Preface
Venous thromboembolic disease (VTE) includes deep vein thrombosis (DVT) and pulmonary embolism (PE), which are now treated as unified diseases due to their interconnected pathogenesis.VTE is common, with an incidence of 1 in 1,000 in the United States and Europe, and is on the increase, and is associated with an increased risk of death, with high early mortality rates for both DVT and PE. 3,8% and 38,9%, respectively. The development of noninvasive diagnostic techniques has simplified the diagnosis of VTE and increased the detection rate. However, fatal PE can be the first manifestation of the disease. In addition, advanced age is a risk factor for VTE and its complications, and the increase in the aging population will certainly lead to an increase in the future mortality and disability of the disease. Pulmonary embolism has serious consequences once it occurs, and venous thromboembolism should focus on prevention.
There is no large-scale survey on the incidence of deep vein thrombosis and pulmonary embolism in China, and the prevention and treatment of venous thromboembolic disease in China is very different from international guidelines, and there is an urgent need for a document to guide the standardized clinical treatment to improve the prevention and treatment of venous thromboembolic disease in China.
Prevention of venous thromboembolism
Epidemiological studies have shown that venous thromboembolism (VTE) is one of the leading causes of death and disability in hospitalized patients, and PE is the most common and preventable cause of in-hospital mortality, and prevention of PE is the most important strategy to reduce in-hospital mortality. The onset of a massive PE is usually not preceded by an aura, and therefore the success rate of CPR in such patients is extremely low. The possibility of PE was not even considered prior to death in 70-80% of patients who died from PE during hospitalization.
Most hospitalized patients have one or more risk factors for VTE, and these risk factors are often confounded. For example, patients with hip fractures are often at high risk for VTE because of their age, proximal lower extremity injury, surgical repair, and the need for several weeks of postoperative braking. The risk of VTE is even higher when there is a coexisting tumor. The risk factors for VTE should be evaluated routinely and preventive measures should be taken for inpatients, as shown in the table below.
Risk stratification
To prevent VTE, patients should first be stratified into risk groups and adopt a group prevention strategy based on criteria such as age, nature of the disease, and the patient’s own factors.
Surgical inpatients
Factors affecting the occurrence of VTE in surgical patients include the type of surgery and duration of surgery, as well as the patient’s own factors. See Table-2
Risk factors: history of VTE, tumor, coagulation factor hypercoagulable state.
In combination with the following risk factors such as advanced age, malignancy, presence of neurological dysfunction, previous history of VTE, or trans-anterior pathway surgery
Inpatients in internal medicine
In addition to the association of VTE with surgery or trauma, in fact 50-70% of symptomatic thromboembolic events and 70-80% of fatal PEs occur in non-surgical patients. The average medical inpatient is at low to moderate risk of VTE if not prevented, with a 5-7% incidence of asymptomatic DVT, mostly confined to the distal veins of the lower extremities. However, patients with certain serious medical conditions are at significantly increased risk of VTE, including: patients hospitalized with congestive heart failure (New York Heart Failure Class III and IV) or severe respiratory disease (worsening chronic obstructive pulmonary disease), bedridden with one or more other risk factors: active cancer, history of venous thromboembolism, sepsis, acute neurological disease (stroke with lower extremity mobility), and inflammatory bowel disease, etc. Many medical patients often have multiple risk factors, which are also more complex.
In addition to hospitalized patients, other special circumstances, such as long-distance travel, can increase the risk of VTE. Flights longer than 6 hours, regardless of the risk of VTE, care should be taken to avoid wearing tight clothing around the lower extremities and waist, to avoid dehydration, and to perform frequent gastrocnemius stretching; those at risk of VTE should consider graduated compression stockings or applying a dose of LMWH or sulforaphane sodium before the trip.
Pharmacologic Prophylaxis
One of the major barriers to thrombosis prevention strategies is the concern about bleeding complications. However, numerous meta-analyses and placebo-controlled, double-blind, randomized clinical studies have confirmed that prophylactic doses of low-dose normal heparin (LDUH), low-molecular-weight heparin (LMWH), or vitamin K antagonists (VKA) increase the risk of clinically significant bleeding complications by little, and there is growing evidence for new anticoagulants such as pentose. There is good evidence that adopting the right prevention strategy can achieve the desired risk/benefit and cost/benefit. Thrombosis prevention strategies not only improve patient prognosis, but also reduce total hospital costs.
