| disease | Deep Vein Thrombosis of the Lower Extremities |
Deep vein thrombosis (DVT) of the lower extremities is a common condition. This disease can lead to sequelae such as lower limb edema, secondary varicose veins, dermatitis, pigmentation, and stasis ulcers, severely impairing the health of the working population. In the United States, approximately 500,000 people suffer from this disease annually. Although no statistical data is available in China, it is not uncommon. From 1957 to 1977, Shanghai Zhongshan Hospital admitted 49 cases of deep vein thrombosis, including 30 cases in the lower extremities, 10 in the superior vena cava, 7 in the inferior vena cava, and only 2 in the upper extremities. From 1978 to 1988, the hospital's vascular surgery department treated 124 cases of deep vein thrombosis, including 106 in the lower extremities, 1 in the superior vena cava, 7 in the inferior vena cava, and 10 in the upper extremities. Thus, the iliac-femoral vein segment of the lower extremities is the most common site for deep vein thrombosis.
bubble_chart Etiology
In the 19th century, the intermediate stage [second stage], Virchow proposed the three major factors of deep vein thrombosis: venous stasis, venous wall injury, and hypercoagulability, which are still widely recognized by scholars worldwide. The details are as follows:
(1) Venous stasis Spinal or general anesthesia during surgery causes peripheral venous dilation and slows venous blood flow. Due to the anesthetic effect, the muscles of the lower limbs become completely paralyzed during surgery, losing their contractile function. Postoperatively, bed rest due to incision pain and other reasons leaves the lower limb muscles in a relaxed state, leading to blood stasis and inducing deep vein thrombosis in the lower limbs. According to Borow, the duration of surgery is related to the occurrence of deep vein thrombosis: 20% incidence for surgeries lasting 1–2 hours, 46.7% for 2–3 hours, and 62.5% for over 3 hours (the reported incidence abroad is much higher than domestically). It was also found that 50% of cases occur on the first postoperative day, and 30% on the second day. Sevitt clinically observed that thrombi often originate in the valve pockets, venous junctions, and venous sinuses such as those in the soleus muscle. Blood flow in the soleus muscle venous sinuses relies on muscle contraction and relaxation for centripetal return, making them prone to thrombosis. Thrombi can also occur in valveless veins but are more likely due to compression by the pulsating right common iliac artery. Approximately 24% of external iliac veins have valves, and the incidence of thrombosis is also relatively high proximal to these valves.
(2) Venous wall injury1. Chemical injury Intravenous injection of various irritating solutions and hypertonic solutions, such as antibiotics, organic iodine solutions, and hypertonic glucose solutions, can irritate the venous intima to varying degrees, leading to phlebitis and venous thrombosis.
2. Mechanical injury Local venous contusion, laceration, or trauma from fracture fragments can all lead to venous thrombosis. Femoral neck fractures may injure the common femoral vein, and pelvic fractures often injure the common iliac vein or its branches, both of which can complicate into iliofemoral vein thrombosis.
3. Infectious injury Suppurative thrombophlebitis, caused by infections around the veins, is relatively rare. For example, infectious endometritis can lead to septic thrombophlebitis in the uterine veins.
(3) Hypercoagulability This is one of the fundamental factors causing venous thrombosis. Major surgeries can enhance platelet adhesion and aggregation, leading to hypercoagulability. Postoperatively, serum levels of inhibitors for both profibrinolytic activators and plasmin increase, reducing fibrinolytic activity. After splenectomy, a sudden increase in platelets can raise blood coagulability. Burns or severe dehydration, which concentrate the blood, can also increase coagulability. Advanced-stage cancers such as lung cancer, pancreatic cancer, and others like ovarian, prostate, gastric, or colorectal cancer often release substances like mucoprotein thromboplastin when cancer cells destroy tissues. Increased activity of certain enzymes can also promote blood coagulation. Hormonal contraceptives can reduce antithrombin III levels, thereby increasing blood coagulability. High doses of hemostatic medications can also induce a hypercoagulable state.
In recent years, among 106 cases of deep vein thrombosis in the lower limbs at Shanghai Zhongshan Hospital, 60 cases had traceable causes: 9 postoperative cases, 9 cancer patients, 8 postpartum cases, 6 cases of chronic illness with prolonged bed rest, 2 cases of poor arterial blood supply, 4 cases of pelvic mass compression, 4 cases of venous or intimal injury, 7 cases of fractures with bed rest, 9 cases of trauma or frostbite followed by bed rest, and 2 cases of prolonged standing or squatting. No obvious cause was identified in 46 cases.Based on the above-mentioned disease causes of venous thrombosis, venous stasis and hypercoagulability are the two main factors. A single factor is usually insufficient to independently cause the disease; deep vein thrombosis often results from the combined effects of two or three factors. For example, the high incidence of deep vein thrombosis postpartum is caused by multiple factors. The rapid hemostasis of the uterus after placental separation in the short term, preventing postpartum hemorrhage, is closely related to the hypercoagulable state of the blood. During pregnancy, the placenta produces large amounts of estrogen, peaking at full term, with the level of estriol increasing up to 1,000 times that of non-pregnant states. Estrogen promotes the liver's production of various clotting factors, and by the end of pregnancy, fibrinogen in the body also increases significantly, leading to a hypercoagulable state. Postpartum bed rest further slows blood flow in the lower limbs, increasing the tendency for deep vein thrombosis. Venous stasis alone is insufficient to cause the disease; sometimes it is accompanied by vascular wall injury, such as direct trauma, chronic diseases, or distant tissue injury, which generates leukocyte chemotactic factors, causing leukocytes to migrate toward the vascular wall. Similarly, the appearance of fissures in the endothelial cell layer and exposure of the subendothelial collagen of the basement membrane can lead to platelet migration toward the vascular intima, triggering the coagulation process.
