Deep venous thrombosis (DVT), a thrombosis caused by slow blood flow and hypercoagulability, is mainly located in deep veins. The thrombus adheres lightly to the vessel wall and can easily dislodge and cause pulmonary embolism. The incidence rate of DVT in western countries is 1/2000, but there are no exact statistics in China.
Etiology
1. Slow blood flow: the increase of blood volume in women during pregnancy leads to venous dilatation and decrease of venous tone; the venous return of lower limb extremities decreases by 50% in late pregnancy; the enlarged uterus compresses the iliac vein and affects the uterine venous return.
2, vascular endothelial damage: mechanical damage to blood vessels caused by cesarean section or vaginal delivery; intrauterine infection causing direct adhesion of pathogens to damage the vascular endothelium, the release of toxins and metabolites of the body cause endothelial damage.
3, hypercoagulable state of blood: increased coagulation factors II, V, VII, VIII, IX, X and fibrinogen; increased platelet aggregation; reduced plasma protein S, tissue-type fibrinogen, Ⅺ and Ⅻ factors; increased resistance to activated plasma protein C.
4, increased chances of thrombosis: due to increased blood viscosity and slow blood flow, the chances of thrombosis increase significantly, the most common are deep vein thrombosis, thrombotic vasculitis and pulmonary embolism. This is the basic reason for the possibility of DVT formation up to 15%-50% in long term bedridden patients. DVT occurs mostly in the lower extremities, leading to severe edema in the lower extremities, often combined with infection; deep vein embolism dislodged can cause lethal pulmonary embolism with a high mortality rate.
Pathogenesis
Venous thrombosis in pregnancy can occur during pregnancy or puerperium, and the puerperium is more common. During pregnancy, the coagulation and anticoagulation systems in the blood undergo physiological changes to adapt to placental abruption during delivery and to prevent postpartum hemorrhage. In addition to a decrease in coagulation factors D and Ⅺ, coagulation factors II, V, VII, VIII, IX and X are increased, especially in the second trimester, and plasma fibrinogen increases by 50% compared to non-pregnant women, reaching 4-5 g/L at the end of pregnancy. the fibrinolytic system, the main anticoagulation system, is inhibited, fibrinogen inhibitors increase, fibrinolytic activity decreases, and the degradation time of euglycin increases. The level and activity of anticoagulant protein S (PS) decreases during pregnancy and can fall to 40%-60% of normal levels, remaining at a low level throughout pregnancy and the puerperium. These physiological changes put the blood of pregnant women in a hypercoagulable state. In addition, the blood volume increases during pregnancy, the veins dilate, and the enlarged pregnant uterus compresses the inferior vena cava, resulting in poor blood return and increased venous pressure in the lower extremities, resulting in lower extremity edema and increased varicose veins. If pregnancy combined with gestational hypertensive disease, diabetes, placental abruption, varicose veins, etc. cause vasospasm, lumen narrowing, wall damage and ischemia and hypoxia make endothelial cells release tissue factor to promote coagulation. Surgical delivery, especially cesarean delivery, can be 3 to 19 times more likely to be complicated by thrombophlebitis than vaginal delivery. The potential risk of thrombosis is further increased by prolonged bed rest or infection during the puerperium. Endometritis during the puerperium increases the risk of infectious thrombophlebitis in the ovarian and pelvic veins.