I. Antiplatelet drugs
Antiplatelet agents such as aspirin are very effective in reducing major vascular events in people with atherosclerosis or at high risk. There is evidence that antiplatelet agents are protective in hospitalized patients with a combined risk of VTE, but aspirin alone is not recommended for VTE prevention, primarily because of the small size and flawed design of clinical studies supporting antiplatelet agents, inconsistent results, and their poorer efficacy than other prevention methods, such as heparin.
II. Anticoagulation therapy
1.General heparin
In the prevention of venous thrombosis, a large number of studies have confirmed the efficacy of subcutaneous injection of common heparin, but the bioavailability of subcutaneous injection of common heparin is reduced compared with that of intravenous drug. Subcutaneous injection of low-dose plain heparin LDVH is suitable for patients at intermediate and high risk, such as: general surgery, medical inpatients, obstetrics and gynecology and urology procedures. However, it is not suitable for very high-risk patients on its own, such as prophylaxis for hip and knee arthroplasty, and other surgical procedures with multiple risk factors.
Dose: Two doses are recommended, depending on the patient’s risk level, without APTT monitoring.
Intermediate-risk dose: 5000 U twice daily by subcutaneous injection.
High-risk dose: 5000 U three times a day, subcutaneously.
Time of treatment initiation.
Internal: no contraindication to anticoagulation to start dosing.
Surgical: LDUH 5000U given subcutaneously 1-2 hours before surgery in most prophylaxis studies.
Time to start the drug after the operation: 12-24 hours after the operation, give 5000U Bid or Tid subcutaneous injection.
2.Low molecular heparin
Although there are significant differences in the pharmacological properties of different LMWH and each LMWH should be treated as a separate drug, the results of studies have shown no significant differences in the efficacy of different LMWH. There are no studies directly comparing the efficacy of different LMWH in surgical patients, and the different formulations need to refer to the recommendations in the product insert.
Intermediate-risk dose: LMWH ≤ 3400 U once daily
High-risk dose: LMWH>3400U/day once daily
Table-3 Doses of different low molecular heparin prophylactic anticoagulation therapy
Time of treatment initiation:
The timing of treatment initiation is influenced by the patient’s surgical and bleeding risk. It is important to fully evaluate the effectiveness of a particular anticoagulant, bleeding risk to determine the time to start prophylaxis, and the type of anesthesia may also have an impact on the choice of prophylaxis and the time to start.
1.For general general surgery, obstetrics and gynecology and urology, appropriate doses of heparin are given subcutaneously 1-2 hours before surgery and daily in the morning after surgery until the patient is mobile, which usually takes 5-7 days or longer.
2. Trauma: For most patients with intermediate and high-risk trauma, once the initial bleeding is controlled, it can be started. Contraindications to early application of LMWH prophylaxis include: intracranial hemorrhage, progressive bleeding, uncontrollable bleeding, uncorrectable severe coagulopathy, and incomplete spinal cord injury with suspected or proven peri-spinal hematoma. Head injury without significant bleeding, lacerations or contusions of internal organs (e.g., lung, liver, spleen, or kidney), retroperitoneal hematoma after pelvic fracture, and complete spinal cord injury are not contraindications to the application of LMWH after possible progressive bleeding has been excluded. The vast majority of patients are able to start the application of LMWH for prophylaxis within 36 hours after trauma.
3. Orthopedics: There is little difference between preoperative and postoperative application of LMWH, both of which can be used. For patients with elective THR, LMWH is started 12 hours preoperatively or 12-24 hours postoperatively, or the first half of the higher prophylactic dose is given 4-6 hours postoperatively, and the higher prophylactic dose is applied the following day.
4. Hip fracture: If HFS is not operated immediately, it is recommended to start preventive measures by giving short-acting anticoagulant such as LDUH or LMWH before surgery.
5, For patients with high risk factors for bleeding, it is recommended that the first application of LMWH should be delayed until 12 to 24 hours after surgery until it is confirmed by examination that bleeding from the surgical site has largely stopped.
6. Patients with acute spinal cord injury are prevented with LMWH and should start applying it once basic hemostasis has been successfully performed. If CT scan or MRI examination suggests the presence of peri-spinal hematoma in patients with incomplete spinal cord injury, the application of LMWH should be delayed for 1-3 days before starting.
Duration of treatment.