bubble_chart Pathological ChangesVenous thrombosis can be divided into three types: ① Red thrombus or coagulation thrombus, which has a relatively uniform composition, with platelets and white blood cells scattered within a gelatinous mass of red blood cells and fibrin; ② White thrombus, consisting of fibrin, layered platelets, and white blood cells, with very few red blood cells; ③ Mixed thrombus, the most common type, comprising a white thrombus forming the head, layered red and white thrombi forming the body, and a red thrombus or layered thrombus forming the tail.
Deep vein thrombosis of the lower limbs originates in some cases from the calf veins, while in others, it originates from the femoral or iliac veins.
The pathophysiological changes caused by venous thrombosis primarily involve various effects resulting from venous reflux obstruction. The degree of venous blood reflux obstruction depends on the size and location of the affected vessels, as well as the extent and nature of the thrombosis. After venous thrombosis occurs, a series of pathophysiological changes arise due to elevated venous pressure distal to the thrombus, such as obvious congestion in small veins and even capillary veins. The osmotic pressure of capillaries increases due to changes in venous pressure, and hypoxia in vascular endothelial cells leads to increased permeability, causing fluid components within the vessels to leak out and move into the interstitial space, often resulting in limb swelling. If red blood cells leak out of the vessels, their metabolic product, hemosiderin, can lead to skin pigmentation.
During venous thrombosis, there may be a certain degree of stirred pulse spasm. When the stirred pulse weakens, it can cause lymphatic stasis and impaired lymphatic reflux, exacerbating limb swelling.
Additionally, the inflammatory response triggered by venous thrombosis in the vein itself and surrounding tissues, along with the rapid increase in venous pressure distal to the thrombus, causes sudden venous dilation. Impaired lymphatic reflux leads to lower limb edema, and stirred pulse spasm caused by venous thrombosis results in limb hypoxia. These pathophysiological changes can all contribute to varying degrees of pain symptoms.
In the acute phase of venous thrombosis, when venous blood reflux in the limb is obstructed, the high-pressure venous blood distal to the thrombus will utilize all normally insignificant collateral pathways to increase reflux. For example, superficial venous anastomoses in the upper thigh and lower abdomen can connect to the contralateral trunk, or extend upward through the abdominal wall to the azygos vein and internal thoracic venous system. In deeper regions, anastomoses can reach the contralateral internal iliac vein via the pelvic venous plexus. The adaptive dilation of these veins facilitates the centripetal reflux of venous blood distal to the thrombus.
Thrombus extension can propagate along the direction of venous blood flow toward the proximal end, such as a calf thrombus extending into the inferior vena cava. When the thrombus completely occludes the main vein, it can extend retrogradely. Fragments of the thrombus may also detach and travel with the blood flow through the right heart, subsequently embolizing the pulmonary stirred pulse, leading to pulmonary embolism.
On the other hand, the thrombus can undergo organization, recanalization, and re-endothelialization, restoring a certain degree of venous patency. The process of thrombus organization begins peripherally and gradually progresses centrally, with varying degrees of progression. The degenerative changes in the thrombus may result from the action of plasmin in the blood or from cellular autolysis and phagocytosis. Another critical aspect of organization is the growth of endothelial cells, which penetrate the thrombus, forming an essential part of recanalization. Animal experiments have observed venous recanalization within 2–5 weeks, but the valve membrane is already damaged. Clinical observations indicate that recanalization is a prolonged process, taking approximately 8–15 years. The final outcome will restore some degree of venous function. However, due to the effects of fibrous tissue contraction on the lumen and damage to the venous valve membrane itself, the valve membrane may disappear or become hypertrophied and adherent to the vessel wall, leading to secondary deep venous valve insufficiency and the post-thrombotic syndrome.
bubble_chart Clinical Manifestations
The most common primary clinical manifestation is sudden swelling of one limb. Patients with deep vein thrombosis (DVT) in the lower extremity experience localized pain that worsens with walking. In mild cases, the affected area may only feel heavy, with symptoms intensifying when standing. Physical examination reveals the following characteristics: ① Swelling of the affected limb. The degree of swelling progression must be assessed by daily precise measurements using a tape measure and compared with the unaffected limb. Relying solely on visual observation is unreliable. This sign holds significant diagnostic value for DVT. Severe calf swelling often leads to increased tissue tension. ② Tenderness. The site of venous thrombosis is often tender. Therefore, the lower limb should be examined for tenderness in the calf muscles, popliteal fossa, adductor canal, and the femoral vein below the groin. ③ Homans' sign. Sharp dorsiflexion of the foot may cause deep pain in the calf muscles. Homans' sign is often positive in cases of deep calf vein thrombosis, as passive stretching of the gastrocnemius and soleus muscles irritates the thrombosed veins. ④ Superficial varicose veins. Deep vein obstruction can elevate superficial venous pressure, leading to varicose veins 1–2 weeks after onset.
