, and alteplase lyse cloys and appear to more effectively prevent postphlebitic syndrome than heparin alone,but risk of bleeding is higher. Thrombolytic may be indicated for large proximal thrombi, especially those in the illeofemoral veins, and for phlegmasia Alba or cerulean dolens.
Without adequate treatment,lower treatment extremity Deep Vein Thrombosis has a 3% risk of fatal Pulmonary Embolism; death due to upper extremity Deep Vein Thrombosis is very rare. Risk of recurrent Deep Vein Thrombosis is least for patients with transient risk factors (eg. Surgery,trauma,temporary immobility) and greatest for patients with persistent risk factors (eg. Heart failure, malignancy), idiopathic Deep Vein Thrombosis, or incomplete resolution of past Deep vein Thrombosis (residual thrombus)
1. Mark H.Beers. Merck Manual of Diagnosis and Therapy. Merck Research Laboratories ver. 10.2.3 : 2007
2. R.Sjamsuhidajat,Wim de Jong. Buku Ajar Ilmu Bedah ed.2 p:168-174. EGC:2005
3. Sylvia A.Price,Lorraine M.Wilson. Patofisiologi: Konsep Klinis Proses Perjalanan Penyakit ed.6.EGC:2006
This part as well as refferat for clerkcship in Departement of Orthopedic Surgery Bekasi Government Hospital