For the vast majority of patients including surgical and medical inpatients, the optimal duration of prophylactic anticoagulation therapy is not well defined.
The general principle: intermediate-risk and high-risk patients should be treated until the patient resumes activity or is discharged from the hospital.
Very high-risk patients require continued application for 2-4 weeks after discharge, and may require longer depending on the situation.
The ideal timeframe for thromboprophylaxis in medical patients is not known, and the duration of evidence-based dosing is generally 2 weeks.
Extended therapy: Extended anticoagulation therapy is required in the following situations.
1. In oncology patients undergoing general surgery, continued use of LMWH for 2-3 weeks after hospital discharge appears to reduce the incidence of asymptomatic DVT.
2.For high-risk patients undergoing major gynecologic surgery, such as those undergoing malignant surgery, age >60 years or previous history of VTE, it is recommended to continue anticoagulation for 2-4 weeks after discharge.
3. Extended prophylaxis up to 28-35 days is recommended for patients with THR or HFS.
Patients undergoing major orthopedic surgery are vulnerable to VTE if they have the following factors, such as a history of VTE or obesity, low activity, advanced age or cancer Other clinically significant risk factors are a history of congestive heart failure or COPD and being female. VKA (INR target value of 2,5, range: 2,0-3,0) can be chosen instead of LMWH for prevention after discharge.
4. After the acute spinal cord injury period, it is recommended to continue with LMWH prophylaxis or switch to oral full-dose VKA during the rehabilitation phase .
3. Fondaparinux sodium
Fondaparinux is a synthetic pentose that selectively inhibits coagulation factor Xa. At least two large clinical studies have demonstrated the effectiveness of fondaparinux in preventing DVT in patients with THR, both of which showed no increased risk of bleeding compared with LMWH, and one study on high-risk general surgery, but it is difficult to recommend.
It is used in the perioperative period for elective THR surgery, TKR surgery, and hip fracture surgery.
The safety of sodium fondaparinux in patients with postoperative indwelling epidural catheter injected analgesia has not been demonstrated. It is recommended that sulforaphane sodium not be used for continuous epidural pain relief.
Dose: 2 or 5 mg daily by subcutaneous injection.
Time of initiation: application started 6-8 hours after elective THR, TKR, HFS.
Duration of treatment is the same as for low molecular heparin.
4.Direct thrombin inhibitor
Several studies have evaluated the role of direct thrombin inhibitors, such as leechin, melagatran and oral preparations such as ximelagatran. 3 randomized clinical studies demonstrated that preoperative use of recombinant complex leechin (15 mg subcutaneously twice daily) was more effective than LDUH or LMWH in THR patients, with no significant difference in the incidence of bleeding. Phase II studies confirmed that the efficacy and safety of preoperative subcutaneous melagatran followed by oral ximelagatran or postoperative oral ximelagatran alone for the prevention of venous thrombosis was similar to that of LMWH. Three double-blind clinical studies compared the prophylactic efficacy of ximelagatran with appropriate doses of warfarin. The efficacy and safety of ximelagatran in the ximelagatran group was similar to that of adjusted doses of warfarin when administered orally at 24 mg twice daily starting early in the morning the day after surgery, with potentially superior mortality. To date the melagatran/ ximelagatran prophylaxis regimen is still not approved in North America.
5. Vitamin K antagonists (VKAs)
VKAs are one of the effective prophylactic measures. Because VKAs are the mainstay of long-term therapy with slow onset of action, they are often used in combination with heparin in the acute phase. The increased risk of bleeding with better efficacy of LMWH and fondaparinux compared to VKAs may be related to their faster anticoagulant effect.
In patients with elective THR or TKA, HFS, the target INR is usually reached only 3 days after surgery when the appropriate dose of VKA is applied preoperatively or on the evening of the postoperative period.
VKA can be used in patients who need extended prophylaxis after THR or TKA.
For patients in the recovery phase after spinal cord injury, it is recommended to continue LMWH prophylaxis or switch to oral VKA prophylaxis, and to start long-term anticoagulation with oral full-dose VKA should be at least 1 week after injury.
Warfarin dosing: INR target value 2,5; INR range 2,0-3,0.
Non-pharmacological methods
1.Activity
Active activity can reduce the occurrence of VTE. For patients with non-severe medical disease and minor surgery with unrestricted activity, it is sufficient to encourage early activity without the application of drugs for thrombosis prevention.
