Pulmonary Thromboembolism

Pulmonary Thromboembolism Cheng Zhang ， Respiratory Medicine ， Affiliated Hospital of Jining Medicine college 23,Feb

GENARAL CONSIDRATIONS • Many substances can embolize to the pulmonary circulation, including air (during neurosurgery, fron central venous catheters, ),amniotic fluid (during active labor), foreign bodies (talc in intravenous drug users), parasite eggs (schistosomiasis), septic emboli(acute infectious endocarditis), and tumor cells

GENARAL CONSIDRATIONS • The most common embolus is thrombus, which may arise anywhere in the venous circulation or heart but most often originates in the deep veins of the major calf muscles • The majority of cases are not recognized antemortem, and fewer than 10% of patients with fatal emboli have received specific treatment for the condition

GENARAL CONSIDRATIONS • 50-60 percent of patients with proximal deep venous thrombosis(DVT) will develop pulmoary emboli; half of these embolic events will be asymptomatic • Nearly 70% of patients who present with symptomatic pulmonary emboli will have lower extremity DVT • The risk factors for pulmonary emboli are the risk factors for thrombus formation within the venous circulation: venous stasis, inlury to the vessel wall, and hypercoagulability(Virchow’s triad)

• Predisposing factors (risk) • Operation (especially spinal bone and joint (hip replacement),neurologic • Traum • Stay bed for long time • Elderly (aged) • Underlying diseases( heart lung kidney) • Tumor • Medicine (contraceptive,women of childbearing age)

epidemiology • High morbidity • High missed diagnosis and misdiagnosis • Prognosis without delay

GENARAL CONSIDRATIONS • Pulmonary thromboembolism(PE) has multiple physiologic effects. Physical obstruction of the vascular bed and vasoconstricction from neurohumoral reflexes both increase pulmonary vascular resistance. Massive thrombus may cause right ventricular failure • Vascular obstruction increases physiologic dead space (wasted ventilation)(V/Q ratio )and leads to hypoxemia through right –to –left shunting, decreased cardiac output, and surfactant depletion causing atelectasis. Reflex bronchoconstriction promotes wheezing and increases work of breathing

CLINICAL FINDINGS • SYMPTOMS AND SIGNS • The clinical findings depend on both the size of the embolus and the patient’s preexisting cardiopulmonary status. Dyspnea and chest pain on inspiration occur in 75%-85% and 65%-75% of patients, respectively. Tachypnea is the only sign reliably foud in more than half of patients • Hemoptysis accompany infarction; syncope may indicate massive embolism. dyspnea ,chest pain,hemoptysis triad is less than 1/3. But no single symptom or sign or combination of clinical findings is specific to PE. To establish the diagnosis or to exclude it definitively, further testing is required in the majority of patients

CLINICAL FINDINGS • LABORATORY FINDINGS •

•

a. The ECG is abnormal in 70% of patients with PE. The most common abnormalities are sinus tachycardia and nonspecific ST and T wave changes. Five percent or less of patients had P pulmonale, right ventricular hypertrophy, right axis deviation, and right bundle branch block. Double-edged sword .

• b. Arterial blood gases usually reveal acute respiratoy alkalosis due to hyperventilation. The arterial PO2 and PA-aDO2 are most often abnormal in patients with PE. Profound hypoxia with a normal chest radiograph in the absence of preexisting lung disease is highly suspicious for PE

CLINICAL FINDINGS •

Plasma levels of D-dimer are elevated in the presence of the thrombus. Usin a D-dimer threshold between 300 and 500 ng/mL has shown a sensitivity for PE of 95%-97% and a specificity of 45%

CLINICAL FINDINGS • IMAGING AND SPECIAL EXAMINATIONS • Chest Radiography

• The most frequent findings were atelectasis, parenchymal infliltrates, and pleural effusions. A prominent central pulmonary artery with local oligemin(westermark’s sign) or pleural-based areas of increased opacity that represent intraparenchymal hemorrhage (Hampton’s hump) are uncommon. The chest radiograph does not establish the diagnosis by itself. But it is necessary to exclude other common lung diseases

CLINICAL FINDINGS • CT • Helical CT arteriography is very sensitive for the detection of thrombus in the proximal pulmonary arteries but less so in the segemental and subsegemental arteries (with sensitivity of 53%-60% and specificity of 81%-97%). False-negative results may occur in up to 20% of helical CTs

CLINICAL FINDINGS • Lung Scanning • A normal perfusion scan excludes the diagnosis of clinically significant PE(negative predictive value of 91%). A high-probability V/Q scan is most of ten defined as having two or more segmental perfusion defects in the presence of normal ventilation and is sufficient to make the diagnosis of PE in the most instances (positive predictive value of 88%)

CLINICAL FINDINGS • Venous Thrombosis Studies • Commonly available diagnostic techniques include venous ultrasonography, impedance plethysmography, and contrast venography. The venous ultrasonography is the test of choice to detect proximal DVT and is diagnostic of firstepisode DVT (positive predictive value of 97%). An intraluminal filling defect in the contrast venography is diagnostic of venous thrombosis

CLINICAL FINDINGS • Pulmonary Arteriography • Pulmonary arteriography remains the reference standard for the diagnosis of PE. An intraluminal filling defect in more than one projection establishes a definitive diagnosis. Secondary findings highly suggestive of PE include abrupt arterial cutoff, asymmetry of blood flow-especially segmental oligemiaor a prolonged arterial phase with slow filling

CLINICAL FINDINGS • A definitive diagnosis was established in 97%. Pulmonary arteriography is a safe but invasive procedure with well-defined morbidity and mortality. Arteriography is indicated in patient in whom the diagnosis is in doubt when there is a high clinical pretest probabity of PE

