Reporter: Hello, Professor Zhang! I heard from your students and many medical colleagues that you are a virtuoso vascular surgeon.
Zhang Qiang: I don’t dare to be so. I just want to be a doctor that my patients like. While relieving patients’ pain, I will also be happy physically and mentally.
Reporter: I know you are usually very busy. Today, I would like to take some of your time to talk about the topic of lower limb deep vein thrombosis, okay?
Zhang Qiang: No problem. I am most willing to talk with people about medical stuff.
Reporter: Some time ago, the topic of a professor in Beijing who died unexpectedly after a lumbar spine surgery in the media triggered medical professionals to pay attention to venous thrombosis. It is said that the professor passed away because the thrombus in the deep vein of lower limb dislodged and flowed to the pulmonary artery, causing pulmonary infarction. What is the deep vein thrombosis of the lower limbs?
Zhang Qiang: I have also been following this incident. This tragedy has given the medical staff a wake-up call: we must pay attention to the prevention of lower limb deep vein thrombosis. The so-called lower limb deep vein thrombosis, named DVT (deep venous thrombosis) in English, refers to the formation of blood clots in the lumen of the veins for various reasons. The typical clinical manifestation of DVT in the lower extremity is often swelling and pain in the unilateral lower extremity (left lower extremity is more common). But the early stage of thrombosis can have no obvious symptoms, which is one of the reasons why venous thrombosis is easily ignored.
Reporter: A friend of mine’s mother suffered from lower extremity venous thrombosis and went through many hospitals. He complained that the treatment plans and statements of each hospital were different, which was confusing. May I ask Professor Zhang, how did this happen?
Zhang Qiang: Lower limb deep vein thrombosis is called DVT in Europe and the United States, and it has been attracting attention since the 1960s. Many ordinary people also know some knowledge about DVT. In China, DVT has been paid attention to in recent years. In the past, due to the occlusion of information and some misconceptions in the medical field, DVT of lower extremities was under-diagnosed and misdiagnosed in a high proportion. The difference in the level of understanding and philosophy of DVT in each medical institution has caused the difference in treatment plan.
Reporter: According to your clinical experience, what are the differences in recognition?
Zhang Qiang: First of all, it is in the judgment of the time of onset. As there is a large amount of collateral circulation in the venous system, early thrombosis does not prevent the smooth return of venous blood. Only when the thrombus spreads to a certain length and blocks the proximal and distal openings of the collateral circulation, does it manifest clinically as swelling of the lower limbs. Therefore, in general, the cases that are diagnosed only when the swelling of the lower extremities appears clinically are often more than a few days old.
Reporter: Does the determination of the time of onset have any guiding significance for the treatment plan?
Zhang Qiang: It is very important. Venous thrombosis is like cement, it can be flushed out early, but once it forms a clot, it cannot be dissolved. Although this analogy is not very appropriate, it is true that venous thrombosis starts to partially mechanize after tens of hours of formation. A mechanized vein clot is very difficult to resolve by thrombolysis. Surgical retrieval is also very unsuitable, as the mechanized thrombus is tightly adhered to the vein wall and forcible retrieval can lead to damage to the vein wall resulting in more extensive thrombosis. Therefore, early diagnosis is very important.
Reporter: How can early diagnosis of lower extremity deep vein thrombosis be made?
Zhang Qiang: Although there are no obvious symptoms of early deep vein thrombosis, experienced doctors can still find some clues through careful physical examination. For example, pain in the deep part of the calf when squeezing the stomach often indicates calf vein thrombosis (known as Homan’s sign in medical science). This is due to the sterile inflammation of the surrounding tissues during venous thrombosis, and by the same token, painful pressure at the base of the thigh often indicates thrombosis of the femoral vein. Of course, as soon as there is a suspicion of DVT, blood D2 aggregates are tested and ultrasound is performed to detect the deep veins for a definitive diagnosis. In this way, most cases of DVT can be diagnosed early. However, ultrasound is easy to ignore for calf vein thrombosis, and also has a low diagnostic rate for iliac or vena cava thrombosis (interference from intestinal gas). Therefore, a high clinical suspicion of venous thrombosis without an ultrasound report showing thrombosis does not mean that thrombosis can be excluded. If necessary, iliac venography or CT of iliac veins can be used.
Reporter: Is there any significance of D2 aggregates testing index?
Zhang Qiang: Plasma D-dimer measurement is a test to understand the secondary fibrinolytic function. D2 aggregates (D-Dimer) can be elevated in many cases: acute deep vein thrombosis, pulmonary embolism, during thrombolysis, myocardial infarction, cerebral infarction, severe hepatitis, surgery, tumor, kidney disease, organ transplant rejection, infection and tissue necrosis can lead to elevated D-dimer. However, it is not elevated in the presence of old thrombosis. Therefore, elevated D2 aggregates (D-Dimer) indicators are not completely diagnostic of venous thrombosis, whereas negative indicators can exclude acute venous thrombosis. A special reminder: once a thrombosis is clinically suspected, plasma D-dimer must be drawn as soon as possible! Otherwise, the significance of the test is lost.
Reporter: Is it possible to dissolve the thrombus found early with drugs?