2.Vena cava filter
Some experts recommend prophylactic implantation of an inferior vena cava filter (IVCF) in trauma patients at high risk for VTE. No randomized clinical trials have studied the prophylactic effect of IVCF, and prophylactic IVCF implantation does not reduce mortality in trauma patients. The greatest challenge to filter implantation is the lack of evidence of filter efficacy or efficacy ratio. Routine implantation of IVCF is not recommended as a prophylactic measure, even in patients at high risk for VTE. Indications: Proximal DVT, patients with contraindications to full-dose anticoagulation therapy or those who have recently undergone major surgery.
3.Mechanical prophylaxis methods
Mechanical prophylaxis methods for VTE that increase venous blood flow and/or reduce venous stasis in the lower extremities include
segment-by-segment compression stockings (GCS) or compression stockings, the
Intermittent balloon compression (IPC) devices
Lower extremity venous pumps (VFP)
Mechanical methods may reduce the risk of DVT in some patients, but are less effective than anticoagulants, with the greatest advantage being the absence of bleeding complications, but GCS should be used with caution in patients with concomitant arterial insufficiency. currently, no mechanical method has been shown to reduce the risk of death or PE. These devices should be applied in both legs whenever possible and continued until LMWH therapy can be initiated. Very high-risk patients have poor efficacy when applied alone and a combination with effective anticoagulation therapy is recommended.
Indications for anticoagulant therapy but with a high risk of bleeding, mechanical methods of thromboprophylaxis are recommended as the first choice until the risk of bleeding decreases, including general surgery, severe trauma, spinal injuries, hip fractures, etc.
Indications for use alone: some intermediate-risk patients, such as laparoscopic operations, large benign gynecologic procedures without other risk factors; large open urologic procedures; elective spine surgery with risk factors in the perioperative period; intracranial neurosurgery: IPC combined with or without GCS is preferable to postoperative LDUH or LMWH.
Combined with anticoagulants for very high-risk patients. Including: general surgery patients with multiple risk factors, gynecologic malignancy expansion or with other risk factors, urology with multiple risk factors; spinal surgery with multiple risk factors; neurosurgery with high-risk factors.
Internal medicine: mechanical prophylaxis such as GCS or IPC is recommended for internal medicine patients with risk factors for VTE and contraindications to anticoagulant prophylaxis (e.g., with high risk of bleeding).
Treatment of venous thromboembolism
Venous thromboembolic disease has been treated as a separate disease, and the disease processes of DVT and PE present similarly, with the exception of massive PE and thromboembolic pulmonary hypertension, and the treatment options for both are similar. Treatment of acute VTE includes antithrombotic and thrombolytic drugs, devices, or surgical techniques. The treatment of post-thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (CTPH), two important complications of acute DVT and PE, will also be addressed.
Once venous thromboembolism occurs, the consequences are severe and the main goals of treatment are to reduce PE, prevent post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension, and prevent recurrence of DVT and PE. Anticoagulation is the basis of venous thromboembolic disease, and the issues to be emphasized are effective drugs and adequate duration of treatment. The most striking changes in the current treatment of VTE compared to previous treatments are the more prominent position of LMWH, the more defined course of oral VK antagonists, and the stricter indications for thrombolysis, interventional or surgical thrombectomy and vena cava filters.
Acute treatment
I. Drug treatment
Anticoagulation therapy
The aim of anticoagulation in the acute phase is to prevent the spread of thrombus and the early and late recurrence of DVT and PE. There are three options for initial treatment.
(1) weight-adjusted subcutaneous LMWH, without monitoring.
(2) Intravenous UFH.
(3) subcutaneous injection of UFH.
1. Time to start anticoagulation therapy
Anticoagulation therapy should be started as soon as the diagnosis is established by objective examination. If there is a high degree of clinical suspicion and the diagnostic test is delayed, treatment should be started while waiting for the results and continued after the diagnosis is clear.
2.Anticoagulant drugs.
2,1 Common heparin.
Intravenous: UFH is still one of the preferred starting treatments for DVT. UFH has a narrow therapeutic window and must be monitored to ensure optimal efficacy and safety. aPTT is the most commonly used monitoring method. aPTT should be standardized after treatment to a range equivalent to the plasma heparin level of anti-factor Xa activity measured by the amidolytic method at 0,3 to 0,7 IU/ml, for For patients requiring daily application of high doses of UFH who cannot achieve the therapeutic range of aPTT, determination of anti-Factor Xa levels is recommended to guide dosing. Repeated intermittent intravenous push of UFH is not recommended, the risk of bleeding is high.
