Deep venous thrombosis (DVT) is a venous reflux disorder caused by abnormal blood clotting in the deep veins, mostly in the lower extremities; thrombus dislodgement can cause pulmonary embolism (PE), and the two together are called venous thromboembolism (VTE). DVT often leads to PE and post-thrombotic syndrome (PTS), which can significantly affect the quality of life and even lead to death in severe cases. In order to improve the diagnosis and treatment of DVT in China and to guide the diagnosis and treatment of DVT in hospitals at all levels, this guideline is formulated.
I. Etiology and risk factors
The main causes of DVT are venous wall damage, slow blood flow and blood hypercoagulation. The risk factors include primary and secondary factors (Table 1), and DVT is mostly seen in patients who are bedridden for a long time, after limb braking, major surgery or trauma, advanced tumor or have obvious family history.
II. Clinical manifestations
DVT mainly manifests as sudden swelling, pain, and increased soft tissue tone of the affected limb; it is aggravated by activity and can be alleviated by elevating the affected limb, and there is often pressure pain at the site of venous thrombosis. One to two weeks after the onset of the disease, superficial veins may appear in the affected limb or dilate. Homans’ sign and Neuhof’s sign are positive when the thrombus is located in the muscular plexus of the calf (Homans’ sign is positive when the affected limb is straightened and the foot is suddenly dorsiflexed, causing pain in the deep muscles of the calf; Neuhof’s sign is positive when pressure is applied to the back of the calf, causing local pain).
Patients with severe DVT of the lower extremities may develop femoral leukomalacia or even femoral cyanosis. Femoral leukomalacia is marked swelling and severe pain in the whole lower extremity, with pressure pain in the femoral triangle, N fossa, and posterior calf, and pale skin, accompanied by elevated body temperature and increased heart rate. Femoral bruise is the most serious case of DVT in the lower extremity, because the iliofemoral vein and its lateral branches are all blocked by thrombus, the venous return is severely obstructed, the tissue tension is extremely high, resulting in arterial spasm in the lower extremity and limb ischemia; the clinical manifestations are severe pain in the affected extremity, the skin is shiny and blue-purple, the skin temperature is low with blisters, the dorsalis pedis artery pulsation disappears, the whole body reacts strongly and the body temperature rises; if not treated in time, shock and venous gangrene may occur If left untreated, shock and venous gangrene may occur.
Once the venous thrombus is dislodged, it can enter and block the pulmonary artery with the blood flow, causing the clinical manifestations of PE.
The main symptoms are swelling and pain in the lower limbs (the severity of which varies with time), and the signs include edema, hyperpigmentation, eczema, varicose veins in the lower limbs, and in severe cases, sebaceous scleroderma and ulcers in the boot area. the incidence of PTS is 20% to 50%.
III. Diagnosis
The diagnosis of DVT cannot be made only by clinical manifestations, but also needs to be confirmed by auxiliary examinations.
(A) Auxiliary examination
1.Plasma D-dimer determination: D-dimer is a specific molecular marker reflecting coagulation activation and secondary fibrinolysis, and has a high sensitivity (>99%) for the diagnosis of acute DVT, and >500 μg/L (ELISA method) has important reference value. It can be used for screening of acute VTE, diagnosis of DVT in special cases, assessment of efficacy, and assessment of the risk level of VTE recurrence.
2.Doppler ultrasonography: with high sensitivity and accuracy, it is the preferred method for DVT diagnosis and is suitable for screening and monitoring of patients. Before ultrasonography, the clinical likelihood of having DVT can be classified as high, moderate or low according to the clinical characteristics score of DVT diagnosis (Table 2). If two consecutive ultrasound examinations are negative, the diagnosis can be excluded for patients with low degree of possibility, and for patients with high and moderate degree of possibility, imaging examinations such as angiography are recommended.
3.Spiral CT venous imaging: it is more accurate and can check the abdomen, pelvis and deep veins of lower limbs at the same time.
4.MRI venous imaging: It can accurately show iliac, femoral and N vein thrombosis, but cannot satisfactorily show calf vein thrombosis. No need to use contrast agent.
5.Venography: High accuracy, not only can effectively determine the presence or absence of thrombus, thrombus site, extent, formation time and collateral circulation, but also is often used to identify the diagnostic value of other methods.
(B) Clinical probability assessment and diagnostic process
The clinical possibility assessment of DVT refers to the Wells clinical score (Table 2), and the diagnosis process of DVT is shown in Figure 1.
IV. Treatment
(I) Early treatment
1.Anticoagulation: anticoagulation is the basic treatment of DVT, which can inhibit the spread of thrombus, facilitate the autolysis of thrombus and lumen recanalization, thus reducing the symptoms, the incidence of PE and the death rate. However, anticoagulation alone cannot effectively eliminate thrombus and reduce the incidence of PTS. The drugs include common heparin, Figure 1: Diagnostic process of deep vein thrombosis
low molecular heparin, vitamin K antagonist, direct factor IIa inhibitor, factor Xa inhibitor, etc.
