Acute pulmonary embolism: magnitude of the problem
Refinements in established diagnostic algorithms, and extension of their use to suspected pulmonary embolism in pregnancy
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Since the specificity of d-dimer testing in suspected PE decreases steadily with age [9], a multinational prospective cohort study evaluated a previously developed age-adjusted cut-off (age × 10 µg/L for patients older than 50 years) in a cohort of 3346 patients [10]. Patients with a normal age-adjusted d-dimer value did not undergo CTPA, but were left without anticoagulation and followed for a 3-month period. In patients aged > 75 years, using the age-adjusted (instead of the standard 500 µg/L) d-dimer cut-off increased the number of patients in whom PE could be excluded from 6.4% to 30%, without adding false-negative findings [10].
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Another prospective management trial used the so-called ‘YEARS’ clinical decision rule, which consists of three clinical items of the Wells score, namely signs of DVT, haemoptysis, and ‘PE more likely than an alternative diagnosis’, combined with d-dimer concentrations [11]. The diagnosis of PE was rejected without further testing in patients without clinical items and d-dimer levels < 1000 ng/mL, and in patients with at least one clinical item and d-dimers < 500 ng/mL. The remaining patients underwent CTPA. Of the 2946 patients (85%) in whom PE was thus ruled out and who were left untreated, 18 (0.61%, 95% confidence interval [CI] 0.36–0.96%) were diagnosed with symptomatic VTE during the 3-month follow-up [11]. Using the YEARS rule allowed to exclude PE without CTPA in 48% of the patients as compared to 34% if the original Wells’ rule and fixed d-dimer threshold of less than 500 ng/mL had been applied [11].
Risk-adjusted anticoagulation strategies
Advanced treatment and support of the patient with high-risk and intermediate–high-risk PE
(1) Cardiac arrest | (3) Persistent hypotension | |
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Need for cardiopulmonary resuscitation | Systolic BP < 90 mmHg, or vasopressors required to achieve a BP ≥ 90 mmHg despite adequate filling status | Systolic BP < 90 mmHg, or systolic BP drop ≥ 40 mmHg, either lasting longer than 15 min and not caused by new-onset arrhythmia, hypovolaemia, or sepsis |
And | ||
End-organ hypoperfusion (altered mental status; cold, clammy skin; oliguria/anuria; increased serum lactate) |
Definition of low-risk PE and implications for early discharge and home (outpatient) treatment
An updated management algorithm for pulmonary embolism
Long-term and extended anticoagulation for secondary VTE prevention
Clinical setting | Suggested management | Comments |
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Subsegmental PE | Single subsegmental PE in an outpatient without cancer and without proximal DVT: Clinical surveillance Single subsegmental PE in a hospitalised patient, or a patient with cancer, or if associated with confirmed proximal DVT: Anticoagulant treatment Multiple subsegmental PE: Anticoagulant treatment | Poor interobserver agreement for the diagnosis of subsegmental PE; diagnosis to be confirmed by an experienced thoracic radiologist Suggestion based on indirect evidence, only limited data available |
Incidental PE | If single subsegmental PE: Proceed as above In all other cases: Αnticoagulant treatment | Suggestion based on retrospective cohort data |
Management of acute PE in a patient with active bleeding | Insert inferior vena cava filter (preferably retrievable) Reassess the possibility of anticoagulation as soon as the bleeding has ceased and the patient is stabilised, and remove the filter as soon as anticoagulant treatment is resumed | |
PE diagnosis and anticoagulation in the elderly, frail patient, and the patient with polypharmacy | Assess clinical probability of PE as in the non-frail patient, but caution needed in the nursing home setting as clinical prediction rules may be unreliable [44] Generally prefer NOACs over VKAs in elderly and frail patients, but observe the following: (a) Avoid NOACs in patients with severe renal impairment (b) Consult the drugs’ SPC and the updated EHRA guide [19] for possible interactions between NOACs and the patient’s concomitant medication Reassess, at regular intervals, drug tolerance and adherence, hepatic and renal function, and the patient’s bleeding risk | Number of diseases mimicking PE symptoms increases with age, making diagnostic delay more common These patients were poorly represented in clinical trials. Whatever the treatment (VKAs or NOACs), these patients are at high risk of bleeding |
Management of acute PE in a patient with signs of chronic pulmonary hypertension on TTE, or findings suggesting pre-existing CTEPH on CTPA (suspected ‘acute-on-chronic’ PE) | If the diagnosis of acute PE has been confirmed, focus on the patient’s acute problem and proceed to risk-adjusted acute-phase treatment of PE as described in Fig. 1 Perform a TTE upon discharge and document any signs of persisting pulmonary hypertension or RV dysfunction Continue anticoagulation for at least 3 months and schedule the patient for a 3-month follow-up visit At the 3-month follow-up visit, assess the presence of persisting or worsening symptoms, or functional limitation, perform follow-up TTE and consider further tests before possible referral to a PH/CTEPH expert centre | |
Initial anticoagulation in the patient with acute PE and end-stage renal disease | Administer UFH; consider anti-Xa (rather than aPTT) monitoring [45] | No truly safe anticoagulation option available, although LMWH with anti-Xa monitoring is also used in clinical practice |
Duration of anticoagulation in the young female patient suffering acute PE while on oral contraceptives | If patient was taking an oestrogen-containing contraceptive, and especially if PE occurred in the first 3 months of initiation of contraception: Discontinue hormonal contraceptives after discussing alternative methods of contraception; consider discontinuing anticoagulation after 3 months All other cases: Manage chronic anticoagulation as after acute PE occurring in the absence of identifiable risk factors Consider using a validated prediction model for quantification of the risk for VTE recurrence; for example, the HERDOO2 score: (a) hyperpigmentation, oedema, or redness in either leg; (b) d-dimer level ≥ 250 μg/L; (c) obesity with body mass index ≥ 30; (d) older age (essentially 0 in this case) A score of 0 or 1 may help identify young women who can safely discontinue anticoagulant treatment Advise patient on the need for prophylaxis with LMWH in case of pregnancy | |
Anticoagulation in the patient with PE and cancer, after the first 6 months | If cancer still activea Continue anticoagulation with LMWH or, alternatively, edoxaban or rivaroxaban If cancer in remission: Continue oral anticoagulation (NOAC or VKA); alternatively, consider discontinuing if the bleeding risk is high. In either case, periodically reassess the risk–benefit ratio of continuing/resuming anticoagulation | In the absence of conclusive evidence, the decision to continue or stop after the first 6 months anticoagulation should be made on a case-by-case basis after considering the success of anti-cancer therapy, the estimated overall risk of VTE recurrence, the bleeding risk, and the preference of the patient |