For the treatment of DVT with UFH, the first dose is pushed with 5000 U, followed by a continuous dose of at least 30,000 U or 80 U/kg by kg body weight over the first 24 hours, followed by 18 U/kg/h maintenance. Thereafter the dose is adjusted using standard arithmetic charts to rapidly achieve and maintain target (heparin treatment level) aPTT.
Subcutaneous injection: UFH twice daily can be used as an alternative to UFH intravenously. Subcutaneous UFH is at least as safe and effective as I.V. UFH as long as an adequate starting dose is used and the dose is adjusted to achieve the therapeutic range APTT. The conventional regimen is: on the first day, 5000 U IV for the first time, followed by 17500 U (2 times/day) SC. When subcutaneous heparin is applied, aPTT is measured 6 hours after morning dosing and the UFH dose is adjusted to maintain APTT at 60-85 S. To date, no RCTs have evaluated the efficacy and safety of UFH or LMWH for upper extremity DVT.
2,2 Low molecular heparin.
Compared with UFH, LMWH has better pharmacokinetic predictability and better bioavailability. In view of these pharmacological characteristics, the dose of subcutaneous injection can be adjusted according to body weight, once or twice daily, and most patients do not need to identify the test. The doses of LMWH available in China are shown in the table below. There is no difference in efficacy and safety between different LMWH, and different manufacturers’ preparations should refer to their product instructions for use.
LMWH is superior to UFH and has comparable efficacy. the main advantage of LMWH is that it is easy to use and can be discharged early and can be treated at home, so it saves money.
LMWH is better than UFH for normal renal function; for severe renal failure, intravenous UFH is better than LMWH.
In some cases such as severe renal failure or pregnancy, plasma anti-Xa levels need to be measured to adjust the dose to achieve therapeutic goals. Adjustment of SC according to body weight 4 hours after LMWH is the most reasonable time to measure anti-Xa. The therapeutic range for twice-daily dosing is 0,6 to 1,0 IU/mL. The target target value of LMWH once daily is unclear, and 1,0 to 2,0 IU/mL seems to be reasonable.
2, 3. Therapeutic regimen.
LMWH or UFH is applied for at least 5 days and VKA is started on the first day of treatment. heparin therapy is stopped when INR is stable and >2,0.
3.Vitamin K antagonist (VKA)
VKA is the drug of choice for long-term treatment of PE. There is no uniform opinion on the optimal starting dose of VKA, and the starting dose has a large window. The starting doses of warfarin reported abroad are 5mg and 10mg respectively, and the occurrence of excessive anticoagulation and transient hypercoagulable state are less with 5mg as the starting dose. There are no relevant clinical studies in Chinese, but based on the experience of treatment of other diseases, it is recommended that the first dose can be chosen as 3mg, while the elderly and patients with high risk bleeding tendency should avoid using loading dose VKA, the first dose can be appropriately reduced, and the dose should be subsequently adjusted to maintain INR at 2,5 (2,0~3,0).
4.New anticoagulant drugs
In recent years, a variety of new anticoagulants have emerged: synthetic pentose fondaparinux is used for the initial treatment of venous thromboembolism at least as safely and effectively as low-molecular heparin or normal heparin. Oral direct thrombin inhibitor therapy is as safe and effective as conventional low-molecular heparin followed by warfarin therapy without monitoring.
5. Additional recommendations for anticoagulation therapy.
Antiplatelet therapy alone (aspirin) VTE is not effective.
There is limited evidence of efficacy of non-steroidal anti-inflammatory drugs for DVT. Non-steroidal anti-inflammatory drugs are not recommended for the treatment of DVT.
Monitoring of special populations.
Obese patients (weight over 150 kg): doses adjusted for body weight may lead to overdose. Conversely, fixed doses are used and underdosing is likely to occur. Anti-factor Xa levels should be monitored at this time.
Heparin-induced thrombocytopenia (HIT)
1, The diagnosis of HIT is based on both clinical manifestations and serology. HIT can be diagnosed in the following cases: HIT antibody formation accompanied by an unexplained decrease in platelet count (usually by ≥50%); skin lesions at the heparin injection site; acute systemic reactions (e.g. chills) after heparin intravenous injection.