Recent studies have identified antithrombin (AT) deficiency, protein C (PC) deficiency, protein S (PS) deficiency, and factor V Leiden mutation as the main causes of hereditary thrombophilia, which is an important factor increasing the risk of venous thrombophilia in pregnancy. Antithrombin (AT) is the most important physiological anticoagulant in the body and has an inhibitory effect on many active coagulation factors, especially Xa, Ⅸa, Ⅺa and thrombin. The prevalence of antithrombin deficiency in the general population is 0.5 to 0.2 per 1,000, and it is an extremely strong risk factor for venous thrombosis, with early onset, extensive thrombosis, and easy recurrence. Pregnancy increases the incidence of venous thrombosis in women with AT deficiency by 20%. 9,3% to 19,3% of pregnant patients with venous thrombosis are found to have AT deficiency, and pregnant women with AT deficiency are at high risk of developing venous thrombosis (30,8%). Protein C (PC) is a physiological anticoagulant, a vitamin K-dependent anticoagulant factor, synthesized by the liver. It is activated by thrombin, and activated protein C (APC) has an inactivating effect mainly on factors Va and VIIIa and, to a lesser extent, on fibrinolytic enzymes. The prevalence of heterozygous PC defects in the general population is 0.15% to 0.8%. PC defects account for 1.3% to 14% of venous thrombosis in pregnancy, mostly in recurrent venous thrombosis in pregnancy, and the risk of venous thrombosis in a second pregnancy is increased threefold in those with a history of venous thrombosis. The risk of venous thrombosis in pregnant women with PC defects is 12.5%. Protein S (PS) is a vitamin K-dependent anticoagulant that is synthesized in hepatic endothelial cells, and megakaryocytes. PS deficiency is a weak risk factor in venous thrombosis and the risk of venous thrombosis in pregnant women with PS deficiency is 10.9%. The occurrence of factor V Leiden mutation varies according to region and race, with an incidence of 3% to 7% in Caucasians and 0,5mg/L in Asians), with the possibility of thrombosis, while the possibility of DVT is low when negative (≤0,5mg/L), which basically excludes DVT, and therefore can be used as a means of early postoperative screening.
2, Venous thrombography is the gold standard for DVT diagnosis, but this invasive test method can have adverse effects on both the fetus and the pregnant woman. Restrictive venography, with a lead skirt covering the abdomen and pelvis of the pregnant woman, can reduce the amount of radiation to less than 0,05 rads, but the development of the iliac veins will be affected to some extent.
3.Continuous impedance volume tracing (IPG) detects the impedance change caused by the change of blood flow in the limb. However, due to the compression of the iliac vein in late pregnancy, its sensitivity and specificity are significantly reduced.
4, 125I-labeled fibrinogen scan (125I-fibrenogenscan-ning): clinical use requires a bedside liftable scintillation counter. Sodium iodide 100-150 mg is administered orally 24h before the experiment to block the uptake of nuclear iodine by the thyroid gland. 125I-labeled fibrinogen is injected into the vein, i.e., it binds to the thrombus. The percentage of radioactivity measured beyond the heart at the site of significant concentration of 125I in the lower extremity is calculated, and an increase of 20% or more indicates a thrombus. This test can be used to do follow-up scans of the limb several days later and is particularly sensitive to thrombosis of the gastrocnemius plexus in the calf shortly after surgery. It is not good for femoroiliac and common iliac vein thrombosis examination.
5.Color Doppler ultrasound detection is a commonly used non-invasive examination method to check the blood flow rate with ultrasound. According to the principle of blood flow change due to thrombus in the lumen, the probe is placed at the proximal end of the vein thrombus and pressure is applied at the distal end of the thrombus, if the signal of enhanced blood flow in the vein cannot be detected, it means there is obstruction between the two. This is a simple and effective method and can be repeatedly checked. The accuracy of gastrocnemius vein thrombosis is poor. This test is safe, non-invasive, and non-contraindicated; the images are visual, clear, and easy to identify, making it a more ideal method for diagnosing lower extremity deep vein thrombosis.
Both color Doppler ultrasound and IPG have low sensitivity for the diagnosis of lower extremity DVT. Repeat testing is required for patients with high clinical suspicion but negative screening, and venous angiography should be performed if noninvasive testing is not available or its results are inconclusive. Anticoagulation therapy should be initiated if the venography photograph or a single noninvasive test suggests thrombosis.
【Treatment】The evidence-based medical evidence level for VTE treatment in pregnancy is grade II
1. Supportive therapy: Elevate the affected limb to facilitate venous reflux, avoid activity in bed during the acute period to prevent thrombus dislodgement, and avoid exertion. The position of the lower limb can be changed in bed, and the foot can be extended and flexed, and getting up and moving can be allowed after 1 to 2 weeks when the inflammation subsides.
2.Antibiotics to prevent infection.
