Pulmonary thromboembolism (PTE) is the most common type of pulmonary embolism, and is caused by the obstruction of the pulmonary artery or its branches by embolus from the venous system or the right heart, with main clinical and pathophysiological features of dysfunction of pulmonary circulation and respiratory system. The thrombus causing PTE mainly originates from deep vein thrombosis (DVT). DVT and PTE are essentially manifestations of the same disease process at different sites and stages, and are collectively termed venous thromboembolism (VTE).
Recurrent thromboembolism in the pulmonary artery, and the non-dissolution and organization of the embolus, resulting in chronic mechanical obstruction in the blood vessels, termed chronic thromboembolic pulmonary disease (CTEPD). In the late stage, pulmonary vascular remodeling gradually occurs with the progression of the disease, leading to further narrowing or occlusion of the blood vessels, increased pulmonary vascular resistance (PVR), and progressive increase in pulmonary artery pressure, ultimately resulting in right ventricular hypertrophy and right heart failure in many months or years, which is termed chronic thromboembolic pulmonary hypertension (CTEPH).
Risk factors
Any factors that can lead to venous blood stasis, vascular endothelial injury, and hypercoagulability (Virchow triad) are risk factors for VTE, which can be divided into hereditary and acquired risk factors.
Hereditary risk factors are mostly genetic variations and are often characterized by recurrent arterial and venous thromboembolism. If patients under the age of 50 have recurrent VTE without apparent precipitating factors or have familial predisposition to the disease, thrombophilia should be vigilantly considered.
Table 1 Risk factors of PTE
Acquired risk factors are various acquired pathophysiological abnormalities that easily lead to the occurrence of VTE, mostly temporary or reversible. Malignant tumors are important risk factors for VTE, and the risk of VTE significantly increases during the active stage of tumors. VTE and arterial diseases have some common risk factors, such as cigarette smoking, obesity, hypercholesterolemia, hypertension, and diabetes. Myocardial infarction and heart failure can also increase the risk of VTE. Age is an independent risk factor for the occurrence of VTE, and the incidence of VTE gradually increases with aging. Some patients cannot identify risk factors through more comprehensive examination, which is termed idiopathic VTE. Some patients with idiopathic VTE have occult malignant tumors, and screening and follow-up should be conducted.
Pathology and pathophysiology
The embolus of PTE can originate from the inferior vena cava, superior vena cava, and right cardiac chamber, mostly deep veins of the lower extremities. About 70% of PTE patients have DVT in the lower extremities, and about 50% of patients with proximal DVT have symptomatic PTE.
Figure 1 Formation of PTE
After the formation of deep vein thrombosis in the periphery, the thrombus detaches and migrates with the venous blood flow to the pulmonary artery, forming a thromboembolism in the pulmonary artery.
Increased PVR and cardiac insufficiency
When the embolus blocks the pulmonary artery and its branches to a certain extent (30% - 50%), the increase of PVR occurs due to mechanical obstruction, which leads to an increase in the afterload of the right ventricle and an increase in pulmonary artery pressure. The enlargement of the right heart causes the interventricular septum to shift to the left, damaging the function of the left ventricle. Therefore, the left ventricle is blocked from filling in the early diastolic phase, resulting in a decrease in cardiac output, which causes hypotension in the systemic circulation and hemodynamic instability. The decrease in cardiac output, hypotension in the aorta, and the increase in right ventricular pressure lead to a decrease in coronary perfusion pressure, especially the subendocardial myocardium of the right ventricle is in a state of hypoperfusion.
Respiratory insufficiency
The decrease in cardiac output leads to a decrease in mixed venous oxygen saturation. PTE causes vascular obstruction, reduced pulmonary blood flow at the embolism site, and an increase in alveolar dead space; pulmonary blood flow is redistributed, and perfusion in unobstructed vessels increases, resulting in ventilation-perfusion mismatch and hypoxemia. About 1/3 of patients have reopening of the foramen ovale due to increased right atrial pressure, resulting in right-to-left shunt, which may lead to severe hypoxemia and increased risk of paradoxical embolism and sudden death. Distal small embolus may cause local hemorrhagic atelectasis, namely pulmonary infarction, cause local alveolar hemorrhage, manifested by hemoptysis, and may be accompanied by pleurisy and pleural effusion, thereby affecting gas exchange.