Depending on the location of the venous thrombosis, various clinical manifestations may occur, as detailed below:
1. **Calf Deep Vein Thrombosis** Although the calf deep veins are the most common site for postoperative thrombosis, they are sometimes misdiagnosed as fistula disease. Common symptoms include calf pain and tenderness, grade I swelling or mild swelling, a possibly positive Homans' sign, and typically normal superficial venous pressure.
2. **Femoral Vein Thrombosis** Most femoral vein thromboses are secondary to calf DVT, but a few may occur independently. Signs include tenderness in the adductor canal, popliteal fossa, and deep calf. The affected calf and ankle often exhibit grade I edema, with venous pressure 2–3 times higher than the unaffected side. Homans' sign may be positive or negative.
3. **Iliac-Femoral Vein Thrombosis** Most iliac-femoral vein thromboses are secondary to calf DVT, but some originate in the iliac-femoral or iliac veins. Postpartum women, pelvic fracture patients, those undergoing pelvic surgery, and advanced-stage cancer patients are at higher risk. The left lower limb is affected 2–3 times more often than the right, possibly due to the longer course of the left common iliac vein and compression by the right common iliac artery. Rarely, congenital web-like anomalies at the junction of the left common iliac vein and inferior vena cava may contribute.
This condition presents abruptly, with pain, tenderness, and significant swelling developing within hours. Superficial varicose veins may appear in the upper thigh and ipsilateral lower abdominal wall. Marked tenderness is noted in the femoral triangle and adductor canal. A cord-like structure may be palpable along the femoral vein, with accompanying tenderness. In severe cases, the limb may turn cyanotic, termed "phlegmasia cerulea dolens," indicating extensive thrombosis of both deep and superficial veins with arterial spasm, occasionally leading to venous gangrene. Systemic symptoms are generally mild, with fever not exceeding 39°C, and may include grade I tachycardia and malaise. "Phlegmasia cerulea dolens" is rare.
bubble_chart Auxiliary Examination
For venous thrombosis that is difficult to diagnose, the following examinations can be selected to confirm the diagnosis.
(1) Ascending Venography This can determine the location and extent of the thrombus. The patient lies supine in a semi-upright position with the head elevated at 30–45 degrees. A rubber tourniquet is first tied around the ankle to compress the superficial veins. A 12-gauge needle is used to percutaneously puncture the dorsal foot superficial vein, and 80–100 ml of 40% meglumine diatrizoate is injected within one minute. Under the guidance of a television screen, X-rays of the lower leg are taken first, followed by X-rays of the thigh and pelvis. After injecting the contrast agent, physiological saline is rapidly infused to flush the venous lumen, reduce irritation from the contrast agent, and prevent superficial phlebitis.
The venogram often reveals spherical or蜿蜒-shaped filling defects within the vein, or non-visualization of the main venous trunk, with distal venous dilation and abundant collateral veins nearby, all of which indicate venous thrombosis.
(2) Venous Pressure Measurement A glass manometer filled with physiological saline is connected to a needle, which is used to puncture the superficial veins of the foot, ankle, or arm to measure venous pressure. The value must be compared with that of the contralateral healthy side. This examination is diagnostically valuable only in the early stages of the disease before collateral vessels have developed.
(3) Vascular Noninvasive Techniques In recent years, significant progress has been made in diagnostic methods for deep vein thrombosis, including vascular noninvasive techniques such as the radioactive fibrinogen test, ultrasound examination, and electrical impedance plethysmography. The radioactive fibrinogen test is highly sensitive for detecting deep vein thrombosis in the calf, while ultrasound is most valuable for diagnosing iliofemoral vein thrombosis. If these two methods yield inconclusive results, venography is still required. To date, no noninvasive method can fully replace traditional venography. The continuous exploration and refinement of noninvasive techniques remain a focus for future efforts.
1. Radioactive Fibrinogen Test First applied clinically by Atkins in 1965, its principle is that 125iodine-labeled human fibrinogen can be taken up by forming thrombi, and the resulting radioactivity can be scanned from the body surface. This test is simple to perform, highly accurate, and particularly effective for detecting small,隐匿型 venous thrombi that are otherwise difficult to identify. Thus, it can serve as a screening test.
Its main disadvantages include: ① It cannot detect old thrombi, as they do not take up 125iodine-labeled fibrinogen. ② It is unsuitable for detecting venous thrombi near the pelvis because this region contains significant stirred pulse and highly vascularized tissues, as well as the bladder filled with isotope-containing urine, making contrast difficult during scanning. ③ It cannot differentiate between the following conditions: fibrinous exudative inflammation, superficial thrombophlebitis, recent surgical incisions, trauma, hematomas, cellulitis, acute arthritis, and primary lymphatic edema.
Recently, the Isotope Laboratory of Zhongshan Hospital in Shanghai collaborated with the Vascular Surgery Department to use 99technetium-labeled urokinase, injected into superficial veins. They found that it could be taken up by thrombi, and the resulting radioactivity could be scanned from the body surface, achieving a diagnostic accuracy of over 90% for iliofemoral vein thrombosis.
