Deep Vein Thrombosis (DVT) is a common disease with an increasing trend in recent years. Untimely treatment or improper treatment often leaves sequelae, i.e., post-DVT syndrome, which can develop edema, varicose veins, dermatitis, hyperpigmentation, depressed ulcers, etc., seriously affecting daily activities and even causing disability. It should be actively prevented and treated. The annual incidence of lower limb DVT is 1 per 1,000 in the world, and about 500,000 people in the United States suffer from this disease every year, and there are no statistics in China yet.
Etiology】
Common risk factors: surgery, lower extremity or major trauma, prolonged braking or paralysis, malignancy, previous history of thrombosis, advanced age, pregnancy and postpartum period, oral estrogen-containing contraceptives or hormone replacement therapy, acute medical disease, heart or respiratory failure, inflammatory bowel disease, nephrotic syndrome, obesity, smoking, varicose veins, hereditary or acquired thrombophilia, general anesthesia for more than 30 minutes etc.
In the mid-nineteenth century, Virchow proposed three major factors for deep vein thrombosis: slow blood flow, venous wall damage, and hypercoagulable blood.
I. Slow venous blood flow
After surgery, bed rest is needed for pain and other reasons, especially after fracture, the muscles of the lower limbs are in a relaxed state, which makes the blood flow slow and easily induces the formation of deep vein thrombosis in the lower limbs.
Second, the damage of the vein wall
1.Chemical damage: intravenous injection of various irritating solutions and hypertonic solutions, such as various antibiotics, hypertonic glucose solution, etc. can damage the venous lining to varying degrees, leading to the formation of venous thrombosis.
2, mechanical injury: local contusion, laceration or fracture fragment trauma can produce venous thrombosis. For example, pelvic fracture can often damage the common iliac vein, which can cause venous thrombosis.
3, infectious injury: infection foci around the veins can cause thrombophlebitis, such as endometritis, which can cause thrombosis of uterine veins.
Third, blood hypercoagulation state
1.The platelet adhesion ability is enhanced and fibrinolysis is reduced after major surgery.
2.Burns or severe dehydration make blood concentrated, which can also increase blood coagulation.
3.Advanced malignant tumors such as lung cancer, pancreatic cancer, others such as ovarian, prostate, stomach or colon cancer, etc. can release hypercoagulable substances.
4.High dose application of hemostatic drugs can also make the blood in a hypercoagulable state.
Pathology】
The degree of venous reflux obstruction after venous thrombosis depends on the location, caliber size of the thrombosed vessel and the extent of thrombosis. After the formation of venous thrombosis, the distal venous pressure rises and is in an obvious depressed state, the osmotic pressure of capillaries rises, the permeability increases due to the lack of oxygen in the vascular endothelial cells, and the intravascular fluid component leaks outward and moves to the tissue interstices, often resulting in swelling of the limb. If there is leakage of red blood cells outside the blood vessels, their metabolites contain iron-containing heme, forming skin pigmentation. In the case of venous thrombosis, it causes lymphatic stasis and impaired return flow, which increases the swelling of the limb.
When the venous blood return to the limb is impaired, the venous hypertension on the distal side of the thrombus will prompt the opening or dilation of small, otherwise tiny collateral veins, and blood will return through these collateral veins. For example, superficial venous anastomotic branches in the upper thigh and lower abdomen may lead to the contralateral trunk and upward through the abdominal wall to the odd vein and the internal thoracic venous system. In the deeper part, the anastomotic branch can reach the contralateral internal iliac vein through the pelvic venous plexus.
Deep vein thrombosis in the lower extremities can originate in the small veins of the lower legs or in the thick veins of the femoral and iliac veins.
The spread of thrombus may follow the direction of venous flow and extend proximally, such that the thrombus in the lower leg may continue to extend into the femoral, iliac, and even inferior vena cava veins. When the thrombus completely obstructs the venous trunk, it can also extend in the opposite direction, such as in the iliac vein, which can extend distally to the calf. Fragments of the thrombus may be dislodged and enter the heart with the blood flow, and then embolize in the pulmonary artery, resulting in pulmonary embolism (link to pulmonary embolism topic).
Clinical manifestations
The most common clinical manifestation of lower limb deep vein thrombosis is the swelling and pain of the limb, which is only locally heavy in mild cases and worsens when standing or walking, and can be relieved by elevating the lower limb. Systemic symptoms are usually not obvious, there may be low fever, body temperature usually does not exceed 39℃, there may be mild tachycardia and acute discomfort and other symptoms.
Physical examination has the following characteristics.
1. Swelling: The degree of development of swelling must be based on accurate daily measurement with a tape measure and comparison with the thickness of the healthy lower extremity to be reliable, relying solely on visual observation is unreliable.