3.Anticoagulation therapy: Once the diagnosis is confirmed, anticoagulant drugs should be given. The effect is to prevent the expansion and recurrence of thrombosis by relieving the hypercoagulable state of blood, which is beneficial to control the development of lesions. A basic complete blood count, including platelet count and activated partial thromboplastin time, should be obtained before treatment. ①General heparin: initial dose is 5000iu, followed by maintenance of 30,000iu for 24 hours. APTT is rechecked 6 hours after each dose, and maintain APTT in the therapeutic range (1,5-2,5 times the normal control value); plasma heparin level is measured and maintained at 0,2-0,4u/ml. ②Low molecular weight heparin (LMWP) is a recent clinical use LMWP is a new drug for clinical use in recent years. Its half-life is 2-4 times longer than that of ordinary heparin, and its bioavailability is 90%-95% (30% for ordinary heparin). The anti-Xa effect of low-molecular-weight heparin is stronger than that of antithrombin, and it binds less to plasma proteins, phagocytes, endothelial cells and platelets, so its anticoagulant effect is stronger than that of ordinary heparin. Low molecular weight heparin anticoagulant treatment dose: 60-100U/kg, 2 times/d, subcutaneous injection around the umbilicus; enoxapaxin sodium (enoxapaxin), 1mg/kg, every 12 hours, subcutaneous injection; Dalteparin Na (Dalteparin Na), 200U/kg, subcutaneous injection, 1 time/d, total amount not more than 1,80,000U per day, or 100 U/kg, subcutaneous injection, 2 times/d. This dose is suitable for patients with a high risk of bleeding.
(iii) Currently, low-dose plain heparin is the standard regimen for the treatment of VTE. After initial heparinization of VTE, maintenance anticoagulation therapy is required throughout pregnancy and 6-12 weeks postpartum, or continuous anticoagulation therapy for a total of three months.
4. Thrombolytic therapy: Fibrinolytic drugs are activators of the fibrinolytic system and have a thrombolytic effect. Generally, they are used within 3 days of the disease, and their effect is very satisfactory. There are two kinds of drugs commonly used, namely streptokinase and urokinase. Allergic reactions are common with streptokinase. Urokinase is non-pyrogenic and can directly activate fibrinogen, which has significant advantages over streptokinase and is more suitable for clinical use. Urokinase: Initial dose: generally 80,000 U per dose, dissolved in 5% glucose solution or low molecular dextrose 250-500 ml, intravenous drip, 2 times/d; maintenance dose: based on daily measurement of fibrinogen, if it is lower than 200 mg/dl, suspend 1 time. Also measure the dissolution time of euglobulin (normal >120min), if <70min also need to suspend 1 time. The medication should be used for 7-10 days.
5.Anti-platelet therapy: It is often used as adjuvant therapy in the treatment of lower limb deep vein thrombosis. ①Dextran: It has the effect of expansion, can dilute blood, reduce blood viscosity, prevent platelet aggregation, and assist other methods to achieve the effect. Dose: 500ml, 1~2 times/d, intravenous infusion for 7~10 days. ②Dipyridamole: It can prevent platelet aggregation and release. 200～400mg/d, taken orally, good effect with aspirin.
6.Surgical treatment: The surgical treatment for deep vein thrombosis of lower limbs is mainly venous thrombectomy. It is necessary to strictly grasp the indications for surgery, which is limited to the acute thrombosis with the disease period not exceeding 72h, so that the adhesions between the thrombosis and the vessel wall have not yet formed, and the surgical removal of the thrombosis is effective.
Prevention
1. Strengthen the management of pregnancy, pay attention to the personal and family history of venous thrombosis, and evaluate the tendency of thrombosis in high-risk groups. Actively prevent pregnancy complications, strictly control the indications for cesarean delivery, prevent puerperal infection, and encourage early activity after delivery.
2. For pregnant women with a history of venous thrombosis, hereditary or acquired thrombophilia, prophylactic anticoagulation therapy with common heparin or low-molecular heparin is advocated. Prophylactic treatment regimen: ①General heparin: 5000iu subcutaneous injection every 12 hours, maintained throughout pregnancy. ②Low molecular weight heparin: Enoxaparin: 40mg subcutaneously once daily. ③Daheparin sodium (Farnesamine): 71Kg body weight, 7500iu subcutaneous injection, once daily.