Zhang Qiang: The issue of thrombolysis has been controversial in the medical field. In China, many people have great expectations when they hear the tempting word “thrombolysis”. In fact, the word “thrombolysis” refers more to the mechanism of the drug rather than the inevitable outcome of the treatment. The latest international ACCP guidelines for thrombosis do not recommend thrombolysis as the preferred treatment for lower extremity DVT for three reasons: first, the clinical manifestation of venous thrombosis lags behind, and thrombolytic drugs are ineffective for mechanized thrombosis; second, the bleeding risk of thrombolytic drugs is great, especially in elderly patients who may have fatal cerebral hemorrhage; third, a large number of comparative studies have shown that the therapeutic effect of thrombolysis is not better than anticoagulation. Of course, with the development of interventional technology in recent years, further experience is still being accumulated on whether the development of cannulated thrombolysis can reduce complications and improve the therapeutic effect. From the current clinical results, it is still relatively optimistic. However, the indications should be strictly controlled. For iliac vein thrombosis or inferior vena cava thrombosis, as long as the onset time is within two weeks, active interventional thrombolytic therapy can be considered.
Reporter: Is the anticoagulation treatment mentioned earlier the preferred treatment option for lower limb deep vein thrombosis?
Zhang Qiang: Yes. As long as the patient has no bleeding tendency or coagulation problems, anticoagulation is generally preferred. The function of anticoagulation is to prevent the thrombus from spreading or forming new thrombus, so as to open the lateral circulation to relieve the symptoms.
Reporter: Does standardized treatment refer to anticoagulation therapy?
Zhang Qiang: As the first choice for lower extremity DVT, anticoagulation therapy is applied with different techniques, which may result in different outcomes. The standard anticoagulation therapy has the following points.
(1) Subcutaneous injection of low molecular heparin precedes oral administration of warfarin. Warfarin has a slow onset of action and can induce thrombosis in the early stages of drug administration. Therefore, it is important to use low-molecular heparin as the initiating anticoagulation regimen.
(2) Wait for warfarin to take effect and become relatively stable before discontinuing subcutaneous injection of low-molecular heparin.
(3) Adjust the dose of warfarin with reference to the INR index, and maintain the TNR at 2.0~3.0 as the best.
(4) The duration of anticoagulation therapy is 3-6 months.
(5) Review INR on the third day after each warfarin dose adjustment. dose adjustment should be 1/4 tablet each time to avoid large reduction and increase.
(6) There are many factors affecting warfarin and individual differences, try to check INR at least every two weeks.
(7) Do not change the brand of warfarin easily. Because the efficacy of each product is different.
(8) Check platelets after using heparin to prevent heparin-induced thrombocytopenia (also known as HIT). For patients with DVT combined with cancer ACCP (American College of Chest Physicians) authoritative antithrombotic guidelines recommend the application of low molecular heparin therapy for at least 3 to 6 months.
Reporter: What are the possible consequences if the treatment is not standardized?
Zhang Qiang: Irregular treatment is often manifested in the following aspects. One is to replace anticoagulants (heparin and warfarin) with adjuvant pharmacotherapy. This situation tends to lead to fresh thrombosis and a much higher probability of pulmonary embolism. Second, the dose and duration of anticoagulant drugs are insufficient (INR not achieved, anticoagulation time less than 3 months), resulting in poor results or legacy of lower extremity venous thrombosis sequelae. Third, the dose of anticoagulant drugs is too high (INR exceeds the standard) or excessive use of thrombolytic drugs, resulting in hemorrhage. Fourth, ultrasound is only done for the veins of the legs, ignoring CT of the iliac veins and CT of the pulmonary arteries, which makes some patients miss the opportunity to prevent pulmonary embolism and lose their lives.
Reporter: Is there a drug called “Bactrim” that can replace warfarin? This will eliminate the need for weekly laboratory tests.
Zhang Qiang: Bactrim is only approved in most countries (including China) for the prevention of venous thrombosis after joint replacement surgery and for the prevention of thrombosis in atrial fibrillation. Its therapeutic effects and potential safety are not fully understood. Therefore, from a legal point of view, it is currently not a substitute for warfarin in the treatment of thrombosis. It has the advantage of not requiring INR monitoring; however, its bleeding complications are not reduced and it lacks effective antagonists. It should be used with caution in the absence of a clear indication.
Reporter: It was mentioned that anticoagulation is generally preferred as long as the patient has no bleeding tendency or problems with coagulation. What is the treatment option for patients with bleeding tendency?
Zhang Qiang: Patients with a recent history of surgery, cerebrovascular accidents and patients with poor coagulation should not use or use anticoagulation with caution. Such patients should have a vena cava filter implanted if they are at risk of pulmonary embolism or if pulmonary embolism has already occurred. Of course, the indication of vena cava filter implantation is one of the ways to test the knowledge and medical ethics of our vascular surgeons. Whether to strictly grasp the indications of surgery and whether to consider the interests of patients is a question that every vascular surgeon must think about.
Reporter: What should be done if the best treatment is missed?
Zhang Qiang: First of all, the site and scope of thrombosis, the presence of pulmonary embolism, the presence of iliac vein thrombosis should be clarified. The treatment is still based on standardized anticoagulation therapy. With the opening of the collateral veins, the swelling will be relieved in most patients, even though the thrombus will persist in the deep veins for a long time. Follow-up treatment focuses on prevention of post-phlebitic sequelae (which usually appear after two years) and recurrence of new thrombi (fresh thrombi are easily dislodged). The main focus is usually on wearing compression stockings. The main function of compression stockings is to strengthen the calf muscle pump action, so only the below-knee type with a pressure of about 20 mmHg is required. The recanalization rate of femoral vein thrombosis is generally high, while the recanalization rate of iliac vein is extremely low. Therefore, knowing the presence or absence of thrombus in the iliac vein can predict the later outcome.
Reporter: This interview about lower extremity deep vein thrombosis gives you a better understanding of this disease. Thank you!
Zhang Qiang: You are welcome.