CTEPH
Acute PTE in some patients cannot be completely dissolved after treatment, the embolus is organized, and the intima of the pulmonary artery undergoes chronic inflammation and thickening, developing into chronic PTE. In addition, repeated embolization of the pulmonary artery due to multiple detachments of DVT is also a major cause of chronic PTE. Organization of pulmonary artery embolus is accompanied by vascular remodeling and in situ thrombosis, resulting in lumen stenosis or occlusion, and the PVR and pulmonary artery pressure gradually increase, forming pulmonary hypertension. Various influencing factors such as hypoxemia can aggravate this process, and the afterload of the right heart further increases, eventually leading to right heart failure.
Clinical manifestations
The clinical manifestations of acute PTE lack specificity, and the severity also varies greatly. Mild patients may be asymptomatic, while severe patients may present hemodynamic instability, shock, and even sudden death. During the diagnosis process, attention should also be paid to whether there are clinical manifestations of DVT.
Symptoms
Dyspnea and tachypnea are the most common symptoms, particularly after activity, and can be relieved at rest. Sometimes patients have chest tightness in case of sudden change of positions, defecation, or ascending the stairs.
Thoracodynia includes pleuritic thoracodynia and angina-like pain. The former is more common, and is characterized by significant exacerbation in case of deep breath or cough. The latter is only seen in few patients, and is severe compressive pain behind the sternum, resembling angina.
Hemoptysis occurs in about 1/3 of patients, mostly within 24 hours after pulmonary infarction, often little hemoptysis, and massive hemoptysis is less common.
Dysphoria, panic, and even near-death experience may be related to thoracodynia or hypoxemia.
Cough, mostly dry cough or little white expectoration, occurs in about 1/3 of patients,
Syncope can be the only or initial symptom of acute PTE, is caused by large thromboembolism blocking more than 50% of the pulmonary vessels, significantly reducing cardiac output and causing insufficient cerebral blood supply, and may be related to neural reflexes in some patients.
Each patient may present different combinations of the above symptoms. Sometimes, the so-called triad of pulmonary infarction can occur in clinical practice; that is, dyspnea, thoracodynia, and hemoptysis occur simultaneously; but are only seen in about 20% of patients.
Signs
Tachypnea and cyanosis can occur, wheezing and/or fine moist crackles can be heard in the lungs, and vascular murmurs can be occasionally heard. Corresponding signs appear in case of concurrent atelectasis and pleural effusion.
Circulatory system signs are mainly pulmonary hypertension, right heart insufficiency, and a sharp decrease in left ventricular output. Sinus tachycardia is the most common, and arrhythmias such as premature contractions, supraventricular tachycardia, atrial flutter, and atrial fibrillation can be seen. The accentuation or splitting of the second heart sound in the pulmonary valve area (P2 > A2) can be heard in some patients, and systolic ejection murmurs can be heard in few patients. Signs of right heart failure such as jugular vein distention or abnormal pulsation, systolic murmurs in the tricuspid area, right ventricular gallop rhythm, hepatomegaly, hepatojugular reflux sign, and lower extremity swelling are present. Few patients have pericardial friction sounds. Severe patients can have hypotension or even shock.
Fever, mostly low-grade fever, but also fever above 38°C, may be present and can be caused by secondary infections such as pulmonary infarction, pulmonary hemorrhage, and atelectasis, as well as thrombophlebitis of the lower extremity.
Manifestations of DVT
The main manifestations are swelling of the affected limb, increased circumference, pain or tenderness, skin pigmentation, and fatigue or increased swelling in the affected limb after walking. Attention should be paid to asymmetrical swelling of both lower extremities. The circumference of both lower extremities can be measured to evaluate the difference. The measurement points of the circumference of the thigh and calf are 15 cm above the upper edge of the patella and 10 cm below the lower edge of the patella, respectively. A difference of more than 1 cm on both sides is of clinical significance. About more than half of patients with lower extremity DVT have no subjective symptoms and obvious signs.
Diagnosis
Diagnosis includes clinical diagnosis, definite diagnosis, and etiological diagnosis.