2.Pressure pain (Neuhof sign): pressure pain is often present at the site of venous thrombosis. Therefore, the lower limbs should be examined for calf muscles, N fossa, adductor canal and femoral vein below the groin.
3.Gastrocnemius muscle pulling test (Homans sign): When the foot is bent sharply to the dorsal side, it can cause pain in the deep calf muscle. This sign is often positive when there is deep vein thrombosis in the calf. This is caused by the passive extension of gastrocnemius and hallux valgus muscles, which stimulates the calf blood full vein.
4.Superficial vein filling and nuchal translucency: deep vein obstruction can cause superficial vein pressure to rise and dilate, and superficial varicose vein can occur after 1 or 2 weeks of onset.
【Typing】
According to the location of the venous thrombosis, there are different clinical manifestations, which are divided into three types: peripheral type, central type and mixed type.
1.Peripheral type: the thrombus is located below the N vein, mainly manifesting as pain and pressure pain in the calf, mild swelling or insignificant swelling in the calf, and the symptoms are aggravated after activity, and Homans’ sign is often positive. Although the deep calf vein is the most vulnerable site for thrombosis after surgery, it is easily missed due to mild symptoms.
This type of thrombus can extend to the thigh and become mixed. Dislodging of small emboli can cause mild pulmonary embolism, which is not easily detected clinically.
Thrombosis of the muscular plexus of the calf is also a peripheral type, but most of the symptoms are mild because the thrombus is limited. Most of them can be dissolved or mechanized by treatment, and they can also be autolyzed.
2. Central type: also called iliofemoral vein thrombosis. It is more common on the left side, manifesting as swelling below the buttocks, anger in the lower limbs, groin and superficial veins of the lower abdominal wall on the affected side, and elevated skin temperature. The thrombus may extend upward into the inferior vena cava or may multiply downward and involve the entire deep veins of the lower extremity in a mixed pattern. Homans sign can be positive or negative.
3.Mixed type: The thrombus is formed in the deep vein of the whole lower extremity, which is extended from the peripheral type or the central type. In the case of peripheral type upward expansion, the symptoms are not noticed at first, and then the swelling level rises gradually until the whole lower extremity is edematous and the deep vein becomes painful to pressure. In this case, the time of onset and clinical manifestations do not coincide with the time of thrombosis. The clinical manifestations are not easily distinguished from those of the central type, which is more common.
The onset of the disease is rapid, with pain, tenderness, and marked swelling of the entire affected limb within a few hours. Superficial varicose veins in the upper femur and ipsilateral lower abdominal wall. There is significant tenderness along the femoral triangle and the internal femoral muscle canal. Stiff objects may be palpable and painful in the femoral vein area. In severe cases, there may be arterial spasm, weakening or disappearance of arterial pulsation in the lower limbs, decreased skin temperature and bruising of the affected limbs, called “femoral cyanosis”, which is the emergency state of DVT and may lead to limb necrosis. The systemic reaction is large, and shock and wet gangrene of the lower limbs are likely to occur. Emergency surgery is needed to remove the embolus to save the limb.
Auxiliary examination
1.Ultrasonic examination: a sensitive, simple and non-invasive diagnostic method, which can be repeatedly checked if necessary. However, the accuracy of the iliac vein with or without thrombosis is poor.
2.Electrical impedance volume tracing method: When a normal person inhales deeply, it can obstruct the venous blood reflux of lower limb, so that the blood in the lower leg can increase easily; when exhaling, the venous blood refluxes again and the blood volume of lower limb returns to the normal state. In patients with lower extremity deep vein thrombosis, there is no obvious corresponding change in calf blood volume during deep breathing. The electrical impedance volume tracing method can measure the change of calf volume, which can correctly diagnose the thrombosis of larger veins, but the effect is not satisfactory for the thrombosis of smaller veins in the calf.
3.Radioactive fibrinogen test: The principle is 125 iodine-labeled human fibrinogen, which can be taken up by the forming thrombus and form radioactivity, and can be scanned from the surface of the body. This test is simple to perform and has a high correct rate, especially it can detect smaller vein occult type thrombus which is difficult to detect. Therefore this can be used as a screening test. Its main disadvantages are: (i) it cannot detect old thrombi because it does not take up 125 iodine fibrinogen; (ii) it is not suitable for examining venous thrombi in the pelvis adjacent to the area where there are larger arteries and tissues with rich blood supply and a bladder containing isotopic urine, which is difficult to compare during the scan; (iii) it cannot identify the following diseases: inflammation of fibrous exudate, superficial venous thrombophlebitis, recent surgical incisions trauma, hematoma, cellulitis, acute arthritis and primary lymphedema, etc.
