Deep vein thrombosis and pulmonary embolism in cancer patients

PE is the closure of the lumen of the main trunk or branches of the pulmonary artery by an embolus (thrombus), which leads to a sharp decrease in blood flow in the lungs.

[ 1 ], [ 2 ], [ 3 ], [ 4 ], [ 5 ], [ 6 ], [ 7 ], [ 8 ], [ 9 ]

Epidemiology

Postoperative thromboembolism in cancer patients develops 5 times more often than in general surgical patients.

[ 10 ], [ 11 ], [ 12 ], [ 13 ], [ 14 ], [ 15 ], [ 16 ]

Causes of Deep Vein Thrombosis

Surgical interventions in cancer patients provoke the formation of a thrombus regardless of the tumor location and the volume of the operation. The advisability of preventing deep vein thrombosis in patients undergoing surgical treatment has now been proven.

The probability of venous thrombosis depends on the nosological forms of tumors. In patients with lung cancer, thrombosis is detected in 28% of cases, with stomach, colon and pancreatic cancer their frequency is 17, 16 and 18%, respectively. In prostate cancer, uterine cancer and ovarian cancer, venous thrombosis is noted in 7% of cases. Postoperative thrombosis of the deep veins of the lower extremities and pelvis is detected in 60-70% of operated patients, and in 70% of cases thrombosis is asymptomatic.

[ 17 ], [ 18 ], [ 19 ], [ 20 ], [ 21 ], [ 22 ]

Symptoms of Deep Vein Thrombosis and PE

In deep vein thrombosis, after surgery, increasing swelling of the limb, tightness during palpation of the calf muscles and pain along the affected veins are detected, however, an asymptomatic course is also possible.

Clinically, PE should be suspected in the case of sudden onset of shortness of breath, chest pain, hypoxemia, tachycardia, and decreased blood pressure up to shock. PE is characterized as severe in the presence of arterial hypotension or moderate shock (with ultrasound signs of decreased contractility of the right ventricle) and non-severe.

Classification

Deep vein thrombosis is classified as proximal (above the popliteal fossa) and distal (below the popliteal fossa).

[ 23 ], [ 24 ], [ 25 ], [ 26 ]

Diagnostics

[ 27 ], [ 28 ], [ 29 ], [ 30 ], [ 31 ], [ 32 ], [ 33 ], [ 34 ], [ 35 ]

Laboratory research

Determination of the O-dimer level in the blood. The studies have shown that in patients with pulmonary embolism, the D-dimer content increases by 10-15 times compared to patients without thrombotic complications. The highest concentration of D-dimer (12-15 μg/ml) is observed in patients with massive thromboembolism, in patients with thrombosis, the D-dimer level is 3.8-6.5 μg/ml.

Instrumental research

Chest X-ray, ECG and echocardiography are of little use in PE.

Ultrasound Dopplerography of the lower extremity vessels is performed once every 3-4 days after surgery in patients with chronic venous insufficiency. The method has average sensitivity, especially in distal deep vein thrombosis (30-50%).

Ventilation-perfusion lung scintigraphy is a non-invasive, fairly informative (90%) method for diagnosing pulmonary embolism.

Ultrasound of the veins of the lower extremities is performed in the preoperative period in the following cases:

• swelling of the lower leg or the entire lower limb,
• pain in the calf muscle when walking,
• the presence of varicose veins,
• pain on palpation of the vascular bundle of the lower limb,
• History of pulmonary embolism and deep vein thrombosis,
• obesity,
• circulatory failure.

Treatment

Non-drug treatment

If deep vein thrombosis is detected, the insertion of a cava filter prior to surgery is indicated.

Drug treatment

Antithrombotic and thrombolytic therapy are indicated as drug treatment.

Antithrombotic therapy is the basis of pathogenetic pharmacotherapy of deep vein thrombosis, which reduces its consequences, prevents further progression and development of complications. The prescription of direct and indirect anticoagulants is indicated.

UFH or LMWH are prescribed as direct acting anticoagulants.