2. Ultrasonography In 1959, Shigeo Satomura first applied this technique, which is based on the principle that when a beam of ultrasound reflects off a moving substance, its frequency changes according to the velocity of the moving object due to the Doppler effect. Red blood cells in the blood serve as reflectors; when the ultrasound beam passes through flowing blood, its frequency changes with the blood flow velocity. During the examination, the probe of the ultrasonic detector is placed on the body surface over larger veins in the lower limbs, such as the femoral vein, external iliac vein, mid-segment superficial femoral vein, popliteal vein, and posterior tibial vein. A sound is emitted when blood flows through, and the sound disappears when there is no blood flow. This is a simple diagnostic method that can be repeated and provides rapid conclusions. However, according to various reports, the accuracy rate varies widely, ranging from 31% to 94%. It has the following drawbacks: ① It is not suitable for detecting smaller venous thrombi, as they do not cause significant changes in blood flow in larger veins; ② In cases of early thrombosis where no obvious obstruction has formed, it may not be detectable; ③ If there are large collateral or superficial veins, a false impression of deep vein patency may be created; ④ It cannot detect thrombi in muscular veins, the deep femoral vein, or the pelvic venous plexus. Currently, domestically produced portable ultrasonic stethoscopes are available, making the assessment of venous patency very simple and rapid.
3. Electrical Impedance Plethysmography. First proposed by Wheeler in 1971, its principle is that during deep inspiration in normal individuals, it impedes venous blood return from the lower limbs, increasing blood volume in the calf; during expiration, venous blood reflows, and lower limb blood volume returns to normal. Electrical impedance plethysmography can measure changes in calf volume. In patients with deep vein thrombosis of the lower limbs, there is no significant corresponding change in calf blood volume during deep breathing. Kakkar pointed out that this examination can accurately diagnose thrombosis in larger veins, but its effectiveness is unsatisfactory for thrombosis in smaller veins of the calf.
1. It is commonly seen in postpartum patients, post-pelvic surgery patients, trauma patients, advanced-stage cancer patients, unconscious patients, or those who are bedridden for long periods.
2. The onset is relatively acute, with swelling and hardening of the affected limb, pain that worsens with activity, often accompanied by fever and a rapid pulse.
3. There is tenderness at the thrombus site, and a cord-like structure can be palpated along the blood vessel. The distal limb or the entire limb is swollen, with cyanotic skin and decreased skin temperature. The dorsalis pedis and posterior tibial pulses are weakened or absent, or venous gangrene may occur. If the thrombus extends to the inferior vena cava, significant edema appears in both lower limbs, buttocks, lower abdomen, and external genitalia. When the thrombus occurs in the calf muscle venous plexus, Homans' sign and Neuhof's sign are positive.
4. In the late stage [third stage], the thrombus is absorbed and organized, often leaving venous insufficiency, resulting in varicose veins, pigmentation, ulcers, swelling, etc., known as post-thrombotic syndrome. It is classified into: ① Peripheral type, primarily characterized by blood reflux. ② Central type, primarily characterized by blood flow obstruction. ③ Mixed type, exhibiting both blood reflux and flow obstruction.
5. Thrombus detachment can lead to pulmonary embolism.
6. Radioactive fibrinogen testing, Doppler ultrasound, and venous flow imaging aid in diagnosis. Venography can confirm the diagnosis.
bubble_chart Treatment Measures
(1) Acute Phase In recent years, the primary treatment for acute deep vein thrombosis has been non-surgical therapy, though surgical intervention is occasionally necessary.
1. Non-Surgical Treatment
(1) Bed rest and elevation of the affected limb: Patients with acute deep vein thrombosis should rest in bed for 1–2 weeks to allow the thrombus to firmly adhere to the venous membrane, alleviate local pain, and promote the resolution of inflammation. During this period, avoid straining during defecation to prevent thrombus detachment and pulmonary embolism. The affected limb should be elevated above heart level, approximately 20–30 cm above the bed, with the knee joint slightly flexed. If elevation is adequate, elastic bandages or stockings are unnecessary. When beginning to move around, elastic stockings or bandages should be worn to moderately compress superficial veins, increase venous return, maintain minimal venous pressure, and prevent lower limb edema. Duration of elastic stocking use: ① For thrombophlebitis of the deep or superficial veins of the calf, they are generally unnecessary unless edema appears in the ankle or lower calf, in which case they may be used for a few weeks; ② For thrombosis of the popliteal or femoral veins, use typically does not exceed 6 weeks; ③ For iliofemoral vein thrombosis, initially use for 3 months, then intermittently remove, generally not exceeding 6 months, but if edema recurs, continued use is necessary. In the early stages, prolonged standing or sitting is contraindicated. For severe iliofemoral vein thrombosis, limit standing and sitting appropriately and elevate the affected limb for 3 months to promote collateral vein development and reduce mild lower limb edema.
(2) Anticoagulation therapy: This is currently the most important treatment for deep vein thrombosis. Proper use of anticoagulants can reduce the incidence of pulmonary embolism and sequelae of deep vein thrombosis. Its role is to prevent the growth of existing thrombi and the formation of new thrombi elsewhere, while promoting faster recanalization of thrombosed veins.
Indications: ① Within 1 month of venous thrombosis; ② When pulmonary embolism is possible after venous thrombosis; ③ Post-thrombectomy.
Contraindications: ① Hemorrhagic diathesis; ② After late abortion; ③ Subacute endocarditis; ④ Ulcer disease.
Common anticoagulants include heparin and coumarin derivatives.