2.The occurrence of HIT in heparin therapy is influenced by the preparation of heparin (bovine UFH > porcine UFH > LMWH) and the population treated (post-surgical > medical treatment > pregnant patients), and the chance of HIT occurring with low-molecular heparin is lower than UFH, but there is a cross-reaction between the two.
3. Platelet count should be monitored during heparin application.
Basal platelet count should be measured in patients who are being treated with UFH or LMWH for the first time, who have received UFH within the last 100 days and whose treatment history is unclear, and should be repeated within 24 hours of starting heparin therapy.
Platelet monitoring was performed every two or three days in postoperative patients receiving prophylactic doses of LMWH therapy or in medical/obstetric patients who started LMWH therapy after the first UFH treatment (HIT risk of 0,1%-1%).
For those on continuous heparin, continuous monitoring continued from day 4 to day 14 or until heparin was discontinued.
Internal medicine/obstetrics patients treated with LMWH only may not require routine monitoring of platelet count.
4. Patients with highly suspicious or confirmed HIT, regardless of thrombosis, should discontinue heparin and substitute other prothrombin inhibitors such as leucovorin, atrobanbiludine or dalteparin. Warfarin cannot be applied and platelet transfusions are not recommended.
Thrombolytic therapy
Anticoagulation therapy significantly reduces mortality and recurrence rates in patients with VTE. Theoretically, thrombolytic drugs dissolve the thrombus and open the obstructed vessel, and thrombolysis improves imaging and hemodynamic abnormalities more rapidly than anticoagulation, but these benefits are short-lived and there is no difference in clinical prognosis such as mortality or symptomatic relief between thrombolytic and anticoagulant therapy in most patients with VTE. Therefore, there has been controversy over which thrombolytic and which anticoagulant therapy to choose for VTE, especially acute pulmonary embolism, and the controversy over thrombolytic therapy for DVT has focused on whether it can prevent PTS from occurring. The benefits of anticoagulation and thrombolysis are evaluated taking into account the risks of treatment, such as bleeding.
Indications
In most patients with VTE, the routine use of intravenous thrombolytic therapy is not recommended and the following should be considered.
Patients with new onset large iliofemoral vascular DVT who are at risk of secondary limb gangrene due to venous occlusion despite adequate heparin therapy.
Patients with acute massive PE, hemodynamic instability, and no bleeding tendency.
In patients with ultrasound-confirmed right ventricular insufficiency and hemodynamic stability, further studies are needed to confirm whether thrombolytic therapy is superior to anticoagulation.
Short-course thrombolytic therapy is recommended for certain patients with acute upper extremity DVT, such as those with a low risk of bleeding and recent new symptoms, but there are no RCTs evaluating the efficacy and safety of thrombolysis for upper extremity DVT.
Time window for thrombolysis
Early studies have shown an increased benefit of early thrombolysis. In the UPET study, urokinase efficacy was better in patients with symptom onset of less than 2 days than in patients with symptom onset of 2-5 days. In conclusion, the efficacy of thrombolysis decreases with increasing time. Therefore, thrombolysis is best in patients immediately after the onset of PE, but may still be beneficial at 14 days, the earlier the better.
Thrombolytic drugs
The use of short-term intravenous thrombolysis is recommended over prolonged intravenous thrombolysis.
Streptokinase is first given as a loading dose of 250,000 IU followed by a 100,000 IU/h drip for 24 h.
Urokinase is given at a loading dose of 4400 IU/kg, followed by 2200 IU/kg for 12h.
tPA 100mg titrated for 2h, together with heparin.
Reteplase for VTE has shown promise for rapid thrombus dissolution. Usage:10 U by intravenous push in two divided doses over 30 minutes intermittently, but not yet approved.
Factors that may put the patient at increased risk of bleeding should be adequately evaluated and removed prior to thrombolysis. Take a detailed history and physical examination to detect signs of gastrointestinal bleeding or intracranial hemorrhagic lesions. Necessary laboratory tests include: hemoglobin, hematocrit and platelet count, and blood type for transfusion.