• UFH is prescribed for the treatment of venous thrombosis at an initial dose of 5,000 U intravenously or subcutaneously, subsequent administrations are carried out intravenously by drip up to 30,000 U per day, the dose of the drug is controlled mainly by determining APTT. In uncomplicated venous thrombosis, UFH therapy is continued for 5 days. The use of the drug for 10-14 days in patients with DVT and PE has become common in clinical practice in the United States. In European countries, the duration of sodium heparin therapy is shorter and is 4-5 days. In Russia, it is recommended to administer sodium heparin for at least 7 days according to the following scheme: UFH intravenously as a bolus of 3,000-5,000 U, then subcutaneously at 250 U/kg, 2 times a day, for a total of 5-7 days. The dose of the drug is selected as follows: UFH intravenously by bolus of 80 U/kg, then intravenously by infusion of 18 U/kg (h), but not less than 1250 U/h, 5-7 days. The drug must be dosed so that APTT is 1.5-2.5 times higher than its normal value for the laboratory of a given medical institution. During the period of dose selection, APTT is determined every 6 hours, with stable therapeutic values of the indicator - once a day. It should be taken into account that the need for heparin is higher in the first few days after the onset of thrombosis.
• The use of LMWH does not require laboratory monitoring, however, in the treatment of severe PE, preference should be given to UFH, since the effectiveness of LMWH has not been fully studied. LMWH drugs dalteparin sodium, nadroparin calcium, enoxaparin sodium. Dalteparin sodium is administered subcutaneously to the abdomen at 200 anti-Xa IU/kg, maximum 18,000 anti-Xa IU once a day, with an increased risk of bleeding at 100 anti-Xa IU/kg 2 times a day, 5-7 days. Nadroparin calcium subcutaneously in the abdomen at 86 anti-Xa IU/kg 2 times a day or 171 anti-Xa IU/kg, maximum 17,100 anti-Xa IU once a day, 5-7 days Enoxaparin sodium subcutaneously in the abdomen at 150 anti-Xa IU/kg (1.5 mg/kg, maximum 180 mg) 1 time per day or 100 anti-Xa IU/kg (1 mg/kg) 2 times a day, 5-7 days
• Indirect anticoagulants are widely used in the treatment of deep vein thrombosis and pulmonary embolism. As a rule, the drugs are prescribed after stabilization of the process with heparins and simultaneously with the start of heparin therapy or in the coming days, the dose is selected based on the INR level, the target values of which are 2.0-3.0. Preference is given to indirect anticoagulants of the coumarin series (warfarin, acenocoumarol) due to their better pharmacokinetic properties and more predictable anticoagulant effect. Acenocoumarol is prescribed orally at 2-4 mg per day (initial dose), and the maintenance dose is selected individually under the control of INR. Warfarin is taken orally at 2.5-5.0 mg / day (initial dose), the maintenance dose is selected similarly. Heparins are discontinued no earlier than 4 days after the start of taking indirect anticoagulants and only if therapeutic INR values are maintained for two consecutive days. The duration of use of indirect anticoagulants is at least 3-6 months.

Thrombolytic therapy

At present, there is no clear evidence of the advantage of thrombolytic therapy over sodium heparin. Thrombolytic therapy for deep vein thrombosis is virtually impossible due to the extremely high risk of hemorrhagic complications in the immediate postoperative period. Such a risk is justified only in cases of a threat to the patient's life due to massive PE. Thrombolytic drugs are indicated for patients with severe PE and arterial hypotension, shock, refractory hypoxemia, or right ventricular failure. Thrombolytic therapy accelerates the process of restoring patency of the occluded pulmonary artery, reducing the severity of pulmonary hypertension and afterload on the right ventricle compared with the effect of sodium heparin. However, there is no convincing evidence that rapid improvement in hemodynamic parameters improves clinical outcomes in severe PE. It remains unclear whether the higher risk of hemorrhagic complications is justified. The period of effective use of thrombolytic therapy is 14 s after the onset of its symptoms. Streptokinase and urokinase are used as monotherapy. Alteplase is administered in combination with sodium heparin and can be administered (or resumed) after thrombolysis is complete and prothrombin time or APTT is less than twice the normal value. One of the following agents is administered:

• alteplase intravenously by infusion at 100 mg for 2 hours,
• streptokinase intravenously by infusion at 250,000 U for 30 minutes, then at a rate of 100,000 U/h for 24 hours,
• urokinase intravenously by infusion at 4400 IU/kg h over 10 minutes, then at a rate of 4400 IU/kg h for 12-24 hours.

Surgical treatment

In specialized vascular surgery departments, thrombectomy is performed in cases of segmental thrombosis of the femoral, iliac and inferior vena cava veins. The radical nature of the intervention on the main veins eliminates the risk of massive pulmonary embolism and improves the long-term prognosis of venous thrombosis.