Heparin is an effective anticoagulant with rapid action, controlling blood coagulation within 10 minutes of intravenous injection. Its duration is short, as it is rapidly degraded in the body, mostly by enzymes and partially excreted by the kidneys. Blood clotting time returns to normal 3–6 hours after intravenous injection. Heparin solutions come in two injection strengths: 12,500 IU and 5,000 IU, with 100 IU equivalent to 1 mg. The usual dose is approximately 1–1.5 mg/kg every 4–6 hours. Administration routes include subcutaneous fat layer, intramuscular, or intravenous injection: ① Deep fat layer injection: Typically injected into the deep fat layer of the abdominal wall using a concentrated heparin solution (100 mg/ml), with the dose calculated as 1–1.5 mg/kg per injection, every 8–12 hours; ② Intramuscular injection: 50 mg per dose, every 6 hours; ③ Intravenous injection: Continuous infusion or intermittent injection, with 50 mg per dose every 4–6 hours.
During heparin therapy, clotting time must be measured to adjust the heparin dose. The tube method is commonly used, measured 1 hour before the next injection to adjust the subsequent dose. Normal clotting time (tube method) is 4–12 minutes. During heparin therapy, clotting time should be maintained at 15–20 minutes. If clotting time is 20–25 minutes, the heparin dose is halved; if it exceeds 25 minutes, skip one injection and re-measure after 4–6 hours to determine the dose. Heparin therapy typically lasts 4–5 days, followed by oral anticoagulants such as coumarin derivatives.
Heparin rarely causes allergic reactions. Excessive dosage may lead to bleeding, such as hematuria, wound bleeding, or visceral bleeding. In case of occurrence, protamine sulfate can be used as an antagonist, with a dose of 1–1.5 mg to counteract 1 mg of heparin. It has a complete antagonistic effect and can be administered every 4 hours until bleeding stops. Fresh blood transfusion may be necessary if required.
Coumarin derivatives are prothrombin inhibitors. They have a long induction period, typically requiring 24 to 48 hours after administration to take effect. The duration of action is also prolonged, with a cumulative drug effect. After discontinuation, it often takes 4 to 10 days for the effects to completely dissipate. Coumarin derivatives are administered orally. The prothrombin level should be maintained at 20–30% (concentration %).
Currently, the commonly used coumarin derivatives in China include dicoumarin, sintrom (acenocoumarol), and warfarin sodium. Warfarin sodium is the most frequently used. The typical dosage regimen is as follows: 5 mg three times daily on the first day, 5 mg twice daily on the second day, and starting from the third day, 2.5 mg or 5 mg once daily, adjusted based on prothrombin time.
In cases of bleeding caused by coumarin derivatives, the treatment involves intravenous injection of vitamin K110–20 mg. For severe bleeding, a high dose of vitamin K1 (50 mg per dose, once or twice daily) should be administered intravenously, along with transfusion of fresh blood.
Anticoagulant therapy is contraindicated in patients with hepatic or renal insufficiency or a bleeding tendency. Typically, heparin is used for 4–5 days, and oral coumarin derivatives are started one day before discontinuing heparin. The duration of therapy depends on the site of the lesion and the presence of pulmonary embolism. In 1975, Hirsh suggested the following treatment durations: 4–6 weeks for deep vein thrombosis of the calf, 3–6 months for iliofemoral vein thrombosis, 4–6 weeks for grade I pulmonary embolism, and 6 months for grade III pulmonary embolism.
(3) Thrombolytic therapy: Acute deep vein thrombosis or pulmonary embolism occurring within one week of onset can be treated with fibrinolytic agents, including streptokinase and urokinase. In 1984, Zimmermann proposed that thrombolytic drugs could still be used within two weeks of thrombosis.
Streptokinase is derived from the culture filtrate of hemolytic streptococci, while urokinase is extracted from human urine. Both are effective activators that convert plasminogen in the blood into plasmin. This enzyme hydrolyzes fibrin into small polypeptides, thereby dissolving the thrombus.
Urokinase administration protocol: ① Initial dose: Typically 50,000 IU per dose, dissolved in 250–500 ml of 5% glucose solution or low-molecular-weight dextran for intravenous infusion, twice daily. ② Maintenance dose: The normal fibrinogen level is 200–400 mg/dl. If the measured value falls below 200 mg/dl, suspend the injection once. Simultaneously, measure the euglobulin lysis time (normal >120 minutes). If it is less than 70 minutes, also suspend the dose once. The treatment duration can extend to 7–10 days. ③ Side effects: Urokinase does not cause pyrogenic reactions, and its side effects are much milder than those of streptokinase. Possible side effects include bleeding (e.g., wound bleeding, though rare), fever, nausea, vomiting, headache, fatigue, chest tightness, and rash. For severe bleeding complications, administer 10–20 ml of 10% epsilon-aminocaproic acid intravenously, and consider fibrinogen transfusion if necessary.
In recent years, new thrombolytic drugs that act only at the site of thrombosis have been successfully developed, adding a new chapter to the history of thrombolytic drugs. ①Human tissue-type plasminogen activator (TPA), extracted from uterine tissue or the culture medium of human melanoma cells, can specifically activate plasminogen in the gel state on the surface of thrombi but has no effect on plasminogen in the dissolved state in the bloodstream, thus causing no systemic effects. The production of this drug is very limited and expensive. In 1989, Krupski reported the clinical application of TPA for treating vascular occlusion, with complete thrombus dissolution in 7 out of 8 cases, partial dissolution in 1 case, and no complications. Domestic experimental research has been completed, but it has not yet been put into clinical application. ②Pro-urokinase (Pro-UK), the active form of urokinase, is still in the experimental stage both domestically and internationally.