Non-pharmacological treatment
Action
Traditionally, bed rest for a few days is recommended in patients with DVT along with anticoagulation to avoid PE due to embolus dislodgement. two small sample randomized studies showed that bed rest on top of anticoagulation did not reduce the incidence of asymptomatic PE. In contrast, relief of pain and swelling was faster in patients with early activity and lower extremity compression. It is recommended that patients with DVT who are able to move do not need bed rest. With aggressive and effective anticoagulation therapy, patients are recommended to be out of bed as tolerated.
Vena cava filter
Routine use of a vena cava filter in addition to anticoagulation is not recommended for most patients with DVT. The most commonly used method for blocking the inferior vena cava is the filter invented by Greenfield and Rutherford.
Indications.
The presence of contraindications or complications to anticoagulation in patients with proximal venous thrombosis.
? The presence of contraindications or complications to anticoagulation in patients at high risk of PE recurrence.
Certain patients with acute upper extremity DVT in whom anticoagulation is contraindicated should be considered for placement of an upper vena cava filter.
Recurrence of thromboembolism (DVT/PE) despite adequate anticoagulation therapy.
Heparin-induced thrombocytopenia.
Chronic recurrent PE with pulmonary hypertension, surgical pulmonary artery embolization or operation of pulmonary thromboendarterectomy.
Contraindications to filter placement include abnormal venous anatomy, pregnancy, and the presence of an embolus proximal to the site of intended implantation.
Most studies of vena cava filters are uncontrolled, and many of them have incomplete results and low credibility. A new direction in the development of venous filters is the removable vena cava filter.
Interventional and surgical treatment
1. Catheter thrombolysis for DVT
Catheter-directed thrombolytic therapy is not routinely recommended.
For occlusive iliofemoral DVT, rapid removal of thrombus and restoration of venous blood flow is considered for patients who need to save the limb.
The most commonly used thrombolytic agents are urokinase and tPA, but there are no well-designed studies to base this on.
Catheter-directed thrombolysis can cause local and systemic bleeding and should be carefully evaluated for benefit/risk.
2. Catheter aspiration or fragmentation and surgical thrombectomy for DVT
Venous thrombectomy is not recommended for the majority of patients with proximal DVT.
Indications: Certain patients who are too critically ill to receive thrombolytic therapy or do not have sufficient time for intravenous thrombolysis; patients with proximal DVT who have post-traumatic, post-operative or post-partum thrombosis and are younger than 40 years of age.
This approach may be considered for certain patients with “femoral cyanosis”.
Surgical thrombectomy is often complicated by recurrent thrombosis, and many patients require secondary dilatation and/or re-intervention and long-term anticoagulation.
3. Catheter aspiration or crushing for PE
Although a variety of new devices have been developed, there is a lack of experience with strong recommendations, which can also be used in combination with drugs.
For most PE patients, mechanical methods of treatment are not recommended.
It can be used for some patients who cannot receive thrombolytic therapy for severe disease, or for patients with severe disease without sufficient time for intravenous thrombolytic therapy.
4. Pulmonary thrombectomy for PE
When drug therapy fails, pulmonary thrombectomy can be used in emergency situations when an experienced cardiac surgery team is available. The indications are: (1) large PE; (2) hemodynamic instability (shock) after measures such as heparin and resuscitation; (3) failure of thrombolysis or contraindication to thrombolysis; (4) surgical thrombectomy or catheter aspiration is recommended for certain patients with acute upper extremity DVT, if anticoagulation or thrombolysis has failed but symptoms persist.
Long-term treatment
Patients with pulmonary embolism, proximal vein thrombosis (N, femoral and iliac vein thrombosis) and gastrocnemius DVT require long-term treatment, especially in patients with unknown or non-removable risk factors; the duration of long-term treatment is not fully defined, but there is a tendency to prolong it.
1. Vitamin K antagonists (VKA)
VKA is the first choice for long-term treatment in most patients with DVT/PE of the lower extremities. Long-term use of adjusted-dose VKA (such as warfarin or coumarin acetate) is very effective in preventing VTE recurrence.
Dose and intensity: The results of two randomized trials showed that low-intensity warfarin treatment was more effective than placebo, but less effective than standard intensity treatment (INR 2,0-3,0), and did not reduce bleeding complications. High-intensity warfarin treatment (INR, 3,1-4,0) did not increase antithrombotic protection and had a high risk of severe bleeding (20%). The INR should be kept at 2,5 (INR range 2,0 to 3,0) during treatment; high-intensity (INR 3,1 to 4,0) and low-intensity (INR 1,5 to 1,9) treatments are opposed.
