Deep vein thrombosis of lower extremities: Treatment

Treatment of deep vein thrombosis of the lower extremities is primarily aimed at the prevention of pulmonary embolism, and in the second place - to reduce symptoms, prevent chronic venous insufficiency and post-phlebitis syndrome. Treatment of deep venous thrombosis of the lower and upper extremities is generally the same.

All patients are prescribed anticoagulants, first an injectable preparation of heparin (unfractionated or low molecular weight), then warfarin (in the first 24-48 hours). Inadequate anticoagulant therapy in the first 24 hours may increase the risk of pulmonary embolism. Acute deep venous thrombosis can be treated on an outpatient basis if there is no suspicion of pulmonary embolism, severe symptoms (in this case, parenteral analgesics are indicated), other nuances that interfere with safe outpatient treatment, and certain specific factors (eg, impaired function, socio- economic aspect). Common measures include pain relief with analgesics (except acetylsalicylic acid and NSAIDs due to their antiplatelet properties) and elevated leg position during periods of rest (under elevated legs it is necessary to put a pillow or other soft surface to avoid veining). Restriction of physical activity is not shown, as there is no evidence that early activity increases the risk of blood clot and pulmonary embolism.

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Antifogging agents

Low molecular weight heparins (for example, enoxaparin sodium, dalteparin sodium, reviparin, tinzaparin) are the initial therapy of choice, since they can be prescribed at an outpatient stage. LMWH are as effective as unfractionated heparin (UFH) to reduce the risk of recurrence of deep venous thrombosis, thrombus spread and death due to pulmonary embolism. Like UFH, LMWH increases the activity of antithrombin III (which inhibits coagulation factor protease), leading to the inactivation of the coagulation factor Xa and (to a lesser extent) Ha. LMWH also have some antithrombin III-mediated anti-inflammatory properties that promote thrombus organization and the resolution of symptoms and inflammation.

LMWH is administered subcutaneously in a standard dose, depending on the body weight (for example, sodium enoxaparin at 1.5 mg / kg subcutaneously once a day or 1 mg / kg subcutaneously every 2 hours to a maximum dose of 200 mg per day or dalaparin sodium 200 U / kg subcutaneously once a day). Obese patients may require higher doses, and with cachexia, lower doses. In patients with renal insufficiency, UFH is more effective. Control of the coagulation system is not needed, because LMWH does not significantly prolong the activated partial thromboplastin time (APTT), the responses are predictable, and there are no reliable links between LMWH overdose and bleeding. Treatment is continued until a complete anticoagulant effect of warfarin is achieved. However, previous experience shows that LMWH are effective for long-term treatment of deep venous thrombosis in high-risk patients, therefore, in some cases LMWH may be an acceptable alternative to warfarin, although warfarin is likely to be a means of choice because of its low price and ease of administration .

UFH can be prescribed instead of LMWH to hospitalized patients and patients with renal insufficiency (creatinine clearance 10-50 ml / min), because UFH is not excreted by the kidneys. UFH is prescribed by bolus and infusion (see Table 50-3 on page 419) to achieve adequate hypocoagulation, defined as an increase in APTT of 1.5-2.5 times compared with reference values (or minimal serum heparin by 0 , 2-0.4 U / ml, determined by the protamine titration probe titration). UFH for 3.5-5 thousand ED subcutaneously every 8-12 hours can replace the parenteral administration of UFH and thus expand the motor activity of the patient. The dose can be selected on the basis of APTTV, determined before the administration of the drug. Treatment is continued until adequate hypocoagulation is achieved with the administration of warfarin.

Complications of heparin therapy include bleeding, thrombocytopenia (sometimes with LMWH), hives, less often thrombosis and anaphylaxis. Long-term use of UFH causes hypokalemia, an increase in hepatic enzyme activity and osteoporosis. Sometimes UFH, administered subcutaneously, causes skin necrosis. Inpatients, and possibly also outpatients, should be screened for possible bleeding (sequential blood tests and tests for concealed blood in the stool). Bleeding due to excessive heparinization can be stopped with protamine sulfate. The dose is 1 mg protamine sulphate per milligram of LMWH, administered at the rate of 1 mg protamine sulphate in 20 ml isotonic sodium chloride solution intravenously slowly for 10-20 min or longer. If you need a second dose, it should be half the first. However, the exact dose is not determined, because protamine sulfate only partially neutralizes the inactivation of factor Xa by low molecular weight heparins. When carrying out all infusions, it is necessary to monitor the patient for development of possible arterial hypotension and reactions similar to anaphylactic.