(4) Other medications: Medium molecular weight (average molecular weight 70,000–80,000) or low molecular weight (average molecular weight 20,000–40,000) dextran intravenous infusion is an adjunctive therapy for acute deep vein thrombosis and has been widely used. Low molecular weight dextran can eliminate red blood cell aggregation, prevent further thrombus growth, and improve microcirculation. The treatment course lasts 10–14 days and can be used concurrently with heparin or urokinase. Side effects: occasional allergic reactions, chest tightness, dyspnea, lumbago, bleeding, and shivering.
2. Surgical Therapy Generally, surgical thrombectomy is not performed for lower extremity deep vein thrombosis. However, for extensive iliofemoral vein thrombosis accompanied by arterial blood flow impairment (phlegmasia cerulea dolens) with impending limb gangrene, surgical thrombectomy is often necessary. The optimal time for iliofemoral vein thrombectomy is within 72 hours of onset, especially within 48 hours. The earlier the surgery, the weaker the adhesion between the thrombus and venous wall, the milder the inflammatory reaction, the less damage to the venous intima, and the fewer secondary thromboses, resulting in more complete thrombus removal and better postoperative outcomes. During iliofemoral vein thrombectomy, temporary occlusion of the inferior vena cava or common iliac vein is required to prevent pulmonary embolism caused by thrombus dislodgement. The traditional transabdominal approach to expose and clamp the inferior vena cava is highly invasive and time-consuming. Currently, the preferred method involves making a small incision under local anesthesia in the groin of the unaffected side to expose the femoral vein, inserting a balloon-tipped vena cava occlusion catheter, and inflating the balloon to temporarily block inferior vena cava blood flow during thrombectomy. Next, an incision is made on the affected groin to expose the femoral vein, and a Fogarty catheter (a balloon-tipped catheter) is inserted proximally to the common iliac vein. After inflating the balloon, the thrombus is slowly withdrawn. The balloon is then deflated to restore venous blood flow. The proximal femoral vein is temporarily controlled with a plastic band, and the Fogarty catheter is inserted distally into the popliteal vein. The balloon is inflated again to withdraw the distal thrombus. Concurrent manual centripetal compression on the calf can help expel thrombi from the calf veins and branches—a crucial step to prevent secondary thrombosis. Venotomy incisions on both sides should be meticulously closed with 7-0 or 5-0 nylon sutures (interrupted or continuous), ensuring proper intimal alignment without adventitial inversion. Postoperative anticoagulation therapy is mandatory.
Andriopulos reported 164 cases of iliac vein thrombectomy, including 87 performed within 4 days of onset and 41 within 8 days. Six cases developed pulmonary embolism, with two fatalities. Among 134 long-term follow-up patients, the best outcomes were in those operated within 1–4 days: 50% achieved complete recovery, 29% had occasional grade II swelling, and only four had severe post-thrombotic syndrome. Results were generally satisfactory. In 1980, Nüllen reported 46 cases of acute iliofemoral vein thrombosis, with 13 undergoing emergency thrombectomy due to suspected pulmonary embolism. Temporary arteriovenous fistulas were created post-thrombectomy and closed after three months. None of these 13 patients developed recurrent thrombosis or pulmonary embolism, all preserved venous valve function, and none exhibited post-thrombotic syndrome symptoms. With proper patient selection, iliofemoral vein thrombectomy remains an effective treatment.
(II) Chronic Phase Within one year of lower extremity deep vein thrombosis onset, venous reconstruction surgery is generally not performed. During this period, extensive collateral circulation may develop. With medication and adjunctive therapies, venous return impairment often significantly improves in many cases.
According to the pathological process, deep vein thrombosis of the lower extremities can be roughly divided into two stages: the obstructive phase and the recanalization phase, with completely different surgical treatment methods. Preoperative ascending and descending venography of the lower extremities is required to clarify the location and extent of the lesion.
1. Obstructive Phase After deep vein thrombosis (DVT) of the lower extremity, the main venous return of the limb is obstructed, and the high-pressure veins distal to the thrombus increase collateral circulation. The superficial venous anastomoses in the upper thigh and lower abdomen can connect to the contralateral trunk, while upward connections may extend through the abdominal wall to the azygos and internal thoracic venous systems. Deep anastomoses can reach the contralateral internal iliac vein via the pelvic venous plexus. The adaptive dilation of these veins facilitates venous return from the thrombus-distal region. However, in many cases, collateral circulation develops too slowly to compensate for the obstructed venous return, leading to lower limb swelling, pigmentation, dermatitis, and ulcers. The goal of various surgical interventions is to enhance collateral circulation and overcome venous return obstruction. The surgical approaches include the following:
(1) In Situ Great Saphenous Vein Graft: This procedure is only suitable for femoral-popliteal vein thrombosis and is relatively simple. It involves exposing the popliteal vein posterior to the knee and performing an end-to-side anastomosis between the distal great saphenous vein and the popliteal vein below the knee. However, the following conditions must be met: the femoral and iliac veins proximal to the great saphenous vein must be patent; the deep veins of the calf must be unobstructed; and the great saphenous vein must be free from varicosity, thrombosis, and have competent valves. This procedure requires only one anastomosis, allowing the ipsilateral great saphenous vein to replace the femoral-popliteal vein in venous return.