2.LMWH
Indications VKA is contraindicated (e.g. pregnancy), cannot be applied or in patients with combined cancer.
Most patients with DVT/PE combined with cancer are better treated with LMWH than VKAs for at least 3 months to 6 months. the LMWH that has conclusively proven effective for long-term treatment in randomized clinical trials is dalteparin, starting with 200 IU/kg body weight once daily for 1 month, followed by a reduction to 150 IU/kg natriuretic heparin 85V/hg twice daily, with the dose reduced by half after two weeks or Tinzaparin 175IU/kg by subcutaneous injection once a day.
There are no studies on the efficacy of long-term use of LMWH for upper extremity venous thrombosis treatment.
3.Subcutaneous injection of UFH
Subcutaneous UFH injection is an effective method for the long-term treatment of DVT, and UFH can also be considered for the long-term treatment of DVT patients in pregnancy.
Course of long-term treatment.
Patients receiving indefinite anticoagulation therapy should be evaluated periodically for risk-benefit from continued therapy.
Repeated probing for residual thrombosis using compression ultrasound or repeated monitoring of plasma D-dimer levels is recommended.
Elastic compression stockings or elastic bandages
An elastic compression stocking with an ankle pressure of 30 to 40 mmHg is recommended for 2 years after the onset of DVT.
In patients with DVT of the upper extremity with persistent edema and pain, an elastic bandage is recommended for symptomatic relief.
Other treatments
Post thromboembolic syndrome (PTS)
Post-thromboembolic syndrome (or post-phlebitis syndrome) is a collective term for a range of signs and symptoms in patients with prior venous thrombosis, often referred to as chronic venous insufficiency. The most prominent symptoms are chronic posture-dependent swelling and pain or local discomfort. The severity of symptoms varies over time, with the most severe manifestation being venous ulceration of the ankle.
Patients with mild leg edema due to PTS are recommended to use elastic compression stockings.
patients with severe edema of the leg due to PTS, intermittent balloon compression is recommended
Patients with mild edema due to PTS, the use of rutin thrombosed superficial phlebitis is recommended
for patients with thrombotic superficial phlebitis complicated by infusion, topical diclofenac gel or oral diclofenac is recommended
For patients with spontaneous thromboembolic superficial phlebitis, treatment with moderate doses of UFH or LMWH is recommended for at least 4 weeks.
Chronic thromboembolic pulmonary hypertension (CTPH)
Pulmonary thromboendarterectomy is currently the only therapy to relieve symptoms and prolong life in patients with CTPH. No RCTs have yet compared surgical treatment with pharmacologic therapy, such as the use of long-term anticoagulation or pulmonary vasodilators.
Only pulmonary segmental vessels or more proximal intra-arterial thrombi are suitable for surgical resection.
Requires the care of an experienced surgical/medical team
Distal vessel thrombosis (subsegment or smaller) or coexisting severe disease is not an indication for surgery.
VKA target INR 2,0 to 3,0, should be given for life after pulmonary thromboendarterectomy
Placement of a vena cava filter is recommended prior to or during pulmonary thromboendarterectomy for patients with CTPH
Summary
Venous thromboembolic disease has received increasing attention, and with advances in anticoagulant drugs, simplicity and lack of monitoring have become the trend in anticoagulation therapy. Therefore, low-molecular heparin occupies an important place in prevention and treatment. The new drug sulforaphane sodium has been studied extensively in the prevention and treatment of venous thromboembolism, and has become the anticoagulant of choice, especially in the prevention of thromboembolism in orthopedic arthroplasty, but its value in treatment remains to be further demonstrated. However, there are still many unresolved issues in both prevention and treatment, such as indications for thrombolytic therapy, indications for thromboembolic prophylaxis and timing of drug administration, etc. There is no ideal method for the treatment of PTS and CTPH. In conclusion, once venous thromboembolism occurs, the consequences are serious, and prevention should be emphasized, and evidence-based treatment should be emphasized. Outpatient clinics for thromboembolic diseases are recommended to standardize treatment monitoring and patient management. Only then can we control from upstream, ensure the continuity and effectiveness of treatment, and narrow the gap between clinical reality and medical evidence. It is important and urgent to unify the understanding of thromboembolic diseases, standardize medical practices, and establish a reasonable three-dimensional prevention system.