At the same time, the severity of the patient's condition, due to the nature and extent of the primary surgical intervention and concomitant diseases, allows resorting to this procedure in a very limited number of cases. That is why the occurrence of thrombi in the femoral, iliac or inferior vena cava forces, in addition to anticoagulant therapy, to resort to partial occlusion of the inferior vena cava. The method of choice in the postoperative contingent of patients is the implantation of a cava filter. If this intervention is impossible in patients who are scheduled for abdominal surgery, it can be started with plication of the inferior vena cava with a mechanical suture.

Prevention

To determine the indications for the use of preventive measures, surgical patients are divided into risk groups. According to the materials of the 6th Consensus Conference on Antithrombotic Therapy of the American College of Thoracic Surgeons (2001), cancer patients have the highest risk of developing thromboembolic complications. In the absence of prophylaxis after surgery, thrombosis develops in 40-50% of cancer patients, of which 10-20% have proximal thrombosis, which in 4-10% of cases is complicated by pulmonary embolism, fatal in 0.2-5% of cases. Prevention of thrombotic complications is necessary at all stages of surgical treatment.

To prevent postoperative deep vein thrombosis (DVT), various physical (mechanical) and pharmacological means are used:

• Mechanical means accelerate venous blood flow, which prevents blood stagnation in the veins of the lower extremities and thrombus formation; these include the “foot pedal”, elastic and intermittent compression.
• Elastic compression of the lower limbs with special elastic knee-highs or stockings.
• Intermittent pneumatic compression of the legs using a special compressor and cuffs.
• The "foot pedal" provides passive contraction of the calf muscles during and after surgery.
• Pharmacological agents maintain APTT between injections at a level that exceeds the APTT value for the laboratory of a given medical institution by 1.5 times. Anticoagulants, antibiotics, and drugs that act on the platelet link of hemostasis are indicated for the prevention of surgical thrombosis.

Direct anticoagulants are prescribed before surgery and continue to be administered in the immediate postoperative period (7-14 days), however, in case of complicated course, longer pharmacotherapy (for at least 1 month) may be required. Sodium heparin is not prescribed in the preoperative and early postoperative periods in surgeries for esophageal cancer, tumors of the hepatopancreatoduodenal zone and rectal extirpation with preoperative irradiation, etc. Preventive therapy with heparins before surgery is not used in patients with expected massive blood loss during surgery or an extensive surgical surface and abundant secretion from injured tissues. The use of sodium heparin in low doses reduces the risk of postoperative deep vein thrombosis by approximately 2/3, and pulmonary embolism - by 2 times.

• Heparin sodium subcutaneously 5000 U 2 hours before surgery, then 2-3 times a day, in the postoperative period the dose is adjusted depending on the APTT.
• Dalteparin sodium subcutaneously at 2500 anti-Xa international units (IU) 12 hours before surgery and 12 hours after it, or 5000 anti-Xa IU 12 hours before, then 5000 anti-Xa IU once a day.
• Nadroparin calcium subcutaneously at 38 anti-Xa IU 12 hours before surgery, 12 hours after it, and then 57 anti-Xa IU once a day.
• Enoxaparin sodium subcutaneously 4000 anti-Xa IU 40 mg 12 hours before surgery, then once a day.
• Acetylsalicylic acid is not the drug of choice for the prevention of deep vein thrombosis, but there is reliable data that the use of the drug for 2 weeks after surgery reduces the incidence of DVT from 34 to 25%.
• Dextran is a glucose polymer that reduces blood viscosity and has an antiplatelet effect.
• Infusions of rheopolyglucin 400 ml daily with pentoxifylline for 5-7 days after surgery or other agents that affect the platelet link of hemostasis (clopidogrel, dipyridamole, etc.) in patients of the indicated nosological groups are effective in combination with mechanical means.

In case of exacerbation of superficial varicose vein thrombosis, a course of antibacterial and anticoagulant therapy is indicated before surgery.

Forecast

In the absence of treatment, mortality from PE reaches 25-30%, with the appointment of anticoagulants it decreases to 8%, the risk of recurrent thromboembolism is highest in the first 4-6 weeks PE can lead to death from shock and severe respiratory failure. Remote consequences are chronic pulmonary hypertension and respiratory failure.

[ 36 ], [ 37 ]