(2) Great Saphenous Vein Bypass Graft: First proposed by Palma in 1958, this technique is suitable for proximal iliac-femoral vein thrombosis where the mid-to-distal femoral vein and calf deep veins show no significant secondary thrombosis. A longitudinal incision is made over the femoral vein on the affected side, and a segment of patent superficial femoral vein is isolated. The great saphenous vein on the contralateral (healthy) side is then dissected, its branches ligated and divided, and extended distally below the knee to achieve sufficient length. The great saphenous vein is temporarily clamped near the femoral vein, transected distally, and flushed with heparin solution (20 mg heparin in 100 mL saline). The distal end of the great saphenous vein is tunneled subcutaneously over the pubis to the superficial femoral vein on the affected side. After systemic heparinization (1 mg/kg heparin), an end-to-side anastomosis is performed between the great saphenous vein and the superficial femoral vein. To improve patency, a temporary arteriovenous fistula may be created distal to the anastomosis on the affected limb, with two sutures pre-placed and externalized. After 3–4 weeks, once the anastomotic endothelial lining has healed, the arteriovenous fistula is ligated.
In 1979, Dale reported 48 cases of great saphenous vein-iliac-femoral vein bypass grafting, with good outcomes in 28 cases, improvement in 9, and failure in 11.
(3) Pedicled Greater Omentum Graft: For patients with iliac-femoral vein thrombosis where neither the contralateral nor ipsilateral great saphenous vein is usable (e.g., due to prior excision, varicosity, or thrombosis), a pedicled greater omentum graft may be employed.
A midline upper abdominal incision is made to access the peritoneal cavity, and the greater omentum is carefully dissected, preserving only the right gastroepiploic artery and vein to maintain its vascular pedicle. Subcutaneous and deep fascial tunnels are created upward and downward. The greater omentum is then exteriorized through an opening in the right pelvic peritoneum and guided along the inguinal subcutaneous tunnel to the mid-thigh. Depending on the vascular course of the greater omentum, it may be tailored and extended, potentially reaching below the knee. Care must be taken during tailoring to avoid compromising its blood supply. If portions of the omentum appear darkened, they should be excised. While leaving the omentum untailored improves survival rates, the graft may not reach an ideal position, often terminating at the mid-to-upper thigh. The decision to tailor the omentum involves trade-offs and should be determined case by case. Once positioned, the omentum is sutured to the peritoneum to prevent iatrogenic femoral hernia.
Since the greater omentum is rich in lymphatics and capillary networks, transplantation can help reduce limb swelling to some extent. Clinical observations at Shanghai Zhongshan Hospital indicate that most patients experience varying degrees of postoperative swelling reduction, though calf swelling rarely resolves completely, typically remaining 2–3 cm larger in circumference than the unaffected limb. This is likely due to insufficient omental graft length and chronic venous stasis leading to muscle swelling and degenerative changes.
2. Recanalization Phase During deep vein thrombosis (DVT) of the lower extremities, inflammatory reactions occur simultaneously in the venous wall and valves, with thrombi obstructing the lumen and adhering to the valves. In the process of thrombus organization and recanalization, the venous valves are further injured, becoming thickened due to scarring, resulting in a deep venous system with a patent lumen but incompetent valves. Valve incompetence can still lead to lower limb swelling, superficial varicose veins, pigmentation, dermatitis, and ulcers. Descending venography of the lower limbs may reveal significant contrast reflux, with severe cases showing reflux extending from the groin down to below the knee or even the ankle.
In the past, ligation of the superficial femoral vein or ligation of perforating veins in the calf was used to treat this condition. While it showed certain short-term efficacy, the long-term results were not satisfactory.
In recent years, we have adopted the transplantation of a valved segment of the brachial vein to the femoral vein. This method has achieved relatively good results in treating sequelae of deep vein thrombosis during the recanalization phase.
The specific procedural steps are as follows: First, a longitudinal incision is made in the thigh to expose and free the common femoral vein, superficial femoral vein, and deep femoral vein. It is often observed that the femoral vein wall is thickened and hardened, with adhesions to surrounding tissues, and the valves are almost entirely destroyed. Next, the brachial vein in the upper arm is exposed. A 2–3 cm segment of the brachial vein carrying 1–2 pairs of functional valves is tested for competence and then excised for transplantation. The valved brachial vein segment is anastomosed end-to-end with the superficial femoral vein. Typically, the transplanted valve is placed distal to the orifice of the deep femoral vein to ensure centripetal blood flow in the deep femoral vein while preventing reflux into the superficial femoral vein. Postoperatively, the affected limb is elevated, and passive and active exercises involving calf muscles and dorsiflexion of the foot are encouraged.
In 1985, Taheri reported performing 66 cases of venous valve transplantation over five years, with follow-up available for 48 cases. Among them, 75% of patients experienced reduced or resolved lower limb swelling. Of the 18 patients with preoperative ulcers, 17 achieved postoperative ulcer healing. Complications included hematomas in five cases—four in the groin and one in the upper arm. Postoperative venography was performed in 31 cases, showing competent valve closure in 28, femoral vein thrombosis in one, and valve insufficiency in two.
Since May 1983, Zhongshan Hospital in Shanghai pioneered the transplantation of valved brachial vein segments for deep vein insufficiency in China and introduced modifications: transitioning from transplanting one pair of valves to potentially transplanting two pairs, and using the great saphenous vein for interposition grafting at the brachial vein defect site. Postoperatively, ankle ulcers healed rapidly, swelling decreased, and follow-up over two years demonstrated favorable outcomes.