4.Venogram: If the above-mentioned examination method cannot make a definite diagnosis, venogram is still needed. So far, there is no non-invasive examination method can completely replace the traditional phlebography. The imaging X-ray often shows spherical or sinuous filling defect in the vein, or the main trunk of the vein does not appear, and the distal vein is dilated, and there are abundant side branch veins nearby, which all suggest the formation of thrombosis in the vein.
Diagnosis】
Deep static thrombosis of the lower extremities can be diagnosed if the following characteristics are present.
1.Most commonly seen in postpartum, post-pelvic surgery, trauma, advanced cancer, coma or patients who are bedridden for a long time.
2.The onset of the disease is acute, the affected limb is swollen and hard, painful, and aggravated after activity, often accompanied by fever and rapid pulse.
3.The thrombus site is painful, cords can be found along the blood vessels, the limb distal to the thrombus or the whole limb is swollen, and the skin is blue-purple; when the thrombus occurs in the calf muscle plexus, Homans’ sign and Neuhof’s sign are positive.
4.Radiofibrinogen test, Doppler ultrasound and venous flow mapping are helpful for diagnosis. Venogram can confirm the diagnosis.
[Differential diagnosis
In the acute and chronic phases of lower extremity deep static thrombosis should be differentiated from the following diseases, respectively.
1.Acute diffuse lymphangitis of lower extremity: the disease also has rapid onset, swollen limbs, often accompanied by chills, high fever, red skin, elevated skin temperature, superficial veins are not varicose, according to the above characteristics, it can be distinguished from deep vein thrombosis of lower extremity.
2.Lymphedema: swelling of superficial soft tissues mainly, concave in the early stage, non-concave in the later stage, but mostly without pain and pressure symptoms, negative Homans’ sign and Neuhof’s sign, and no thrombus in the vein as shown by ultrasonography, which can be distinguished.
3, other diseases: acute calf myositis, acute calf fibrous tissue inflammation, calf muscle strain, calf deep vein rupture and bleeding and Achilles tendon rupture. The latter all have a history of trauma, with rapid onset and severe local pain, accompanied by skin ecchymosis in the calf, especially in the ankle, which can be distinguished.
Treatment
I. Non-surgical treatment
Applicable to peripheral thrombosis, central thrombosis and mixed thrombosis with a history of more than 7 days, serious comorbidity of important organs, advanced malignant tumor, and extremely poor physical condition that cannot tolerate surgery.
It mainly includes.
1.To prevent the occurrence of pulmonary embolism, absolute bed rest, braking, and prohibition of massage for more than 2 weeks are required.
2. Elevation of the affected limb: it should be higher than the level of the heart.
3.Anticoagulation therapy: its role is to prevent the continued expansion of thrombus and the formation of new thrombus in other parts. Commonly used anticoagulants are heparin, low molecular heparin and coumarin derivatives.
When applying heparin, the dose should be adjusted by measuring the clotting time. Excessive doses can cause bleeding, such as hematuria and visceral bleeding. Once it occurs, it can be antagonized by fisetin sulfate and, if necessary, fresh blood can be transfused.
Coumarin derivatives are a kind of thrombinogen inhibitor. They have a long induction period and generally take effect 24 to 48 hours after administration. It also takes a long time to disappear and has a cumulative effect. It takes 4-10 days after stopping the drug for the effect to disappear completely. The prothrombin value should be maintained at 20-30%. The commonly used coumarin derivative is Warfarin Sodium, and the dose is adjusted according to the prothrombin time. In case of bleeding caused by coumarin derivatives, vitamin K can be used and fresh blood can be transfused if necessary.
Anticoagulation therapy is contraindicated in hepatic and renal insufficiency and in those with bleeding tendencies.
The duration of anticoagulation therapy is determined on a case-by-case basis.
5, dispel aggregation therapy: reduce platelet aggregation, mainly aspirin, Pansentin, resistaclitaxel, Bolivar, etc.. No monitoring of coagulation time is required during the drug administration.
6.Thrombolytic therapy: Thrombolytic agents can be applied in the early stage of thrombosis, including streptokinase and urokinase, both of which can promote the transformation of fibrinogen into fibrinase. This enzyme can hydrolyze fibrin and achieve the purpose of dissolving thrombus. Thrombolytic therapy has good clinical effect on patients with DVT, but the complete dissolution rate of thrombus is very low.
New thrombolytic drugs include: ① human tissue-type fibrinogen activator (rt-PA), which can specifically activate the fibrinogen on the gel state of the thrombus surface, but has no effect on the fibrinogen in the dissolved state of the blood circulation, with good thrombolytic effect and no systemic effect. However, the production of this drug is very small and the price is expensive. Urokinase precursor (Pro-UK) is in the experimental stage both at home and abroad.
7.Other drugs: low molecular weight dextran, thromboxane, Chuan Douzin, Salvia and other drugs are auxiliary drugs for the treatment of acute deep vein thrombosis, which are now widely used to eliminate red blood cell coagulation, prevent the thrombus from continuing to grow and improve microcirculation.