CLINICAL FINDINGS • MRI • The test is noninvasive and avoids the use if potentially nephrotoxic adiocontrast dye. However, it remains expensive and not widly available

CLINICAL FINDINGS • Integrated Approach • The integrated approach uses the clinical likelihood of venous thromboembolism along with the overlapping results of noninvasive testing to come to one of three decision points: to establish venous thromboemblolism(PE or DVT) as the diagnosis; to exclude venous thromboembolism with sufficient confidence to follow the patient without therapy; or to refer the patient for pulmonary arteriography. An ideal diagnositic algorithm would proceed in a stepwise fashion to come to these decision points in a cost-effective way at minimal risk to the patient

Standard algorithm Clinical suspicion of Pulmonary Thromboembolism Ventilation-perfusion lung scan normal Pulmonary Thromboembolism excluded

Low or indeterminate probability

high probability treatment

Testing for deep venous thrombosis positive

negtive

treatment Pulmonary arteriogram or serial noninvasive testing for venous thrombosis

positive treatment

negtive Pulmonary Thromboembolism excluded

TREATMENT • ANTICOAGULATION • Heparin binds to and accelarates the ability of an antithrombin III to inactive thrombin, factor Xa, and factor Ixa. It thus retards additional thrombus formation, allowing endogenous fibrinolytic mechanisms to lyse existing clot. The standrd regimen of heparin followed by 6 months of oral warfarin results in an 80%-90% reduction in the risk if both recurrent venous thrombosis and death from PE

TREATMENT • Once the diagnosis of proximal DVT or pulmonary thromoembolism is established, it is critical to ensure adequate therapy (full anticoagulation with heparin without contraindications). The weightbased regimen in (Table 1-7-1) is superior to standard dosing. It is necessary to monitor the activated partial thromboplastin time (APTT) and ajust dosing to maintain the aPTT 1.5-2.5 times control

TREATMENT • LMW heparins appear to carry an equivalent or lower risk of hemorrhage ， and immune-mediated thrombocytopenia is less common • They are as effective as heparin in the treatment of venous thromboembolism • They are administered in dosages determined by body weight once or twice daily without the need for coagulation monitoring

TREATMENT • Anticoagulation therapy for venous thromboembolism is continued for a minimum of 3 months ， so oral anticoagulant therapy with warfarin is usually initiated concurrently with heparin ， initially at a dose of 2.5-10mg/d • The lower dose is preferred in elderly patients • Maintenanse therapy usually requires 2-15mg /d • Adequacy of therapy must be monitored by following the prothrombin time ， most often adjusted for differences in reagents and reported as the international normalized ratio ， or INR

TREATMENT • The target INR is 2.5 ， with the acceptable range from 2.0 to 3.0 • When oral anticoagulation with warfarin is contraindicated ， LMW heparin is a convenient alternative • It is reasonable to continue therapy for 6 months after a first episode when there is a reversible risk factor ， 12 months after a first-episode idiopathic thrombus ， and 6-12 months to indefinitely in patients with nonreversible risk factor or recurrent disease

TREATMENT • Thrombolytic therapy • Streptokinase ， urokinase ， and recombinant tissue plasminogen activator （ rt-PA ； altepiase ） increase plasmin levels and thereby directly lyse intravascular thrombi • In patients with established PE ， thrombolytic therapy accelerates resolution of emboli within the first 24 hours compared with standard heparin therapy

TREATMENT • However ， at 1 week and 1 month after diagnosis ， these agents show no difference in outcome compared with heparin and warfarin • There is no evidence that thrombolytic therapy improves mortality • The major disadvantages of thrombolytic therapy compared with heparin are its greater cost and a significant increase in major hemorrhagic complications

TREATMENT • Currents evidence supports thrombolytic therapy for PE in patients at high risk for death in whom the more rapid resolution of thrombus may be lifesaving • Such patients are usually hemodynamically unstable despite heparin therapy • Absolute contraindications to thrombolytic therapy include active internal bleeding and stroke within the past 2 months • Major contraindications include uncontrolled hypertension and surgery or trauma within the past 6 weeks

TREATMENT • Additional measures • Interruption of the inferior vena cava may be indicated in patients with a major contraindication to anticoagulation who have or are at high risk for development of proximal DVT or PE • Placement of an inferior vena cava filter is also recommended for recurrent thromboembolism ， for chronic recurrent thromboembolism with pulmonary hypertension ， and with the concurrent perfomance of surgical pulmonary embolectomy or pulmonary thromboendarterectomy

TREATMENT • These devices reduce the short-term incidence of PE in patients presenting with proximal lower extremity DVT • Pulmonary embolectomy is an emergency procedure of last resort with a very high mortality rate • Several catheter divices to fragment and extract thrombus through a transvenous approach have been reported in small numbers of patients

Prognosis • In the majority of deaths ， PE is not recognized antemortem or death occurs before specific treatment can be initiated • The outlook for patients with diagnosed and appropriately treated PE is generally good • Overall prognosis depends on the underlying disease rather than the PE itself • Approximately 1% of patients develop chronic thromboembolism pulmonary hypertension

Prevention • It is a prevalent disease ， clearly associated with identifiable risk factors • There is unambiguous evidence of the efficacy of prophylactic therapy ， yet it remains underused • Options for venous thromboembolism therapy begin with machanical devices such as graduatedcompression stockings and intermittent pneumatic compression • Stanard pharmacologic therapy in medical patients is low-dose unfractionated heparin ， 5000 units subcutaneously every 8-12 hours