New techniques continue to evolve, including the experimental use of valved segments from the axillary vein, contralateral femoral vein, and jugular vein for transplantation.
It is worth noting that surgical treatment for lower limb deep vein thrombosis must be combined with medication and other adjuvant therapies. Different surgical approaches should be tailored to the location, severity, and stage of thrombosis. Current surgical methods still require refinement, and their efficacy needs further improvement. It is foreseeable that through the persistent efforts of vascular surgeons worldwide, more effective, innovative, and simplified approaches will emerge, ushering in a new era of comprehensive treatment for lower limb deep vein thrombosis.
Preventive measures for acute deep vein thrombosis of the lower extremities include: gentle manipulation around the adjacent limbs or pelvic veins to avoid intimal injury. Avoid placing pillows under the calves postoperatively to prevent obstruction of deep venous return in the lower legs. Encourage patients to frequently move their feet and toes actively and advise them to perform deep breathing and coughing exercises. Early ambulation should be encouraged whenever possible, and medical elastic stockings should be worn on the lower limbs if necessary. Special attention should be paid to the elderly, cancer or heart disease patients after major thoracic, abdominal, or pelvic surgeries, post-femoral fracture, and postpartum women. Additionally, the following preventive methods are available:
(1) Mechanical Prevention Methods Abroad, tilt-table devices, pneumatic boots, or electrical stimulation are used to accelerate venous blood flow and reduce the incidence of postoperative deep vein thrombosis in the limbs.
(2) Pharmacological Prevention Methods Primarily aimed at counteracting hypercoagulability. Currently, two methods are applied:
1. Dextran In 1975, Grubr suggested that the preventive effect of dextran lies in: ① Reducing platelet activity and viscosity; ② Altering fibrin clot structure; ③ Increasing thrombus solubility; ④ Acting as a plasma expander to improve blood circulation. Commonly used dextrans include dextran 70 (average molecular weight 70,000–80,000) and dextran 40 (average molecular weight 20,000–40,000), which can be administered preoperatively and intraoperatively. Alternatively, 500 ml may be infused intravenously on the morning of anesthesia, followed by another 500 ml postoperatively, and then every other day for a total of three doses.
In 1976, Verstrate noted that prophylactic use of dextran significantly reduces thrombosis incidence in gynecological surgeries such as abdominal or vaginal hysterectomy and orthopedic surgeries, especially hip procedures. However, it has no significant effect in patients over 40 undergoing elective abdominal surgeries, such as gastric, colonic, biliary, or prostate surgeries.
2. Antiplatelet Aggregation Drugs In recent years, drugs such as dipyridamole and enteric-coated aspirin have been used abroad to prevent deep vein thrombosis in the lower limbs, with some success. Typically, dipyridamole 25 mg three times daily and enteric-coated aspirin 0.3 g three times daily are combined for better efficacy.
In the acute and chronic phases of deep vein thrombosis in the lower limbs, the following diseases should be differentiated:
(1) Acute arterial embolism: This condition also often manifests as sudden pain in one lower limb, similar to deep vein thrombosis. However, in acute arterial embolism, there is no limb swelling. The main symptoms include cold skin temperature in the foot and calf, severe pain, numbness, autonomic dysfunction, and loss of skin sensation. The pulsation of the dorsalis pedis artery and posterior tibial artery disappears, and sometimes the femoral and popliteal artery pulsations also vanish. Based on these characteristics, differentiation is relatively straightforward.
(2) Acute diffuse lymphangitis of the lower limb: This condition also develops rapidly, with limb swelling, often accompanied by chills, high fever, red skin, elevated skin temperature, and no varicose superficial veins. These features help differentiate it from deep vein thrombosis.
(3) Lymphedema: This condition shares similarities with the chronic phase of deep vein thrombosis. The key points for differentiation are as follows (see Table 49-2).
Table 49-2: Differentiation between deep vein thrombosis and lymphedema
| Clinical manifestations | Deep vein thrombosis | Lymphedema |
| Medical history | Sudden onset, often with a history of surgery, childbirth, or fever | Slow onset, often with a history of several years or more |
| Pain | Pain in the acute phase, gradually subsiding later | None or mild dull pain, with a heavy sensation in the affected limb |
| Skin | Not thickened | Thickened in advanced stages |
| Color | Possibly cyanotic | No change |
| Superficial veins | Dilated | Not dilated |
| Ulcer and eczema | Often occur in advanced stages | Generally do not occur |
| Edema | Soft. Prominent in the thigh and calf, less so in the ankle, dorsum of the foot, and toes | Firm. Prominent in the thigh, calf, ankle, dorsum of the foot, and middle toe |
| Elevating the affected limb | Edema subsides quickly | Edema subsides slowly |
(4) Other diseases: For bedridden patients due to surgery, childbirth, severe trauma, or systemic diseases who suddenly experience deep calf pain, tenderness, and a positive Homans sign, deep vein thrombosis should be considered first. However, differentiation should be made with the following conditions: acute calf myositis, acute calf fibrositis, calf muscle strain, deep calf vein rupture with hemorrhage, and Achilles tendon rupture. The latter conditions all have a history of trauma, sudden onset, severe local pain, and accompanying skin ecchymosis, especially in the ankle area, which aids in differentiation.
For cases where diagnosis is truly difficult, in addition to observing clinical manifestations, selecting one or more of the above special examinations can confirm the diagnosis.
