Deep vein thrombosis and pulmonary embolism in cancer patients

PE - closure of the lumen of the main trunk or branches of the pulmonary artery 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 patients with general surgical profile.

[10], [11], [12], [13], [14], [15], [16], [17],

Causes of deep vein thrombosis

Surgical interventions in cancer patients provoke the occurrence of thrombus regardless of the location of the tumor and the volume of the operation. At present, it has been proved expedient to prevent deep vein thrombosis in patients undergoing surgical treatment.

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 cancer of the stomach, colon and pancreas, their frequency is 17, 16 and 18%, respectively. In prostate cancer, uterine and ovarian cancer, venous thrombi are noted in 7% of cases. Postoperative thrombosis of deep veins of the lower extremities and pelvis reveals in 60-70% of operated patients, and in 70% of cases, thrombosis proceeds asymptomatically.

[18], [19], [20], [21], [22], [23],

Symptoms of deep vein thrombosis and PE

In deep vein thrombosis, after surgery, the swelling of the limb is increased, the density of the palpation of the calf muscles and soreness along the course of the affected veins, however, an asymptomatic course is also possible.

Clinically, PE should be suspected when sudden onset of shortness of breath, chest pain, hypoxemia, tachycardia, and lowering blood pressure until shock PE are characterized as severe in the presence of arterial hypotension or shock of moderate severity (with ultrasound signs of reducing the contractility of the right ventricle) and not severe.

Classification

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

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Diagnostics

[28], [29], [30], [31], [32], [33], [34], [35], [36],

Laboratory research

Determination of the level of O-dimer in the blood. The conducted studies showed that in patients with PE, the content of D-dimer increases by 10-15 times in comparison with patients without thrombotic complications. The highest concentration of D-dimer (12-15 μg / ml) was observed in patients with massive thromboembolism, in patients with thrombosis, the D-dimer level was 3.8-6.5 μg / ml.

Instrumental research

Chest X-ray, ECG and EchoCG in PE are of little informative.

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

Ventilation-perfusion lung scintigraphy is a noninvasive, informative (90%) method for diagnosing PE.

Ultrasound of the veins of the lower extremities is performed during the preoperative period with:

• edema of the lower leg or the entire lower limb,
• pain in the calf muscle when walking,
• presence of varicose veins,
• painfulness upon palpation of the vascular bundle of the lower limb,
• PE and deep vein thrombosis in the anamnesis,
• obesity,
• circulatory insufficiency.

Treatment

Non-medicamentous treatment

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

Medication

As a drug treatment, antithrombotic and thrombolytic therapy is indicated.

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

As a direct anticoagulant, NFH or LMWH is prescribed.

• UFH is prescribed in the treatment of venous thrombosis at an initial dose of 5000 units I / O or SC, subsequent injections are performed intravenously dripping up to 30,000 units per day, the dose of the drug is controlled predominantly by the determination of APTT. With uncomplicated venous thrombosis, UFH therapy continues 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 therapy with heparin sodium is shorter and is 4-5 days. In Russia, it is recommended to inject heparin sodium at least 7 days according to the scheme: UFH in / in a bolus of 3000-5000 units, then sc, 250 units / kg, 2 times a day, only 5-7 days. The dose of the drug is selected as follows UFH in / in the bolus at 80 units / kg, then / infusion of 18 units / kgh), but not less than 1250 units per hour, 5-7 days. Dosage of the drug is necessary in such a way that the APTT is 1.5-2.5 times higher than its normal value for the laboratory of this medical institution. During the selection of the dose, the APTT is determined every 6 hours, with stable therapeutic values of the indicator - 1 time per day. It should be noted 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, but in the treatment of severe PE, preference should be given to UFH, since the effectiveness of LMWH has not been fully studied. Preparations of LMW dalteparin sodium, supraparin calcium, enoxaparin sodium. Dalteparin sodium is injected under the skin of the abdomen for 200 anti-Ha IU / kg, maximum 18,000 anti-Ha IU once a day, with an increased risk of bleeding of 100 anti-Ha IU / kg 2 times a day, 5-7 days. Nadroparin calcium under the skin of the abdomen is 86 anti-Ha IU / kg 2 times a day or 171 anti-Ha IU / kg, maximum 17 100 anti-XA ME once daily, 5-7 days Enoxaparin sodium under the skin of the abdomen 150 anti-Ha IU / kg (1.5 mg / kg, maximum 180 mg) once a day or 100 anti-Ha IU / kg (1 mg / kg) twice daily, 5-7 days.
• Anticoagulants of indirect action are widely used in the treatment of deep vein thrombosis and PE. As a rule, drugs are prescribed after stabilization of the process with the help of heparins and simultaneously with the onset of heparin therapy or in the coming days, the dose is selected according to the level of INR, the target values being 2.0-3.0. Preference is given to anticoagulants of indirect action of the coumarin series (warfarin, acenocumarol) because of better pharmacokinetic properties and a more predictable anticoagulant effect. Aceococamarol is administered internally at 2-4 mg per day (initial dose), and the maintenance dose is selected individually under the control of the INR. Warfarin is taken orally 2.5-5.0 mg / day (the initial dose), the maintenance dose is chosen similarly. Heparins are canceled no earlier than 4 days after the beginning of taking anticoagulants of indirect action and only if therapeutic values of INR remain intact for two consecutive days. Duration of application of anticoagulants of indirect action not less than 3-6 months.