8.When you start to get up and move around in the later stage, you should not stand and sit for a long time. You need to wear elastic stockings or use elastic bandages to moderately compress the superficial veins to increase the venous plus return flow as well as maintain the minimum venous pressure to stop the development of lower limb edema.
With non-surgical treatment, thrombus expansion can be controlled, limb edema can be reduced, and pain can be relieved. However, after non-surgical treatment, about 50% or more patients will be left with sequelae, i.e. post-DVT syndrome, with edema, varicose veins, dermatitis, hyperpigmentation, depressed ulcers, etc., which seriously affect the ability of daily activities.
Second, surgical treatment
It is suitable for central and mixed thrombosis in which the history does not exceed 7 days, no serious comorbidity, and good physical condition can tolerate the surgery. Femoral cyanosis is an absolute indication for surgical thrombus removal.
For patients in the acute stage, the earlier the surgery, the less the thrombus adheres to the vein wall, the less the inflammatory reaction, the less the destruction of the vein lining, the less the secondary thrombosis, the more complete the surgical removal of the thrombus and the better the result. Generally, it is best to remove the thrombus within 3 days of the onset of the disease, but it is difficult to remove the thrombus that is more than 7 days old because it is mechanized and adheres to the vein wall. The effect of thrombus removal is related to the type of thrombus, central type is significantly better than mixed type. If there is a severe stenosis or occlusion of the left common iliac vein (i.e. Cockett syndrome) (link to Cockett syndrome), this must be corrected at the same time, otherwise there is a high risk of recurrence after thrombectomy. Postoperative treatment is combined with anticoagulation, depolymerization, thrombolysis and other adjuvant therapy to prevent recurrence of thrombosis.
Interventional treatment
In recent years, minimally invasive interventional methods have emerged for the treatment of acute lower extremity DVT, and the clinical efficacy is better than that of simple anticoagulation and systemic thrombolysis. At present, the minimally invasive techniques carried out clinically for the treatment of acute DVT mainly include: catheter direct thrombolysis, deep vein mechanical thrombus removal and iliac vein endovenous molding (venous balloon dilation and stent implantation). Interventional treatment has the characteristics of less trauma, fewer complications and faster recovery, and can be used to treat cases that cannot tolerate surgery, but the cost required is high.
【After-effects
Inadequate treatment of lower extremity deep vein thrombosis or improper treatment often leaves sequelae, i.e. post-DVT syndrome, which can result in edema, varicose veins, dermatitis, hyperpigmentation, depressed ulcers, etc., seriously affecting the ability of daily activities and even causing disability. The main treatment is to elevate the lower limbs, avoid prolonged standing and walking, wear elastic stockings to promote blood return and reduce edema, and take some drugs to promote circulation.
According to the pathological process, post-DVT syndrome can be divided into two stages: obstructive stage and recanalization stage.
1.Obstructive phase: After the formation of lower limb DVT, the venous return of the main limb is obstructed, the venous pressure on the distal side of the thrombus is increased, and the lateral branches open. However, the establishment of collateral circulation is slow in most cases, which is not enough to compensate the return function of the obstructed vein, causing swelling, hyperpigmentation, dermatitis and ulcers in the lower limbs. The purpose of surgical treatment in this period is to strengthen the lateral branch circulation, which can be selected according to the situation: in situ saphenous vein grafting, saphenous vein diversion grafting, tipped outline membrane grafting, etc.
2.Recanalization phase: In the process of thrombosis and recanalization, the lumen of the vein can be partially recanalized, but the thickening of the vein wall and the loss of valve function cause blood reflux, which can cause swelling, superficial varicose veins, hyperpigmentation, dermatitis and ulcers in the lower limbs. Significant contrast reflux can be seen on downgrade venograms of the lower extremities. At this stage, the surgical treatment options are ligation of the penetrating branch vein of the lower leg, transplantation of venous segments with valves, and muscle collaterals in lieu of valves.
Prevention
Active preventive measures should be taken for patients with thrombotic tendency and those who may cause thrombosis.
Mechanical prevention: After major surgery, especially pelvic surgery and orthopedic surgery, encourage the patient’s feet and toes to move actively as early as possible, and those who cannot get out of bed can do active or passive activities of the lower limbs in bed, and wear medical elastic stockings for the lower limbs to reduce the incidence of deep vein thrombosis in the lower limbs after surgery.
Second, drug prevention: mainly to counteract blood hypercoagulation state, can be applied.
1.Dextran
2.Anti-platelet adhesion drugs: enteric aspirin, pentoxifylline, resistacrid, clopidogrel, etc.
3.For cases with high risk of thrombosis, low molecular heparin can be applied prophylactically, such as Sulforaphane, etc.