(1) Common heparin: The therapeutic dose varies greatly among individuals, and coagulation function must be monitored when using it. The starting dose is 80-100 U/kg intravenous push, followed by 10-20 U?kg-1?h-1 intravenous pump, and then adjusted every 4-6 hours according to the activated partial thromboplastin time (APTT), so that the international normalized ratio (INR) of APTT is maintained at 1,5-2,5. Heparin can cause hepain induced thrombocytopenia (HIT), and the platelet count should be rechecked on the 3rd to 6th day of use; once the diagnosis of HIT is established, common heparin should be discontinued.
(2) Low-molecular heparin: less bleeding side effects, lower incidence of HIT than ordinary heparin, no need to monitor coagulation function in most patients when using. It is administered clinically by body mass, 100 U/kg per dose, once every 12 hours, subcutaneously, with caution in renal insufficiency.
(3) Direct factor IIa inhibitors (e.g., argatroban): low relative molecular mass, can enter the thrombus, and have a stronger ability to inhibit thrombin in the thrombus than common heparin, which is more suitable for patients with HIT and those at risk of HIT.
(4) Indirect factor Xa inhibitors (e.g., sodium fondaparinux): small individual differences in therapeutic dose, once daily, no need to monitor coagulation function. The effect on renal function is less than that of low molecular heparin.
(5) Vitamin K antagonists (e.g., warfarin): the main oral drug for long-term anticoagulation therapy, the evaluation of the effect requires monitoring of the INR of coagulation function. The first day of treatment is combined with low molecular heparin or normal heparin at the recommended dose of 2,5-6,0 mg/d. INR measurement is started after 2-3 d. When INR is stable at 2,0-3,0 and lasts for 24 h, stop low molecular heparin or normal heparin and continue warfarin therapy.
(6) Direct factor Xa inhibitors (such as rivaroxaban): individual differences in treatment dose are small and monitoring of coagulation function is not required. The efficacy of monotherapy for acute DVT is comparable to its standard treatment (low molecular heparin in combination with warfarin).
Recommendation: for acute DVT, vitamin K antagonists in combination with low molecular heparin or normal heparin are recommended; stop low molecular heparin or normal heparin after the INR has been achieved and stabilized for 24 h. Direct (or indirect) factor Xa inhibitors may also be used.
In patients with high suspicion of DVT, if there is no contraindication to anticoagulation, anticoagulation is feasible while waiting for test results, and the decision to continue anticoagulation is based on the confirmed results.
Patients with severe renal insufficiency are recommended to use common heparin.
2.Thrombolytic therapy
(1) Thrombolytic drugs: Urokinase is the most commonly used, with fast onset of action, good thrombolytic effect and few allergic reactions to acute thrombosis; common adverse reactions are bleeding; there is no uniform standard for treatment dose, generally the first dose is 4000 U/kg, intravenous push within 30 min; maintenance dose is 600-1.2 million U/d for 48-72 h, and 5-7 d if necessary. recombinant streptokinase, with better thrombolytic The effect is better, but there are many allergic reactions and a high incidence of bleeding. Recombinant tissue-type fibrinogen activator has good thrombolytic effect, low incidence of bleeding, and can be used repeatedly.
(2) Thrombolytic methods: including catheter-contact thrombolysis and systemic thrombolysis. Catheter-contact thrombolysis is to place the thrombolytic catheter into the venous thrombus, and the thrombolytic drug acts directly on the thrombus; systemic thrombolysis is to apply the thrombolytic drug systemically through peripheral veins. Catheter-contact thrombolysis has certain advantages, which can improve the dissolution rate of thrombus, reduce the incidence of venous thrombosis sequelae, short treatment time and fewer complications. Systemic thrombolysis has a lower rate of thrombus dissolution than catheter-contact thrombolysis, but it is effective in early DVT, preserves DVT function in some patients, and reduces the occurrence of PTS.
Plasma fibrinogen (FG) and prothrombin time (TT) must be monitored during thrombolytic therapy, FG <1,0 g/L should be discontinued, and INR of TT should be controlled at 2,0 to 3,0.
RECOMMENDATION: For acute phase central or mixed DVT, catheter-contact thrombolysis is preferred under the premise of good systemic condition, expected survival ≥ 1 year, and low risk of bleeding. If the conditions of catheter thrombolysis are not available, systemic thrombolysis is feasible.
3.Surgical thrombus retrieval: It is an effective method to eliminate thrombus and can quickly release venous obstruction. Fogarty catheter is often used to remove the iliac vein thrombus through the femoral vein, and the femoral N vein thrombus can be removed by squeezing and driving out the thrombus or by taking the thrombus in the parallelepiped.