Warfarin is the remedy for long-term anticoagulant therapy for all patients, except for pregnant women (heparin therapy is indicated) and patients who have had new episodes or worsening of existing venous thromboembolism during treatment with warfarin (such patients may be candidates for cava filtering). Warfarin 5-10 mg can be administered concomitantly with heparin preparations, except for patients with protein C deficiency, who have adequate hypocoagulation with heparins (APTTV 1.5-2.5 times higher than the reference value) before treatment with warfarin begins. Elderly and patients with impaired liver function usually need lower doses of warfarin. The therapeutic goal is to achieve MHO 2.0-3.0. MHO is monitored weekly in the first 1 -2 months of treatment with warfarin, then monthly. The dose is increased or decreased by 0.5-3 mg to maintain MHO within this range. Patients taking warfarin should be informed of possible interactions of the drug, including interactions with over-the-counter medicinal herbs.

Patients with transient risk factors for deep venous thrombosis (such as immobilization or surgery) may stop taking warfarin after 3-6 months. Patients with persistent risk factors (eg, hypercoagulability), spontaneous deep venous thrombosis without known risk factors, repeated deep venous thrombosis, and patients with pulmonary embolism in history should take warfarin at least up to 6 months and probably all life if there are no complications therapy. In low-risk patients, warfarin in small doses (to maintain MHO within 1.5-2.0) can be safe and effective for at least 2-4 years, but such treatment requires further safety evidence before it can be widely recommended.

Bleeding is the most common complication. Risk factors for severe bleeding (defined as life-threatening bleeding or loss> 2 units of blood volume for <7 days) are as follows:

• age 65 years and over;
• anamnesis of previous gastrointestinal bleeding or stroke;
• recent acute myocardial infarction;
• concomitant anemia (Ht <30%), renal insufficiency [serum creatinine concentration> 132.5 μmol / L (1.5 mg / dL)] or diabetes mellitus.

Anticoagulant effect can be completely leveled with sodium menadione bisulphite (vitamin K). Its dose is 1-4 mg per day, if MHO 5-9; 5 mg per day, if MHO> 9; 10 mg intravenously (slowly administered to avoid anaphylaxis) if bleeding occurs. In severe bleeding, blood clotting factors, freshly frozen plasma or the concentrate of the prothrombin complex are transfused. Excessive hypocoagulation (MH> 3-4) without bleeding can be eliminated by skipping several anticoagulant medications against a background of more frequent MHO control, and then prescribing warfarin at a lower dose. Sometimes warfarin causes skin necrosis in patients with deficiency of protein C or S.

Other anticoagulants such as direct thrombin inhibitors (eg, hirudin administered subcutaneously, lepirudin, bivalirudin, desurodin, argatroban, ximelagatran) and selective factor Xa inhibitors (eg fondaparinox) are under investigation for use in the treatment of acute GHT . Ximelagatran is an oral prodrug that is metabolized to melethran (a direct thrombin inhibitor that is difficult to use); ximelagatran does not require monitoring of the patient and seems comparable in effectiveness with LMWH and warfarin.

Filter of the inferior vena cava (cava filter)

The inferior vena cava filter (FNPV) can help prevent pulmonary embolism in patients with deep venous thrombosis of the lower limb and contraindications to the use of anticoagulants or with recurrent deep venous thrombosis (or embolism) that have arisen despite adequate anticoagulation therapy. FNPV is placed in the inferior hollow vein below the renal veins by catheterization of the internal jugular or femoral vein. FNPV reduce the risk of acute and subacute thrombotic complications, but have delayed complications (for example, venous collaterals can be developed that provide a pathway for embolism bypassing FNPV). In addition, the FNPV can be shifted. Thus, patients with recurrent deep venous thrombosis or unaffected risk factors for deep venous thrombosis may need anticoagulant therapy. FNPV provide some protection, until contraindications to anticoagulant treatment decrease or disappear. Despite the widespread use of FNPV, the effectiveness in preventing LE is not studied and not proven.

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Thrombolytic preparations

Streptokinase, urokinase and alteplase dissolve thrombi and probably more effectively prevent post-phlebitis syndrome than one sodium heparin, but the risk of bleeding is higher. The use of these drugs is at the stage of study. Thrombolytic agents can be prescribed in the presence of large proximal thrombi, especially in the iliac and femoral veins, and with circulatory white venous or blue gangrene. Local administration using a permanent catheter is preferable to an intravenous catheter.

Surgical treatment of deep vein thrombosis of lower extremities

Surgical treatment is rare. However, thromboembolism, fasciotomy or both interventions are mandatory with white or blue phlegmase, resistant to thrombolytic therapy, to prevent the development of gangrene of the extremity.