Clinical diagnosis
In case of clinical manifestations such as unexplained dyspnea, thoracodynia, syncope, and shock, with or without asymmetric swelling and pain in the lower extremities, the following examinations should be conducted.
Plasma D-dimer test
The diagnostic sensitivity of D-dimer for acute PTE is between 92% and 100%, and the test has a high negative predictive value for patients with low clinical possibility of suspected PTE. The use of enzyme-linked immunosorbent assay, enzyme-linked immunofluorescence analysis, highly sensitive quantitative microparticle agglutination assay, and chemiluminescence immunoassay for D-dimer detection has high sensitivity. If D-dimer < 500μg/L, acute PTE can be basically excluded.
The diagnostic specificity of D-dimer gradually decreases with the increase of age. The age-adjusted D-dimer cutoff value [in patients age > 50, age (years) × 10μg/L] can increase the specificity. Malignant tumors, inflammation, hemorrhage, trauma, surgery, and necrosis can cause a certain level of increase in D-dimer, which requires dynamic observation in combination with clinical interpretation.
Arterial blood gas analysis
Hypoxemia can occur when more than 15% of the pulmonary vascular bed is obstructed. Acute PTE often presents with hypoxemia, hypocapnia, and an increase in the alveolar-arterial oxygen partial pressure difference [PA-aO2]. The results in some patients can be normal.
Plasma troponin assay
Plasma troponin includes cardiac troponin I (cTNI) and cardiac troponin T (cTNT). Acute PTE complicated by right ventricular dysfunction (RVD) can cause an increase in troponin. The high level of troponin suggests severe myocardial injury and poor prognosis.
Brain natriuretic peptide (BNP) and N-terminal pro b-type natriuretic peptide (NT-proBNP) assays
BNP and NT-proBNP are cardiac hormones synthesized and secreted by ventricular myocytes when the pressure load increases or the ventricle dilates. In patients with acute PTE, the afterload of the right ventricle increases, the ventricular wall tension increases, and the levels of BNP and NT-proBNP in the blood increase. The increased levels can reflect the severity of right ventricular insufficiency and hemodynamic disorder. In patients without clear underlying heart disease, if the levels of BNP or NT-proBNP are increased, the possibility of PTE should be considered. This indicator can also be used to assess prognosis.
Electrocardiogram (ECG)
Most patients present non-specific ECG abnormalities. Sinus tachycardia and T-wave changes and ST-segment abnormalities in V1 - V4 are more common. Some patients may present the SIQIIITIII` sign (deepened S wave in lead I, and Q/q wave and inverted T wave in lead Ⅲ). Other ECG changes include complete or incomplete right bundle branch block, pulmonary P wave, right axis deviation, and clockwise rotation. Dynamic changes of ECG are more significant than static abnormalities in suggesting PTE.
Echocardiography
Echocardiography is of great value in suggesting the diagnosis of PTE, detecting right ventricular dysfunction, and excluding other cardiovascular diseases. Signs of increased afterload of the right ventricle can be found. In few suspected PTE patients, embolism in the right atrium, right ventricle, and pulmonary artery can be found simultaneously.
Through different possibility assessment scales, suspected PTE can be classified into different clinical possibilities.
Definite diagnosis
The confirmatory tests for PTE include computed tomography pulmonary angiography (CTPA), ventilation/perfusion imaging (V/Q imaging), magnetic resonance pulmonary angiography (MRPA), and pulmonary angiography; while the confirmatory imaging tests for DVT include compression venous ultrasound, CT venography, radionuclide venography, and venography.
CTPA
CTPA can visually display the morphology, location, and severity of vascular occlusion of the embolus in the pulmonary artery, and has been the preferred test for the diagnosis of PTE. Direct signs are filling defects in the pulmonary artery, partially or completely surrounded by opaque blood flow (railway track sign), or complete filling defects, and nonvisualized distal blood vessels; indirect signs include wedgy or linear opacities with increased density or discoid atelectasis in the lung field, dilation of the central pulmonary artery, and reduction or absence of distal vascular branches.
