How should anticoagulants and thrombolytics be used in patients with pulmonary embolism❓❓❓

Coronary heart disease, stroke and pulmonary embolism are the top three
causes of death in patients with cardiovascular disease. Pulmonary embolism includes pulmonary thromboembolism, air embolism, fat embolism and tumor embolism. Among them, pulmonary thromboembolism is the most common type of pulmonary embolism. Deep vein thrombosis of the lower extremities is the main cause of pulmonary thromboembolism. Pulmonary thromboembolism has a high morbidity and mortality rate. Therefore, the correct and rational use of anticoagulant and thrombolytic drugs in the treatment of pulmonary thromboembolism is very important.

Treatment of acute pulmonary thromboembolism.

Risk classification for acute pulmonary embolism.

	Hypotension or shock	Right ventricular insufficiency	Elevated cardiac biomarkers
Low risk	-	-	-
Low to moderate risk	-	Either is positive.
Moderate to high risk	-	+	+
High risk	+	+	+/-
Cardiac biomarkers: Markers of heart failure (eg, B-type Natriuretic Peptide, N-terminal pro-brain natriuretic peptide) and markers of myocardial injury (eg, cardiac troponin T, cardiac troponin I)

The treatment regimen is administered according to the risk classification.

Low risk: Anticoagulant therapy is used in low-risk patients. It is recommended for clinical observation in patients with subsegmental pulmonary embolism without proximal deep vein thrombosis of the lower extremities and in patients with a low risk of recurrent venous thromboembolism.

Low to moderate risk: Low to moderate risk patients are treated with anticoagulants.

Moderate to high risk: Patients at moderate to high risk are initially treated with anticoagulants. When the clinical symptoms of the patients worsen after treatment and there are no contraindications for thrombolytic drugs, the patients can be treated with thrombolytic drugs.

High risk: Treat high-risk patients with thrombolytic drugs. If the patient has contraindications to thrombolytic drugs, the patient should be treated with surgery or interventional therapy.

Thrombolytic therapy.

Commonly used thrombolytic drugs are alteplase, streptokinase and urokinase. Their thrombolytic effects are similar, and they are selected according to the clinical situation of the patient.

• Alteplase 50 mg is given by continuous intravenous infusion for 2 hours.
• Recombinant streptokinase 1.5 million U is given by continuous intravenous infusion for 2 hours.
• Urokinase 20,000 U/kg is given by continuous intravenous infusion for 2 hours.

Thrombolytic drugs activate plasminogen, which is converted into plasmin. Fibrin is hydrolyzed by plasmin and leads to thrombolysis. Thrombolytics are most effective when started within 48 hours and they can dissolve some or all of the thrombus rapidly. The treatment period is generally within 14 days.

Anticoagulation therapy.

Anticoagulant drugs can promote the action of the fibrinolytic mechanism to dissolve the formed thrombus. They are also effective in preventing the recurrence of embolism and the re-formation of thrombus. There are three recommended anticoagulation regimens for the treatment of pulmonary thromboembolism. Anticoagulation therapy should take at least 3 months.

Monotherapy: The following regimens may be considered for most patients with low to moderate risk pulmonary embolism.

• The loading dose of rivaroxaban was 15 mg twice daily for 21 days, then changed to 20 mg once daily.

• Or a loading dose of 10 mg apixaban twice a day for 7 days, then changed to 5 mg twice a day.

Sequential therapy: Patients are initially treated with a parenteral anticoagulant such as heparin. Because warfarin has a slower onset of action, overlap warfarin within 24 hours of initial treatment to adjust INR values within 2.0 to 3.0. After reaching the INR target, heparin was discontinued.

Sequential therapy: Patients are initially treated with a parenteral anticoagulant such as heparin for 5 to 14 days, and then switched to edoxaban or dabigatran.

Commonly used parenteral anticoagulant drugs are low molecular weight heparin, unfractionated heparin and fondaparinux. Unfractionated heparin is recommended for severely obese patients and with severe renal impairment (creatinine clearance <30ml/min). Unfractionated heparin has the highest risk of inducing thrombocytopenia, followed by low molecular weight heparin. Fondaparinux has the lowest risk of induction. If the platelet count decreases by more than 50% of the baseline value, heparin anticoagulants should be discontinued and non-heparin anticoagulants such as bivalirudin and argatroban should be used instead. 

Warfarin: Its anticoagulant effect is mainly by inhibiting the synthesis of new coagulation factor Xa. Because it has no effect on the already synthesized clotting factors, its onset will be slower.

Edoxaban, Apixaban and Rivaroxaban: Its anticoagulant effect is mainly by inhibiting the activity of coagulation factor Xa thereby reducing the synthesis of thrombin.

Dabigatran: Its anticoagulant effect works by directly inhibiting the activity of thrombin.