Recommendation: In case of femoral bruising, the thrombus should be removed surgically immediately. For patients with central or mixed DVT within 7 days of onset, surgical thrombus removal is also feasible in good general condition and without important organ dysfunction.
4.The treatment of combined iliac vein stenosis or occlusion: iliac vein stenosis or occlusion plays an important role in the development of DVT, and the correction of iliac vein stenosis or occlusion at the same time after catheter thrombolysis or surgical embolization can increase the patency rate, improve the treatment effect and reduce the occurrence of PTS.
Recommendation: After successful catheter thrombolysis or incisional thrombectomy, if iliac vein stenosis >50% is found on imaging, balloon dilation and, , , (or) stent placement are recommended as the first choice, and surgical removal of iliac vein obstruction is used if necessary.
5.Indications for inferior vena cava filter placement: Inferior vena cava filter can prevent and reduce the occurrence of PE, but the complications such as inferior vena cava obstruction and high recurrence rate of DVT caused by long-term placement are gradually attracting attention.
Recommendation: Routine use of inferior vena cava filters is not recommended for most patients with DVT; placement of inferior vena cava filters is recommended for those with contraindications to anticoagulation or complications, or for those who develop PE despite adequate anticoagulation.
An inferior vena cava filter may be considered in the following cases.
(1) floating thrombus in the iliac or femoral vein or in the inferior vena cava.
(2) Acute DVT with proposed thrombectomy such as catheter thrombolysis or surgical thrombectomy.
(3) Patients with high risk factors for PE undergoing abdominal, pelvic or lower extremity surgery.
(B) Long-term treatment
Patients with DVT need long-term anticoagulation treatment to prevent the spread of thrombus and/or recurrence of thrombus.
1.Anticoagulation therapy
(1) Anticoagulation drugs and intensity: Vitamin K antagonists (such as warfarin), direct factor Xa inhibitors (such as rivaroxaban), etc. are effective in preventing recurrence. Low standard intensity therapy (INR 1,5 to 1,9) has limited effect and does not reduce the incidence of bleeding. High standard-intensity therapy (INR 3,1 to 4,0) does not provide better antithrombotic treatment and instead increases the risk of bleeding.
Recommendation: If vitamin K antagonists are used, the INR should be maintained at 2,0 to 3,0 during treatment, and regular monitoring is required.
(2) Course of anticoagulation: The course of anticoagulation varies according to the occurrence of DVT: (1) 3 months of anticoagulation therapy is sufficient for patients with first occurrence of DVT secondary to transient risk factors (e.g. surgery); (2) a randomized controlled trial was conducted in patients with first occurrence of DVT in the case of unknown risk factors, comparing the effect of anticoagulation therapy with a course of 1 to 2 years and 3 to 6 months, and found that (2) A randomized controlled trial comparing the effect of anticoagulation therapy for 1 to 2 years with that for 3 to 6 months in patients with first-ever DVT with unknown risk factors found that a longer course of therapy was effective in reducing the recurrence rate of VTE, but the risk of bleeding increased; the decision on whether to administer a long course of anticoagulation therapy to such patients with DVT should be made after full consideration of its advantages and disadvantages; (3) Patients with first-ever DVT with cancer were treated with long-term oral vitamin K antagonists after 3 to 6 months of low-molecular heparin application; (4) Patients with first-ever DVT with primary risk factors for thrombosis DVT with a high recurrence rate, long-term oral treatment with vitamin K antagonists is beneficial; ⑤ In patients with recurrent DVT, long-term anticoagulation therapy is also beneficial to prevent recurrence and control the spread of thrombosis.
Recommendations: 3 months of vitamin K antagonist for patients with first-onset DVT secondary to transient risk factors; 6-12 months or longer of vitamin K antagonist for patients with first-onset DVT with unknown risk factors; 3-6 months of low-molecular heparin application followed by long-term vitamin K antagonist for DVT with cancer and first-onset DVT. For patients with recurrent DVT and embolism-prone patients, long-term anticoagulation is recommended, but risk-benefit assessment is required periodically.
2.Other treatments
(1) Intravenous vasoactive drugs: such as flavonoids, hesperidin, etc. The former can promote venous blood return and reduce swelling and pain in the affected limbs, thus improving symptoms. The latter has the effects of anti-inflammation, reducing exudation, increasing venous vascular tone, improving blood circulation and protecting blood vessel walls.
(2) Physiotherapy: including compression stockings and intermittent pneumatic compression therapy (also known as circulation-driven therapy). Both of them can promote venous reflux, reduce bruising and edema, and are important measures to prevent the occurrence and recurrence of DVT.
Recommendation: For patients in the chronic phase, intravenous vasoactive drugs and long-term use of compression stockings are recommended; if available, limb circulation-promoting devices can be used as an adjunct to treatment.