Figure 2 CTPA (Right pulmonary artery level)
The embolus at the distal right pulmonary artery (A) extends into the artery of the dorsal segment of the right lower lobe (B); the mural embolus adheres to the lateral wall at the distal left pulmonary artery (C).
V/Q imaging
The typical sign is a pulmonary perfusion defect distributed in the pulmonary segment, which does not match the ventilation imaging, and has higher diagnostic value for distal pulmonary embolism. Because many diseases can simultaneously affect lung ventilation and blood flow, the result interpretation of V/Q imaging is relatively complex and needs clinical data. V/Q imaging can be preferentially applied to outpatients with a low clinical possibility, young patients (especially female patients), pregnant patients, patients allergic to contrast agents, and patients with severe renal insufficiency.
MRPA
MRPA can directly show the embolus in the pulmonary artery and the low perfusion area caused by PTE, but its diagnostic value for PTE below the pulmonary segment level is limited. MRPA has no x-ray radiation, does not use iodine-containing contrast agents, and can be imaged in any orientation, but it has high requirements for instruments and techniques, and the examination time is long. MRPA is suitable for patients with severely impaired renal function or allergy to iodine contrast agents and pregnant patients.
Pulmonary angiography
Pulmonary angiography is the gold standard for the diagnosis of PTE, with both high sensitivity and specificity. The direct signs include contrast agent filling defects in the pulmonary vessels, with or without flow interruption accompanied by railway track sign; the indirect signs include slow flow of the contrast agent, local hypoperfusion, and delayed venous return. If the direct signs of PTE are absent, PTE cannot be diagnosed. Pulmonary angiography is an invasive examination, and the possibility of fatal or serious complications is 0.1% and 1.5%, respectively. Indications should be strictly required.
In patients with suspected PTE, it is recommended to adopt different diagnostic strategies depending on whether there is concurrent hemodynamic disorder.
In suspected PTE patients with hemodynamic instability, if conditions permit, it is recommended to complete CTPA examination to confirm the diagnosis or exclude PTE; if there are no conditions or it is not suitable for CTPA examination, it is recommended to perform bedside echocardiography. If evidence of increased right heart load and/or embolus in the pulmonary artery or right heart cavity is found, after the possibility of other diseases is excluded, it is recommended this condition can be treated as PTE.
In suspected patients with hemodynamic stability, CTPA is the preferred confirmatory examination. If there are relative contraindications to CTPA examination such as contrast agent allergy, renal insufficiency, and pregnancy, it is recommended to choose other imaging confirmatory examinations, including V/Q imaging and MRPA.
Etiological diagnosis
For suspected PTE, regardless of presence or absence of DVT symptoms, examinations such as compression ultrasound of the deep veins of the lower extremities should be conducted to determine whether there is DVT and the source of the embolus.
Precipitating factors for DVT and PTE, including immobilization, trauma, long-term oral contraceptives, and diseases that lead to prothrombotic tendency such as antiphospholipid syndrome should be researched. Antiphospholipid antibody tests include lupus anticoagulant, anticardiolipin antibody, and anti-β2 glycoprotein 1 antibody tests. The diagnosis of antiphospholipid syndrome, in addition to the clinical criteria, requires the laboratory criteria composed of two positive antiphospholipid antibody tests with an interval of at least 12 weeks and exclusion of false positives caused by anticoagulants.
Attention should also be paid to whether patients have hereditary prothrombotic tendency, recurrent PTE, or prominent family history of VTE, particularly in patients under the age of 50. The most common manifestations of thrombophilia include hereditary deficiencies of antithrombin, protein C, and protein S. When conducting anticoagulant protein activity assay and interpreting the results, attention should be paid to the time to the test and the influence of anticoagulants on the results.
In patients with unexplained PTE and with hereditary prothrombotic tendency (early onset, recurrence, VTE in less common sites, family history), genetic testing can be considered. In older patients, potential malignant tumors should be vigilantly considered and close follow-up should be conducted.
Clinical classification
Acute PTE
High-risk PTE
Hemodynamic instability indicates high-risk PTE. Clinical symptoms in combination with significant right heart failure and hemodynamic instability indicate a high risk of early death (in hospital or within 30 days after onset).