Thrombolytic therapy

At present, there is no clear evidence of the benefits of thrombolytic therapy before using sodium heparin. The thrombolytic therapy for deep vein thrombosis is almost impossible because of the extremely high risk of hemorrhagic complications in the immediate postoperative period. Such a risk is justified only in cases of threat to the life of a patient with massive PE. Thrombolytic drugs are indicated in patients with severe PE and arterial hypotension, shock, refractory hypoxemia, or right ventricular failure. Thrombolytic therapy accelerates the process of restoring the patency of the occluded pulmonary artery, reducing the severity of pulmonary hypertension and postnagruzka on the right ventricle in comparison with the effect of administration of heparin sodium. However, there is no convincing evidence that rapid improvement of hemodynamic parameters improves clinical outcomes in severe PE. It remains unclear whether a higher risk of developing hemorrhagic complications is justified. The period of effective use of thrombolytic therapy is 14 seconds after the onset of her symptoms. Streptokinase and urokinase are used as monotherapy. The introduction of alteplase is combined with the use of heparin sodium, it can be prescribed (or restarted) after the end of thrombolysis, when the prothrombin time or APTT is less than twice the normal value. Assign one of the following:

• alteplase intravenously infusion 100 mg for 2 hours,
• streptokinase IV infusion of 250,000 units for 30 minutes, then at a rate of 100,000 U / h for 24 hours,
• urokinase IV infusion at 4400 IU / kghh) for 10 min, then at a rate of 4400 IU / kghh) for 12-24 hours.

Surgery

In specialized angiosurgical units perform thrombectomy in cases of segmental thrombosis of the femoral, iliac and inferior vena cava. The radical nature of the intervention on the main veins eliminates the risk of massive PE and improves the long-term prognosis of venous thrombosis.

At the same time, the severity of the condition of patients, conditioned by the nature and extent of primary surgical intervention and concomitant diseases, makes it possible to resort 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 causes, 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 can not be carried out in patients who have an operation on the abdominal cavity, it can be started with the plication of the inferior vena cava by 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 Conciliation Conference on Antithrombotic Treatment 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% are observed proximal thrombosis, which in 4-10% of cases is complicated by PE, which is 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 agents are used:

• Mechanical means accelerate the venous blood flow, which prevents the stagnation of blood in the veins of the lower limbs and thrombosis, they include a "foot pedal", elastic and intermittent compression.
• Elastic compression of the lower extremities by special elastic golfs or stockings.
• Intermittent pneumocompression of the legs with a special compressor and cuffs.
• "Foot pedal" provides a passive reduction of gastrocnemius muscles during and after surgery.
• Pharmacological agents support APTT between injections at a level that exceeds the APTT value for the laboratory of this hospital by 1.5 times. For the prevention of operative thrombosis, anticoagulants, antibiotics and drugs acting on the platelet hemostasis are shown.

Anticoagulants of direct action are prescribed before surgery and continue to be administered in the nearest postoperative period (7-14 days), however, in case of complicated course, longer pharmacotherapy may be required (for at least 1 month). Sodium heparin is not prescribed for preoperative and early postoperative periods in operations for esophageal cancer, hepatopancreatoduodenal tumor and rectal extirpation with preoperative irradiation, etc. Preventive therapy with heparins before surgery is not used in patients with suspected massive blood loss during surgery or extensive The surgical surface and abundant secretion from injured tissues. The use of heparin sodium in low doses reduces the risk of development of postoperative deep vein thrombosis by about 2/3, and PE - by 2 times.

• Heparin sodium s / c to 5000 units for 2 hours before the operation, then 2-3 times a day, during the postoperative period, the dose is adjusted depending on the APTT.
• Dalteparin sodium s / c to 2500 anti-Xa international units (IU) 12 hours before the operation and 12 hours after it or 5000 anti-Ha IU for 12 hours before, then 5000 anti-Ha IU once a day.
• Nadroparin calcium sc in 38 anti-Ha IU for 12 hours before the operation, 12 hours after it and then 57 anti-Ha IU once a day.
• Enoxaparin sodium n / c 4000 anti-Ha IU 40 mg for 12 hours before surgery, then 1 time per day.
• Acetylsalicylic acid is not a drug of choice for the prophylaxis of deep vein thrombosis, but there are reliable data that the use of drugs within 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.
• Infusion of rheopolyglucin 400 ml daily with pentoxifylline for 5-7 days after surgery or other means acting on the platelet hemostasis unit (clopidogrel, dipyridamole, etc.) in patients with these nosological groups are effective in combination with mechanical means.

With an exacerbation of thrombosis of superficial varicose veins before the operation, a course of antibacterial and anticoagulant therapy is indicated.

Forecast

In the absence of treatment, the lethality from PE makes up 25-30%, with the appointment of anticoagulants it drops 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. Long-term consequences are chronic pulmonary hypertension and respiratory failure.

[37], [38]