Table 2 Definition of hemodynamic instability
Intermediate-risk PTE
Hemodynamics is stable, but there is imaging evidence of right ventricular dysfunction (RVD) and/or elevated cardiac biomarkers.
Intermediate-high-risk PTE
Both RVD and elevated cardiac biomarkers exist simultaneously.
Intermediate-low-risk PTE
Either RVD or elevated cardiac biomarkers is present.
Diagnostic criteria for RVD
Imaging evidence including echocardiography and CT suggests RVD.
Ultrasound examination conforms to the following manifestations:
- Right ventricular dilation (right ventricular end-diastolic diameter / left ventricular end-diastolic diameter > 1.0)
- Reduced amplitude of the free wall movement of the right ventricle
- Increased tricuspid regurgitation velocity
- Reduced tricuspid annular systolic displacement (< 17mm)
If four-chamber CTPA shows right ventricular dilation (right ventricular end-diastolic diameter / left ventricular end-diastolic diameter > 1.0), RVD can also be diagnosed.
Cardiac biomarkers include BNP, NT-proBNP, and troponin.
Chronic thromboembolic pulmonary hypertension (CTEPH)
CTEPH mostly has related clinical manifestations of chronic and progressive pulmonary hypertension, such as progressively aggravated dyspnea, malaise, and decreased exercise tolerance, as well as right heart failure in the late stage; Imaging examinations confirm pulmonary artery obstruction, often multiple, extensive obstructions. Chronic embolism signs such as eccentrical masses adhered to the vascular wall in the pulmonary artery, with a tendency of calcification, can be seen. The presence of DVT is often found. At sea level, in the resting state, the mean pulmonary artery pressure (mPAP) measured by right heart catheterization is ≥ 25 mmHg, and vasculitis and pulmonary artery sarcoma are excluded. Echocardiography shows thickening of the right ventricular wall, which conforms to the diagnostic criteria of chronic pulmonary heart disease.
Differential diagnosis
Concurrent thoracodynia
Acute coronary syndrome
Some PTE patients may have insufficient coronary artery blood supply and myocardial hypoxia, manifested by chest tightness and angina-like thoracodynia; the electrocardiogram shows changes of myocardial ischemia; this condition can be easily misdiagnosed as angina or myocardial infarction caused by coronary heart disease. Coronary heart disease has its own onset characteristics. Dynamic changes in electrocardiogram and myocardial enzyme levels, and coronary angiography can confirm the diagnosis. Some PTE coexists with coronary heart disease.
Aortic dissection
Most patients have hypertension and severe pain. Chest x-ray films often show mediastinal widening. Cardiovascular ultrasound and chest CT angiography can show signs of aortic dissection.
Concurrent dyspnea
Pneumonia
When PTE presents with cough, hemoptysis, dyspnea, and pleurisy-like thoracodynia; and imaging shows atelectasis and pulmonary opacities, especially when there is concurrent fever; PTE needs to be differentiated from pneumonia.
Bronchial asthma
Most PTE patients have manifestations such as chest tightness and tachypnea, and PTE needs to be differentiated from bronchial asthma.
Concurrent pleural effusion
PTE may have pleurisy-like thoracodynia and pleural effusion, and needs to be differentiated from other diseases that cause pleural effusion, such as tuberculosis, pneumonia, tumors, and left heart failure.
Concurrent syncope
When PTE has syncope, PTE needs to be differentiated from other diseases that cause syncope, such as vasovagal syncope, cerebrovascular syncope, and arrhythmia.
Concurrent shock
The shock caused by PTE is obstructive shock, manifested by low arterial blood pressure and high venous pressure. PTE needs to be differentiated from cardiogenic, hypovolemic, and distributive shock.
Concurrent hemoptysis
Hemoptysis is seen in many diseases. Hematemesis caused by gastrointestinal hemorrhage needs to be excluded. PTE needs to be differentiated from tuberculosis, bronchiectasis, tumors, and left heart failure.
Space-occupying lesions in the pulmonary artery
PTE needs to be differentiated from fat embolism syndrome, amniotic fluid embolism, air embolism, tumor embolism, and foreign body embolism, as well as primary malignant tumors of the pulmonary artery and pulmonary arteritis.
Treatment
General supportive treatment
The changes of respiration, heart rate, blood pressure, electrocardiogram, and blood gas should be closely monitored.
In patients with concurrent hypoxemia, nasal cannula oxygen therapy, facemask oxygen therapy, or high-flow nasal cannula oxygen therapy should be used. In patients with respiratory failure, non-invasive mechanical ventilation or invasive mechanical ventilation through tracheal intubation can be adopted. Vasoactive drugs such as dopamine, dobutamine, or norepinephrine can be applied to maintain effective hemodynamics and improve right heart function.
Appropriate sedatives and analgesics can be used; Attention should be paid to maintaining unobstructed defecation and avoiding straining.
Anticoagulation therapy
Anticoagulation therapy is the basic treatment for PTE. Once acute PTE is identified, anticoagulation therapy should be initiated as soon as possible.
In patients with low-risk PTE, anticoagulation therapy should be given; in patients with high-risk PTE, thrombolytic therapy should be performed and followed by anticoagulation therapy; in patients with intermediate-risk PTE, whether thrombolysis is performed or not, anticoagulation therapy should be conducted.
Contraindications include active hemorrhage and uncontrolled severe hypertension, which are mostly not absolute contraindications in acute PTE. The main complication is hemorrhage.
Anticoagulants can be divided into parenteral anticoagulants and oral anticoagulants.
Unfractionated heparin (UFH) intravenously 2,000-5,000 U or 80 U/kg, followed by 18 U/(kg.h), can be administered. The dose can be adjusted according to monitored APTT. During treatment, platelet count needs to be monitored, and heparin-induced thrombocytopenia should be vigilantly considered.
Low molecular weight heparin (LMWH) subcutaneously once or twice a day can be given. Platelet count also needs to be monitored during treatment. LMWH is cleared by the kidneys, and should be used with caution in patients with renal insufficiency.
Fondaparinux sodium is a selective factor Xa inhibitor, and mediates the inhibitory effect on factor Xa by specifically binding to antithrombin. The treatment regimen is subcutaneously 5 mg once a day (body weight < 50 kg), 7.5 mg once a day (body weight between 50 and 100 kg), 10 mg once a day (body weight > 100 kg), and the dose should be adjusted according to renal function.
After the initiation of parenteral initial anticoagulation treatment, oral anticoagulants should be administered according to the clinical situation.
Warfarin is the most common, and the initial dose is generally 3.0-5.0 mg, but 2.5-3.0 mg in patients over age 75 or with high risk of hemorrhage. The international normalized ratio (INR) can be detected once every 1-2 weeks after reaching the standard. It is recommended to maintain INR at 2.0-3.0, and INR can be detected once every 4-12 weeks after stability.
Direct oral anticoagulants (DOACs) directly inhibit a certain target point in the coagulation pathway to produce anticoagulant effects, mainly including direct factor Xa inhibitors and direct thrombin inhibitors. The representatives of direct factor Xa inhibitors are rivaroxaban, apixaban, and edoxaban; the representative of direct thrombin inhibitors is dabigatran etexilate.
Once hemorrhage occurs, the drugs should be discontinued immediately, and prothrombin complex and fresh frozen plasma can be given.
For acute PTE with a clear diagnosis, if there are no special circumstances, at least 3 months of anticoagulation therapy should be received. In initially diagnosed patients secondary to short-term or reversible risk factors, after 3 months of anticoagulation therapy, if acute PTE is cured, drug withdrawal can be considered. In patients without short-term or reversible risk factors, including recurrent VTE (at least one episode of PTE or DVT), antiphospholipid syndrome, and hereditary thrombophilia, it is recommended to extend the anticoagulation time. In patients with initially diagnosed PTE and no identifiable risk factors, with persistent risk factors, or with mild short-term or reversible risk factors, extended anticoagulation time can be considered, and the relevant risk factors should be searched and removed. In PTE patients with concurrent tumor, it is recommended to perform long-term or even lifelong anticoagulation therapy until the tumor is completely relieved.
Thrombolytic therapy
The time window for thrombolysis is generally set within 14 days, and thrombolysis should be conducted prudently on the premise of confirmed diagnosis of acute PTE.
Thrombolysis is mainly indicated to high-risk acute PTE. As long as patients have no contraindications to thrombolytic therapy, thrombolysis should be initiated as early as possible. For intermediate-risk PTE, routinely systematic thrombolysis is not recommended, and the benefits and risks of thrombolytic therapy should be weighed. For low-risk PTE, thrombolytic therapy is not recommended. In patients whose hemodynamics deteriorate during anticoagulation therapy, salvage thrombolytic therapy is recommended.
The contraindications of thrombolytic therapy are divided into absolute contraindications and relative contraindications. For fatal high-risk PTE, absolute contraindications should also be regarded as relative contraindications.
Table 3 Contraindications of thrombolytic therapy
The common thrombolytics include urokinase, streptokinase, and recombinant tissue-type plasminogen activator (rt-PA). rt-PA may have a faster dissolving effect on embolus. Low-dose thrombolysis (50mg rt-PA) has similar efficacy compared to the recommended dose (100mg rt-PA), but with better safety.
After the thrombolytic therapy is completed, APTT should be measured once every 2 hours. When its level is < 2 times of the normal value, standard anticoagulation therapy should be restarted, and UFH anticoagulation is preferred.
The main complication of thrombolytic therapy is hemorrhage. The risk of hemorrhage should be fully evaluated before medication, and blood transfusion should be prepared if necessary. Before thrombolysis, a peripheral venous cannula should be indwelled to facilitate blood sampling and monitoring during thrombolysis. Other side effects of thrombolytic therapy include fever, allergic reactions (more common in streptokinase), hypotension, nausea, emesis, myalgia, and headache.
Interventional therapy
The purpose of interventional therapy is to remove embolus to facilitate the recovery of right heart function and improve symptoms and survival. Interventional therapy is mainly transcatheter aspiration and mechanical embolectomy, with local low-dose thrombolysis. Complications include distal embolism, pulmonary artery perforation, pulmonary hemorrhage, cardiac tamponade, cardiac conduction block or bradycardia, hemolysis, renal insufficiency, and puncture-related complications.
In most acute PTE patients, it is not recommended to routinely implant inferior vena cava filters. In acute PTE patients with contraindications to anticoagulation, in order to prevent large thrombus in the deep veins of the lower extremities from detaching again and blocking the pulmonary artery, placement of inferior vena cava filters can be considered. It is recommended to use retrievable filters, which are usually removed within 2 - 4 weeks.
Surgical treatment
Pulmonary artery thrombectomy can be used as an alternative and remedial measure for systemic thrombolysis, and is indicated to acute high-risk PTE ineffective after active medical or interventional treatment.
Treatment of CTEPH
Treatment of CTEPH includes basic treatment, surgical treatment, drug treatment, and interventional treatment. Basic treatment mainly includes long-term anticoagulation therapy, home oxygen therapy, improvement of cardiac function, and rehabilitation therapy. Long-term anticoagulation therapy should be conducted for CTEPH patients. If the obstruction site is at the proximal pulmonary artery accessible by surgery, pulmonary endarterectomy is preferred. For distal lesions, balloon pulmonary angioplasty can be considered. In patients who cannot undergo surgery or intervention, or have residual pulmonary hypertension after surgery, targeted drug therapy for pulmonary hypertension can be considered.
Prevention
Early identification of high-risk patients and prompt prevention can significantly reduce the incidence of nosocomial VTE. In patients with risk factors for DVT-PTE, the risk of DVT-PTE and the risk of hemorrhage should be evaluated according to the severity of the disease, age, and whether there are other risk factors, and corresponding preventive measures should be given.
Basic prevention includes reinforcement of health education, activities, and avoidance of dehydration.
In patients with a high risk of VTE and a low risk of hemorrhage, prophylaxis such as LMWH, UFH, fondaparinux sodium, and DOACs should be considered. In patients receiving long-term prophylaxis, the effect of prevention and the potential risk of hemorrhage should be evaluated dynamically.
In patients with a high risk of VTE but with active hemorrhage or risk of hemorrhage, mechanical prophylaxis, including intermittent pneumatic compression, graduated compression elastic stockings, and plantar venous pumps, can be given.